@article {pmid39890520,
year = {2025},
author = {Baker, SG and Etzioni, R},
title = {Letter to the editor regarding "Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies".},
journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pan.2025.01.009},
pmid = {39890520},
issn = {1424-3911},
}

@article {pmid39890296,
year = {2025},
author = {Cheng, GS and Ramirez, JA and Staitieh, BS and Evans, SE},
title = {Challenges of Managing Pulmonary Disease in the Immunocompromised Host.},
journal = {Clinics in chest medicine},
volume = {46},
number = {1},
pages = {xiii-xvii},
doi = {10.1016/j.ccm.2024.12.001},
pmid = {39890296},
issn = {1557-8216},
}

@article {pmid39889280,
year = {2025},
author = {Santiago-Torres, M and Mull, KE and Sullivan, BM and Cupertino, AP and Salloum, RG and Triplette, M and Zvolensky, MJ and Bricker, JB},
title = {Evaluating the Impact of Pharmacotherapy in Augmenting Quit Rates Among Hispanic Adults in an App-Delivered Smoking Cessation Intervention: Secondary Analysis of a Randomized Controlled Trial.},
journal = {JMIR formative research},
volume = {9},
number = {},
pages = {e69311},
doi = {10.2196/69311},
pmid = {39889280},
issn = {2561-326X},
mesh = {Humans ; *Smoking Cessation/methods ; Female ; Male ; Adult ; *Hispanic or Latino ; *Mobile Applications ; Middle Aged ; *Varenicline/therapeutic use ; *Tobacco Use Cessation Devices ; Smoking Cessation Agents/therapeutic use ; Bupropion/therapeutic use ; White ; },
abstract = {BACKGROUND: Hispanic adults receive less advice to quit smoking and use fewer evidence-based smoking cessation treatments compared to their non-Hispanic counterparts. Digital smoking cessation interventions, such as those delivered via smartphone apps, provide a feasible and within-reach treatment option for Hispanic adults who smoke and want to quit smoking. While the combination of pharmacotherapy and behavioral interventions are considered best practices for smoking cessation, its efficacy among Hispanic adults, especially alongside smartphone app-based interventions, is uncertain.

OBJECTIVE: This secondary analysis used data from a randomized controlled trial that compared the efficacy of 2 smoking cessation apps, iCanQuit (based on acceptance and commitment therapy) and QuitGuide (following US clinical practice guidelines), to explore the association between pharmacotherapy use and smoking cessation outcomes among the subsample of 173 Hispanic participants who reported on pharmacotherapy use. Given the randomized design, we first tested the potential interaction of pharmacotherapy use and intervention arm on 12-month cigarette smoking abstinence. We then examined whether the use of any pharmacotherapy (ie, nicotine replacement therapy [NRT], varenicline, or bupropion) and NRT alone augmented each app-based intervention efficacy.

METHODS: Participants reported using pharmacotherapy on their own during the 3-month follow-up and cigarette smoking abstinence at the 12-month follow-up via web-based surveys. These data were used (1) to test the interaction effect of using pharmacotherapy to aid smoking cessation and intervention arm (iCanQuit vs QuitGuide) on smoking cessation at 12 months and (2) to test whether the use of pharmacotherapy to aid smoking cessation augmented the efficacy of each intervention arm to help participants successfully quit smoking.

RESULTS: The subsample of Hispanic participants was recruited from 30 US states. They were on average 34.5 (SD 9.3) years of age, 50.9% (88/173) were female, and 56.1% (97/173) reported smoking at least 10 cigarettes daily. Approximately 22% (38/173) of participants reported using pharmacotherapy to aid smoking cessation at the 3-month follow-up, including NRT, varenicline, or bupropion, with no difference between intervention arms. There was an interaction between pharmacotherapy use and intervention arm that marginally influenced 12-month quit rates at 12 months (P for interaction=.053). In the iCanQuit arm, 12-month missing-as-smoking quit rates were 43.8% (7/16) for pharmacotherapy users versus 28.8% (19/16) for nonusers (odds ratio 2.21, 95% CI 0.66-7.48; P=.20). In the QuitGuide arm, quit rates were 9.1% (2/22) for pharmacotherapy users versus 21.7% (15/69) for nonusers (odds ratio 0.36, 95% CI 0.07-1.72; P=.20). Results were similar for the use of NRT only.

CONCLUSIONS: Combining pharmacotherapy to aid smoking cessation with a smartphone app-based behavioral intervention that teaches acceptance of cravings to smoke (iCanQuit) shows promise in improving quit rates among Hispanic adults. However, this combined approach was not effective with the US clinical guideline-based app (QuitGuide).

TRIAL REGISTRATION: ClinicalTrials.gov NCT02724462; https://clinicaltrials.gov/study/NCT02724462.

RR2-10.1001/jamainternmed.2020.4055.},
}

Humans
*Smoking Cessation/methods
Female
Male
Adult
*Hispanic or Latino
*Mobile Applications
Middle Aged
*Varenicline/therapeutic use
*Tobacco Use Cessation Devices
Smoking Cessation Agents/therapeutic use
Bupropion/therapeutic use
White

@article {pmid39889250,
year = {2025},
author = {Bhatia, S and Topalian, SL and Sharfman, W and Meyer, T and Steven, N and Lao, CD and Fariñas-Madrid, L and Devriese, LA and Moore, K and Ferris, RL and Honma, Y and Elias, I and Srirangam, A and Garnett-Benson, C and Lee, M and Nghiem, P},
title = {Nivolumab With or Without Ipilimumab in Patients With Recurrent or Metastatic Merkel Cell Carcinoma: A Nonrandomized, Open-Label, International, Multicenter Phase I/II Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2402138},
doi = {10.1200/JCO-24-02138},
pmid = {39889250},
issn = {1527-7755},
abstract = {PURPOSE: Approximately 50% of patients with advanced Merkel cell carcinoma (MCC) have primary or acquired resistance to PD-(L)1 blockade, which may be overcome using combination immune checkpoint inhibition (ICI) with anti-cytotoxic T lymphocyte antigen-4 antibody. We present results from the recurrent/metastatic MCC cohort in CheckMate 358, a nonrandomized, multicohort, phase I/II study of nivolumab (NIVO) with or without ipilimumab (IPI) in virus-associated cancers (ClinicalTrials.gov identifier: NCT02488759).

METHODS: ICI-naïve patients with recurrent/metastatic MCC and 0-2 previous systemic therapies were administered NIVO monotherapy at 240 mg once every 2 weeks or combination therapy with NIVO 3 mg/kg once every 2 weeks + IPI 1 mg/kg once every 6 weeks. The primary end point was objective response. Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

RESULTS: Sixty-eight patients received NIVO (n = 25) or NIVO + IPI (n = 43). The objective response rate (95% CI) and median DOR (95% CI), respectively, were 60% (38.7 to 78.9) and 60.6 months (16.7 to not applicable [NA]) with NIVO and 58% (42.1 to 73) and 25.9 months (10.4 to NA) with NIVO + IPI. The median PFS (95% CI) and OS (95% CI), respectively, were 21.3 (9.2 to 62.5) and 80.7 (23.3 to NA) months with NIVO and 8.4 (3.7 to 24.3) and 29.8 (8.5 to 48.3) months with NIVO + IPI. The incidence of grade 3/4 treatment-related adverse events was 28% with NIVO and 47% with the combination.

CONCLUSION: This nonrandomized study showed frequent and durable responses with both NIVO and NIVO + IPI in patients with ICI-naïve advanced MCC. However, it did not show improvement in efficacy with the combination, thus contradicting previous study reports that had suggested clinical benefit with combination ICI. A randomized trial of NIVO + IPI versus NIVO monotherapy is warranted.},
}

@article {pmid39888950,
year = {2025},
author = {Montaño, MA and Sindelo, S and Fata, A and Rousseau, E and Bekker, LG and Katz, IT and Drain, PK},
title = {Urine tenofovir adherence testing: Perspectives of recently diagnosed South African adolescents and young adults with HIV accessing care via mobile HIV clinics.},
journal = {PloS one},
volume = {20},
number = {1},
pages = {e0318308},
pmid = {39888950},
issn = {1932-6203},
mesh = {Humans ; *HIV Infections/drug therapy/diagnosis/psychology/urine ; Adolescent ; Male ; Female ; Young Adult ; *Tenofovir/therapeutic use ; South Africa ; *Medication Adherence ; *Anti-HIV Agents/therapeutic use ; Adult ; Focus Groups ; Ambulatory Care Facilities ; },
abstract = {BACKGROUND: Adolescents and young adults (AYA) living with HIV face several challenges to engaging in HIV care, which can impact adherence to antiretroviral therapy (ART). Point-of-care (POC) diagnostics that detect tenofovir in urine may be a useful tool to support ART adherence, but perspectives from AYA in South Africa have not been explored.

METHODS: We conducted in-depth interviews (IDIs) among young people (age 18-24) newly diagnosed with HIV in Cape Town, and a focus group discussion (FGD) with HIV care providers to understand their perspectives regarding the use of POC urine tenofovir testing to support ART adherence. Transcripts were analyzed using Dedoose, with an iterative thematic approach.

RESULTS: Transcripts from 8 IDI participants and 8 FGD participants were included in the analysis. Major themes identified during analysis related to beliefs about POC urine adherence testing and recommendations for future clinical implementation. Most IDI participants indicated they would want to use the tests if clinically available, and both IDI and FGD participants believed the tests would be helpful to clinicians. Participants believed the tests could motivate people to take their ART regularly, either by reassuring them ART was present in their bodies, or to avoid the negative consequences of being found to be non-adherent. Drawbacks of POC adherence testing identified by respondents included not wanting to be caught skipping ART doses, concerns about privacy, how the test results would be explained, and adding to the amount of testing required for HIV clinical care.

CONCLUSIONS: AYA living with HIV in South Africa had favorable views toward POC tenofovir adherence testing and felt utilizing these tests in HIV clinical care would motivate people to remain adherent to ART.},
}

Humans
*HIV Infections/drug therapy/diagnosis/psychology/urine
Adolescent
Male
Female
Young Adult
*Tenofovir/therapeutic use
South Africa
*Medication Adherence
*Anti-HIV Agents/therapeutic use
Adult
Focus Groups
Ambulatory Care Facilities

@article {pmid39887373,
year = {2025},
author = {Byrd, DA and Damerell, V and Gomez Morales, MF and Hogue, SR and Lin, T and Ose, J and Himbert, C and Ilozumba, MN and Kahlert, C and Shibata, D and Toriola, AT and Li, CI and Figueiredo, J and Stephens, WZ and Warby, CA and Hardikar, S and Siegel, EM and Round, J and Ulrich, CM and Gigic, B},
title = {The gut microbiome is associated with disease-free survival in stage I-III colorectal cancer patients.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.35342},
pmid = {39887373},
issn = {1097-0215},
support = {//ERA-NET on Translational Cancer Research (TRANSCAN)/ ; //Heidelberger Stiftung Chirurgie, Heidelberg University Hospital/ ; //Medizinische Fakultät Heidelberg, Universität Heidelberg/ ; //Matthias-Lackas Foundations/ ; //Stiftung LebensBlicke/ ; R01 CA189184/NH/NIH HHS/United States ; U01 CA206110/NH/NIH HHS/United States ; //Rahel Goitein-Straus-Program/ ; 01KD2101D//German Federal Ministry of Education and Research/ ; 01KT1503//German Federal Ministry of Education and Research/ ; },
abstract = {Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HRrectum = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes.},
}

@article {pmid39885116,
year = {2025},
author = {Edwards, ER and Geraci, JC and Gildea, SM and Houtsma, C and Holdcraft, JA and Kennedy, CJ and King, AJ and Luedtke, A and Marx, BP and Naifeh, JA and Sampson, NA and Stein, MB and Ursano, RJ and Kessler, RC},
title = {Improving explainability of post-separation suicide attempt prediction models for transitioning service members: insights from the Army Study to Assess Risk and Resilience in Servicemembers - Longitudinal Study.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {37},
pmid = {39885116},
issn = {2158-3188},
support = {HU0001-15-2-0004//U.S. Department of Defense (United States Department of Defense)/ ; Project SPR-002-24F//U.S. Department of Veterans Affairs (Department of Veterans Affairs)/ ; },
mesh = {Humans ; *Military Personnel/psychology ; *Suicide, Attempted/psychology/statistics & numerical data ; Male ; Female ; Adult ; Longitudinal Studies ; *Resilience, Psychological ; Young Adult ; United States ; Machine Learning ; Risk Assessment ; Risk Factors ; },
abstract = {Risk of U.S. Army soldier suicide-related behaviors increases substantially after separation from service. As universal prevention programs have been unable to resolve this problem, a previously reported machine learning model was developed using pre-separation predictors to target high-risk transitioning service members (TSMs) for more intensive interventions. This model is currently being used in a demonstration project. The model is limited, though, in two ways. First, the model was developed and trained in a relatively small cross-validation sample (n = 4044) and would likely be improved if a larger sample was available. Second, the model provides no guidance on subtyping high-risk TSMs. This report presents results of an attempt to refine the model to address these limitations by re-estimating the model in a larger sample (n = 5909) and attempting to develop embedded models for differential risk of post-separation stressful life events (SLEs) known to mediate the association of model predictions with post-separation nonfatal suicide attempts (SAs; n = 4957). Analysis used data from the Army STARRS Longitudinal Surveys. The revised model improved prediction of post-separation SAs in the first year (AUC = 0.85) and second-third years (AUC = 0.77) after separation, but embedded models could not predict post-separation SLEs with enough accuracy to support intervention targeting.},
}

Humans
*Military Personnel/psychology
*Suicide, Attempted/psychology/statistics & numerical data
Male
Female
Adult
Longitudinal Studies
*Resilience, Psychological
Young Adult
United States
Machine Learning
Risk Assessment
Risk Factors

@article {pmid39885052,
year = {2025},
author = {Grady, WM},
title = {Are Non-invasive Multi-cancer Early Cancer Detection Tests the Future?.},
journal = {Digestive diseases and sciences},
volume = {},
number = {},
pages = {},
pmid = {39885052},
issn = {1573-2568},
support = {U2CCA271902/CA/NCI NIH HHS/United States ; },
abstract = {Current cancer screening methods are effective for detecting early stage cancers and even preventing some cancers, but their effectiveness has only been demonstrated for a handful of cancers, and for many cancers, there are no screening tests clinically available. In addition, the majority of the screening methods are not ideal, resulting in suboptimal compliance and the occurrence of preventable cancers. A screening test that is convenient, safe, accurate and that can screen for multiple cancers is an ideal screening test that would address many of the shortcomings of the current tests. Multi-cancer detection tests (MCD) have the potential to meet these challenges and have engendered substantial enthusiasm in light of this. Using advances in DNA sequencing technology, cancer epigenetics and artificial intelligence, they are able to detect a large number of cancers predominantly via the patterns of methylated DNA alterations, DNA sequence alterations, and DNA fragment patterns of cell free DNA in the plasma and can accurately distinguish the cancer site of origin. Of note, some of the tests also combine circulating free DNA (cfDNA) with protein-based markers. However, for the majority of early stage cancers, the sensitivity is modest and below that of most of the current standard of care cancer screening tests. Furthermore, the clinical utility of screening for many of the cancers detectable by MCD tests remains to be proven. Here we describe the features of MCD tests, review the current data supporting their potential to be used in the clinic for cancer screening, and discuss the knowledge gaps surrounding understanding their clinical utility, with a focus on GI cancer screening.},
}

@article {pmid39884302,
year = {2025},
author = {Deming, ME and Brown, ER and McArthur, MA and Schrag, SJ and Arvay, M and Humphrys, M and Ravel, J and Adelglass, J and Essink, B and Musante, DB and Maguire, R and Gorman, R and Formentini, E and Mason, R and Robb, ML and Neuzil, KM and Rapaka, RR and Wolff, P and Kotloff, KL and , },
title = {Vaccine efficacy of NVX-CoV2373 against SARS-CoV-2 infection in adolescents in the USA: an ancillary study to a phase 3, observer-blinded, randomised, placebo-controlled trial.},
journal = {The Lancet. Microbe},
volume = {},
number = {},
pages = {100984},
doi = {10.1016/j.lanmic.2024.100984},
pmid = {39884302},
issn = {2666-5247},
abstract = {BACKGROUND: Although existing COVID-19 vaccines are known to be highly effective against severe disease and death, data are needed to assess their ability to reduce SARS-CoV-2 infection. We aimed to estimate the efficacy of the NVX-CoV2373 protein subunit vaccine against SARS-CoV-2 infection, regardless of symptoms, among adolescents.

METHODS: We performed an ancillary observational study (SNIFF) to the phase 3, observer-blinded, randomised, placebo-controlled PREVENT-19 trial that assessed vaccine efficacy against symptomatic COVID-19 in the USA. Participants in the PREVENT-19 trial included healthy adolescents aged 12-17 years and with no history of laboratory-confirmed SARS-CoV-2 infection. They were randomly assigned (2:1) to receive either the NVX-CoV2373 (Novavax, Gaithersburg, MD, USA) vaccine (immediate NVX-CoV2373 group) or placebo (delayed NVX-CoV2373 group) on days 0 and 21 (initial series). After 2 months, in a crossover series, participants received two doses, 21 days apart, of the intervention that they did not receive in their initial series. Participants at 47 of the PREVENT-19 sites were invited to participate in the SNIFF study and self-collect nasal swabs at home twice weekly for SARS-CoV-2 testing to assess vaccine efficacy against SARS-CoV-2 infection. This primary outcome was defined as the first identification of SARS-CoV-2 detected by RT-PCR, regardless of symptoms, with onset within 4 weeks after the second dose of the initial vaccination series until the second dose of the crossover series. Secondary outcomes were vaccine efficacy against asymptomatic and minimally symptomatic SARS-CoV-2 infection, durability of vaccine efficacy against SARS-CoV-2 infection, and durability of vaccine efficacy against asymptomatic and minimally symptomatic infections. Outcomes were analysed in the modified intention-to-treat population, which included all participants without previous SARS-CoV-2 infection and was restricted to participants enrolled within 4 weeks of the second dose of the primary (primary analysis population) or crossover (post-crossover analysis population) series. This study is registered with ClinicalTrials.gov (NCT04611802).

FINDINGS: Between June 1 and Dec 17, 2021, 1196 (53·2%) of the 2247 adolescent participants recruited in the PREVENT-19 trial enrolled in the SNIFF study. The primary analysis population included 471 participants in the immediate NVX-CoV2373 group and 220 in the delayed NVX-CoV2373 group. Incidence of SARS-CoV-2 infection was 14·9 cases per 100 person-years (95% CI 7·9-25·5) in the immediate group and 54·2 cases per 100 person-years (33·6-82·9) in the delayed group; vaccine efficacy was 73·5% (95% CI 47·1-86·7; p=0·0002). Incidence of minimally symptomatic or asymptomatic SARS-CoV-2 infection was 10·3 cases per 100 person-years (95% CI 4·7-19·6) in the immediate group and 36·1 cases per 100 person-years (19·8-60·7) in the delayed group; vaccine efficacy was 72·8% (95% CI 37·1-88·2; p=0·0023). After the second crossover dose, incidence of SARS-CoV-2 was 14·6 cases per 100 person-years (95% CI 8·6-23·0) in the immediate group (receiving placebo at crossover) and 9·1 cases per 100 person-years (3·0-21·3) in the delayed group, with a durability ratio of 160·3 (95% CI 59·5-431·6; p=0·35). Almost all infections after crossover were minimally symptomatic or asymptomatic, with a durability ratio of 151·4 (55·9-410·4; p=0·41).

INTERPRETATION: Among adolescents participating in the PREVENT-19 trial during the delta (B.1.617.2) variant wave of the COVID-19 pandemic, the NVX-CoV2373 vaccine was highly efficacious against SARS-CoV-2 infection regardless of symptoms, indicating its potential to reduce the reservoir of infections that contribute to community transmission.

FUNDING: US Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, National Institute of Allergy and Infectious Diseases, and National Institutes of Health.},
}

@article {pmid39868296,
year = {2025},
author = {Guccione, C and Sfiligoi, I and Gonzalez, A and Shaffer, JP and Kazachkova, M and Weng, Y and McDonald, D and Shah, SC and Minot, SS and Paulson, T and Grady, WM and Alexandrov, LB and Knight, R and Curtius, K},
title = {Community assembly modeling of microbial evolution within Barrett's esophagus and esophageal adenocarcinoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39868296},
issn = {2692-8205},
support = {K12 GM068524/GM/NIGMS NIH HHS/United States ; R01 CA241728/CA/NCI NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; IK2 CX002027/CX/CSRD VA/United States ; T32 GM007198/GM/NIGMS NIH HHS/United States ; R21 CA259687/CA/NCI NIH HHS/United States ; R01 CA270235/CA/NCI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; U24 CA248454/CA/NCI NIH HHS/United States ; },
abstract = {Mathematical modeling of somatic evolution, a process impacting both host cells and microbial communities in the human body, can capture important dynamics driving carcinogenesis. Here we considered models for esophageal adenocarcinoma (EAC), a cancer that has dramatically increased in incidence over the past few decades in Western populations, with high case fatality rates due to late-stage diagnoses. Despite advancements in genomic analyses of the precursor Barrett's esophagus (BE), prevention of late-stage EAC remains a significant clinical challenge. Previous microbiome studies in BE and EAC have focused on quantifying static microbial abundance differences rather than evolutionary dynamics. Using whole genome sequencing data from esophageal tissues, we first applied a robust bioinformatics pipeline to extract non-host DNA reads, mapped these putative reads to microbial taxa, and retained those taxa with high genomic coverage. When applying mathematical models of microbial evolution to sequential stages of progression to EAC, we observed evidence of neutral dynamics in community assembly within normal esophageal tissue and BE, but not EAC. In a case-control study of BE patients who progressed to EAC cancer outcomes (CO) versus those who had non-cancer outcomes (NCO) during follow-up (mean=10.5 years), we found that Helicobacter pylori deviated significantly from the neutral expectation in BE NCO, suggesting that factors related to H. pylori or H. pylori infection itself may influence EAC risk. Additionally, simulations incorporating selection recapitulated non-neutral behaviors observed in the datasets. Formally modeling dynamics during progression holds promise in clinical applications by offering a deeper understanding of microbial involvement in cancer development.},
}

@article {pmid39883890,
year = {2025},
author = {Bellmunt, J and Russell, BM and Szabados, B and Valderrama, BP and Nadal, R},
title = {Current and Future Role of Circulating DNA in the Diagnosis and Management of Urothelial Carcinoma.},
journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting},
volume = {45},
number = {2},
pages = {e471912},
doi = {10.1200/EDBK-25-471912},
pmid = {39883890},
issn = {1548-8756},
mesh = {Humans ; *Circulating Tumor DNA/blood ; Liquid Biopsy/methods ; *Biomarkers, Tumor/blood ; Urinary Bladder Neoplasms/therapy/blood/diagnosis/genetics/pathology ; Disease Management ; Prognosis ; Cell-Free Nucleic Acids/blood ; Carcinoma, Transitional Cell/therapy/blood/genetics/diagnosis ; Urologic Neoplasms/diagnosis/therapy/genetics/blood/pathology ; },
abstract = {The growing sophistication of tumor molecular profiling has helped to slowly transition oncologic care toward a more personalized approach in different tumor types, including in bladder cancer. The National Comprehensive Cancer Network recommends that all patients with stage IVA and stage IVB urothelial carcinoma have molecular analysis that integrates at least FGFR3 testing to help facilitate the selection of future therapeutic options. Sequencing of tumor-derived tissue is the mainstay to obtain this genomic testing, but as in other cancers, there has been extensive research into the integration of liquid biopsies in longitudinal management. Liquid biopsies broadly refer to the isolation of both cellular and noncellular tumor components including proteins and nucleic acids such as mRNA and circulating free DNA within a liquid sample. Although protein-based testing and testing of circulating tumor cells are options, the bulk of promising research in bladder cancer is investigating the role of plasma-based circulating tumor DNA (ctDNA). Currently, a universal consensus on optimal preanalytic and analytic approaches has not been fully defined, and the exact role that liquid biopsies should have in screening, diagnosis, prognostication, treatment selection, and monitoring is not yet known. Still, it can be expected that ctDNA testing will be a part of appropriate management of muscle-invasive bladder cancer and metastatic bladder cancer in the near future. In this review, the goal is to provide a practical overview of the current and future role of ctDNA in bladder cancer including ongoing trials.},
}

Humans
*Circulating Tumor DNA/blood
Liquid Biopsy/methods
*Biomarkers, Tumor/blood
Urinary Bladder Neoplasms/therapy/blood/diagnosis/genetics/pathology
Disease Management
Prognosis
Cell-Free Nucleic Acids/blood
Carcinoma, Transitional Cell/therapy/blood/genetics/diagnosis
Urologic Neoplasms/diagnosis/therapy/genetics/blood/pathology

@article {pmid39883451,
year = {2025},
author = {Hunter, N and Hurvitz, S},
title = {Where Did the Passion Go?-Rethinking Adjuvant Immune Therapy for Triple-Negative Breast Cancer.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2024.26811},
pmid = {39883451},
issn = {1538-3598},
}

@article {pmid39883059,
year = {2025},
author = {Phipps, W and Bhinder, B and Towlerton, A and Mooka, P and Kafeero, J and Fitzgibbon, M and Elemento, O and Cesarman, E},
title = {Exome sequencing reveals a sparse genomic landscape in Kaposi sarcoma.},
journal = {Molecular cancer research : MCR},
volume = {},
number = {},
pages = {},
doi = {10.1158/1541-7786.MCR-24-0373},
pmid = {39883059},
issn = {1557-3125},
abstract = {Kaposi Sarcoma (KS) is a frequently aggressive malignancy caused by Kaposi sarcoma herpesvirus (KSHV/HHV-8). People with immunodeficiencies, including HIV, are at increased risk for developing KS, but our understanding of the contributions of the cellular genome to KS pathogenesis remains limited. To determine if there are cellular genetic alterations in KS that might provide biological or therapeutic insights, we performed whole exome sequencing on 78 KS tumors and matched normal control skin from 59 adults with KS (46 with HIV-associated KS and 13 with HIV-negative KS) receiving treatment at the Uganda Cancer Institute in Kampala, Uganda. We found a very low mutational burden in all but one specimen (median=11 mutations), which is the lowest number of mutations among all 33 tumor types in The Cancer Genome Atlas (TCGA). No recurrent mutations were seen and the most commonly affected oncogenic pathway was RTK/RAS. Mutational signatures included defective DNA mismatch repair and smoking. There was no evidence suggesting that multiple tumors from the same patient originated from the same original clone. The number of genome copy alterations per genome were higher in tumors from those without HIV infection and in tumors from participants with advanced stage disease, suggesting that lesions that take longer to develop may accumulate more alterations, although the number of alterations remain low compared to other cancers. Implications: Our findings indicate that the pathogenesis of KS differs from other malignancies, and that the primary driver of carcinogenesis is KSHV viral infection and expression of viral oncogenes, rather than clonal oncogenic transformation.},
}

@article {pmid39882642,
year = {2025},
author = {Özcan, M and Cassaday, RD and Zarzycka, E and Vandendries, E and Zhang, F and Chen, Y and Nieto, A and Demirkan, F and Montesinos, P and Altuntas, F},
title = {Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.286091},
pmid = {39882642},
issn = {1592-8721},
abstract = {Inotuzumab ozogamicin (InO) is approved for treatment of relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Previous studies reported higher rates of post- hematopoietic stem cell transplant (HSCT) hepatic sinusoidal obstruction syndrome (SOS) in patients receiving InO versus chemotherapy prior to HSCT. It is unknown if a lower InO dose would reduce risk of post-HSCT SOS or if it would impact efficacy. This study evaluated efficacy and safety of the currently approved InO starting dose and a lower dose in adults with R/R ALL who were eligible for HSCT and were identified as being at higher risk of post- HSCT SOS. This open-label, phase 4 study (NCT03677596) had 2 phases: in the run-in phase patients received InO at 1.2 mg/m2/cycle (n=22); in the randomized phase patients received InO starting at dose levels of 1.8 mg/m2/cycle (n=38) or 1.2 mg/m2/cycle (n=42). Primary endpoints were rate of SOS and rate of hematologic remission. Overall, SOS was reported in 10 patients (9.8%); all were post-HSCT SOS. In patients who proceeded to HSCT, post-HSCT SOS rates were 20%, 28.6%, 25.8%, and 16.7% in 1.2 mg/m2/cycle (run-in), 1.2 mg/m2/cycle (randomized), 1.2 mg/m2/cycle (run-in and randomized), and 1.8 mg/m2/cycle (randomized), respectively. The CR/CRi rates were 50.0%, 83.3%, 71.9%, and 68.4% in the respective subgroups. The study found that a starting dose of 1.2mg/m2/cycle demonstrated consistent efficacy and safety to the recommended 1.8 mg/m2/cycle dose in adults with R/R ALL who were eligible for HSCT and had a higher risk of post-HSCT SOS.},
}

@article {pmid39881206,
year = {2025},
author = {Vo, PT and Sandmaier, BM and Othus, M and Ali, N and Rodríguez-Arbolí, E and Orvain, C and Davis, C and Basom, RS and Storb, R and Walter, RB},
title = {Relationship between age, conditioning intensity, and outcome after allografting in adults age ≥60 years with AML.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {39881206},
issn = {1476-5365},
abstract = {Methodological advancements now allow older adults with AML to receive allografts although conflicting data exist regarding relative outcomes across age groups and benefits of different conditioning intensities. We retrospectively analyzed 495 adults aged 60-64 (n = 184), 65-69 (n = 189), or ≥70 (n = 122) allografted for AML in remission at our institution from 2006 to 2023. There were no significant differences in relapse or relapse-free survival (RFS) among the 3 age cohorts after multivariable adjustment. Patients aged ≥70 years had higher non-relapse mortality (NRM) than those aged ≥60-64 (P = 0.022) but their overall survival (OS) was only statistically non-significantly shorter (P = 0.11). There was an important interplay between age, conditioning intensity, and outcomes. Relative to age 60-64, age ≥70 years was associated with a higher risk of relapse (hazard ratio [HR] = 3.47; P = 0.012) and NRM (HR = 3.88; P = 0.001) with reduced intensity conditioning (RIC), leading to shorter RFS (HR = 3.79; P < 0.001) and OS (HR = 3.46; P < 0.001), while no such associations were found with nonmyeloablative (NMA) conditioning. Underlying, patients aged 60-64 and 65-69, but not those aged ≥70, had a significantly lower relapse risk with RIC relative to NMA conditioning, whereas NRM risks increased across all age cohorts. Our findings support allografting for adults ≥70 with AML in remission, especially with NMA conditioning.},
}

@article {pmid39881190,
year = {2025},
author = {Toghani, D and Gupte, S and Zeng, S and Mahammadov, E and Crosse, EI and Seyedhassantehrani, N and Burns, C and Gravano, D and Radtke, S and Kiem, HP and Rodriguez, S and Carlesso, N and Pradeep, A and Georgiades, A and Lucas, F and Wilson, NK and Kinston, SJ and Göttgens, B and Zong, L and Beerman, I and Park, B and Janssens, DH and Jones, D and Toghani, A and Nerlov, C and Pietras, EM and Mesnieres, M and Maes, C and Kumanogoh, A and Worzfeld, T and Cheong, JG and Josefowicz, SZ and Kharchenko, P and Scadden, DT and Scialdone, A and Spencer, JA and Silberstein, L},
title = {Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.},
journal = {Nature aging},
volume = {},
number = {},
pages = {},
pmid = {39881190},
issn = {2662-8465},
support = {HL148189//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL148189//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL148189//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL148189//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
abstract = {Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress. We show that, in the absence of Sema4A, myHSC inflammatory hyper-responsiveness in young mice drives excessive myHSC expansion, myeloid bias and profound loss of regenerative function with age. Mechanistically, Sema4A is mainly produced by neutrophils, signals via a cell surface receptor, plexin D1, and safeguards the myHSC epigenetic state. Our study shows that, by selectively protecting a distinct stem cell subset, an extrinsic factor preserves functional diversity of somatic stem cell pool throughout organismal lifespan.},
}

@article {pmid39875703,
year = {2025},
author = {Harris, HR and Lind, K and Fest, S and Thomson, CA and Saquib, N and Shadyab, AH and Schnatz, PF and Robles-Morales, R and Qi, L and Strickler, HD and Roe, DJ and Farland, LV},
title = {Infertility and risk of ovarian cancer in the women's health initiative.},
journal = {Cancer causes & control : CCC},
volume = {},
number = {},
pages = {},
pmid = {39875703},
issn = {1573-7225},
support = {R03 HD102403/HD/NICHD NIH HHS/United States ; },
abstract = {PURPOSE: There is a consistent relationship with greater ovulation frequency and increased risk of ovarian cancer. However, prior research on infertility, which may be associated with ovulation frequency through multiple mechanisms, and ovarian cancer has yielded conflicting results, possibly due to prior research conflating fertility treatment with infertility and restricting follow-up to premenopausal cases. Our objective was to determine the association between infertility and risk of postmenopausal ovarian cancer, overall and by histotype, in a population that had not received treatment with IVF.

METHODS: We utilized data from the Women's Health Initiative (n = 112,925 postmenopausal participants) with over 25 years of follow-up. At baseline, participants were asked whether they had ever tried to become pregnant for more than one year without becoming pregnant and whether a reason was found. Cox proportional hazards models were used to calculate hazard ratios (HRs) of incident adjudicated ovarian cancer comparing participants with a history of infertility to fertile participants overall and by histotype.

RESULTS: 17% of participants reported a history of infertility at baseline and 1,109 ovarian cancer cases were diagnosed during follow-up. No statistically significant association was observed between infertility and risk of any ovarian cancer (HR: 1.09, 95% CI 0.92-1.29), but those reporting infertility had a 90% higher risk of endometrioid and clear cell ovarian cancers (HR: 1.90 95% CI 1.09-3.34) compared to fertile participants. The reported reason(s) for infertility had no discernable impact on these associations.

CONCLUSIONS: Infertility may be associated with clear cell and endometrioid ovarian cancer but not other ovarian tumor histotypes.},
}

@article {pmid39874304,
year = {2025},
author = {Sabo, MC and Mustafa, S and Saha, A and Oyaro, B and Fiedler, TL and Krueger, M and Fuchs, E and Mureithi, M and Mandaliya, K and Jaoko, W and Richardson, BA and Gharib, SA and Fredricks, DN and Shah, JA and McClelland, RS},
title = {Bacterial vaginosis is associated with transcriptomic changes but not higher concentrations of cervical leukocytes in a study of women at high risk for HIV acquisition.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf049},
pmid = {39874304},
issn = {1537-6613},
abstract = {BACKGROUND: The association between bacterial vaginosis (BV) and increased HIV acquisition risk may be related to concentrations of HIV-susceptible immune cells in the cervix.

METHODS: Participants (31 with BV and 30 with normal microbiota) underwent cervical biopsy at a single visit. Immune cells were quantified and sorted using flow cytometry (N=55), localization assessed by immunofluorescence (N=16), and function determined by bulk RNA sequencing (RNA-seq) of live CD45+ cells (N=21).

RESULTS: Linear regression analyses demonstrated no differences in mean log2 [cells/mg tissue] between women with BV vs normal microbiota for antigen presenting cell (APC) subtypes linked to HIV risk (including CD1a+HLA-DR+ Langerhans cells, CD11c+CD14+ dendritic cells [DCs], and CD11c+HLA-DR+ DCs) and CD4+ T cells. Women with BV had a higher median proportion of CD11c+HLA-DR+ APCs (out of total cells) in cervical epithelium (0.1% vs 0.0%; p=0.03 using Mann-Whitney testing). RNA-seq identified 1,032 differentially expressed genes (adjusted p-value <0.05) in CD45+ cells between women with BV vs normal microbiota. Women with BV demonstrated downregulation of pathways linked to translation, metabolism, cell stress, and immune signaling.

CONCLUSIONS: BV alters immune cell localization and function; future studies are needed to address how these changes may mediate HIV acquisition risk.},
}

@article {pmid39763728,
year = {2024},
author = {Gauderman, WJ and Fu, Y and Queme, B and Kawaguchi, E and Wang, Y and Morrison, J and Brenner, H and Chan, A and Gruber, SB and Keku, T and Li, L and Moreno, V and Pellatt, AJ and Peters, U and Samadder, NJ and Schmit, SL and Ulrich, CM and Um, C and Wu, A and Lewinger, JP and Drew, DA and Mi, H},
title = {Pathway Polygenic Risk Scores (pPRS) for the Analysis of Gene-environment Interaction.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763728},
issn = {2692-8205},
support = {U01 HG004438/HG/NHGRI NIH HHS/United States ; U01 HG004446/HG/NHGRI NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; U01 CA167551/CA/NCI NIH HHS/United States ; R01 CA081488/CA/NCI NIH HHS/United States ; R01 CA042182/CA/NCI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; R01 CA059045/CA/NCI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; R01 CA197350/CA/NCI NIH HHS/United States ; R01 CA076366/CA/NCI NIH HHS/United States ; R35 CA197735/CA/NCI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; U10 CA037429/CA/NCI NIH HHS/United States ; R01 CA072520/CA/NCI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; R01 CA273198/CA/NCI NIH HHS/United States ; K05 CA154337/CA/NCI NIH HHS/United States ; P01 CA055075/CA/NCI NIH HHS/United States ; R01 CA151993/CA/NCI NIH HHS/United States ; U01 CA152753/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; R01 CA048998/CA/NCI NIH HHS/United States ; R01 CA189184/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; Z01 CP010200/ImNIH/Intramural NIH HHS/United States ; U24 CA074794/CA/NCI NIH HHS/United States ; R01 CA066635/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; R01 CA137178/CA/NCI NIH HHS/United States ; U01 CA074794/CA/NCI NIH HHS/United States ; HHSN268201200008C/HL/NHLBI NIH HHS/United States ; R01 CA242218/CA/NCI NIH HHS/United States ; R01 CA143237/CA/NCI NIH HHS/United States ; R01 CA201407/CA/NCI NIH HHS/United States ; R01 CA063464/CA/NCI NIH HHS/United States ; P01 CA033619/CA/NCI NIH HHS/United States ; U01 CA093326/CA/NCI NIH HHS/United States ; U01 CA086308/CA/NCI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R01 CA207371/CA/NCI NIH HHS/United States ; R03 CA153323/CA/NCI NIH HHS/United States ; R01 CA060987/CA/NCI NIH HHS/United States ; R01 CA136726/CA/NCI NIH HHS/United States ; K05 CA152715/CA/NCI NIH HHS/United States ; U01 CA122839/CA/NCI NIH HHS/United States ; KL2 TR000421/TR/NCATS NIH HHS/United States ; U01 CA074783/CA/NCI NIH HHS/United States ; R35 CA253185/CA/NCI NIH HHS/United States ; UM1 CA182883/CA/NCI NIH HHS/United States ; HHSN268201200008I/HL/NHLBI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; R01 CA097325/CA/NCI NIH HHS/United States ; HHSN268201700006C/HL/NHLBI NIH HHS/United States ; U19 CA148107/CA/NCI NIH HHS/United States ; U01 AG018033/AG/NIA NIH HHS/United States ; },
abstract = {A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e. interacts with, important environmental (E) risk factors. Detection of a PRS by environment (PRS × E) interaction may provide clues to underlying biology and can be useful in developing targeted prevention strategies for modifiable risk factors. The standard PRS may include a subset of variants that interact with E but a much larger subset of variants that affect disease without regard to E. This latter subset will 'water down' the underlying signal in former subset, leading to reduced power to detect PRS × E interaction. We explore the use of pathway-defined PRS (pPRS) scores, using state of the art tools to annotate subsets of variants to genomic pathways. We demonstrate via simulation that testing targeted pPRS × E interaction can yield substantially greater power than testing overall PRS × E interaction. We also analyze a large study (N=78,253) of colorectal cancer (CRC) where E = non-steroidal anti-inflammatory drugs (NSAIDs), a well-established protective exposure. While no evidence of overall PRS × NSAIDs interaction (p=0.41) is observed, a significant pPRS × NSAIDs interaction (p=0.0003) is identified based on SNPs within the TGF-β / gonadotropin releasing hormone receptor (GRHR) pathway. NSAIDS is protective (OR=0.84) for those at the 5[th] percentile of the TGF-β/GRHR pPRS (low genetic risk, OR), but significantly more protective (OR=0.70) for those at the 95[th] percentile (high genetic risk). From a biological perspective, this suggests that NSAIDs may act to reduce CRC risk specifically through genes in these pathways. From a population health perspective, our result suggests that focusing on genes within these pathways may be effective at identifying those for whom NSAIDs-based CRC-prevention efforts may be most effective.},
}

@article {pmid39873851,
year = {2025},
author = {Javid, SH and Kazerouni, AS and Hippe, DS and Hirano, M and Schnuck-Olapo, J and Biswas, D and Bryant, ML and Li, I and Xiao, J and Kim, AG and Guo, A and Dontchos, B and Kilgore, M and Kim, J and Partridge, SC and Rahbar, H},
title = {Preoperative MRI to Predict Upstaging of DCIS to Invasive Cancer at Surgery.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {39873851},
issn = {1534-4681},
support = {ROI CA203883 (Rahbar)/GF/NIH HHS/United States ; },
abstract = {BACKGROUND: Ductal carcinoma in situ (DCIS) is overtreated, in part because of inability to predict which DCIS cases diagnosed at core needle biopsy (CNB) will be upstaged at excision. This study aimed to determine whether quantitative magnetic resonance imaging (MRI) features can identify DCIS at risk of upstaging to invasive cancer.

METHODS: This prospective observational clinical trial analyzed women with a diagnosis of DCIS on CNB. All the participants underwent preoperative 3T MRI. Quantitative MRI features from routine dynamic contrast-enhanced (DCE) MR images (e.g., peak percent enhancement [PE]) and from advanced high temporal-resolution DCE MR images (e.g., Ktrans) were measured. Clinical, pathologic, and mammographic features were reviewed. Associations with upstaging were summarized using the area under the receiver operating characteristic curve (AUC).

RESULTS: Of 58 DCIS lesions at CNB, 15 (26%) were upstaged to invasive cancer at surgery. Of the 58 lesions, 46 (79%) enhanced on MRI, although enhancement alone was not significantly associated with upstaging (p = 0.71). Among the DCIS lesions that enhanced, higher PE was most strongly associated with upstaging (AUC, 0.81; adjusted p = 0.009) and outperformed MRI features acquired via high temporal resolution DCE-MRI (AUC, 0.50-0.73). Lesion span on MRI was not significantly associated with upstaging risk (AUC, 0.55; adjusted p = 0.61), nor were any clinical, pathologic, or mammographic features (p > 0.24).

CONCLUSIONS: Quantitative features acquired from routine clinical breast MRI and advanced DCE-MRI demonstrated good performance in identifying which DCIS lesions were upstaged to invasive cancer at excision. These features may prove valuable for appropriate selection of active surveillance in future DCIS de-escalation trials.},
}

@article {pmid39873699,
year = {2025},
author = {Huang, Y and Kwan, ML and Heckbert, SR and Smith, NL and Othus, M and Laurent, CA and Roh, JM and Rillamas-Sun, E and Lee, VS and Kolevska, T and Cheng, RK and Irribarren, C and Nguyen-Huynh, M and Hershman, DL and Kushi, LH and Greenlee, H},
title = {Duration of aromatase inhibitor use and long-term cardiovascular risk in breast cancer survivors.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkaf009},
pmid = {39873699},
issn = {2515-5091},
abstract = {BACKGROUND: There are limited data on duration of aromatase inhibitor (AI) and cardiovascular disease (CVD) risk in breast cancer (BC) survivors. We examined risk of CVD and mortality associated with duration of AI use in postmenopausal women with early-stage hormone receptor-positive BC.

METHODS: Postmenopausal women diagnosed with hormone receptor-positive BC (n = 5,853) who used an AI were included. Cause-specific hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between AI use duration (short-term: >0 and <2 years; intermediate-term: ≥2 and <5 years; long-term: ≥5 years) and CVD and mortality outcomes. The landmark method was used to avoid immortal time bias; the selected landmark was 6 years after BC diagnosis.

RESULTS: Anastrozole was the AI predominantly prescribed (95.4%). Over a median follow-up of 3 years for women who survived 6 years after BC diagnosis, a lower risk of stroke was observed in intermediate-term AI users (HR = 0.60, 95% CI: 0.37-0.96) and long-term AI users (HR = 0.51, 95% CI: 0.30-0.85), than in short-term AI users. The longer duration of AI use was also associated with lower risk of all-cause mortality and non-CVD-related mortality. In addition, long-term AI users were at 37% lower risk of CVD-related mortality than short-term AI users. No significant differences were observed in risks of major adverse cardiovascular events, ischemic heart disease, and heart failure across the three groups.

CONCLUSION: Among postmenopausal women with early-stage hormone receptor-positive BC who survived to 6 years after BC diagnosis, longer duration of AI use was not associated with elevated CVD risk.},
}

@article {pmid39871186,
year = {2025},
author = {Pinto-Santini, D and Jalil, EM and Fernandes, GT and Hilaire, G and Kolevic, L and Cabello, R and Grinsztejn, B and Pape, W and Deschamps, MM and House, MG and Brofsky, E and Sahasrabuddhe, VV and Dasgupta, S and Pasalar, S and Madeleine, MM and Carter, J and Prabhu, PR and Galloway, D and Duerr, A},
title = {ULACNet-301, OPTIMO protocol: optimizing HPV vaccination regimen for cancer prevention in children and adolescents living with HIV.},
journal = {BMC cancer},
volume = {25},
number = {1},
pages = {151},
pmid = {39871186},
issn = {1471-2407},
support = {U54 CA242977/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Child ; Adolescent ; *HIV Infections/prevention & control/immunology/complications ; *Papillomavirus Infections/prevention & control/immunology/virology/complications ; Female ; *Papillomavirus Vaccines/administration & dosage/immunology ; Male ; Uterine Cervical Neoplasms/prevention & control/virology/immunology ; Immunization Schedule ; Vaccination/methods ; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage/immunology ; },
abstract = {BACKGROUND: Persistent infection with human papillomavirus (HPV) is associated with most cervical and anal cancer cases and a large fraction of other anogenital and oropharyngeal cancers. The prophylactic HPV vaccines are known to prevent HPV infections and HPV-associated disease, although there is evidence of reduced response to the HPV vaccination among individuals living with HIV. Prior studies among individuals without HIV suggest that a single HPV vaccine dose induces humoral immune responses that, while lower than those induced by two or three doses, still confer protection against HPV infection. Current recommendations for HPV vaccine include a single-dose schedule for children 9-14-years-olds without HIV. Although two to three doses are recommended for children living with HIV (CLWH), there is very limited data comparing responses to one vs. 2-3 doses in CLWH.

METHODS: The OPTIMO study will compare immune responses to HPV vaccination in CLWH by measuring antibody and memory B cell (Bmem) responses after 1, 2, or 3 doses of the 9-valent HPV (9vHPV) vaccine, Gardasil-9. A comparison group of children without HIV will receive one dose of the vaccine. The durability of the response will be assessed at 24 months after the last dose of a given regimen. The OPTIMO trial will take place among CLWH from low and middle-income country (LMIC) settings in Peru, Brazil, and Haiti.

DISCUSSION: Previous studies of single-dose regimens in individuals without HIV raise questions about whether one dose would suffice for CLWH and, if not, whether two or three doses are needed to provide protection against HPV-related cancers. These questions have operational consequences in LMICs given the barriers to delivering multiple doses, uneven availability, and intermittent shortages of HPV vaccines. In addition, information on HIV status for children and adolescents is rarely available during vaccination campaigns based in schools or public health clinics, so CLWH may receive a single dose despite policy recommendations that they receive two or three. This study will provide evidence on the optimal number of doses needed for CLWH that can inform HPV vaccination campaigns in LMICs, especially those with a higher burden of HIV infection and higher incidence of HPV-related cancers.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04265950.},
}

Humans
Child
Adolescent
*HIV Infections/prevention & control/immunology/complications
*Papillomavirus Infections/prevention & control/immunology/virology/complications
Female
*Papillomavirus Vaccines/administration & dosage/immunology
Male
Uterine Cervical Neoplasms/prevention & control/virology/immunology
Immunization Schedule
Vaccination/methods
Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18/administration & dosage/immunology

@article {pmid39870767,
year = {2025},
author = {Costa, LJ and Banerjee, R and Mian, H and Weisel, K and Bal, S and Derman, BA and Htut, MM and Nagarajan, C and Rodriguez, C and Richter, J and Frigault, MJ and Ye, JC and van de Donk, NWCJ and Voorhees, PM and Puliafito, B and Bahlis, N and Popat, R and Chng, WJ and Ho, PJ and Kaur, G and Kapoor, P and Du, J and Schjesvold, F and Berdeja, J and Einsele, H and Cohen, AD and Mikhael, J and Biru, Y and Rajkumar, SV and Lin, Y and Martin, TG and Chari, A},
title = {International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {39870767},
issn = {1476-5551},
abstract = {T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies. The International Myeloma Working Group conveyed panel of experts to review patient and disease-related factors affecting efficacy and safety of immunotherapy, summarize existing information on sequencing therapy and provide a series of core recommendations.},
}

@article {pmid39870766,
year = {2025},
author = {Othus, M and Garcia-Manero, G and Appelbaum, FR and Erba, HP and Dietrich, E and Raychaudhuri, S and Appelbaum, J and Estey, E and Percival, ME},
title = {Probability of remission with reinduction with 7+3 versus high-dose cytarabine: analysis of SWOG trial S1203.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {39870766},
issn = {1476-5551},
support = {CA180819//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
}

@article {pmid39869930,
year = {2025},
author = {Cardle, II and Scherer, DR and Jensen, MC and Pun, SH and Sellers, DL},
title = {In Situ Bioconjugation of Synthetic Peptides onto Universal Chimeric Antigen Receptor T Cells for Targeted Cancer Immunotherapies.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.4c16824},
pmid = {39869930},
issn = {1936-086X},
abstract = {The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials in vivo by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting. SpyCatcher003-modified CARs, nicknamed DB5 CARs, displayed fast, low-nanomolar reaction kinetics with a synthetic αvβ6-binding peptide that incorporates a SpyTag003 peptide via branched peptide synthesis to comprise a bifunctional intermediate. Prearming DB5 CAR T cells or prelabeling target cells with the bifunctional peptide produced selective CD4[+] and CD8[+] CAR T-cell responses against αvβ6[+] cancer cells in vitro. Furthermore, the synthetic targeting intermediate showed robust DB5 CAR T-cell arming in vivo and selectively reduced αvβ6[+] tumor progression in a dual flank xenograft model. We demonstrate the versatility and therapeutic potential of "Cyborg" CAR T-cell therapies that utilize synthetic biomaterials to direct CAR T-cell activity via highly selective bioconjugation that occurs in vivo.},
}

@article {pmid39866881,
year = {2025},
author = {Vo, P and Ng, K and Schoch, HG and Cooper, J and Vupalanchi, A and Flowers, M and Sandmaier, B and Gooley, T and Storb, R},
title = {Subsequent Cancers following Non-myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplantation.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {39866881},
issn = {2693-5015},
support = {P01 CA078902/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {We examined the risk of subsequent malignant neoplasms (SMNs) in 1720 patients with hematologic cancers given allogeneic hematopoietic grafts from 03/1998 to 08/2023 after nonmyeloablative conditioning regimens. With a median follow-up of 12 years, the cumulative incidence of SMNs was 17% (95% CI, [15%, 19%]). Most SMNs (n = 543) were non-melanoma skin cancers seen in 208 patients; unfortunately, information on these cancers was not available in the Surveillance, Epidemiology, and End Results (SEER) database for comparison with such tumors in the general population. However, developing non-melanoma skin cancers was statistically significantly associated with chronic GVHD and, thus, unlikely to be conditioning regimen related. Eighty-six patients (5%) developed 93 other SMNs. This number (93 SNMs) significantly exceeded the expected 73.4 cases in the comparison group (p = 0.03). This increase was driven exclusively by increases in uterine adenocarcinoma (n = 2), squamous lip cancer (n = 5), and squamous penile cancer (n = 2); the latter two cancers were, again, associated with chronic GVHD. Apart from these three tumor types, there were no observed increases in the risk of other tumors compared to those in the general population.},
}

@article {pmid39871876,
year = {2024},
author = {Sokolov, D and Sullivan, LB},
title = {A metabolic signalling role for arginine in liver cancer.},
journal = {Life metabolism},
volume = {3},
number = {1},
pages = {load046},
pmid = {39871876},
issn = {2755-0230},
}

@article {pmid39869835,
year = {2025},
author = {Mascarenhas, L and DuBois, SG and Albert, CM and Bielack, S and Orbach, D and Federman, N and Geoerger, B and Nagasubramanian, R and Zhang, Y and Chisholm, J and Gallego Melcon, S and Goto, H and Morgenstern, DA and Owens, C and Pappo, AS and Perreault, S and Schulte, JH and Shukla, N and Zwaan, CM and Neu, N and Bernard-Gauthier, V and De La Cuesta, E and van Tilburg, CM and Laetsch, TW},
title = {Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2400848},
doi = {10.1200/JCO.24.00848},
pmid = {39869835},
issn = {1527-7755},
abstract = {Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma. This cohort included 91 patients (younger than 18 years) from two clinical trials: infantile fibrosarcoma (49), other soft tissue sarcomas or related mesenchymal tumors (41), and bone sarcoma (1). Treatment-related adverse events were of maximum grade 1 or 2 in 25% and 25% of patients, respectively. The overall response rate was 87% (95% CI, 78 to 93). In the wait-and-see analysis, 47 patients discontinued larotrectinib. Median time from discontinuation to disease progression was not reached. Sixteen patients had tumor progression during the wait-and-see period. All 16 patients resumed larotrectinib, and 15 (94%) achieved disease control, with 11 objective responses. Larotrectinib continues to demonstrate durable responses with favorable safety in children with TRK fusion sarcomas. Treatment discontinuation is feasible in select patients with objective response and clinical benefit noted in those who have disease progression after elective treatment discontinuation.},
}

@article {pmid39869680,
year = {2025},
author = {Lum, MA and Jonas, KA and Parmar, S and Black, AR and O'Connor, CM and Dobersch, S and Yamamoto, N and Robertson, TM and Schutter, A and Giambi, M and Avelar, RA and DiFeo, A and Woods, NT and Kugel, S and Narla, G and Black, JD},
title = {Small molecule modulators of B56-PP2A restore 4E-BP function to suppress eIF4E-dependent translation in cancer cells.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI176093},
pmid = {39869680},
issn = {1558-8238},
abstract = {Dysregulated eIF4E-dependent translation is a central driver of tumorigenesis and therapy resistance. eIF4E binding proteins (4E-BP1/2/3) are major negative regulators of eIF4E-dependent translation that are inactivated in tumors through inhibitory phosphorylation or downregulation. Previous studies have linked PP2A phosphatase(s) to activation of 4E-BP1. Here, we leveraged biased small molecule activators of PP2A (SMAPs) to explore the role of B56-PP2A(s) in 4E-BP regulation and the potential of B56-PP2A activation for restoring translational control in tumors. SMAP treatment promoted PP2A-dependent hypophosphorylation of 4E-BP1/2, supporting a role for B56-PP2As (e.g., B56α-PP2A) as 4E-BP phosphatases. Unexpectedly, SMAPs induced transcriptional upregulation of 4E-BP1 through a B56 PP2A→TFE3/TFEB→ATF4 axis. Cap-binding and co-immunoprecipitation assays showed that B56-PP2A(s) activation blocks assembly of the eIF4F translation initiation complex, and cap-dependent translation assays confirmed the translation inhibitory effects of SMAPs. Thus, B56-PP2A(s) orchestrate a translation repressive program involving transcriptional induction and activation of 4E-BP1. Notably, SMAPs promoted 4E-BP1-dependent apoptosis in tumor cells and potentiated 4E-BP1 function in the presence of ERK or mTOR inhibitors, agents that rely on inhibition of eIF4E-dependent translation for antitumor activity. These findings, combined with the ability of SMAPs to regulate 4E-BP1 in vivo, highlight the potential of PP2A activators for cancer therapy and overcoming therapy resistance.},
}

@article {pmid39868116,
year = {2025},
author = {Gupta, A and Morella, N and Sutormin, D and Li, N and Gaisser, K and Robertson, A and Ispolatov, Y and Seelig, G and Dey, N and Kuchina, A},
title = {Combinatorial phenotypic landscape enables bacterial resistance to phage infection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39868116},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R21 DE032890/DE/NIDCR NIH HHS/United States ; R35 GM150994/GM/NIGMS NIH HHS/United States ; },
abstract = {Success of phage therapies is limited by bacterial defenses against phages. While a large variety of anti-phage defense mechanisms has been characterized, how expression of these systems is distributed across individual cells and how their combined activities translate into protection from phages has not been studied. Using bacterial single-cell RNA sequencing, we profiled the transcriptomes of ~50,000 cells from cultures of a human pathobiont, Bacteroides fragilis, infected with a lytic bacteriophage. We quantified the asynchronous progression of phage infection in single bacterial cells and reconstructed the infection timeline, characterizing both host and phage transcriptomic changes as infection unfolded. We discovered a subpopulation of bacteria that remained uninfected and determined the heterogeneously expressed host factors associated with protection. Each cell's vulnerability to phage infection was defined by combinatorial phase-variable expression of multiple genetic loci, including capsular polysaccharide (CPS) biosynthesis pathways, restriction-modification systems (RM), and a previously uncharacterized operon likely encoding fimbrial genes. By acting together, these heterogeneously expressed phase-variable systems and anti-phage defense mechanisms create a phenotypic landscape where distinct protective combinations enable the survival and re-growth of bacteria expressing these phenotypes without acquiring additional mutations. The emerging model of complementary action of multiple protective mechanisms heterogeneously expressed across an isogenic bacterial population showcases the potent role of phase variation and stochasticity in bacterial anti-phage defenses.},
}

@article {pmid39869261,
year = {2025},
author = {Stearns, V and Chen, R and Blackford, AL and Saylor, E and Mull, J and Folmer, A and Jelinek, J and Hodgdon, C and Bacon, J and Engle, J and Shah, M and Sheinberg, R and Pedraza-Cardozo, S and Wilkinson, M and Alvendia, M and Snyder, C and Smith, KL},
title = {The Johns Hopkins Hope at Hopkins Clinic: supporting the comprehensive needs of individuals with metastatic breast cancer.},
journal = {Breast cancer research and treatment},
volume = {},
number = {},
pages = {},
pmid = {39869261},
issn = {1573-7217},
support = {5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; 5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; 5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; 5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; 5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; 5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; 5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; 5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; 5 NU58DP006673//Centers for Disease Control and Prevention Foundation/ ; P30CA006973//Johns Hopkins Cancer Center Support Grant/ ; P30CA006973//Johns Hopkins Cancer Center Support Grant/ ; P30CA006973//Johns Hopkins Cancer Center Support Grant/ ; },
abstract = {PURPOSE: Individuals with metastatic breast cancer (MBC) may live with their disease for many years. We initiated the Johns Hopkins Hope at Hopkins Clinic to assess the needs and optimize the care of these patients.

PATIENTS AND METHODS: Patients with MBC who agreed to participate in the Clinic in addition to usual care completed patient-reported outcome (PRO) surveys. They met with a navigator and underwent core consults (cancer rehabilitation, integrative medicine, supportive and palliative care, social work, and nutrition), clinical trial eligibility assessment, and optional services based on PRO responses and selection from a Clinic Menu. A medical oncologist provided a Care Plan during a final consult. Participants were asked to complete 3- and 6-month follow-up PRO surveys. We report on initial Clinic implementation, participant characteristics, and baseline PROs.

RESULTS: From 11/2020 to 6/2022, 45 patients completed baseline surveys and participated in the Clinic. Median age was 58 (32-86); the majority (71%) were white and had estrogen receptor-positive (84%) tumors. Baseline physical and mental health were not good for ≥ 14 days of the past month for 22 and 10%, respectively. PROMIS measure scores were > 1 standard deviation worse than average for 32% for Physical Health, 16% for Mental Health, and 23% for Physical Function. PHQ-8 and GAD-7 scores suggested depression and anxiety for 22 and 7%, respectively. More than 80% of participants received specific recommendations from the core consultants. Only 20% of participants completed follow-up surveys.

CONCLUSION: Patients living with MBC have multiple needs. We used our results to implement routine PRO assessments and to expand services for patients with MBC. Our experience can serve as a model for coordinated care in other systems.},
}

@article {pmid39868844,
year = {2025},
author = {Elyaman, W and Stern, LJ and Jiang, N and Dressman, D and Bradley, P and Klatzmann, D and Bradshaw, EM and Farber, DL and Kent, SC and Chizari, S and Funk, K and Devanand, D and Thakur, KT and Raj, T and Dalahmah, OA and Sarkis, RA and Weiner, HL and Shneider, NA and Przedborski, S},
title = {Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {},
number = {},
pages = {e14548},
doi = {10.1002/alz.14548},
pmid = {39868844},
issn = {1552-5279},
support = {AG R01AG055422/NH/NIH HHS/United States ; R35GM141457/NH/NIH HHS/United States ; R01AI137198/NH/NIH HHS/United States ; R01AG076018/NH/NIH HHS/United States ; AI106697/NH/NIH HHS/United States ; R01AG067581/NH/NIH HHS/United States ; R13AG090018-01/NH/NIH HHS/United States ; T32AI148099-4/NH/NIH HHS/United States ; },
abstract = {This proceedings article summarizes the inaugural "T Cells in the Brain" symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia-T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau. The symposium also examined immunotherapies for AD, including the Valacyclovir Treatment of Alzheimer's Disease (VALAD) trial, and two clinical trials leveraging regulatory T cell approaches for multiple sclerosis and amyotrophic lateral sclerosis therapy. Additionally, single-cell RNA/TCR sequencing of T cells and other immune cells provided insights into immune dynamics in neurodegenerative diseases. This article highlights key findings from the symposium and outlines future research directions to further understand the role of T cells in neurodegeneration, offering innovative therapeutic approaches for AD and other neurodegenerative diseases. HIGHLIGHTS: Researchers gathered to discuss approaches to study T cells in brain disorders. New technologies allow high-throughput screening of antigen-specific T cells. Microbial infections can precede several serious and chronic neurological diseases. Central and peripheral T cell responses shape neurological disease pathology. Immunotherapy can induce regulatory T cell responses in neuroinflammatory disorders.},
}

@article {pmid39866245,
year = {2025},
author = {Knäusl, B and Vestergaard, A and Schwarz, M and Muren, LP},
title = {New guidelines and recommendations to advance treatment planning in proton therapy.},
journal = {Physics and imaging in radiation oncology},
volume = {33},
number = {},
pages = {100695},
pmid = {39866245},
issn = {2405-6316},
}

@article {pmid39866161,
year = {2025},
author = {Goldberg, SR and Ko, LK and Hsu, L and Yin, H and Kooperberg, C and Peters, U and Burnett-Hartman, AN},
title = {Patient Perspectives on Personalized Risk Communication Using Polygenic Risk Scores to Inform Colorectal Cancer Screening Decisions.},
journal = {AJPM focus},
volume = {4},
number = {1},
pages = {100308},
pmid = {39866161},
issn = {2773-0654},
support = {R01 CA244588/CA/NCI NIH HHS/United States ; },
abstract = {INTRODUCTION: Colorectal cancer is increasingly diagnosed in people aged <50 years. New U.S. guidelines recommend screening initiation at age 45 years. Providing personalized risk for colorectal cancer using polygenic risk scores may be an opportunity to engage this younger population in colorectal cancer screening. There is limited research on patient understanding of polygenic risk scores results and use of polygenic risk scores to inform colorectal cancer screening decisions.

METHODS: From May 2022 to June 2023, 20 Kaiser Permanente Colorado members aged 46-51 years who had been offered colorectal cancer screening but had never completed it signed consent to provide a saliva sample for colorectal cancer polygenic risk score analysis. After receiving personalized polygenic risk scores for colorectal cancer, participants completed a semistructured interview regarding the understanding of their polygenic risk scores, perceived colorectal cancer risk, and intention to screen. Thematic analysis was conducted using Atlas.ti, Version 8.

RESULTS: Of the 19 participants who successfully completed polygenic risk score-related testing and a semistructured interview, 13 were female, 14 never smoked cigarettes, 6 were Hispanic, and 13 were non-Hispanic White. One participant had high risk for colorectal cancer on the basis of polygenic risk score results. Qualitative interviews showed participants' understanding of their results, trust in polygenic risk scores, perception of risk for colorectal cancer, plans to complete colorectal cancer screening, intent to share polygenic risk scores with healthcare providers, and concerns about genetic results impacting health care.

CONCLUSIONS: Qualitative analyses suggest that participants were interested in and understood their polygenic risk score results. Further study is needed to develop guidelines, effective calls to action, provider engagement, and health education materials on use of polygenic risk scores for health decision making.},
}

@article {pmid39866156,
year = {2025},
author = {Marcotte, LM and Khor, S and Wong, ES and Akinsoto, N and Lee, ES and Onstad, S and Issaka, RB},
title = {A Pilot Analysis of Patient Portal Use and Breast Cancer Screening Among Black Patients in a Large Academic Health System.},
journal = {AJPM focus},
volume = {4},
number = {1},
pages = {100305},
pmid = {39866156},
issn = {2773-0654},
abstract = {INTRODUCTION: Patient portals may facilitate breast cancer screening and could be an important factor to address inequities; however, this association is not well characterized. The authors sought to examine this association in a large academic health system to inform interventions to address breast cancer screening inequities.

METHODS: The authors conducted a cross-sectional study among Black patients in a large academic health system using logistic regression to examine the association between breast cancer screening and portal use, adjusting for multilevel covariates and interactions. The authors estimated average marginal effects to examine the additive probability of breast cancer screening completion given portal use in the prior 12 months.

RESULTS: In the unadjusted model, portal use was associated with an estimated mean 24.8 percentage points (95% CI=20.7, 29.0) increased likelihood of completing breast cancer screening. In the adjusted model, portal use was associated with an estimated mean 16.2 percentage points (95% CI=11.2, 21.3) increased likelihood for completing breast cancer screening.

CONCLUSIONS: Improving portal access and use among racialized groups who face both portal and breast cancer screening inequities could be one strategy to address inequities. These pilot data will inform subsequent community-engaged research to better understand this association and develop and test a portal intervention to facilitate breast cancer screening access among Black patients eligible for screening.},
}

@article {pmid39866001,
year = {2025},
author = {Karvonen, KA and Doody, DR and Barry, D and Bona, K and Winestone, LE and Rosenberg, AR and Mendoza, JA and Schwartz, SM and Chow, EJ},
title = {Historical redlining and survival among children, adolescents, and young adults with cancer diagnosed between 2000-2019 in Seattle and Tacoma, Washington.},
journal = {Cancer},
volume = {131},
number = {3},
pages = {e35677},
doi = {10.1002/cncr.35677},
pmid = {39866001},
issn = {1097-0142},
support = {T32CA009351/NH/NIH HHS/United States ; 2023YIA-6719883013//Conquer Cancer Foundation/ ; HE-FY24-MS-07-Karvonen//Mentored Scholars Grant by Seattle Children's Hospital Center for Diversity and Health/ ; N01-CN-67009//Cancer Surveillance System of the Fred Hutchinson Cancer Center/ ; N01-PC-35142//Cancer Surveillance System of the Fred Hutchinson Cancer Center/ ; N01-PC-2010-00029//Cancer Surveillance System of the Fred Hutchinson Cancer Center/ ; HHSN261201800004I//Cancer Surveillance System of the Fred Hutchinson Cancer Center/ ; },
mesh = {Humans ; Adolescent ; Washington/epidemiology ; Male ; Female ; *Neoplasms/mortality/epidemiology ; Young Adult ; Adult ; Child ; Child, Preschool ; Infant ; Proportional Hazards Models ; Poverty/statistics & numerical data ; Kaplan-Meier Estimate ; },
abstract = {BACKGROUND: Historical redlining has been associated with inferior survival in adult-onset cancers. However, its relationship with pediatric, adolescent, and young-adult-onset cancer outcomes is unknown.

METHODS: This study identified incident cancer among individuals <40 years of age living in Seattle and Tacoma between 2000-2019 via the population-based Cancer Surveillance System. The authors determined case redlining status using Home Owners' Loans Corporation data overlaid with 2000 and 2010 census tracts. Kaplan-Meier methods and multivariable Cox proportional hazards models were used to determine 5- and 10-year overall survival and hazard ratio (HR) of death according to redlined status. Cox models adjusted for patient and tumor characteristics and area-level poverty; interaction between redlining and area-level poverty was also assessed.

RESULTS: Among 4355 cases (median age at diagnosis 32 years), overall survival at 5 years was lower (85.1%; 95% confidence interval [CI], 83.5%-86.5%) among individuals residing in redlined neighborhoods compared with those in unexposed neighborhoods (90.3%; 95% CI, 89.0%-91.5%). Survival differences persisted at 10 years. The unadjusted hazard of death for redlined exposed individuals with cancer was higher than redlined unexposed (hazard ratio [HR], 1.62; 95% CI, 1.39-1.89). In the fully adjusted model, mortality remained higher for redlined cases (HR, 1.32; 95% CI, 1.12-1.56). There did not appear to be effect modification from area-level poverty in the relationship between redlining and death (p = .49).

CONCLUSIONS: Among young individuals with cancer, residence at diagnosis in previously redlined neighborhoods was associated with lower survival compared with those residing in nonredlined neighborhoods, supporting the hypothesis that structural racism exerts persistent effects on contemporary health outcomes.},
}

Humans
Adolescent
Washington/epidemiology
Male
Female
*Neoplasms/mortality/epidemiology
Young Adult
Adult
Child
Child, Preschool
Infant
Proportional Hazards Models
Poverty/statistics & numerical data
Kaplan-Meier Estimate

@article {pmid39865921,
year = {2025},
author = {Yanes, R and Saridogan, T and Gorantla, V and Overacre, A and Hsieh, RW and Celebrezze, J and Magge, T and Singhi, M and Saeed, A and Zureikat, AH and Dasari, AN and Sahin, IH},
title = {Shedding Light on the Prognostic and Predictive Value of Circulating Tumor DNA for Management of Patients with Early-Stage Colon Cancer.},
journal = {Technology in cancer research & treatment},
volume = {24},
number = {},
pages = {15330338251317094},
doi = {10.1177/15330338251317094},
pmid = {39865921},
issn = {1533-0338},
mesh = {Humans ; *Circulating Tumor DNA/blood ; *Colonic Neoplasms/pathology/blood/genetics/diagnosis/therapy ; Prognosis ; *Biomarkers, Tumor/blood ; *Neoplasm Staging ; *Disease Management ; Liquid Biopsy/methods ; },
abstract = {The management of early-stage colon cancer involves surgical resection of the primary tumor with or without chemotherapy, depending on pathological staging. The benefit of adjuvant chemotherapy for stage II and III colon cancer is approximately 5% and 15%, indicating the need for optimization for risk stratification and patient selection. Several studies have revealed that current clinicopathological factors lack precision. Circulating tumor DNA (ctDNA) is cell-free DNA originating from cancer cells and can be detected even in the absence of radiologically detectable disease among patients with colon cancer. Recent cohort studies revealed that ctDNA is one of the most significant prognostic factors for patients with early-stage colon cancer, surpassing pathological and clinical risk factors. Prospective cohort studies also suggest there may be a predictive role for ctDNA on the decision for consideration of adjuvant therapy. Currently, randomized clinical trials are enrolling to better define this role. In this review article, we review recent literature on ctDNA and its role in patients with colon cancer. We also elaborate on the future clinical utility of ctDNA in clinical practice and the unmet need for research to optimize currently available ctDNA assays.},
}

Humans
*Circulating Tumor DNA/blood
*Colonic Neoplasms/pathology/blood/genetics/diagnosis/therapy
Prognosis
*Biomarkers, Tumor/blood
*Neoplasm Staging
*Disease Management
Liquid Biopsy/methods

@article {pmid39863610,
year = {2025},
author = {Reddi, S and Senyshyn, L and Ebadi, M and Podlesny, D and Minot, SS and Gooley, T and Kabage, AJ and Hill, GR and Lee, SJ and Khoruts, A and Rashidi, A},
title = {Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1034},
pmid = {39863610},
issn = {2041-1723},
support = {ACT9016-24//Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Graft vs Host Disease/prevention & control/microbiology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Middle Aged ; Adult ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Double-Blind Method ; *Tissue Donors ; *Transplantation, Homologous/adverse effects ; Feces/microbiology ; Acute Disease ; Aged ; Young Adult ; },
abstract = {Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase. The primary and key secondary endpoints were microbiota engraftment and severe aGVHD, respectively. Three cohorts of patients (20 total) received FMT, each from a different donor. FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing data, correlated with larger microbiota compositional shifts toward donor and better clinical outcomes. Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 (P = 0.02) and 2 (P = 0.03) in multivariable analysis. Three patients developed severe aGVHD; all 3 had received FMT from donor 1. Donor 3 was selected as the sole donor for the randomized phase. Our findings suggest a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection. FMT is a holistic microbiota restoration approach that can be performed as a precision therapeutic. ClinicalTrials.gov identifier NCT06026371.},
}

Humans
*Graft vs Host Disease/prevention & control/microbiology
*Fecal Microbiota Transplantation/methods
Male
Female
Middle Aged
Adult
*Gastrointestinal Microbiome
*Hematopoietic Stem Cell Transplantation/adverse effects
Double-Blind Method
*Tissue Donors
*Transplantation, Homologous/adverse effects
Feces/microbiology
Acute Disease
Aged
Young Adult

@article {pmid39862925,
year = {2025},
author = {Nguyen, TK and Louie, AV and Kotecha, R and Saxena, A and Zhang, Y and Guckenberger, M and Kim, MS and Scorsetti, M and Slotman, BJ and Lo, SS and Sahgal, A and Tree, AC},
title = {Stereotactic body radiotherapy for non-spine bone metastases: A meta-analysis and international stereotactic radiosurgery society (ISRS) clinical practice guidelines.},
journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology},
volume = {},
number = {},
pages = {110717},
doi = {10.1016/j.radonc.2025.110717},
pmid = {39862925},
issn = {1879-0887},
abstract = {BACKGROUND: While SBRT to NSBM has become common, particularly in the oligometastatic population, the approach to treating non-spine bone metastases (NSBM) with stereotactic body radiotherapy (SBRT) varies widely across institutions and clinical trial protocols. We present a comprehensive systematic review of the literatures to inform practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS).

METHODS: A systematic literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies with at least 10 patients receiving SBRT for NSBM were identified and meta-analyses were completed to estimate pooled local control and overall survival rates. Published guidelines on NSBM SBRT were reviewed and consolidated.

RESULTS: There were 25 studies included for qualitative analysis and 18 studies for quantitative analysis consisting of 13 retrospective studies, 2 non-randomized prospective studies, 1 randomized phase 2/3 trial, and a subgroup analysis of a phase I trial. The pooled local control rates at 1 and 2 years were 95 % (95 % CI: 89 %-98 %) and 94 % (95 % CI: 86 %-98 %), respectively. Pooled overall survival rates at 1 year and 2 years were 84 % (95 % CI: 73 %-91 %) and 81 % (95 % CI: 45 %-95 %), respectively. Consensus was reached on recommendations to inform treatment simulation, target delineation, dose fractionation, and anatomic site-specific recommendations.

CONCLUSION: We present ISRS-endorsed consensus recommendations to inform best practice of SBRT to NSBM, which we found to be efficacious and associated with low rates of adverse events.},
}

@article {pmid39862490,
year = {2025},
author = {Nickel, B and Ayre, J and Marinovich, ML and Smith, DP and Chiam, K and Lee, CI and Wilt, TJ and Taba, M and McCaffery, K and Houssami, N},
title = {Are AI chatbots concordant with evidence-based cancer screening recommendations?.},
journal = {Patient education and counseling},
volume = {134},
number = {},
pages = {108677},
doi = {10.1016/j.pec.2025.108677},
pmid = {39862490},
issn = {1873-5134},
abstract = {OBJECTIVE: This study aimed to assess whether information from AI chatbots on benefits and harms of breast and prostate cancer screening were concordant with evidence-based cancer screening recommendations.

METHODS: Seven unique prompts (four breast cancer; three prostate cancer) were presented to ChatGPT in March 2024. A total of 60 criteria (30 breast; 30 prostate) were used to assess the concordance of information. Concordance was scored between 0 and 2 against the United States Preventive Services Task Force (USPSTF) breast and prostate cancer screening recommendations independently by international cancer screening experts.

RESULTS: 43 of 60 (71.7 %) criteria were completely concordant, 3 (5 %) were moderately concordant and 14 (23.3 %) were not concordant or not present, with most of the non-concordant criteria (9 of 14, 64.3 %) being from prompts for the oldest age groups. ChatGPT hallucinations (i.e., completely made up, non-sensical or irrelevant information) were found in 9 of 60 criteria (15 %).

CONCLUSIONS: ChatGPT provided information mostly concordant with USPSTF breast and prostate cancer screening recommendations, however, important gaps exist. These findings provide insights into the role of AI to communicate cancer screening benefits and harms and hold increased relevance for periods of guideline change.

PRACTICE IMPLICATIONS: AI generated information on cancer screening should be taken in conjunction with official screening recommendations and/or information from clinicians.},
}

@article {pmid39861671,
year = {2024},
author = {Lee, YS and Kwon, RJ and Lee, HS and Chung, JH and Kim, YS and Jeong, HS and Park, SJ and Lee, SY and Kim, T and Yoon, SH},
title = {The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.},
journal = {Pharmaceutics},
volume = {17},
number = {1},
pages = {},
pmid = {39861671},
issn = {1999-4923},
support = {2024 research grant//Pusan National University Yangsan Hospital/ ; },
abstract = {Lung cancer remains a major global health problem because of its high cancer-related mortality rate despite advances in therapeutic approaches. Non-small cell lung cancer (NSCLC), a major subtype of lung cancer, is more amenable to surgical intervention in its early stages. However, the prognosis for advanced NSCLC remains poor, owing to limited treatment options. This underscores the growing need for novel therapeutic strategies to complement existing treatments and improve patient outcomes. In recent years, pentacyclic triterpenoids, a group of natural compounds, have emerged as promising candidates for cancer therapy due to their anticancer properties. Pentacyclic triterpenoids, such as lupeol, betulinic acid, betulin, oleanolic acid, ursolic acid, glycyrrhetinic acid, glycyrrhizin, and asiatic acid, have demonstrated the ability to inhibit cell proliferation and angiogenesis, induce apoptosis, suppress metastasis, and modulate inflammatory and immune pathways in NSCLC cell line models. These compounds exert their effects by modulating important signaling pathways such as NF-κB, PI3K/Akt, and MAPK. Furthermore, advances in drug delivery technologies such as nanocarriers and targeted delivery systems have improved the bioavailability and therapeutic efficacy of triterpenoids. However, despite promising preclinical data, rigorous clinical trials are needed to verify their safety and efficacy. This review explores the role of triterpenoids in NSCLC and therapeutic potential in preclinical models, focusing on their molecular mechanisms of action.},
}

@article {pmid39858050,
year = {2025},
author = {Hatashima, A and Shadman, M and Raghunathan, V},
title = {Chimeric Antigen Receptor-T Cells in the Modern Era of Chronic Lymphocytic Leukemia Treatment.},
journal = {Cancers},
volume = {17},
number = {2},
pages = {},
pmid = {39858050},
issn = {2072-6694},
abstract = {Pathway inhibitors targeting Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) have dramatically changed the treatment landscape for both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL). However, with increased utilization, a growing number of patients will experience progressive disease on both agents. This subgroup of "double refractory" patients has limited treatment options and poor prognosis. Chimeric antigen receptor (CAR)-T cells have transformed the treatment of relapsed/refractory B-cell malignancies. Although the earliest success of CAR-T cell therapy was in CLL, the clinical application of this modality has lagged until the recent approval of the first CAR-T cell product for CLL. In this review, we describe the current treatment options for upfront and subsequent therapies and the unmet need for novel agents highlighted by the burgeoning role and challenges of CAR-T cell therapy.},
}

@article {pmid39857099,
year = {2025},
author = {Cicero, KI and Banerjee, R and Kwok, M and Dima, D and Portuguese, AJ and Chen, D and Chalian, M and Cowan, AJ},
title = {Illuminating the Shadows: Innovation in Advanced Imaging Techniques for Myeloma Precursor Conditions.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {2},
pages = {},
pmid = {39857099},
issn = {2075-4418},
abstract = {Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), the asymptomatic precursors to multiple myeloma, affect up to 5% of the population over the age of 40. Bone involvement, a myeloma-defining event, represents a major source of morbidity for patients. Key goals for the management of myeloma precursor conditions include (1) identifying patients at the highest risk for progression to MM with bone involvement and (2) differentiating precursor states from active myeloma requiring treatment. Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT with [[18]F]fluorodeoxyglucose (FDG) have improved sensitivity for the detection of myeloma bone disease compared to traditional skeletal surveys, and such advanced imaging also provides this field with better tools for detecting early signs of progression. Herein, we review the data supporting the use of advanced imaging for both diagnostics and prognostication in myeloma precursor conditions.},
}

@article {pmid39856213,
year = {2025},
author = {Patel, SP and Cano-Linson, E and Chae, YK and Schokrpur, S and Lao, CD and Powers, BC and Victor, AI and Onitilo, AA and Shin, S and Takebe, N and Threlkel, S and McLeod, CM and Chen, HX and Sharon, E and Othus, M and Ryan, CW and Blanke, CD and Kurzrock, R},
title = {Dual anti-CTLA-4 and anti-PD-1 blockade in metastatic basal cell carcinoma.},
journal = {NPJ precision oncology},
volume = {9},
number = {1},
pages = {24},
pmid = {39856213},
issn = {2397-768X},
support = {CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA180888 CA180819 U10CA180820 CA180821 CA233331 CA233320 CA180828//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {We report the basal cell cancer (BCC) cohort of the SWOG/NCI 1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART), a phase II prospective, multicenter basket trial of nivolumab and ipilimumab. The primary endpoint was objective response rate (ORR) (RECIST v1.1). Overall survival (OS), progression-free survival (PFS), and toxicity were secondary endpoints. Sixteen patients with advanced/metastatic BCC were evaluable. The ORR was 31% (95% CI, 19-50%), and the 12-month OS, 75% (95% CI, 57-100%). Median PFS was 9.3 months (95% CI, 3.3-NA). Of 15 patients evaluable for clinical benefit, five partial responses (PRs) and five stable disease >6 months (total = 10/15 (66.7%)) were seen. The most common toxicities included fatigue (37.5%), pruritis (31.3%), and diarrhea (25%). In patients with advanced/metastatic BCC, ipilimumab and nivolumab produced an ORR of 31% and prolonged (>6 months) PFS in 73% of patients, with seven PFS/iPFS of >1 year, including one with prior anti-PD-1. ClinicalTrials.gov ID: NCT02834013 (Registered 7/15/2016; https://clinicaltrials.gov/ct2/show/NCT02834013).},
}

@article {pmid39856067,
year = {2025},
author = {Pareja, F and Bhargava, R and Borges, VF and Brogi, E and Canas Marques, R and Cardoso, F and Desmedt, C and Harigopal, M and Lakhani, SR and Lee, A and Leone, JP and Linden, H and Lord, CJ and Marchio, C and Merajver, SD and Rakha, E and Reis-Filho, JS and Richardson, A and Sawyer, E and Schedin, P and Schwartz, CJ and Tutt, A and Ueno, NT and Vincent-Salomon, A and Weigelt, B and Wen, YH and Schnitt, SJ and Oesterreich, S},
title = {Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.},
journal = {NPJ breast cancer},
volume = {11},
number = {1},
pages = {6},
pmid = {39856067},
issn = {2374-4677},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30CA008748//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; AACR-BRCF 09-06-26BORG//Breast Cancer Research Foundation (BCRF)/ ; P50 CA24779 01//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases. Uncommon BC presentations like male, inflammatory and pregnancy-related BC pose challenges. Emerging therapeutic strategies targeting genetic alterations or immune microenvironment are being explored.},
}

@article {pmid39855565,
year = {2025},
author = {Dávila, SB and Schultz, K and Ramgopal, A and Boiko, JR and Beebe, K and Carpenter, P and Chan, S and Paczesny, S and Aguayo-Hiraldo, P and Cuvelier, G and Rotz, SJ and Duncan, CN and Williams, KM},
title = {Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-versus-Host Disease Survivorship after Hematopoietic Cell Transplantation: Part II. Organ Dysfunction and Immune Reconstitution Considerations for children with chronic GVHD after Hematopoietic Cell Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.01.885},
pmid = {39855565},
issn = {2666-6367},
abstract = {While highly morbid forms of chronic graft versus host disease (cGVHD) and severe late effects of allogeneic hematopoietic cell transplant (HCT) can impact children and adults alike, unique considerations arise in pediatric cases regarding diagnosis, monitoring, treatment, and likelihood of resolution. As children can present with atypical features of cGVHD, and with more significant disease due to inability to communicate symptoms, they may be at increased risk for highly morbid forms of cGVHD and incur greater subsequent late effects, which may be more pronounced in those with underlying chromosomal breakage syndromes, with higher prevalence in pediatric HCT recipients. The long-term effects of cGVHD and its therapies include impaired immune reconstitution, leading to increased risks of infection and secondary malignant neoplasms. However, children also have the greatest potential for full immune reconstitution, due to thymus recovery that could impact the timing of vaccination with respect to tolerance and restoration of optimal immunity. Developing strategies to mitigate the late effects incurred with, and as a result of cGVHD, is of critical importance. The working group recommends surveillance strategies for late effects in patients with cGVHD, increased utilization of emerging diagnostic tools, integration of monitoring for cGVHD treatment response, development of new treatments, and provides aims for future research endeavors.},
}

@article {pmid39830263,
year = {2025},
author = {Esmaeili, S and Owens, K and Standing, JF and Lowe, DM and Zhang, S and Watson, JA and Schilling, WHK and Wagoner, J and Polyak, SJ and Schiffer, JT},
title = {Molnupiravir clinical trial simulation suggests that polymerase chain reaction underestimates antiviral potency against SARS-CoV-2.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39830263},
abstract = {Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication. Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes. Model simulations suggest lower antiviral potency against pre-omicron SARS-CoV-2 variants than against omicron. We estimate that in vitro assays underestimate in vivo potency 7-8 fold against omicron variants. Our model suggests that because polymerase chain reaction detects molnupiravir mutated variants, the true reduction in non-mutated viral RNA is underestimated by ~0.5 log10 in the two trials conducted while omicron variants dominated. Viral area under the curve estimates differ significantly between non-mutated and mutated viral RNA. Our results reinforce past work suggesting that in vitro assays are unreliable for estimating in vivo antiviral drug potency and suggest that virologic endpoints for respiratory virus clinical trials should be catered to the drug mechanism of action.},
}

@article {pmid39829847,
year = {2025},
author = {Haddox, HK and Angehrn, G and Sesta, L and Jennings-Shaffer, C and Temple, SD and Galloway, JG and DeWitt, WS and Bloom, JD and Matsen, FA and Neher, RA},
title = {The mutation rate of SARS-CoV-2 is highly variable between sites and is influenced by sequence context, genomic region, and RNA structure.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39829847},
issn = {2692-8205},
support = {R01 AI146028/AI/NIAID NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; },
abstract = {RNA viruses like SARS-CoV-2 have a high mutation rate, which contributes to their rapid evolution. The rate of mutations depends on the mutation type (e.g., A→C, A→G, etc.) and can vary between sites in the viral genome. Understanding this variation can shed light on the mutational processes at play, and is crucial for quantitative modeling of viral evolution. Using the millions of available SARS-CoV-2 full-genome sequences, we estimate rates of synonymous mutations for all 12 possible nucleotide mutation types and examine how much these rates vary between sites. We find a surprisingly high level of variability and several striking patterns: the rates of four mutation types suddenly increase at one of two gene boundaries; the rates of most mutation types strongly depend on a site's local sequence context, with up to 56-fold differences between contexts; consistent with a previous study, the rates of some mutation types are lower at sites engaged in RNA secondary structure. A simple log-linear model of these features explains ~15-60% of the fold-variation of mutation rates between sites, depending on mutation type; more complex models only modestly improve predictive power out of sample. We estimate the fitness effect of each mutation based on the number of times it actually occurs versus the number of times it is expected to occur based on the model. We identify several small regions of the genome where synonymous or noncoding mutations occur much less often than expected, indicative of strong purifying selection on the RNA sequence that is independent of protein sequence. Overall, this work expands our basic understanding of SARS-CoV-2's evolution by characterizing the virus's mutation process at the level of individual sites and uncovering several striking mutational patterns that arise from unknown mechanisms.},
}

@article {pmid39829843,
year = {2025},
author = {Xie, J and Chen, DG and Chour, W and Ng, RH and Zhang, R and Yuan, D and Choi, J and McKasson, M and Troisch, P and Smith, B and Jones, L and Webster, A and Rasheed, Y and Li, S and Edmark, R and Hong, S and Murray, KM and Logue, JK and Franko, NM and Lausted, CG and Piening, B and Algren, H and Wallick, J and Magis, AT and Watanabe, K and Mease, P and Greenberg, PD and Chu, H and Goldman, JD and Su, Y and Heath, JR},
title = {APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39829843},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA264090/CA/NCI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; },
abstract = {Elucidating the relationships between a class I peptide antigen, a CD8 T cell receptor (TCR) specific to that antigen, and the T cell phenotype that emerges following antigen stimulation, remains a mostly unsolved problem, largely due to the lack of large data sets that can be mined to resolve such relationships. Here, we describe Antigen-TCR Pairing and Multiomic Analysis of T-cells (APMAT), an integrated experimental-computational framework designed for the high-throughput capture and analysis of CD8 T cells, with paired antigen, TCR sequence, and single-cell transcriptome. Starting with 951 putative antigens representing a comprehensive survey of the SARS-CoV-2 viral proteome, we utilize APMAT for the capture and single cell analysis of CD8 T cells from 62 HLA A*02:01 COVID-19 participants. We leverage this unique, comprehensive dataset to integrate with peptide antigen properties, TCR CDR3 sequences, and T cell phenotypes to show that distinct physicochemical features of the antigen-TCR pairs strongly associate with both T cell phenotype and T cell persistence. This analysis suggests that CD8+ T cell phenotype following antigen stimulation is at least partially deterministic, rather than the result of stochastic biological properties.},
}

@article {pmid39829744,
year = {2025},
author = {Tang, G and Carr, AV and Perez, C and Sarmiento, KR and Levy, L and Lampe, JW and Diener, C and Gibbons, SM},
title = {Metagenomic estimation of absolute bacterial biomass in the mammalian gut through host-derived read normalization.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39829744},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 DK133468/DK/NIDDK NIH HHS/United States ; },
abstract = {Absolute bacterial biomass estimation in the human gut is crucial for understanding microbiome dynamics and host-microbe interactions. Current methods for quantifying bacterial biomass in stool, such as flow cytometry, qPCR, or spike-ins (i.e., adding cells or DNA from an organism not normally found in a sample), can be labor-intensive, costly, and confounded by factors like water content, DNA extraction efficiency, PCR inhibitors, and other technical challenges that add bias and noise. We propose a simple, cost-effective approach that circumvents some of these technical challenges: directly estimating bacterial biomass from metagenomes using bacterial-to-host (B:H) read ratios. We compare B:H ratios to the standard methods outlined above, demonstrating that B:H ratios are useful proxies for bacterial biomass in stool and possibly in other host-associated substrates. We show how B:H ratios can be used to track antibiotic treatment response and recovery in both mice and humans, which showed 403-fold and 45-fold reductions in bacterial biomass during antibiotic treatment, respectively. Our results indicate that host and bacterial metagenomic DNA fractions in human stool fluctuate longitudinally around a stable mean in healthy individuals, and the average host read fraction varies across healthy individuals by < 8-9 fold. B:H ratios offer a convenient alternative to other absolute biomass quantification methods, without the need for additional measurements, experimental design considerations, or machine learning algorithms, enabling retrospective absolute biomass estimates from existing stool metagenomic data.},
}

@article {pmid39829743,
year = {2025},
author = {Nguyen, A and Heim, JB and Cordara, G and Chan, MC and Johannesen, H and Charlesworth, C and Li, M and Azumaya, CM and Madden, B and Krengel, U and Meves, A and Campbell, MG},
title = {Structural and functional characterization of integrin α5-targeting antibodies for anti-angiogenic therapy.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39829743},
issn = {2692-8205},
support = {R35 GM147414/GM/NIGMS NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; F31 HL174166/HL/NHLBI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; K08 CA215105/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Integrins are a large family of heterodimeric receptors important for cell adhesion and signaling. Integrin α5β1, also known as the fibronectin receptor, is a key mediator of angiogenesis and its dysregulation is associated with tumor proliferation, progression, and metastasis. Despite numerous efforts, α5β1-targeting therapeutics have been unsuccessful in large part due to efficacy and off-target effects. To mediate activation and signaling, integrins undergo drastic conformational changes. However, how therapeutics influence or are affected by integrin conformation remains incompletely characterized. Using cell biology, biophysics, and electron microscopy, we shed light on these relationships by characterizing two potentially therapeutic anti-α5β1 antibodies, BIIG2 and MINT1526A. We show that both antibodies bind α5β1 with nanomolar affinity and reduce angiogenesis in vitro. We demonstrate BIIG2 reduces tumor growth in two human xenograft mouse models and exhibits a strong specificity for connective tissue-resident fibroblasts and melanoma cells. Using electron microscopy, we map out the molecular interfaces mediating the integrin-antibody interactions and reveal that although both antibodies have overlapping epitopes and block fibronectin binding via steric hindrance, the effect on the conformational equilibrium is drastically different. While MINT1526A constricts α5β1's range of flexibility, BIIG2 binds without restricting the available conformational states. These mechanistic insights, coupled with the functional analysis, guide which aspects should be prioritized to avoid off-target effects or partial agonism in the design of future integrin-targeted therapeutics.},
}

@article {pmid39855457,
year = {2025},
author = {Jenkins, MT and Chu, YE and Franceski, AM and Potts, CR and Dubin, R and Dickerson, KM and Lee, SC and Lu, R and Welner, RS and Ferrell, PB},
title = {TET2-loss enhances immediate and time-resolved IFNγ signaling responses across myeloid differentiation.},
journal = {Experimental hematology},
volume = {},
number = {},
pages = {104727},
doi = {10.1016/j.exphem.2025.104727},
pmid = {39855457},
issn = {1873-2399},
abstract = {Signaling responses to cytokines are disrupted in clonal hematopoiesis and myeloid malignancies. To better identify specific signaling response alterations in the presence or absence of TET2, we developed a 36-parameter CyTOF panel of both surface marker and phosphoprotein antigens in murine BM. We show diverse, cell-type specific inflammatory cytokine responses in healthy hematopoietic cells. We next investigated changes associated with bone marrow cells from Tet2[KO] mice. High dimensional surface marker phenotyping revealed expansion of HSPCs, committed cKIT[+]Ly6C[+] myeloid progenitors, and monocytes. Loss of TET2 function increased the magnitude of response to extracellular perturbations, including IFNγ and H2O2. Response time courses revealed that IFNγ-mediated pSTAT1 remains elevated over time in Tet2[KO]. Further, IFNγ resulted in a more significant increase in major histocompatibility complex class II (MHCII) expression in Tet2[KO] immortalized progenitor cells than in Tet2[WT]. Inhibition of Janus kinase 1 and 2 (JAK1/2) with ruxolitinib significantly reduced STAT1 phosphorylation and MHCII expression in Tet2[KO] cells. Our results identify targetable disrupted signaling responses in Tet2[KO] cells.},
}

@article {pmid39854241,
year = {2025},
author = {Langley, CA and Dietzen, PA and Emerman, M and Tenthorey, JL and Malik, HS},
title = {Antiviral Mx proteins have an ancient origin and widespread distribution among eukaryotes.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {4},
pages = {e2416811122},
doi = {10.1073/pnas.2416811122},
pmid = {39854241},
issn = {1091-6490},
support = {T32 GM007270/GM/NIGMS NIH HHS/United States ; Hannay Gray Fellowship GT11096/GT16732//Howard Hughes Medical Institute (HHMI)/ ; Mathilde Krim Fellowship 110298-71-RKHF/110537-74-RKHF//amfAR, The Foundation for AIDS Research (amfAR)/ ; U54 AI170792/AI/NIAID NIH HHS/United States ; Investigator Award//Howard Hughes Medical Institute (HHMI)/ ; },
mesh = {*Phylogeny ; *Myxovirus Resistance Proteins/genetics/metabolism ; Animals ; *Dynamins/metabolism/genetics ; *Eukaryota/genetics ; *Evolution, Molecular ; Humans ; Antiviral Agents ; DNA Viruses/genetics ; },
abstract = {Mx proteins, first identified in mammals, encode potent antiviral activity against a wide range of viruses. Mx proteins arose within the Dynamin superfamily of proteins (DSP), which mediate critical cellular processes, such as endocytosis and mitochondrial, plastid, and peroxisomal dynamics. Despite their crucial role, the evolutionary origins of Mx proteins are poorly understood. Through comprehensive phylogenomic analyses with progressively expanded taxonomic sampling, we demonstrate that Mx proteins predate the interferon signaling system in vertebrates. Our analyses find an ancient monophyletic DSP lineage in eukaryotes that groups vertebrate and invertebrate Mx proteins with fungal MxF proteins, the largely uncharacterized plant and algal Dynamin 4A/4C proteins, and representatives from several other eukaryotic lineages, suggesting that Mx-like proteins date back close to the origin of Eukarya. Our phylogenetic analyses also find host-encoded and nucleocytoplasmic large DNA viruses-encoded DSPs interspersed in four distinct DSP lineages, indicating recurrent viral theft of host DSPs. Our analyses thus reveal an ancient history of viral and antiviral functions encoded by the Dynamin superfamily in eukaryotes.},
}

*Phylogeny
*Myxovirus Resistance Proteins/genetics/metabolism
Animals
*Dynamins/metabolism/genetics
*Eukaryota/genetics
*Evolution, Molecular
Humans
Antiviral Agents
DNA Viruses/genetics

@article {pmid39853979,
year = {2025},
author = {Li, NHY and Li, CI},
title = {Incidence Rate Trends of Breast Cancer Overall and by Molecular Subtype by Race and Ethnicity and Age.},
journal = {JAMA network open},
volume = {8},
number = {1},
pages = {e2456142},
doi = {10.1001/jamanetworkopen.2024.56142},
pmid = {39853979},
issn = {2574-3805},
mesh = {Humans ; Female ; Middle Aged ; Incidence ; *Breast Neoplasms/ethnology/epidemiology/genetics ; Aged ; United States/epidemiology ; Adult ; *SEER Program ; Ethnicity/statistics & numerical data ; Cohort Studies ; Hispanic or Latino/statistics & numerical data ; Age Factors ; Racial Groups/statistics & numerical data ; White People/statistics & numerical data ; White ; },
abstract = {IMPORTANCE: Black and Hispanic women in the US experience higher incidence rates of aggressive molecular subtypes of breast cancer, including triple-negative disease. However, how these rates are changing, particularly across different age groups, has not been well documented.

OBJECTIVE: To assess changes in overall and subtype-specific breast cancer incidence rates in the US by age and race and ethnicity.

This cohort study used Surveillance, Epidemiology, and End Results program cancer registry data from 22 US cancer registries on 1 123 658 females who received a diagnosis of invasive breast cancer from 2010 to 2019. Statistical analysis was conducted from August 2023 to October 2024.

EXPOSURES: Age and race and ethnicity.

MAIN OUTCOMES AND MEASURES: Age-adjusted incidence rates of invasive breast cancer overall and across the 4 major molecular subtypes by age and by race and ethnicity, as well as their associated annual percentage changes using Joinpoint Trend Analysis software.

RESULTS: Of the 1 123 658 participants in the study, 219 112 (19.5%) were younger than 50 years, 409 257 (36.4%) were aged 50 to 64 years, and 495 289 (44.1%) were 65 years or older. A total of 141 703 participants (12.6%) were Hispanic, 3253 (0.3%) were non-Hispanic American Indian or Alaska Native, 78 306 (7.0%) were non-Hispanic Asian or Pacific Islander, 124 560 (11.1%) were non-Hispanic Black, 769 043 (68.4%) were non-Hispanic White, and 6793 participants (0.6%) had an unknown race and/or ethnicity. Overall, breast cancer incidence rates increased 0.5% per year from 2010 to 2019. Variation by race and ethnicity was observed, with increases of 1.4% per year among Hispanic females, 1.9% per year among non-Hispanic American Indian or Alaska Native females, and 2.1% per year among non-Hispanic Asian or Pacific Islander females, while rates increased only 0.8% per year among non-Hispanic Black females and 0.5% per year among non-Hispanic White females. In subtype analyses, increases of the greatest magnitude in recent years were observed in the incidence rates of triple-negative breast cancer per year among participants aged 65 years or older (Hispanic females, 2.3%; non-Hispanic Asian or Pacific Islander females, 5.5%; and non-Hispanic Black females, 4.3%), while remaining unchanged among non-Hispanic White females.

CONCLUSIONS AND RELEVANCE: In this cohort study of 1 123 658 females with breast cancer over the 10-year period from 2010 to 2019, there were substantial differences in trends in the incidence rates of breast cancer overall and by subtype across different racial and ethnic groups. Further research is needed to understand the factors associated with these trends.},
}

Humans
Female
Middle Aged
Incidence
*Breast Neoplasms/ethnology/epidemiology/genetics
Aged
United States/epidemiology
Adult
*SEER Program
Ethnicity/statistics & numerical data
Cohort Studies
Hispanic or Latino/statistics & numerical data
Age Factors
Racial Groups/statistics & numerical data
White People/statistics & numerical data
White

@article {pmid39853273,
year = {2025},
author = {Brown, JR and Li, J and Eichhorst, B and Lamanna, N and O'Brien, SM and Tam, CS and Qiu, L and Huang, R and Shi, Y and Idoine, A and Salmi, T and Cohen, AC and Shadman, M},
title = {ACQUIRED MUTATIONS IN PATIENTS WITH RELAPSED/REFRACTORY CLL WHO PROGRESSED IN THE ALPINE STUDY.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014206},
pmid = {39853273},
issn = {2473-9537},
abstract = {Some CLL patients who develop progressive disease (PD) during treatment with covalent Bruton tyrosine kinase inhibitors (cBTKi) acquire pathway resistance mutations in BTK or PLCG2. Here, we report gene mutation data from paired baseline and PD peripheral blood samples from 52 patients (zanubrutinib, n=24; ibrutinib, n=28) who, at an early median follow-up time of 25.7 months, progressed on zanubrutinib or ibrutinib treatment in the ALPINE trial (NCT03734016). No BTK mutations were observed at baseline; at PD, eight patients (zanubrutinib, n=5, ibrutinib, n=3) acquired a total of 17 BTK mutations. Among BTK mutations, 82.4% (zanubrutinib, n=11/14; ibrutinib, n=3/3) were at C481. Non-C481 mutations were detected in 12.5% (3/24) of zanubrutinib-treated patients (L528W: n=2, cancer cell fraction [CCF]=9.58% and 17.6%; A428D, n=1, CCF=37.03%); these were not detected in ibrutinib-treated patients. At baseline, 48/52 patients had ≥1 driver gene mutation/s, most frequently in: NOTCH1 (n=21), TP53 (n=19), BRAF (n=10), SF3B1 (n=8), and ATM (n=8). At PD, acquired driver gene mutations were observed in one zanubrutinib-treated patient (TP53, XPO1) and five ibrutinib-treated patients (TP53, n=1 patient; SETD2, n=1; SF3B1, n=1; ASXL1, n=2). Baseline driver gene mutations were not associated with later development of BTK mutations, but patients with ≥2 baseline driver gene mutations were more likely to acquire BTK mutations at PD. In conclusion, patients in this data set had a short treatment duration and a low incidence of BTK mutations, suggesting that mechanisms other than BTK/PLCG2 mutations are driving most instances of early PD. NCT03734016.},
}

@article {pmid39847539,
year = {2025},
author = {Bea, JW and Ochs-Balcom, HM and Valencia, CI and Chen, Z and Blew, RM and Lind, KE and Caan, BJ and Roe, DJ and Rohan, TE and Reeves, KW and Manson, JE and Ballinger, T and Reding, KW and Follis, S and Ziller, SG and Odegaard, AO},
title = {Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkaf007},
pmid = {39847539},
issn = {2515-5091},
abstract = {BACKGROUND: Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear.

METHODS: We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated. Dual-energy X-ray absorptiometry scans assessed adiposity at baseline, year 3, and year 6. Competing risks multivariable sub-hazard ratios (SHR), with adjustments for sociodemographic, behavioral, reproductive, and anthropometric characteristics, were estimated for baseline and time-dependent associations between VAT, SAT, and incident BCa.

RESULTS: Participants averaged 63.3 ± 7.4 years of age and a BMI of 28.20 ± 5.72 kg/m2 at baseline. The models included 738 incident BCa cases (N = 593 invasive; N = 145 in situ). Baseline VAT and SAT area were associated with significantly increased BCa risk, by 36% and 19% respectively. Increasing VAT/SAT ratio was associated with an 8% increase in incident BCa. Time-dependent models produced similar results. VAT and VAT/SAT associated BCa risk was highest for African American/Black women, though not significantly different from other groups. Quartiles (Q) of VAT/SAT were also explored; the SHR for Q4 compared to Q1 was 1.49 (95% CI: 1.18, 1.87).

CONCLUSION: Higher abdominal VAT and SAT are associated with an increased risk of postmenopausal BCa, and VAT/SAT may provide a distinctive risk estimate. Potential racial and ethnic differences require replication in a larger sample.(NCT00000611).},
}

@article {pmid39846783,
year = {2024},
author = {Lee, MA and Hatcher, CA and Hazelwood, E and Goudswaard, LJ and Tsilidis, KK and Vincent, EE and Martin, RM and Smith-Byrne, K and Brenner, H and Cheng, I and Kweon, SS and Le Marchand, L and Newcomb, PA and Schoen, RE and Peters, U and Gunter, MJ and Van Guelpen, B and Murphy, N},
title = {A proteogenomic analysis of the adiposity colorectal cancer relationship identifies GREM1 as a probable mediator.},
journal = {International journal of epidemiology},
volume = {54},
number = {1},
pages = {},
pmid = {39846783},
issn = {1464-3685},
support = {//Wereld Kanker Onderzoek Fonds/ ; INCa SHSESP20//French National Cancer Institute/ ; },
mesh = {Humans ; *Adiposity/genetics ; *Colorectal Neoplasms/genetics/epidemiology ; *Body Mass Index ; Female ; Male ; *Mendelian Randomization Analysis ; *Waist-Hip Ratio ; Risk Factors ; Intercellular Signaling Peptides and Proteins/genetics ; Obesity/genetics ; Proteomics ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Adiposity is an established risk factor for colorectal cancer (CRC). The pathways underlying this relationship, and specifically the role of circulating proteins, are unclear.

METHODS: Utilizing two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and colocalization, based on summary data from large sex-combined and sex-specific genetic studies, we estimated the univariable associations between: (i) body mass index (BMI) and waist-hip ratio (WHR) and overall and site-specific (colon, proximal colon, distal colon, and rectal) CRC risk, (ii) BMI and WHR and circulating proteins, and (iii) adiposity-associated circulating proteins and CRC risk. We used MVMR to investigate the potential mediating role of adiposity- and CRC-related circulating proteins in the adiposity-CRC association.

RESULTS: BMI and WHR were positively associated with CRC risk, with similar associations by anatomical tumor site. In total, 6591 adiposity-protein (2628 unique circulating proteins) and 33 protein-CRC (7 unique circulating proteins) associations were identified using UVMR and colocalization. One circulating protein, GREM1, was associated with BMI (only) and CRC outcomes in a manner that was consistent with a potential mediating role in sex-combined and female-specific analyses. In MVMR, adjusting the BMI-CRC association for GREM1, effect estimates were attenuated-suggestive of a potential mediating role-most strongly for the BMI-overall CRC association in women.

CONCLUSION: Results highlight the impact of adiposity on the plasma proteome and of adiposity-associated circulating proteins on the risk of CRC. Supported by evidence from UVMR and colocalization analyses using cis-single-nucleotide polymorphisms, GREM1 was identified as a potential mediator of the BMI-CRC association, particularly in women.},
}

Humans
*Adiposity/genetics
*Colorectal Neoplasms/genetics/epidemiology
*Body Mass Index
Female
Male
*Mendelian Randomization Analysis
*Waist-Hip Ratio
Risk Factors
Intercellular Signaling Peptides and Proteins/genetics
Obesity/genetics
Proteomics
Polymorphism, Single Nucleotide

@article {pmid39845432,
year = {2024},
author = {Santiago-Torres, M and Mull, KE and Sullivan, BM and Prochaska, JJ and Zvolensky, MJ and Bricker, JB},
title = {Can an Acceptance and Commitment Therapy-Based Smartphone App Help Individuals with Mental Health Disorders Quit Smoking?.},
journal = {Depression and anxiety},
volume = {2024},
number = {},
pages = {},
pmid = {39845432},
issn = {1520-6394},
support = {R01 CA192849/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; *Acceptance and Commitment Therapy/methods ; *Smoking Cessation/methods ; Female ; *Mobile Applications ; Adult ; Middle Aged ; *Smartphone ; Mental Disorders/therapy ; United States ; Schizophrenia/therapy ; Bipolar Disorder/therapy ; },
abstract = {BACKGROUND: Individuals with mental health disorders face major barriers in accessing smoking cessation care, often due to the stigmas associated with mental disorders and addiction. Consequently, accessible population-based smoking cessation interventions are needed for this vulnerable group.

OBJECTIVE: This secondary analysis utilized data from a 12-month randomized trial to examine whether an acceptance and commitment therapy-based app (iCanQuit) demonstrated greater efficacy, engagement, and satisfaction compared to a United States (US) Clinical Practice Guidelines-based app (QuitGuide) in helping adults with mental health disorders quit smoking.

MATERIALS AND METHODS: Participants self-reported having bipolar disorder or schizophrenia, or screened positive for depression, generalized anxiety, panic disorder, posttraumatic stress disorder, or social anxiety. We compared the primary outcome of self-reported 30-day cigarette abstinence at 12 months between iCanQuit (n = 770) and QuitGuide (n = 785) using complete-case and multiple imputation analyses and compared engagement and satisfaction between arms. Mediation analyses were conducted to examine whether the intervention apps functioned by reinforcing hypothesized mechanisms of action, namely, acceptance of triggers to smoke and through app engagement.

RESULTS: Participants represented all 50 US states and had 30.2% non-White or Hispanic backgrounds. Among participants with any mental health disorder, iCanQuit demonstrated higher 30-day cigarette abstinence than QuitGuide at 12 months (complete-case: 24.4% vs. 20.4%, P = 0.04; multiple imputation: 24.6% vs. 20.4%, P = 0.04). A comparable effect size was observed in iCanQuit participants with bipolar disorder or schizophrenia compared to QuitGuide, albeit not statistically significant (multiple imputation: 27.1% vs. 20.9%; P = 0.06). iCanQuit's cessation efficacy was mediated by acceptance of emotions triggering smoking (P < 0.001) and app engagement (P < 0.001). iCanQuit was more satisfying than QuitGuide (88.5% vs. 77.2%; P < 0.001).

CONCLUSIONS: In the largest known study of ACT for smoking cessation among adults with mental health disorders, the smoking cessation, engagement, and satisfaction outcomes were all significantly greater with iCanQuit than QuitGuide. Acceptance of emotions triggering smoking and iCanQuit app engagement were important mechanisms of efficacy. This trial is registered with NCT02724462.},
}

Humans
Male
*Acceptance and Commitment Therapy/methods
*Smoking Cessation/methods
Female
*Mobile Applications
Adult
Middle Aged
*Smartphone
Mental Disorders/therapy
United States
Schizophrenia/therapy
Bipolar Disorder/therapy

@article {pmid39844469,
year = {2025},
author = {Cooper, N and Jansen, AJG and Bird, R and Mayer, J and Sholzberg, M and Tarantino, MD and Garg, M and Ypma, PF and McDonald, V and Percy, C and Košťál, M and Goncalves, I and Bogdanov, LH and Gernsheimer, TB and Diab, R and Yao, M and Daak, A and Kuter, DJ},
title = {Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.27539},
pmid = {39844469},
issn = {1096-8652},
support = {//Sanofi/ ; },
abstract = {Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 10[9]/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 10[9]/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 10[9]/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 10[9]/L or ≥ 30 × 10[9]/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 10[9]/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.},
}

@article {pmid39844041,
year = {2025},
author = {Crisp, AM and Halloran, ME and Hitchings, MDT and Longini, IM and Dean, NE},
title = {Analysis methods for covariate-constrained cluster randomized trials with time-to-event outcomes.},
journal = {BMC medical research methodology},
volume = {25},
number = {1},
pages = {16},
pmid = {39844041},
issn = {1471-2288},
support = {U01-AI148069/NH/NIH HHS/United States ; U01-AI148069/NH/NIH HHS/United States ; U01-AI148069/NH/NIH HHS/United States ; U01-AI148069/NH/NIH HHS/United States ; U01-AI148069//National Institute of Allergy and Infectious Diseases/ ; U01-AI148069//National Institute of Allergy and Infectious Diseases/ ; U01-AI148069//National Institute of Allergy and Infectious Diseases/ ; U01-AI148069//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Randomized Controlled Trials as Topic/methods/statistics & numerical data ; Cluster Analysis ; *Proportional Hazards Models ; Mexico ; Child ; Computer Simulation ; },
abstract = {BACKGROUND: Cluster randomized trials, which often enroll a small number of clusters, can benefit from constrained randomization, selecting a final randomization scheme from a set of known, balanced randomizations. Previous literature has addressed the suitability of adjusting the analysis for the covariates that were balanced in the design phase when the outcome is continuous or binary. Here we extended this work to time-to-event outcomes by comparing two model-based tests and a newly derived permutation test. A current cluster randomized trial of vector control for the prevention of mosquito-borne disease in children in Mexico is used as a motivating example.

METHODS: We assessed type I error rates and power between simple randomization and constrained randomization using both prognostic and non-prognostic covariates via a simulation study. We compared the performance of a semi-parametric Cox proportional hazards model with robust variance, a mixed effects Cox model, and a permutation test utilizing deviance residuals.

RESULTS: The permutation test generally maintained nominal type I error-with the exception of the unadjusted analysis for constrained randomization-and also provided power comparable to the two Cox model-based tests. The model-based tests had inflated type I error when there were very few clusters per trial arm. All three methods performed well when there were 25 clusters per trial arm, as in the case of the motivating example.

CONCLUSION: For time-to-event outcomes, covariate-constrained randomization was shown to improve power relative to simple randomization. The permutation test developed here was more robust to inflation of type I error compared to model-based tests. Gaining power by adjusting for covariates in the analysis phase was largely dependent on the number of clusters per trial arm.},
}

Humans
*Randomized Controlled Trials as Topic/methods/statistics & numerical data
Cluster Analysis
*Proportional Hazards Models
Mexico
Child
Computer Simulation

@article {pmid39841165,
year = {2025},
author = {Peters, BA and Xue, X and Hanna, DB and Wang, Y and Wang, Z and Sharma, A and Floris-Moore, M and Konkle-Parker, D and Alcaide, ML and Sheth, AN and Topper, EF and Weber, KM and Tien, PC and Merenstein, D and Vásquez, E and Chen, Y and Mimiaga, MJ and Stosor, V and Brown, TT and Erlandson, KM and Dillon, SM and Elsayed, NS and Usyk, M and Sollecito, CC and Kaplan, RC and Burk, RD and Qi, Q},
title = {Healthy Aging and the Gut Microbiome in People With and Without HIV.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiae644},
pmid = {39841165},
issn = {1537-6613},
support = {U01-HL146241/HL/NHLBI NIH HHS/United States ; //Eunice Kennedy Shriver/ ; //National Institute of Child Health and Human Development/ ; /AG/NIA NIH HHS/United States ; /DE/NIDCR NIH HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; /NS/NINDS NIH HHS/United States ; /MH/NIMH NIH HHS/United States ; /DA/NIDA NIH HHS/United States ; /NR/NINR NIH HHS/United States ; /CA/NCI NIH HHS/United States ; /AA/NIAAA NIH HHS/United States ; /DC/NIDCD NIH HHS/United States ; /DK/NIDDK NIH HHS/United States ; /MD/NIMHD NIH HHS/United States ; /NH/NIH HHS/United States ; UL1 -TR000004//Office of AIDS Research/ ; },
abstract = {BACKGROUND: Aging-related comorbidities are more common in people with human immunodeficiency virus (HIV) compared to people without HIV. The gut microbiome may play a role in healthy aging; however, this relationship remains unexplored in the context of HIV.

METHODS: 16S rRNA gene sequencing was conducted on stool from 1409 women (69% with HIV; 2304 samples) and 990 men (54% with HIV; 1008 samples) in the MACS/WIHS Combined Cohort Study. Associations of age with gut microbiome diversity, uniqueness, and genus-level abundance were examined in women and men separately, followed by examining relationships of aging-related genera with frailty (Fried frailty phenotype) and mortality risk (Veterans Aging Cohort Study [VACS] index).

RESULTS: Older age was associated with greater microbiome diversity and uniqueness, greater abundance of Akkermansia and Streptococcus, and lower abundance of Prevotella and Faecalibacterium, among others; findings were generally consistent by sex and HIV status. An aging-related microbiome score, generated via combination of 18 age-related genera, significantly increased with age in both women and men independently of demographic, behavioral, and cardiometabolic factors. In general, age was more strongly related to microbiome features (eg, diversity, microbiome score) in men without compared to with HIV, but age-microbiome associations were similar in women with and without HIV. Some age-related genera associated with healthy/unhealthy aging, such as Faecalibacterium (related to reduced frailty) and Streptococcus (related to higher VACS index).

CONCLUSIONS: Age is associated with consistent changes in the gut microbiome in both women and men with or without HIV. Some aging-related microbiota are associated with aging-related declines in health.},
}

@article {pmid39838067,
year = {2025},
author = {Haseli, S and Park, C and Azhideh, A and Karande, G and Chalian, M},
title = {Performance and reliability comparison: original vs. revised bone reporting and data system (Bone-RADS).},
journal = {Skeletal radiology},
volume = {},
number = {},
pages = {},
pmid = {39838067},
issn = {1432-2161},
abstract = {OBJECTIVE: To propose a revised bone reporting and data system (Bone-RADS) and evaluate its diagnostic performance and inter-reader reliability compared to the original Bone-RADS for solitary bone lesions on CT.

MATERIALS AND METHODS: This retrospective study included 159 adult patients (mean age: 56 ± 19 years; 88 men) who underwent bone biopsy for solitary bone lesions between March 2005 and September 2021. Two radiologists (R1/2) independently categorized the lesions twice, once using the original Bone-RADS and once using the revised version. Lesions were classified as follows: (1, benign; 2, incompletely assessed; 3, indeterminate; 4, malignancy or requiring treatment). The revised Bone-RADS excluded the original criteria for lesion related pain and history of malignancy. Diagnostic performance was assessed using histopathology as the reference standard, and inter-reader reliability was analyzed.

RESULTS: The bone lesions included 96 lucent and 63 sclerotic/mixed lesions. Sensitivity showed no significant difference between the original and revised Bone-RADS for both readers across lucent and sclerotic/mixed lesions (all P ≥ .05). However, the specificity of the revised Bone-RADS was significantly higher than that of the original (lucent: 11% vs. 50% [R1], 11% vs. 46% [R2]; sclerotic/mixed: 32% vs. 92% [R1], 32% vs. 86% [R2]). Other performance metrics, including positive/negative predictive value and accuracy, were also higher in the revised Bone-RADS. Inter-reader reliability was higher for the revised Bone-RADS compared to the original (κ = .744 vs .854).

CONCLUSION: The revised Bone-RADS significantly improved specificity while maintaining sensitivity compared to the original version.},
}

@article {pmid39834946,
year = {2024},
author = {O'Halloran, K and Crotty, EE and Christodoulou, E and Leary, SE and Miller, A and Paulson, VA and Lockwood, CM and Margol, AS and Biegel, JA},
title = {Targeted detection of sequence variants in cell-free DNA from cerebrospinal fluid in pediatric central nervous system tumors.},
journal = {Frontiers in oncology},
volume = {14},
number = {},
pages = {1513073},
pmid = {39834946},
issn = {2234-943X},
abstract = {The emergence of liquid biopsy technologies holds great promise in the cancer setting, including in pediatric central nervous system (CNS) tumors. In contrast to broad lower-depth sequencing, commonly referred to as low pass whole genome sequencing (WGS), targeted platforms with a higher depth of coverage have also been established. Here, we review targeted liquid biopsy techniques with applicability to pediatric CNS tumors. These include polymerase chain reaction (PCR), both droplet digital PCR and reverse transcription-based PCR, Sanger sequencing, and next-generation sequencing approaches that incorporate amplicon- and hybrid capture-based methods. The goal of this paper is to facilitate an understanding of these targeted techniques and provide a context for clinical relevance within disease categories, as well as a discussion on optimizing real-world implementation for pediatric CNS tumors.},
}

@article {pmid39831734,
year = {2025},
author = {Moussa, MJ and Tabet, GC and Siefker-Radtke, AO and Xiao, L and Wilson, NR and Gao, J and Logothetis, CJ and Grivas, P and Lee, B and Shah, AY and Msaouel, P and Li, R and Clemente, LC and Zhao, J and Tannir, NM and Kamat, AM and Hansel, DE and Guo, CC and Campbell, MT and Alhalabi, O},
title = {Histopathologic Progression and Metastatic Relapse Outcomes in Small Cell Neuroendocrine Carcinomas of the Urinary Tract.},
journal = {Cancer medicine},
volume = {14},
number = {2},
pages = {e70594},
pmid = {39831734},
issn = {2045-7634},
support = {//Ingram Family Fund/ ; },
mesh = {Humans ; Male ; Female ; *Carcinoma, Neuroendocrine/pathology/therapy/drug therapy/surgery ; Aged ; Middle Aged ; *Neoplasm Recurrence, Local/pathology ; *Carcinoma, Small Cell/pathology/therapy ; Disease Progression ; Urologic Neoplasms/pathology/therapy/mortality ; Neoadjuvant Therapy ; Prognosis ; Adult ; Retrospective Studies ; Aged, 80 and over ; },
abstract = {INTRODUCTION: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

MATERIALS AND METHODS: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time-to-event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine-Gray distribution models assessed covariate associations.

RESULTS: Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) patients had relapse with 77 (83.7%) having distant organs as first metastatic sites, including 10 (10.9%) with exclusive central nervous system (CNS) metastases, mostly (9/10) within 1 year of surgery. Patients with pathologic complete response (pCR) after neoCTx had the lowest 5-year CIF (16.5% [95% CI 9.3%-25.6%]). Patients with remaining exclusively small cell (SC) histology had the highest CIF (85.7% [95% CI 46.6-96.9]). Patients with eradicated SCNEC but remaining UC components had an intermediate-risk CIF (32.5% [95% CI 18.6-47.2]). Multivariable analysis adjusting for neoCTx, clinical stage at diagnosis (T3/4, N0/N+ vs. T1/T2, N0), and pathologic stage (pN+ vs. pN0) demonstrated that any SCNEC histology at resection (vs. pCR) was associated with relapse risk (hazard ratio = 3.69 [95% CI 1.91-7.13], p = 0.0001).

CONCLUSIONS: SCNEC-URO is a systemic disease with high risk of distant relapse including CNS. Our findings highlight unmet needs for neoadjuvant/adjuvant approaches targeting the rare SCNEC subtype and suggest adding CNS surveillance within the first year after definitive surgery to high-risk patients. PRÉCIS (CONDENSED ABSTRACT): Alongside neoadjuvant chemotherapy and cancer stage, histology at resection strongly impacts relapse risk in small cell neuroendocrine carcinomas of the urinary tract. The incidence of brain metastasis is notably higher than in "traditional" urothelial cancer within the first year after surgery, especially if small cell cancer persists, thus necessitating close neurological monitoring during this period.},
}

Humans
Male
Female
*Carcinoma, Neuroendocrine/pathology/therapy/drug therapy/surgery
Aged
Middle Aged
*Neoplasm Recurrence, Local/pathology
*Carcinoma, Small Cell/pathology/therapy
Disease Progression
Urologic Neoplasms/pathology/therapy/mortality
Neoadjuvant Therapy
Prognosis
Adult
Retrospective Studies
Aged, 80 and over

@article {pmid39831552,
year = {2025},
author = {Lichauco, C and Foss, EJ and Gatbonton-Schwager, T and Athow, NF and Lofts, B and Acob, R and Taylor, E and Marquez, JJ and Lao, U and Miles, S and Bedalov, A},
title = {Sir2 and Fun30 regulate ribosomal DNA replication timing via MCM helicase positioning and nucleosome occupancy.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {39831552},
issn = {2050-084X},
support = {R01GM117446/NH/NIH HHS/United States ; },
mesh = {*Silent Information Regulator Proteins, Saccharomyces cerevisiae/metabolism/genetics ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; *Sirtuin 2/metabolism/genetics ; *Saccharomyces cerevisiae/genetics/metabolism ; *Nucleosomes/metabolism ; *DNA, Ribosomal/genetics/metabolism ; DNA Replication Timing ; Transcription Factors/metabolism/genetics ; DNA Replication ; DNA Helicases/metabolism/genetics ; Gene Expression Regulation, Fungal ; },
abstract = {The association between late replication timing and low transcription rates in eukaryotic heterochromatin is well known, yet the specific mechanisms underlying this link remain uncertain. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA (rDNA) arrays. We have previously reported that in the absence of SIR2, a de-repressed RNA PolII repositions MCM replicative helicases from their loading site at the ribosomal origin, where they abut well-positioned, high-occupancy nucleosomes, to an adjacent region with lower nucleosome occupancy. By developing a method that can distinguish activation of closely spaced MCM complexes, here we show that the displaced MCMs at rDNA origins have increased firing propensity compared to the nondisplaced MCMs. Furthermore, we found that both activation of the repositioned MCMs and low occupancy of the adjacent nucleosomes critically depend on the chromatin remodeling activity of FUN30. Our study elucidates the mechanism by which Sir2 delays replication timing, and it demonstrates, for the first time, that activation of a specific replication origin in vivo relies on the nucleosome context shaped by a single chromatin remodeler.},
}

*Silent Information Regulator Proteins, Saccharomyces cerevisiae/metabolism/genetics
*Saccharomyces cerevisiae Proteins/metabolism/genetics
*Sirtuin 2/metabolism/genetics
*Saccharomyces cerevisiae/genetics/metabolism
*Nucleosomes/metabolism
*DNA, Ribosomal/genetics/metabolism
DNA Replication Timing
Transcription Factors/metabolism/genetics
DNA Replication
DNA Helicases/metabolism/genetics
Gene Expression Regulation, Fungal

@article {pmid39830606,
year = {2025},
author = {Adsul, P and Sanchez-Youngman, S and Dickson, E and Jacquez, B and Kuhlemeier, A and Muhammad, M and Briant, KJ and Hempstead, B and Mendoza, JA and Rosas, LG and Patel, A and Rodriguez Espinosa, P and Akintobi, T and Castro-Reyes, P and Carter-Edwards, L and Wallerstein, N},
title = {Assessing the context within academic health institutions toward improving equity-based, community and patient-engaged research.},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e6},
pmid = {39830606},
issn = {2059-8661},
abstract = {INTRODUCTION: The continued momentum toward equity-based, patient/community-engaged research (P/CenR) is pushing health sciences to embrace principles of community-based participatory research. Much of this progress has hinged on individual patient/community-academic partnered research projects and partnerships with minimal institutional support from their academic health institutions.

METHODS: We partnered with three academic health institutions and used mixed methods (i.e., institution-wide survey (n = 99); qualitative interviews with institutional leadership (n = 11); and focus group discussions (6 focus groups with patients and community members (n = 22); and researchers and research staff (n = 9)) to gain a deeper understanding of the institutional context.

RESULTS: Five key themes emerged that were supported by quantitative data. First, the global pandemic and national events highlighting social injustices sparked a focus on health equity in academic institutions; however, (theme 2) such a focus did not always translate to support for P/CenR nor align with institutional reputation. Only 52% of academics and 79% of community partners believed that the institution is acting on the commitment to health equity (Χ[2] = 6.466, p < 0.05). Third, institutional structures created power imbalances and community mistrust which were identified as key barriers to P/CenR. Fourth, participants reported that institutional resources and investments are necessary for recruitment and retention of community-engaged researchers. Finally, despite challenges, participants were motivated to transform current paradigms of research and noted that accountability, communication, and training were key facilitators.

CONCLUSIONS: Triangulating findings from this mixed-methods study revealed critical barriers which provide important targets for interventions to improving supportive policies and practices toward equity-based P/CenR.},
}

@article {pmid39828431,
year = {2025},
author = {Begnel, ER and Ojee, E and Adhiambo, J and Mabele, E and Wandika, B and Ogweno, V and Lim, ES and Gantt, S and Kinuthia, J and Lehman, DA and Slyker, J and Wamalwa, D},
title = {The Linda Kizazi study: a comparison of morbidity and mortality from birth to 2 years between children who are HIV-unexposed and HIV-exposed, uninfected in the era of universal antiretroviral therapy.},
journal = {BMJ global health},
volume = {10},
number = {1},
pages = {},
pmid = {39828431},
issn = {2059-7908},
support = {R01 HD092311/HD/NICHD NIH HHS/United States ; },
mesh = {Humans ; *HIV Infections/drug therapy/mortality/epidemiology ; Female ; Infant ; Kenya/epidemiology ; Infant, Newborn ; Pregnancy ; Male ; Adult ; Child, Preschool ; Malaria/mortality/drug therapy/epidemiology ; Cohort Studies ; Diarrhea/epidemiology/mortality ; Respiratory Tract Infections/mortality/epidemiology ; Hospitalization/statistics & numerical data ; Morbidity ; Pregnancy Complications, Infectious/drug therapy/epidemiology ; Anti-Retroviral Agents/therapeutic use ; },
abstract = {BACKGROUND: Historically, children who are HIV-exposed, uninfected (CHEU) have been found to have greater morbidity and mortality than children who are HIV-unexposed, uninfected (CHUU). To assess whether this difference persists in the era of universal antiretroviral therapy (ART), we conducted a cohort study to compare the risk of acute diarrhoea, respiratory tract infections (RTI), malaria, hospitalisation, and all-cause mortality between Kenyan CHEU and CHUU from birth to 2 years.

METHODS: From December 2018 to March 2020 at Mathare North Health Centre in Nairobi, we recruited pregnant women living with HIV on ART for ≥6 months and pregnant women without HIV from the same community. We followed the mother-infant pairs for 2 years post partum and collected data on symptoms of illness, clinical visits and diagnoses, and infant feeding every 3 months; a self-selected subset of participants also received weekly data collection for up to 1 year. We compared the risk of each outcome between CHEU versus CHUU using HRs from Andersen-Gill (recurrent morbidity outcomes) and Cox proportional hazards (mortality) regression models adjusted for maternal age, marital status and education level.

RESULTS: Among 187 mother-infant pairs with postpartum data, 86 (46%) infants were CHEU and 101 (54%) were CHUU. All initiated breastfeeding, and 88% of CHEU and 57% of CHUU were exclusively breastfed (EBF) for ≥6 months. There was no significant difference in risk of diarrhoea (HR=0.79, 95% CI 0.52 to 1.22), malaria (HR=0.44, 95% CI 0.16 to 1.21), hospitalisation (HR=1.11, 95% CI 0.30 to 4.14), or mortality (HR=1.87, 95% CI 0.17 to 20.5). However, CHEU had lower risk of any RTI (HR=0.60, 95% CI 0.44 to 0.82) and pneumonia (HR=0.29, 95% CI 0.091 to 0.89).

CONCLUSIONS: CHEU born to women on effective long-term ART experienced similar overall morbidity and mortality as CHUU. However, CHEU had substantially lower risk of pneumonia and other RTI, possibly due to longer EBF in this group.},
}

Humans
*HIV Infections/drug therapy/mortality/epidemiology
Female
Infant
Kenya/epidemiology
Infant, Newborn
Pregnancy
Male
Adult
Child, Preschool
Malaria/mortality/drug therapy/epidemiology
Cohort Studies
Diarrhea/epidemiology/mortality
Respiratory Tract Infections/mortality/epidemiology
Hospitalization/statistics & numerical data
Morbidity
Pregnancy Complications, Infectious/drug therapy/epidemiology
Anti-Retroviral Agents/therapeutic use

@article {pmid39827422,
year = {2025},
author = {Sierra, J and de León, UA and Padilla-Longoria, P},
title = {Tumor microenvironment noise-induced polarization: the main challenge in macrophages' immunotherapy for cancer.},
journal = {Molecular and cellular biochemistry},
volume = {},
number = {},
pages = {},
pmid = {39827422},
issn = {1573-4919},
abstract = {Disturbance of epigenetic processes can lead to altered gene function and malignant cellular transformation. In particular, changes in the epigenetic landscape are a central topic in cancer biology. The initiation and progression of cancer are now recognized to involve both epigenetic and genetic alterations. In this paper, we study the epigenetic mechanism (related to the tumor microenvironment) responsible for increasing tumor-associated macrophages that promote the occurrence and metastasis of tumor cells, support tumor angiogenesis, inhibit T-cell-mediated anti-tumor immune response, and lead to tumor progression. We show that the tumor benefits from the macrophages' high degree of plasticity and larger epigenetic basins corresponding to phenotypes that favor cancer development through a process that we call noise-induced polarization. Moreover, we propose a mechanism to promote the appropriate epigenetic stability for immunotherapies involving macrophages, which includes p53 and APR-246 (eprenetapopt). Our results show that a combination therapy may be necessary to ensure the proper epigenetic stability of macrophages, which otherwise will contribute to cancer progression. On the other hand, we conclude that macrophages may remain in the anti-tumoral state in types of cancer that exhibit less TP53 mutation, like colorectal cancer; in these cases, macrophages' immunotherapy may be more suitable. We finally mention the relevance of the epigenetic potential (Waddington's landscape) as the backbone for our study, which encapsulates the biological information of the system.},
}

@article {pmid39826256,
year = {2025},
author = {Lim, FY and Lea, HG and Dostie, AM and Kim, SY and van Neel, TL and Hassan, GW and Takezawa, MG and Starita, LM and Adams, KN and Boeckh, M and Schiffer, JT and Hyrien, O and Waghmare, A and Berthier, E and Theberge, AB},
title = {homeRNA self-blood collection enables high-frequency temporal profiling of presymptomatic host immune kinetics to respiratory viral infection: a prospective cohort study.},
journal = {EBioMedicine},
volume = {112},
number = {},
pages = {105531},
doi = {10.1016/j.ebiom.2024.105531},
pmid = {39826256},
issn = {2352-3964},
abstract = {BACKGROUND: Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a Tasso-SST based self-blood collection and stabilization tool (homeRNA) to profile detailed kinetics of the presymptomatic to convalescence host immunity to contemporaneous respiratory pathogens.

METHODS: We enrolled non-symptomatic adults with recent exposure to ARIs who subsequently tested negative (exposed-uninfected) or positive for respiratory pathogens. Participants self-collected blood and nasal swabs daily for seven consecutive days followed by weekly blood collection for up to seven additional weeks. Symptom burden was assessed during each collection. Nasal swabs were tested for SARS-CoV-2 and common respiratory pathogens. 92 longitudinal blood samples spanning the presymptomatic to convalescence phase of eight participants with SARS-CoV-2 infection and 40 interval-matched samples from four exposed-uninfected participants were subjected to high-frequency longitudinal profiling of 785 immune genes. Generalized additive mixed models (GAMM) were used to identify temporally dynamic genes from the longitudinal samples and linear mixed models (LMM) were used to identify baseline differences between exposed-infected (n = 8), exposed-uninfected (n = 4), and uninfected (n = 13) participant groups.

FINDINGS: Between June 2021 and April 2022, 68 participants across 26 U.S. states completed the study and self-collected a total of 691 and 466 longitudinal blood and nasal swab samples along with 688 symptom surveys. SARS-CoV-2 was detected in 17 out of 22 individuals with study-confirmed respiratory infection, of which five were still presymptomatic or pre-shedding, enabling us to profile detailed expression kinetics of the earliest blood transcriptional response to contemporaneous variants of concern. 51% of the genes assessed were found to be temporally dynamic during COVID-19 infection. During the pre-shedding phase, a robust but transient response consisting of genes involved in cell migration, stress response, and T cell activation were observed. This is followed by a rapid induction of many interferon-stimulated genes (ISGs), concurrent to onset of viral shedding and increase in nasal viral load and symptom burden. Finally, elevated baseline expression of antimicrobial peptides was observed in exposed-uninfected individuals.

INTERPRETATION: We demonstrated that unsupervised self-collection and stabilization of capillary blood can be applied to natural infection studies to characterize detailed early host immune kinetics at a temporal resolution comparable to that of human challenge studies. The remote (decentralized) study framework enables conduct of large-scale population-wide longitudinal mechanistic studies.

FUNDING: This study was funded by R35GM128648 to ABT for in-lab developments of homeRNA and data analysis, a Packard Fellowship for Science and Engineering from the David and Lucile Packard Foundation to ABT for the study execution, sample collection, and analysis, and R01AI153087 to AW for data analysis.},
}

@article {pmid39826253,
year = {2025},
author = {Montaño, MA and Jatho, A and Nassolo, C and Mugisha, N and Bula, A and Chagomerana, MB and Borok, M and Mtisi, TJ and Joffe, M and Bender Ignacio, RA and Ndlovu, N},
title = {Healthcare provider perspectives on integrating HIV care into cancer centers in Malawi, South Africa, Uganda, and Zimbabwe.},
journal = {Translational oncology},
volume = {53},
number = {},
pages = {102273},
doi = {10.1016/j.tranon.2025.102273},
pmid = {39826253},
issn = {1936-5233},
abstract = {BACKGROUND: In East and Southern Africa, treatment of people with concomitant cancer and HIV is complicated by siloed service delivery pathways, which exacerbate barriers to care and impact clinical decision-making. Integrating HIV care into cancer treatment centers may improve service delivery and overall patient outcomes.

METHODS: We administered a questionnaire to clinicians and support staff at tertiary cancer referral centers in Malawi, Zimbabwe, Uganda, and South Africa to assess level of concern about clinical management of people with HIV (PWH) and cancer, barriers to integrating HIV service delivery into cancer treatment delivery, and beliefs related to HIV, antiretroviral therapy (ART), and integrated care.

RESULTS: Of 195 clinician and support staff participants, 165 (85 %) were direct providers of cancer-associated care. Over 50 % indicated that they held concerns about survival, treatment complications, co-morbidities, and drug-drug interactions in PWH compared to patients without HIV. Over 80 % agreed that knowing cancer patients' HIV status, ART status, and ART regimen would facilitate better care and should be considered in cancer care decision-making. Overall, respondents were optimistic that HIV-related care could be easily integrated into cancer care provision. The most-frequently endorsed barriers to integrated care were workspace limitations, disruptions to workflow, availability of staff, and cost to the hospital and to patients.

CONCLUSIONS: Cancer clinicians and support staff report overall positive attitudes toward integrating HIV and cancer service delivery. Research to elucidate service delivery pathways and contextualize system-based barriers to integrating care are critical next steps to optimize linked HIV and cancer care delivery.},
}

@article {pmid39825826,
year = {2025},
author = {Mughal, TI and Mascarenhas, J and Rampal, RK and Bose, P and Lion, T and Ajufo, H and Yacoub, A and Meshinchi, S and Masarova, L and Mesa, R and Jamieson, C and Barbui, T and Saglio, G and Van Etten, RA},
title = {Impact of Recent Translational and Therapeutic Developments on Clinical Course of BCR::ABL1-Positive and -Negative Myeloproliferative Neoplasms.},
journal = {Hematological oncology},
volume = {43},
number = {1},
pages = {e70013},
doi = {10.1002/hon.70013},
pmid = {39825826},
issn = {1099-1069},
support = {//Alpine Oncology Foundation/ ; },
mesh = {Humans ; *Myeloproliferative Disorders/therapy/genetics/diagnosis/metabolism/drug therapy ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-abl/genetics/metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy/genetics/drug therapy/pathology ; Fusion Proteins, bcr-abl/genetics/antagonists & inhibitors ; },
abstract = {Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues. The introduction of the ABL1 tyrosine kinase inhibitors have been extremely successful in the treatment of chronic myeloid leukemia with most patients having a near-normal life expectancy. Similar success has, however, not been achieved for BCR::ABL1-negative MPNs in terms of disease course modification and most patients remain incurable. In both disease categories, genomic instability seems to increase the risk of disease progression to accelerated/blast phase, which is resistant/refractory to conventional treatment and associated with a poor prognosis. To address some of these issues, the late John Goldman and Tariq Mughal founded a scientific and clinical platform in 2006, the Post-American Society of Hematology (ASH) MPN workshop, to appraise novel cancer biology, candidate therapeutic targets, treatments and other clinical challenges and pay tribute to all the many scientists and clinicians around the world instrumental to the progress made and continuing advances being made. This paper summarizes some of the recent data discussed at the 18[th] edition of the workshop and includes reference to some data presented or published after the workshop, including the 26[th] John Goldman CML conference.},
}

Humans
*Myeloproliferative Disorders/therapy/genetics/diagnosis/metabolism/drug therapy
Protein Kinase Inhibitors/therapeutic use
Proto-Oncogene Proteins c-abl/genetics/metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy/genetics/drug therapy/pathology
Fusion Proteins, bcr-abl/genetics/antagonists & inhibitors

@article {pmid39825500,
year = {2025},
author = {Prizment, A and Standafer, A and Qu, C and Beutel, KM and Wang, S and Huang, WY and Lindblom, A and Pearlman, R and Van Guelpen, B and Wolk, A and Buchanan, DD and Grant, RC and Schmit, SL and Platz, EA and Joshu, CE and Couper, DJ and Peters, U and Starr, TK and Scott, P and Pankratz, N},
title = {Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf007},
pmid = {39825500},
issn = {1460-2083},
support = {/NH/NIH HHS/United States ; R21CA256749/CA/NCI NIH HHS/United States ; //University of Minnesota Academic Health Center/ ; //Whiteside Institute for Clinical Research/ ; },
abstract = {BACKGROUND: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

METHODS: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk. For replication, we used whole exome sequencing data from UK Biobank (UKB; 5126 cases and 20 504 controls matched 4:1 based on genetic distance, age, and sex), and extended our analyses to all other heterozygous CFTR variants annotated as CF-causing.

RESULTS: In our meta-analysis of GECCO-CORECT-CCFR-ARIC, the odds ratio (OR) for CRC risk associated with Phe508del was 1.11 (P = 0.010). In our UKB replication, the OR for CRC risk associated with Phe508del was 1.28 (P = 0.002). The sequencing data from UKB also revealed an association between the presence of any other single CF-causing variant (excluding Phe508del) and CRC risk (OR = 1.33; P = 0.030). When stratifying CFTR variants by functional class, class I variants (no protein produced) had a stronger association (OR = 1.77; p = 0.002), while class II variants (misfolding and retention of the protein in the endoplasmic reticulum) other than Phe508del (OR = 1.75; p = 0.107) had similar effect size as Phe508del, and variants in classes III-VI had non-significant ORs less than 1.0 and/or were not present in cases.

CONCLUSIONS: CF-causing heterozygous variants, especially class I variants, are associated with a modest but statistically significant increased CRC risk. More research is needed to explain the biology underlying these associations.},
}

@article {pmid39819674,
year = {2025},
author = {Bordeaux, J and Blitzblau, R and Aasi, SZ and Alam, M and Amini, A and Bibee, K and Bolotin, D and Chen, PL and Contreras, CM and DiMaio, D and Donigan, JM and Farma, JM and Ghosh, K and Harms, K and LeBoeuf, N and Lukens, JN and Manber, S and Mark, L and Medina, T and Nehal, KS and Nghiem, P and Olino, K and Paragh, G and Park, S and Patel, T and Rich, J and Shaha, AR and Sharma, B and Sokumbi, Y and Srivastava, D and Thomas, V and Tomblinson, C and Venkat, P and Xu, YG and Yu, S and Yusuf, M and McCullough, B and Espinosa, S},
title = {Dermatofibrosarcoma Protuberans, Version 1.2025, NCCN Clinical Practice Guidelines In Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {1},
pages = {},
doi = {10.6004/jnccn.2025.0001},
pmid = {39819674},
issn = {1540-1413},
mesh = {*Dermatofibrosarcoma/therapy/diagnosis/pathology ; Humans ; *Skin Neoplasms/therapy/diagnosis/pathology ; Medical Oncology/standards/methods ; Combined Modality Therapy/methods ; Neoplasm Recurrence, Local/therapy ; },
abstract = {Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma and affects an estimated 1,500 people annually in the United States. DFSP frequently exhibits extensive local infiltration. Initial treatment is through surgical excision, and care should be taken to ensure that negative margins are achieved to minimize recurrence. Although DFSP has a reported high rate of recurrence, metastasis is more uncommon. Fibrosarcomatous DFSP is an aggressive variant with an increased risk for local recurrence and metastasis. If achieving negative margins or resection is not feasible, radiation therapy or systemic treatment are options that may be considered by a multidisciplinary team. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline recommended treatment options available for DFSP.},
}

*Dermatofibrosarcoma/therapy/diagnosis/pathology
Humans
*Skin Neoplasms/therapy/diagnosis/pathology
Medical Oncology/standards/methods
Combined Modality Therapy/methods
Neoplasm Recurrence, Local/therapy

@article {pmid39819601,
year = {2025},
author = {Wood, DE and Kazerooni, EA and Aberle, DR and Argento, C and Baines, J and Boer, B and Brown, LM and Donington, J and Eapen, GA and Ferguson, JS and Hou, L and Klippenstein, D and Kolansky, AS and Kumar, R and Leard, LE and Leung, ANC and Mazzone, P and Merritt, RE and Norris, K and Onaitis, M and Pipavath, S and Puri, V and Raz, D and Reddy, C and Reid, ME and Sandler, KL and Sands, J and Schabath, MB and Sears, CR and Studts, JL and Tanoue, L and Thacker, AL and Tong, BC and Travis, WD and Wei, B and Westover, K and McCullough, B and Ramakrishnan, S},
title = {NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2025.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {1},
pages = {},
doi = {10.6004/jnccn.2025.0002},
pmid = {39819601},
issn = {1540-1413},
mesh = {Humans ; *Lung Neoplasms/diagnosis ; *Early Detection of Cancer/standards/methods ; Mass Screening/standards/methods ; },
abstract = {The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide criteria for selecting individuals for screening and offer recommendations for evaluating and managing lung nodules detected during initial and subsequent annual screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.},
}

Humans
*Lung Neoplasms/diagnosis
*Early Detection of Cancer/standards/methods
Mass Screening/standards/methods

@article {pmid39825152,
year = {2025},
author = {Okines, AFC and Curigliano, G and Mizuno, N and Oh, DY and Rorive, A and Soliman, H and Takahashi, S and Bekaii-Saab, T and Burkard, ME and Chung, KY and Debruyne, PR and Fox, JR and Gambardella, V and Gil-Martin, M and Hamilton, EP and Monk, BJ and Nakamura, Y and Nguyen, D and O'Malley, DM and Olawaiye, AB and Pothuri, B and Reck, M and Sudo, K and Sunakawa, Y and Van Marcke, C and Yu, EY and Ramos, J and Tan, S and Bieda, M and Stinchcombe, TE and Pohlmann, PR},
title = {Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {39825152},
issn = {1546-170X},
abstract = {Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated. SGNTUC-019 is an open-label, phase 2 basket study evaluating tucatinib, a HER2-targeted tyrosine kinase inhibitor, in combination with trastuzumab in patients with HER2-altered solid tumors. The study included a cohort of 31 heavily pretreated female patients with HER2-mutated metastatic breast cancer who were also HER2 negative per local testing. Hormone receptor (HR)-positive patients also received fulvestrant. The overall response rate (primary endpoint) was 41.9% (90% confidence interval (CI): 26.9-58.2). Secondary endpoints of duration of response and progression-free survival were 12.6 months (90% CI: 4.7 to not estimable) and 9.5 months (90% CI: 5.4-13.8), respectively. No new safety signals were detected. Responses were observed across various HER2 mutations, including mutations in the tyrosine kinase and extracellular domains. The chemotherapy-free regimen of tucatinib and trastuzumab showed clinically meaningful antitumor activity with durable responses and favorable tolerability in heavily pretreated patients with HER2 mutations. These data support further investigation of HER2-targeted therapies in this patient population. ClinicalTrials.gov registration: NCT04579380 .},
}

@article {pmid39824819,
year = {2025},
author = {Zhang, B and Fong, Y and Dang, L and Fintzi, J and Chen, S and Wang, J and Rouphael, NG and Branche, AR and Diemert, DJ and Falsey, AR and Graciaa, DS and Baden, LR and Frey, SE and Whitaker, JA and Little, SJ and Kamidani, S and Walter, EB and Novak, RM and Rupp, R and Jackson, LA and Yu, C and Magaret, CA and Molitor, C and Borate, B and Busch, S and Benkeser, D and Netzl, A and Smith, DJ and Babu, TM and Kottkamp, AC and Luetkemeyer, AF and Immergluck, LC and Presti, RM and Bäcker, M and Winokur, PL and Mahgoub, SM and Goepfert, PA and Fusco, DN and Atmar, RL and Posavad, CM and Mu, J and Makowski, M and Makhene, MK and Nayak, SU and Roberts, PC and Gilbert, PB and Follmann, D and , },
title = {Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {759},
pmid = {39824819},
issn = {2041-1723},
support = {contract 75N910D00024, task order 75N91022F00007//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; contract 75N910D00024, task order no. 75N91022F00007//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; 75N93021C00012/AI/NIAID NIH HHS/United States ; UM1AI148684//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; 75N93021C00014/AI/NIAID NIH HHS/United States ; R37AI054165//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; Contract no. 75A50122C00008//U.S. Department of Health & Human Services | Biomedical Advanced Research and Development Authority (BARDA)/ ; 75A50122C00008//U.S. Department of Health & Human Services | Biomedical Advanced Research and Development Authority (BARDA)/ ; 75N93021D00021/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Antibodies, Neutralizing/immunology/blood ; *COVID-19/prevention & control/immunology/virology ; *COVID-19 Vaccines/immunology/administration & dosage ; *SARS-CoV-2/immunology ; *Antibodies, Viral/immunology/blood ; *Immunization, Secondary ; Female ; Male ; Adult ; Middle Aged ; Spike Glycoprotein, Coronavirus/immunology ; mRNA Vaccines/immunology ; },
abstract = {Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ("predicted-at-exposure") titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.},
}

Humans
*Antibodies, Neutralizing/immunology/blood
*COVID-19/prevention & control/immunology/virology
*COVID-19 Vaccines/immunology/administration & dosage
*SARS-CoV-2/immunology
*Antibodies, Viral/immunology/blood
*Immunization, Secondary
Female
Male
Adult
Middle Aged
Spike Glycoprotein, Coronavirus/immunology
mRNA Vaccines/immunology

@article {pmid39822915,
year = {2025},
author = {Cooper, DJ and Karten, J and Hoffe, SE and King, DA and Weiss, M and DePeralta, DK and Coveler, AL and Hingorani, SR and Shefter, T and Meguid, C and Roberts, H and Hong, TS and Narang, A and Hacker-Prietz, A and Fisher, GA and Sandler, J and Singer, L and Korah, B and Hoos, W and Stricker, CT and Herman, JM},
title = {The power of personas: Exploring an innovative model for understanding stakeholder perspectives in an oncology learning health network.},
journal = {Learning health systems},
volume = {9},
number = {1},
pages = {e10422},
pmid = {39822915},
issn = {2379-6146},
abstract = {INTRODUCTION: Learning health networks (LHNs) improve clinical outcomes by applying core tenets of continuous quality improvements (QI) to reach community-defined outcomes, data-sharing, and empowered interdisciplinary teams including patients and caregivers. LHNs provide an ideal environment for the rapid adoption of evidence-based guidelines and translation of research and best practices at scale. When an LHN is established, it is critical to understand the needs of all stakeholders. To accomplish this, we used ethnographic methods to develop personas of different stakeholders within The Canopy Cancer Collective, the first oncology LHN.

METHODS: We partnered with a firm experienced in qualitative research and human-centered design to conduct interviews with stakeholders of The Canopy Cancer Collective, a newly developed pancreatic cancer LHN. Together with the firm, we developed a personas model approach to represent the wide range of diverse perspectives among the representative stakeholders, which included care team members, patients, and caregivers.

RESULTS: Thirty-one stakeholders from all facets of pancreatic cancer care were interviewed, including 20 care team members, 8 patients, and 3 caregivers. Interview transcripts were analyzed to construct 10 personas felt to represent the broad spectrum of stakeholders within The Cancer Canopy Collective. These personas were used as a foundation for the design and development of The Cancer Canopy Cancer Collective key drivers and aims.

CONCLUSIONS: As LHNs continue to facilitate comprehensive approaches to patient-centered care, interdisciplinary teams who understand each other's needs can improve Network unity and cohesion. We present the first model utilizing personas for LHNs, demonstrating this framework holds significant promise for further study. If validated, such an approach could be used as a dynamic foundation for understanding individual stakeholder needs in similar LHN ecosystems in the future.},
}

@article {pmid39820690,
year = {2025},
author = {Nascimento de Lima, P and Matrajt, L and Coronado, G and Escaron, AL and Rutter, CM},
title = {Cost-Effectiveness of Noninvasive Colorectal Cancer Screening in Community Clinics.},
journal = {JAMA network open},
volume = {8},
number = {1},
pages = {e2454938},
pmid = {39820690},
issn = {2574-3805},
mesh = {Humans ; *Colorectal Neoplasms/diagnosis/economics ; *Cost-Benefit Analysis ; Middle Aged ; *Early Detection of Cancer/economics/methods/statistics & numerical data ; Female ; Male ; *Colonoscopy/economics/statistics & numerical data ; California ; Occult Blood ; Aged ; Mass Screening/economics/methods ; Quality-Adjusted Life Years ; },
abstract = {IMPORTANCE: Several noninvasive tests for colorectal cancer screening are available, but their effectiveness in settings with low adherence to screening and follow-up colonoscopy is not well documented.

OBJECTIVE: To assess the cost-effectiveness of and outcomes associated with noninvasive colorectal cancer screening strategies, including new blood-based tests, in a population with low adherence to screening and ongoing surveillance colonoscopy.

The validated microsimulation model used for the decision analytical modeling study projected screening outcomes from 2025 to 2124 for a simulated cohort of 10 million individuals aged 50 years in 2025 and representative of a predominantly Hispanic or Latino patient population served by a Federally Qualified Health Center in Southern California. The simulated population had low adherence to first-step noninvasive testing (45%), second-step follow-up colonoscopy after an abnormal noninvasive test result (40%), and ongoing surveillance colonoscopy among patients with high-risk findings at follow-up colonoscopy (80%).

EXPOSURES: Colorectal cancer screening strategies included no screening, an annual or biennial fecal immunochemical test, a triennial multitarget stool DNA test, and a triennial blood-based test. Using a blood-based test was assumed to increase first-step adherence by 17.5 percentage points.

MAIN OUTCOMES AND MEASURES: Outcomes included colorectal cancer incidence and mortality, life-years gained and quality-adjusted life-years gained relative to no screening, costs, and net monetary benefit assuming a willingness to pay of $100 000 per quality-adjusted life-year gained.

RESULTS: Under realistic adherence assumptions, a program of annual fecal immunochemical testing was the most effective and cost-effective strategy, yielding 121 life-years gained per 1000 screened individuals and a net monetary benefit of $5883 per person. Triennial blood testing was the least effective, yielding 23 life-years gained per 1000, and was not cost-effective, with a negative net monetary benefit. Annual fecal immunochemical testing with 45% first-step adherence and 80% adherence to follow-up and surveillance colonoscopy yielded greater benefit than triennial blood testing with perfect adherence (88 vs 77 life-years gained per 1000).

CONCLUSIONS AND RELEVANCE: This study suggests that in a federally qualified health care setting, prioritizing the convenience of blood tests over less costly and more effective existing stool-based tests could result in higher costs and worse population-level outcomes. Novel screening modalities should be carefully evaluated for performance in community settings before widespread adoption.},
}

Humans
*Colorectal Neoplasms/diagnosis/economics
*Cost-Benefit Analysis
Middle Aged
*Early Detection of Cancer/economics/methods/statistics & numerical data
Female
Male
*Colonoscopy/economics/statistics & numerical data
California
Occult Blood
Aged
Mass Screening/economics/methods
Quality-Adjusted Life Years

@article {pmid39820359,
year = {2025},
author = {Gauthier, J and Liang, EC and Huang, JJ and Kimble, EL and Hirayama, AV and Fiorenza, S and Voutsinas, JM and Wu, QV and Jaeger-Ruckstuhl, CA and Pender, BS and Kirchmeier, DR and Torkelson, A and Braathen, K and Basom, R and Shadman, M and Kopmar, NE and Cassaday, RD and Riddell, SR and Maloney, DG and Turtle, CJ},
title = {Phase I study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naïve adult B-ALL patients.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015314},
pmid = {39820359},
issn = {2473-9537},
abstract = {CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971). Twenty-three patients received lymphodepletion chemotherapy and JCAR021 infusion. Nineteen patients developed CRS (any grade, 83%; grade 2, 61%) and 12 developed neurotoxicity (52%; grade ≥3, 35%). The overall response and CR/CRi rates were 82% and 64%, respectively. We observed MRD-negative marrow responses in 82% of those with marrow disease and extramedullary responses by PET-CT in 79% (CR, 50%) of those with measurable FDG-avid disease. The median duration of remission (DOR) was 10 months with a 4-year DOR probability of 29%. Four patients underwent allo-HCT while in CR/CRi after JCAR021. Durable remissions were observed in patients with low marrow disease burden. In contrast, the DOR was limited in those with high marrow burden, highlighting a remaining critical need to identify new strategies to prolong remissions. We observed similar outcomes in CAR-naïve adult B-ALL patients receiving CD19 CAR T-cells expressing a fully human or murine scFv-containing CAR.},
}

@article {pmid39818460,
year = {2025},
author = {Daneshmand, S and Kamat, AM and Shore, ND and Meeks, JJ and Galsky, MD and Jacob, JM and van der Heijden, MS and Williams, SB and Powles, T and Chang, SS and Catto, JWF and Psutka, SP and Guerrero-Ramos, F and Xylinas, E and Miyake, M and Simone, G and Daniel, K and Sweiti, H and Cutie, C and Necchi, A},
title = {Development of TAR-200: A novel targeted releasing system designed to provide sustained delivery of gemcitabine for patients with bladder cancer.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2024.12.264},
pmid = {39818460},
issn = {1873-2496},
abstract = {Treatment options for recurrent high-risk non-muscle-invasive bladder cancer (HR NMIBC) and muscle-invasive bladder cancer (MIBC) are limited, highlighting a need for clinically effective, accessible, and better-tolerated alternatives. In this review we examine the clinical development program of TAR-200, a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine to address the needs of patients with NMIBC and of those with MIBC. We describe the concept and design of TAR-200 and the clinical development of this gemcitabine intravesical system in the SunRISe portfolio of studies. This includes 3 phase I studies evaluating the safety and initial tumor activity of TAR-200 and 5 phase II/III studies assessing the efficacy and safety of TAR-200, with or without systemic cetrelimab, as a treatment option for patients with HR NMIBC (bacillus Calmette-Guérin naive [papillary and carcinoma in situ] and MIBC (neoadjuvant and patients ineligible for or refusing radical cystectomy). Pharmacokinetics demonstrate intravesical gemcitabine delivery via TAR-200 over a prolonged period without detectable plasma levels. Phase I studies showed that TAR-200 is well tolerated, with preliminary antitumor activity in intermediate-risk NMIBC and MIBC. Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin-unresponsive high-risk NMIBC. TAR-200 represents an innovative approach to the local treatment of bladder cancer.},
}

@article {pmid39817910,
year = {2025},
author = {Termote, M and Marques, RC and Hyllner, E and Guryleva, MV and Henskens, M and Brutscher, A and Baken, IJL and Dopico, XC and Gasull, AD and Murrell, B and Stamatatos, L and Westerberg, LS and Dosenovic, P},
title = {Antigen affinity and site of immunization dictate B cell recall responses.},
journal = {Cell reports},
volume = {44},
number = {1},
pages = {115221},
doi = {10.1016/j.celrep.2024.115221},
pmid = {39817910},
issn = {2211-1247},
abstract = {Protective antibodies against HIV-1 require unusually high levels of somatic mutations introduced in germinal centers (GCs). To achieve this, a sequential vaccination approach was proposed. Using HIV-1 antibody knockin mice with fate-mapping genes, we examined if antigen affinity affects the outcome of B cell recall responses. Compared to a high-affinity boost, a low-affinity boost resulted in decreased numbers of memory-derived B cells in secondary GCs but with higher average levels of somatic mutations, indicating an affinity threshold for memory B cells to enter GCs. Furthermore, upon boosting local lymph nodes (LNs), the composition of primary GCs was modified in an antigen-affinity-dependent manner to constitute less somatically mutated B cells. Our results demonstrate that antigen affinity and location of the boost affect the outcome of the B cell recall response. These results can help guide the design of vaccine immunogens aiming to selectively engage specific B cell clones for further diversification.},
}

@article {pmid39817771,
year = {2025},
author = {Cohen, P and Lambson, BE and Mkhize, NN and Moodley, C and Yssel, AEJ and Moyo-Gwete, T and York, T and Gwashu-Nyangiwe, A and Ndabambi, N and Thebus, R and Juraska, M and deCamp, AC and Williamson, BD and Magaret, CA and Gilbert, PB and Westfall, D and Deng, W and Mullins, JI and Morris, L and Williamson, C and Moore, PL},
title = {Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0173024},
doi = {10.1128/jvi.01730-24},
pmid = {39817771},
issn = {1098-5514},
abstract = {The Antibody Mediated Prevention (AMP) trials showed that passively infused VRC01, a broadly neutralizing antibody (bNAb) targeting the CD4 binding site (CD4bs) on the HIV-1 envelope protein (Env), protected against neutralization-sensitive viruses. We identified six individuals from the VRC01 treatment arm with multi-lineage breakthrough HIV-1 infections from HVTN703, where one variant was sensitive to VRC01 (IC50 < 25 ug/mL) but another was resistant. By comparing Env sequences of resistant and sensitive clones from each participant, we identified sites predicted to affect VRC01 neutralization and assessed the effect of their reversion in the VRC01-resistant clone on neutralization sensitivity. In four pairs, a single mutation restored partial or full sensitivity to VRC01, whereas in the fifth participant, transfer of the entire [Formula: see text]23-V5 loop was required. No VRC01 resistance mutations could be identified in the sixth participant, with the discordant clones differing by >100 amino acids. Mutations responsible for the differential neutralization phenotypes occurred at distinct sites across Env, including residues in loop D, the CD4-binding loop, and between the [Formula: see text]23 and V5 loops. Analysis of deep sequencing env data showed that VRC01 resistance was likely the property of the acquired virus, rather than occurring through post-acquisition evolution. Although VRC01-resistant parental clones generally retained sensitivity to other CD4-binding site bNAbs, they were less potently neutralized than the VRC01-sensitive clones. In conclusion, VRC01 resistance mutations occurred through multiple mutational pathways, but sensitivity to second-generation CD4bs bNAbs was retained even in VRC01-resistant transmitted viruses, confirming the potential of these bNAbs for HIV-1 prevention studies.IMPORTANCEThe Antibody Mediated Prevention (AMP) trials provided proof of principle that VRC01, a CD4-binding site (CD4bs) HIV-1 broadly neutralizing antibody (bNAb), prevented the acquisition of antibody-sensitive viruses. However, understanding common mutations that confer resistance to different bNAbs provides important insights into the genetic barrier to resistance. Here we studied six AMP trial participants with breakthrough infections mediated by multiple viral lineages with discordant VRC01 sensitivity. We identified different mutations across the CD4-binding site that conferred resistance to VRC01 and showed that these mutations were a property of the acquired virus, rather than a result of post-acquisition evolution. We found that although VRC01 resistance was associated with reduced neutralization potency of second-generation CD4-binding site bNAbs, overall neutralization sensitivity was generally retained, which is promising for future use of such bNAbs in clinical trials.},
}

@article {pmid39817189,
year = {2025},
author = {Kundel, V and Devarakonda, K and Khan, S and Suarez-Farinas, M and Cohen, O and Santos-Gallego, C and Menegus, MA and Kini, A and Vengrenyuk, Y and Okamoto, N and Ueda, H and Gidwani, U and Kizer, JR and Redline, S and Kaplan, R and Shah, N},
title = {Exploring the Relationship Between Sleep Apnea, Myocardial Infarct Size, and Coronary Collaterals in Acute Myocardial Infarction: A Multidisciplinary Study.},
journal = {Nature and science of sleep},
volume = {17},
number = {},
pages = {27-42},
pmid = {39817189},
issn = {1179-1608},
support = {K23 HL125923/HL/NHLBI NIH HHS/United States ; K23 HL161324/HL/NHLBI NIH HHS/United States ; },
abstract = {PURPOSE: We designed a study investigating the cardioprotective role of sleep apnea (SA) in patients with acute myocardial infarction (AMI), focusing on its association with infarct size and coronary collateral circulation.

METHODS: We recruited adults with AMI, who underwent Level-III SA testing during hospitalization. Delayed-enhancement cardiac magnetic resonance (CMR) imaging was performed to quantify AMI size (percent-infarcted myocardium). Rentrop Score quantified coronary collateralization (scores 0-3, higher scores indicating augmented collaterals). Group differences in Rentrop grade and infarct size were compared using the Wilcoxon Rank-Sum test and Fisher's Exact test as appropriate, with a significance threshold set at p <0.05.

RESULTS: Among 33 adults, mean age was 54.4±11.5 and mean BMI was 28.4±5.9. 8 patients (24%) had no SA, and 25 (76%) had SA (mild n=10, moderate n=8, severe n=7). 66% (n=22) underwent CMR, and all patients had Rentrop scores. Median infarct size in the no-SA group was 22% versus 28% in the SA group (p=0.79). While we did not find statistically significant differences, moderate SA had a trend toward a smaller infarct size (median 15.5%; IQR 9.23) compared to the other groups (no SA [22.0%; 16.8,31.8], mild SA [27%; 23.8,32.5], and severe SA [34%; 31.53], p=0.12). A higher proportion of moderate SA patients had a Rentrop grade >0, with a trend toward significance (moderate SA versus other groups: 62.5% versus 28%, p=0.08).

CONCLUSION: Our study did not find statistically significant differences in cardiac infarct size and the presence of coronary collaterals by sleep apnea severity among patients with AMI. However, our results are hypothesis-generating, and suggest that moderate SA may potentially offer cardioprotective benefits through enhanced coronary collaterals. These insights call for future research to explore the heterogeneity in ischemic preconditioning by SA severity and hypoxic burden to guide tailored clinical strategies for SA management in patients with AMI.},
}

@article {pmid39817081,
year = {2024},
author = {Tereshchenko, LG and Haq, KT and Howell, SJ and Mitchell, EC and Hyde, J and Martínez, J and Ahmed, CA and Briceno, G and Patel, H and Pena, J and Khan, A and Soliman, EZ and Lima, JAC and Kapadia, SR and Misra-Hebert, AD and Kattan, MW and Kansal, MM and Daviglus, ML and Kaplan, R},
title = {Electrical Heterogeneity in Hispanic Background Subpopulations: The HCHS/SOL.},
journal = {JACC. Advances},
volume = {3},
number = {12},
pages = {101225},
pmid = {39817081},
issn = {2772-963X},
abstract = {BACKGROUND: The Hispanic/Latino population is not uniform. Prevalence and clinical outcomes of cardiac arrhythmias in ethnic background subgroups are variable, but the reasons for differences are unclear. Vectorcardiographic Global Electrical Heterogeneity (GEH) has been shown to be associated with adverse cardiovascular outcomes.

OBJECTIVES: The purpose of this study was to compare GEH in Hispanic/Latino background subpopulations. We hypothesized that ethnicity category moderates an association of prevalent cardiovascular disease (CVD) with GEH.

METHODS: Cross-sectional analysis of the HCHS/SOL (Hispanic Community Health Study/Study of Latinos) included 15,684 participants (mean age 41 years; 38% Mexican, 20% Cuban, 16% Puerto Rican, 10% Dominican, 7% Central American, 5% South American, 4% mixed Hispanic/Latino background). Acculturation and socioeconomic data were collected. GEH was measured as spatial QRS-T angle, spatial ventricular gradient (SVG) azimuth, SVG elevation, SVG magnitude, and sum absolute QRST integral. Linear regression models included interaction terms of ethnic background category by CVD and were adjusted for age, sex, education attainment, hypertension, diabetes, smoking, dyslipidemia, obesity, chronic kidney disease, physical activity, diet quality, heart rate, and rhythm.

RESULTS: The adjusted spatial QRS-T angle was significantly (P < 0.0001) narrower in Dominican background (-3.4°[95% CI -5.0° to -1.7°]) as compared to a total mean. SVG azimuth pointed farther posteriorly in Dominican (+2.9 [95% CI: 1.6-4.2]) and Puerto Rican (+3.8 [2.4-5.2]), but farther anteriorly in South American (-2.9 [95% CI: -4.4 to -1.4]) and Mexican (-3.5 [95% CI: -4.3 to -2.6]) vs total mean. An association of coronary heart disease with GEH was especially strong in Cuban background subpopulation.

CONCLUSIONS: In CVD-free Hispanic/Latino subpopulations, cardiovascular risk factors do not fully explain GEH differences across ethnic background categories, which likely reflect unmeasured health disparities.},
}

@article {pmid39817038,
year = {2025},
author = {Bradley, J and Floyd, S and Piwowar-Manning, E and Laeyendecker, O and Baker, OR and Bell-Mandla, N and Bwalya, J and Moore, A and Eshleman, SH and Donnell, D and Bock, P and Fidler, S and Ayles, H and Hayes, RJ},
title = {Strong Association Between HIV Incidence and Herpes Simplex Virus Type 2 in Zambia and South Africa: Prospective Data From the HPTN 071 (PopART) Trial.},
journal = {Open forum infectious diseases},
volume = {12},
number = {1},
pages = {ofae721},
pmid = {39817038},
issn = {2328-8957},
abstract = {BACKGROUND: Herpes simplex virus type 2 (HSV2) is an important cofactor for HIV acquisition and transmission. Associations between the infections are reexamined in longitudinal data from an HIV prevention trial.

METHODS: The HPTN 071 (PopART) trial evaluated a combination prevention intervention in 21 urban communities in Zambia and South Africa. HIV incidence was measured in a cohort of approximately 2000 adults (age, 18-44 years) selected randomly from each community and followed up for 36 months. Incidence of HSV2 infection was estimated, and the effects of risk factors were examined. The association between HIV incidence and HSV2 infection was examined at individual and community levels.

RESULTS: An overall 10 539 participants were HSV2 negative at baseline and retested after 36 months. Estimated HSV2 incidence was 5.4 per 100 person-years (95% CI, 5.0-5.7) for women and 2.9 per 100 person-years (95% CI, 2.6-3.2) for men. When compared with those remaining HSV2 negative, HIV incidence was higher in those who were HSV2 positive at baseline (women: adjusted rate ratio [aRR], 3.24 [95% CI, 2.50-4.20]; men: aRR, 2.57 [95% CI, 1.60-4.11]) and even higher in those who seroconverted to HSV2 during follow-up (women: aRR, 5.94 [95% CI, 4.42-7.98]; men: aRR, 8.37 [95% CI, 5.18-13.52]). At the community level, strong associations were seen between HIV incidence and HSV2 prevalence (R [2] = 0.48, P < .001) and incidence (R [2] = 0.36, P = .004).

CONCLUSIONS: There were strong associations between HIV incidence and HSV2 prevalence and incidence at individual and community levels. HSV2 control could contribute to HIV prevention.},
}

@article {pmid39815807,
year = {2025},
author = {Lim, SYT and Cole, FM and Laszlo, GS and Lunn-Halbert, MC and Huo, J and Li, J and Kehret, AR and Walter, RB},
title = {Targeting the membrane-proximal domain of CD33 to maximize the efficacy of natural killer cell-based immunotherapies.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.286593},
pmid = {39815807},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid39815460,
year = {2025},
author = {Moseley, A and LeBlanc, M and Freidlin, B and Shallis, RM and Zeidan, AM and Sallman, DA and Erba, HP and Little, RF and Othus, M},
title = {Evaluating the impact of stratification on the power and cross-arm balance of randomized phase 2 clinical trials.},
journal = {Clinical trials (London, England)},
volume = {},
number = {},
pages = {17407745241304065},
doi = {10.1177/17407745241304065},
pmid = {39815460},
issn = {1740-7753},
abstract = {BACKGROUND/AIMS: Randomized clinical trials often use stratification to ensure balance between arms. Analysis of primary endpoints of these trials typically uses a "stratified analysis," in which analyses are performed separately in each subgroup defined by the stratification factors, and those separate analyses are weighted and combined. In the phase 3 setting, stratified analyses based on a small number of stratification factors can provide a small increase in power. The impact on power and type-1 error of stratification in the setting of smaller sample sizes as in randomized phase 2 trials has not been well characterized.

METHODS: We performed computational studies to characterize the power and cross-arm balance of modestly sized clinical trials (less than 170 patients) with varying numbers of stratification factors (0-6), sample sizes, randomization ratios (1:1 vs 2:1), and randomization methods (dynamic balancing vs stratified block).

RESULTS: We found that the power of unstratified analyses was minimally impacted by the number of stratification factors used in randomization. Analyses stratified by 1-3 factors maintained power over 80%, while power dropped below 80% when four or more stratification factors were used. These trends held regardless of sample size, randomization ratio, and randomization method. For a given randomization ratio and sample size, increasing the number of factors used in randomization had an adverse impact on cross-arm balance. Stratified block randomization performed worse than dynamic balancing with respect to cross-arm balance when three or more stratification factors were used.

CONCLUSION: Stratified analyses can decrease power in the setting of phase 2 trials when the number of patients in a stratification subgroup is small.},
}

@article {pmid39763725,
year = {2024},
author = {Aditham, AK and Radford, CE and Carr, CR and Jasti, N and King, NP and Bloom, JD},
title = {Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763725},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 AI141707/AI/NIAID NIH HHS/United States ; },
abstract = {Rabies virus causes nearly 60,000 human deaths annually. Antibodies that target the rabies glycoprotein (G) are being developed as post-exposure prophylactics, but mutations in G can render such antibodies ineffective. Here, we use pseudovirus deep mutational scanning to measure how all single amino-acid mutations to G affect cell entry and neutralization by a panel of antibodies. These measurements identify sites critical for rabies G's function, and define constrained regions that are attractive epitopes for clinical antibodies, including at the apex and base of the protein. We provide complete maps of escape mutations for eight monoclonal antibodies, including some in clinical use or development. Escape mutations for most antibodies are present in some natural rabies strains. Overall, this work provides comprehensive information on the functional and antigenic effects of G mutations that can help inform development of stabilized vaccine antigens and antibodies that are resilient to rabies genetic variation.},
}

@article {pmid38088119,
year = {2024},
author = {Brown, JR and Eichhorst, B and Hillmen, P and Jurczak, W and Kaźmierczak, M and Lamanna, N and O'Brien, SM and Tam, CS and Qiu, L and Zhou, K and Simkovic, M and Mayer, J and Gillespie-Twardy, A and Ferrajoli, A and Ganly, PS and Weinkove, R and Grosicki, S and Mital, A and Robak, T and Osterborg, A and Yimer, HA and Salmi, T and Wang, MD and Fu, L and Li, J and Wu, K and Cohen, A and Shadman, M},
title = {Plain language summary of zanubrutinib or ibrutinib in chronic lymphocytic leukemia that is resistant to treatment or has come back after treatment.},
journal = {Future oncology (London, England)},
volume = {20},
number = {12},
pages = {717-726},
doi = {10.2217/fon-2023-0849},
pmid = {38088119},
issn = {1744-8301},
mesh = {Humans ; *Adenine/analogs & derivatives ; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/pathology ; *Lymphoma, B-Cell/drug therapy ; Piperidines/therapeutic use ; Pyrazoles/adverse effects ; *Pyrimidines ; },
abstract = {WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a research study called ALPINE. The study involved people who had been diagnosed with, and previously treated at least once for, relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Lymphocytes help to find and fight off viruses and infections in the body, but when someone has CLL or SLL, the body creates abnormal lymphocytes, leaving the patient with a weakened immune system and susceptible to illness. In CLL, these lymphocytes are in the bone marrow and bloodstream, whereas for SLL, they are mostly found in the lymph nodes, such as those in the neck.

HOW WAS THE RESEARCH DONE?: The ALPINE study was designed to directly compare the cancer-fighting effects and side effects of zanubrutinib and ibrutinib as treatment for patients with relapsed or refractory CLL/SLL.

WHAT WERE THE RESULTS?: After 30 months, zanubrutinib was more effective than ibrutinib at reducing and keeping the cancer from coming back. Clinical Trial Registration: NCT03734016 (ClinicalTrials.gov).},
}

Humans
*Adenine/analogs & derivatives
*Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/pathology
*Lymphoma, B-Cell/drug therapy
Piperidines/therapeutic use
Pyrazoles/adverse effects
*Pyrimidines

@article {pmid39815416,
year = {2025},
author = {Powles, T and Park, SH and Gurney, H and Loriot, Y and Sridhar, SS and Bellmunt, J and di Pietro, A and Grivas, P},
title = {Avelumab maintenance treatment for advanced urothelial cancer: plain language summary of long-term results from the JAVELIN Bladder 100 study.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/14796694.2024.2435208},
pmid = {39815416},
issn = {1744-8301},
}

@article {pmid39814501,
year = {2025},
author = {Karvonen, KA},
title = {Challenging the Status Quo: Multi-level Solutions for Equitable Hematopoietic Cell Transplantation Clinical Trial Representation.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {1},
pages = {7-9},
doi = {10.1016/j.jtct.2024.12.014},
pmid = {39814501},
issn = {2666-6367},
}

@article {pmid39814200,
year = {2025},
author = {Rangelova, E and Stoop, TF and van Ramshorst, TME and Ali, M and van Bodegraven, EA and Javed, AA and Hashimoto, D and Steyerberg, E and Banerjee, A and Jain, A and Sauvanet, A and Serrablo, A and Giani, A and Giardino, A and Zerbi, A and Arshad, A and Wijma, AG and Coratti, A and Zironda, A and Socratous, A and Rojas, A and Halimi, A and Ejaz, A and Oba, A and Patel, BY and Björnsson, B and Reames, BN and Tingstedt, B and Goh, BKP and Payá-Llorente, C and Domingo Del Pozo, C and González-Abós, C and Medin, C and van Eijck, CHJ and de Ponthaud, C and Takishita, C and Schwabl, C and Månsson, C and Ricci, C and Thiels, CA and Douchi, D and Hughes, DL and Kilburn, D and Flanking, D and Kleive, D and Sousa Silva, D and Edil, BH and Pando, E and Moltzer, E and Kauffman, EF and Warren, E and Bozkurt, E and Sparrelid, E and Thoma, E and Verkolf, E and Ausania, F and Giannone, F and Hüttner, FJ and Burdio, F and Souche, FR and Berrevoet, F and Daams, F and Motoi, F and Saliba, G and Kazemier, G and Roeyen, G and Nappo, G and Butturini, G and Ferrari, G and Kito Fusai, G and Honda, G and Sergeant, G and Karteszi, H and Takami, H and Suto, H and Matsumoto, I and Mora-Oliver, I and Frigerio, I and Fabre, JM and Chen, J and Sham, JG and Davide, J and Urdzik, J and de Martino, J and Nielsen, K and Okano, K and Kamei, K and Okada, K and Tanaka, K and Labori, KJ and Goodsell, KE and Alberici, L and Webber, L and Kirkov, L and de Franco, L and Miyashita, M and Maglione, M and Gramellini, M and Ramera, M and João Amaral, M and Ramaekers, M and Truty, MJ and van Dam, MA and Stommel, MWJ and Petrikowski, M and Imamura, M and Hayashi, M and D'Hondt, M and Brunner, M and Hogg, ME and Zhang, C and Ángel Suárez-Muñoz, M and Luyer, MD and Unno, M and Mizuma, M and Janot, M and Sahakyan, MA and Jamieson, NB and Busch, OR and Bilge, O and Belyaev, O and Franklin, O and Sánchez-Velázquez, P and Pessaux, P and Strandberg Holka, P and Ghorbani, P and Casadei, R and Sartoris, R and Schulick, RD and Grützmann, R and Sutcliffe, R and Mata, R and Patel, RB and Takahashi, R and Rodriguez Franco, S and Sánchez Cabús, S and Hirano, S and Gaujoux, S and Festen, S and Kozono, S and Maithel, SK and Chai, SM and Yamaki, S and van Laarhoven, S and Mieog, JSD and Murakami, T and Codjia, T and Sumiyoshi, T and Karsten, TM and Nakamura, T and Sugawara, T and Boggi, U and Hartman, V and de Meijer, VE and Bartholomä, W and Kwon, W and Koh, YX and Cho, Y and Takeyama, Y and Inoue, Y and Nagakawa, Y and Kawamoto, Y and Ome, Y and Soonawalla, Z and Uemura, K and Wolfgang, CL and Jang, JY and Padbury, R and Satoi, S and Messersmith, W and Wilmink, JW and Abu Hilal, M and Besselink, MG and Del Chiaro, M and , },
title = {The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2024.12.015},
pmid = {39814200},
issn = {1569-8041},
abstract = {PURPOSE: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

BACKGROUND: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

METHODS: International multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated.

RESULTS: Overall, 2,282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared to upfront surgery (adjusted HR=0.69 [95%CI 0.58-0.83]) with an adjusted median OS of 53 vs. 37 months (P=0.0003) and adjusted 5-year OS rates of 47% vs. 35% (P=0.0001) compared to upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction=0.003) and higher serum CA19-9 (Pinteraction=0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction=0.43), splenic vein (Pinteraction=0.30), retroperitoneal (Pinteraction=0.84), and multivisceral (Pinteraction=0.96) involvement.

CONCLUSIONS: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared to upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.},
}

@article {pmid39813621,
year = {2025},
author = {Gore, S and Blyth, E and Bleakley, M and Lee, K and Micklethwaite, KP and Gowrishankar, K},
title = {Current developments in T-cell receptor therapy for Acute Myeloid Leukaemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014105},
pmid = {39813621},
issn = {2473-9537},
abstract = {T-cell receptor (TCR) therapies are a promising modality for the treatment of cancers, with significant efforts being directed towards acute myeloid leukaemia (AML), a particularly challenging disease. Chimeric antigen receptor (CAR) T-cells targeting single surface antigens have shown remarkable efficacy for B-cell lymphoblastic leukaemia, lymphomas and multiple myeloma. However, AML presents formidable obstacles to the effectiveness of CAR T-cells due to the widespread expression of heterogenous leukaemia immunophenotypes and surface antigen targets additionally present on normal myeloid cells. TCR therapies are an evolving field of cell therapies that allow targeting intracellular antigenic peptides presented via HLA molecules. The development of TCR therapy for AML is progressing rapidly through preclinical research and successful clinical trials. This review specifically explores the antigens targeted in AML, the diverse methodologies and strategies employed in TCR identification and preclinical TCR T-cell development. The review also discusses innovative molecular designs to improve functional efficacy, mitigate safety concerns and overcome HLA restriction. Specific outcomes of early clinical trials targeting important antigens WT1, PRAME and HA-1 are also highlighted. Ultimately, this review underscores why TCR therapy is poised to become an indispensable component of AML immunotherapy.},
}

@article {pmid39812506,
year = {2025},
author = {Little, A and Zhao, N and Mikhaylova, A and Zhang, A and Ling, W and Thibord, F and Johnson, AD and Raffield, LM and Curran, JE and Blangero, J and O'Connell, JR and Xu, H and Rotter, JI and Rich, SS and Rice, KM and Chen, MH and Reiner, A and Kooperberg, C and Vu, T and Hou, L and Fornage, M and Loos, RJF and Kenny, E and Mathias, R and Becker, L and Smith, AV and Boerwinkle, E and Yu, B and Thornton, T and Wu, MC},
title = {General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.},
journal = {Genetic epidemiology},
volume = {49},
number = {1},
pages = {e22610},
doi = {10.1002/gepi.22610},
pmid = {39812506},
issn = {1098-2272},
support = {//U.S. Department of Health and Human Services, National Institute on Minority Health and Health Disparities, National Institutes of Health, National Human Genome Research Institute, National Center for Research Resources, COPD Foundation, National Heart, Lung, and Blood Institute, National Science Foundation, National Institute on Aging, and National Institute of Neurological Disorders and Stroke./ ; },
mesh = {Humans ; *Genome-Wide Association Study/methods ; *Genomics/methods ; Phenotype ; Algorithms ; Models, Genetic ; Polymorphism, Single Nucleotide ; Genotype ; Computer Simulation ; Machine Learning ; Multiomics ; },
abstract = {Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.g. genotypes and gene expression levels) on a phenotype, particularly while accommodating routine issues, such as having related subjects' data in analyses. In this paper, we extend an existing composite kernel machine regression model to integrate two multi-omics data types, while accommodating for general correlation structures amongst outcomes. Due to the kernel machine regression framework, our methods allow for the integration of high-dimensional omics data with small, nonlinear, and interactive effects, and accommodation of general study designs. Here, we focus on scientific questions that aim to assess the association between a functional grouping (such as a gene or a pathway) and a quantitative trait of interest. We use a kernel machine regression to integrate the two multi-omics data types, as they may relate to the trait, and perform a global test of association. We demonstrate the advantage of this approach over single data type association tests via simulation. Finally, we apply this method to a large, multi-ethnic data set to investigate how predicted gene expression and rare genetic variation may be related to two platelet traits.},
}

Humans
*Genome-Wide Association Study/methods
*Genomics/methods
Phenotype
Algorithms
Models, Genetic
Polymorphism, Single Nucleotide
Genotype
Computer Simulation
Machine Learning
Multiomics

@article {pmid39809874,
year = {2025},
author = {Mao, JJ and Bryl, K and Gillespie, EF and Green, A and Hung, TKW and Baser, R and Panageas, K and Postow, MA and Daly, B},
title = {Randomized clinical trial of a digital integrative medicine intervention among patients undergoing active cancer treatment.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {29},
pmid = {39809874},
issn = {2398-6352},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; K08 CA252640/CA/NCI NIH HHS/United States ; 1P50CA271357-01//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Exercise and mindfulness-based interventions have growing evidence for managing fatigue and comorbid symptoms; however, packaging them in a cohesive digital way for patients undergoing cancer treatment has not been evaluated. We conducted a randomized controlled trial to assess the impact of a 12 week digital integrative medicine program, Integrative Medicine at Home (IM@Home), versus enhanced usual care on fatigue severity (primary outcome), comorbid symptoms and acute healthcare utilization (secondary outcomes), in 200 patients with solid tumors experiencing fatigue during treatment. Fatigue severity decreased more in IM@Home than in the control (1.99 vs. 1.51 points; p = 0.04). IM@Home participants also had reduced symptom distress (p = 0.003), anxiety (p = 0.03), and depression (p = 0.02). Acute healthcare utilization was lower with IM@Home, with fewer emergency department visits (rate ratio 0.49; p = 0.04), hospitalizations (4% vs. 12.9%; p = 0.03), and shorter hospital stays (4.25 vs. 10 days; p < 0.001). These promising findings should be confirmed in phase III clinical trials. "Study registered at clinicaltrials.gov (NCT05053230) on 09-20-2021".},
}

@article {pmid39809842,
year = {2025},
author = {Popchock, AR and Hedouin, S and Mao, Y and Asbury, CL and Stergachis, AB and Biggins, S},
title = {Stable centromere association of the yeast histone variant Cse4 requires its essential N-terminal domain.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {39809842},
issn = {1460-2075},
support = {NIH 1DP5OD029630//HHS | National Institutes of Health (NIH)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; NIH R35GM134842//HHS | National Institutes of Health (NIH)/ ; R35 GM149357/GM/NIGMS NIH HHS/United States ; NIH R35 GM149357//HHS | National Institutes of Health (NIH)/ ; NIH F32GM136010//HHS | National Institutes of Health (NIH)/ ; },
abstract = {Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo. The extended Cse4 N-terminal tail binds to the chaperone Scm3, and a short essential region called END within the N-terminal tail binds the inner kinetochore complex Okp1/Ame1. To address the roles of these interactions, we utilized single-molecule fluorescence assays to monitor Cse4 during kinetochore assembly. We found that Okp1/Ame1 and Scm3 independently stabilize Cse4 at centromeres via their END interaction. Scm3 and Cse4 stability at the centromere are enhanced by Ipl1/Aurora B phosphorylation of the Cse4 END, identifying a previously unknown role for Ipl1 in ensuring Cse4 stability. Strikingly, a phosphomimetic mutation in the Cse4 END restores Cse4 recruitment in mutants defective in Okp1/Ame1 binding. Together, these data suggest that a key function of the essential Cse4 N-terminus is to ensure Cse4 localization at centromeres.},
}

@article {pmid39808799,
year = {2025},
author = {Baumrin, E and Pidala, JA and Mitchell, S and Onstad, L and Lee, SJ},
title = {Development of the Lee Symptom Scale-Skin Sclerosis for chronic GVHD-associated sclerosis.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024027334},
pmid = {39808799},
issn = {1528-0020},
abstract = {Sclerosis is a highly morbid manifestation of chronic GVHD (cGVHD), associated with distressing symptoms and significant long-term disability. A patient-reported outcome measure (PRO) for cGVHD-associated sclerosis is essential to advance therapeutic trials. We aimed to develop a PRO for adults with cGVHD-associated sclerosis and evaluate and refine its content validity. Adults age ≥18 years with cGVHD-associated sclerosis participated in semi-structured interviews to identify salient symptoms and functions. Sclerosis-relevant symptoms and functions from existing PROs were also used to prompt discussion of topics not spontaneously mentioned. Symptoms and functions (subcodes) of importance were clustered and mapped to overarching domains (codes) using inductive analysis, and candidate items were developed. Cognitive interviews were employed to evaluate content validity of the items, response options, recall period, and respondent instructions.Thirty-five open-ended interviews, conducted to saturation, revealed the breadth of the patient experience with cGVHD-associated sclerosis including 5 overarching domains: (1) skin changes, (2) symptoms, (3) emotional and social functioning, (4) mobility restrictions, and (4) activity limitations. A pool of 54 items was tested and iteratively refined through cognitive debriefing interviews (n=25). Phrasing changes were made to improve relevance and comprehension. One item was removed and two items were added to address respondent feedback, resulting in 55 items. Results support the relevance, comprehensibility, and comprehensiveness of the provisional Lee Symptom Scale-Skin Sclerosis. Concept elicitation and cognitive interviewing have informed the development of the Lee Symptom Scale-Skin Sclerosis. Psychometric testing and determination of minimal clinically important difference are underway in an external cohort to validate the PRO.},
}

@article {pmid39808648,
year = {2025},
author = {Friedland, BA and Gundacker, H and Achilles, SL and Chen, BA and Hoesley, C and Richardson, BA and Kelly, CW and Piper, J and Johnson, S and Devlin, B and Steytler, J and Kleinbeck, K and Dangi, B and Friend, C and Song, M and Mensch, B and van der Straten, A and Jacobson, C and Hendrix, CW and Brown, J and Blithe, D and Hiller, SL and , },
title = {Acceptability of a dapivirine levonorgestrel vaginal ring in two Phase 1 trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019): Implications for multipurpose prevention technology development.},
journal = {PloS one},
volume = {20},
number = {1},
pages = {e0312957},
pmid = {39808648},
issn = {1932-6203},
mesh = {Humans ; Female ; Adult ; *Levonorgestrel/administration & dosage ; *Pyrimidines/administration & dosage/therapeutic use ; *Contraceptive Devices, Female ; *HIV Infections/prevention & control ; Young Adult ; Adolescent ; Middle Aged ; Patient Acceptance of Health Care ; Anti-HIV Agents/administration & dosage/therapeutic use ; Contraceptive Agents, Female/administration & dosage ; Pregnancy ; },
abstract = {End-user feedback early in product development is important for optimizing multipurpose prevention technologies for HIV and pregnancy prevention. We evaluated the acceptability of the 90-day dapivirine levonorgestrel ring (DPV-LNG ring) used for 14 days compared to a dapivirine-only ring (DVR-200mg) in MTN-030/IPM 041 (n = 23), and when used for 90 days cyclically or continuously in MTN-044/IPM 053/CCN019 (n = 25). We enrolled healthy, non-pregnant, HIV-negative women aged 18-45 in Pittsburgh, PA and Birmingham, AL (MTN-030 only). Self-reports of vaginal bleeding and adherence (ring removals, expulsions) were collected via daily short message service. Acceptability data were recorded in face-to-face interviews at study exit. We assessed differences in acceptability by product characteristics and adherence; and associations between baseline characteristics/demographics, number of bleeding days, adherence, and overall acceptability. Most (21/23) women in the 14-day MTN-030 study and about half (13/25) in the 90-day MTN-044 study liked their assigned rings. In MTN-030 there were no significant associations between any variables and overall acceptability of either ring. In MTN-044, women who disliked the DPV-LNG ring had a significantly higher incidence of unanticipated vaginal bleeding, and reporting that vaginal bleeding changes were unacceptable than those who liked it. Although we found no overall association between adherence and acceptability, significantly more women who disliked (versus liked) the DPV-LNG ring reported expulsions during toileting. The DPV-LNG ring could meet the needs of women seeking simultaneous protection from HIV and unintended pregnancy. Addressing issues related to vaginal bleeding and expulsions early in product development will likely enhance acceptability of the DPV-LNG ring. Trial registration: Clinical Trial Registration: MTN-030/IPM 041: ClinicalTrials.gov NCT02855346; MTN-044/IPM 053/CCN019: ClinicalTrials.gov NCT03467347.},
}

Humans
Female
Adult
*Levonorgestrel/administration & dosage
*Pyrimidines/administration & dosage/therapeutic use
*Contraceptive Devices, Female
*HIV Infections/prevention & control
Young Adult
Adolescent
Middle Aged
Patient Acceptance of Health Care
Anti-HIV Agents/administration & dosage/therapeutic use
Contraceptive Agents, Female/administration & dosage
Pregnancy

@article {pmid39764024,
year = {2024},
author = {Arends, T and Bennett, SR and Tapscott, SJ},
title = {DUX4-induced HSATII RNA accumulation drives protein aggregation impacting RNA processing pathways.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39764024},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 AR045203/AR/NIAMS NIH HHS/United States ; T32 CA009657/CA/NCI NIH HHS/United States ; },
abstract = {RNA-driven protein aggregation leads to cellular dysregulation by sequestering regulatory proteins, disrupting normal cellular processes, and contributing to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar-associated RNA and human satellite II (HSATII) repeat RNA. Stable intranuclear RNAs drive protein aggregation in DUX4-expressing muscle cells. Specifically, HSATII RNA sequesters m[6]A and m[5]C RNA methylation factors. Furthermore, HSATII-YBX1 ribonucleoprotein (RNP) complex formation is mediated by HSATII RNA accumulation, NSUN2 activity and RNA methylation. YBX-1 specifically associates with HSATII double-stranded RNA. Aberrant HSATII-RNP complexes affect key RNA processing pathways, including mRNA splicing. Differential splicing of genes mediated by HSATII-RNP complexes are associated with pathways known to be dysregulated by DUX4 expression. These findings highlight the broader influence of DUX4 on nuclear RNA dynamics and suggest that HSATII RNA could be a critical mediator of RNA processing regulation in DUX4-expressing cells. Understanding the impact of HSATII-RNP formation on RNA processing pathways provides valuable insight into the molecular mechanisms underlying FSHD.},
}

@article {pmid39763963,
year = {2024},
author = {Frouard, J and Telwatte, S and Luo, X and Elphick, N and Thomas, R and Arneson, D and Roychoudhury, P and Butte, AJ and Wong, JK and Hoh, R and Deeks, SG and Lee, SA and Roan, NR and Yukl, S},
title = {HIV-SEQ REVEALS GLOBAL HOST GENE EXPRESSION DIFFERENCES BETWEEN HIV-TRANSCRIBING CELLS FROM VIREMIC AND SUPPRESSED PEOPLE WITH HIV.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39763963},
issn = {2692-8205},
support = {P01 AI169606/AI/NIAID NIH HHS/United States ; UM1 AI164559/AI/NIAID NIH HHS/United States ; R01 AI183286/AI/NIAID NIH HHS/United States ; R01 DK120387/DK/NIDDK NIH HHS/United States ; UM1 AI164560/AI/NIAID NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; R21 AI170166/AI/NIAID NIH HHS/United States ; UM1 AI164567/AI/NIAID NIH HHS/United States ; R01 AI132128/AI/NIAID NIH HHS/United States ; R01 DK131526/DK/NIDDK NIH HHS/United States ; R01 AI147777/AI/NIAID NIH HHS/United States ; },
abstract = {"Active" reservoir cells transcribing HIV can perpetuate chronic inflammation in virally suppressed people with HIV (PWH) and likely contribute to viral rebound after antiretroviral therapy (ART) interruption, so they represent an important target for new therapies. These cells, however, are difficult to study using single-cell RNA-seq (scRNA-seq) due to their low frequency and low levels of HIV transcripts, which are usually not polyadenylated. Here, we developed "HIV-seq" to enable more efficient capture of HIV transcripts - including non-polyadenylated ones - for scRNA-seq analysis of cells from PWH. By spiking in a set of custom-designed capture sequences targeting conserved regions of the HIV genome during scRNA-seq, we increased our ability to find HIV RNA+ cells from PWH by up to 44%. Implementing HIV-seq in conjunction with surface phenotyping by CITE-seq on paired blood specimens from PWH before vs. after ART suppression, we found that HIV RNA+ cells were enriched among T effector memory (Tem) cells during both viremia and ART suppression, but exhibited a cytotoxic signature during viremia only. By contrast, HIV RNA+ cells from the ART-suppressed timepoints exhibited a distinct anti-inflammatory signature involving elevated TGF-β and diminished IFN signaling. Overall, these findings demonstrate that active reservoir cells exhibit transcriptional features distinct from HIV RNA+ cells during viremia, and underscore HIV-seq as a useful tool to better understand the mechanisms by which HIV-transcribing cells can persist during ART.},
}