@article {pmid40053727,
year = {2025},
author = {Benjet, C and Zainal, NH and Albor, Y and Alvis-Barranco, L and Carrasco Tapia, N and Contreras-Ibáñez, CC and Cortés-Morelos, J and Cudris-Torres, L and de la Peña, FR and González, N and Gutierrez-Garcia, RA and Vargas-Contreras, E and Medina-Mora, ME and Patiño, P and Gildea, SM and Kennedy, CJ and Luedtke, A and Sampson, NA and Petukhova, MV and Zubizarreta, JR and Cuijpers, P and Kazdin, AE and Kessler, RC},
title = {The Effect of Predicted Compliance With a Web-Based Intervention for Anxiety and Depression Among Latin American University Students: Randomized Controlled Trial.},
journal = {JMIR mental health},
volume = {12},
number = {},
pages = {e64251},
doi = {10.2196/64251},
pmid = {40053727},
issn = {2368-7959},
mesh = {Humans ; Female ; Male ; *Students/psychology ; Universities ; *Cognitive Behavioral Therapy/methods ; *Internet-Based Intervention ; Young Adult ; Adult ; *Depression/therapy ; Anxiety/therapy ; Patient Compliance ; Colombia ; Mexico ; Adolescent ; },
abstract = {BACKGROUND: Web-based cognitive behavioral therapy (wb-CBT) is a scalable way to reach distressed university students. Guided wb-CBT is typically superior to self-guided wb-CBT over short follow-up periods, but evidence is less clear over longer periods.

OBJECTIVE: This study aimed to compare short-term (3 months) and longer-term (12 months) aggregate effects of guided and self-guided wb-CBT versus treatment as usual (TAU) in a randomized controlled trial of Colombian and Mexican university students and carry out an initially unplanned secondary analysis of the role of differential predicted compliance in explaining these differences.

METHODS: The 1319 participants, recruited either through email and social media outreach invitations or from waiting lists of campus mental health clinics, were undergraduates (1038/1319, 78.7% female) with clinically significant baseline anxiety (Generalized Anxiety Disorder-7 score≥10) or depression (Patient Health Questionnaire-9 score≥10). The intervention arms comprised guided wb-CBT with weekly asynchronous written human feedback, self-guided wb-CBT with the same content as the guided modality, and TAU as provided at each university. The prespecified primary outcome was joint remission (Generalized Anxiety Disorder-7 score=0-4 and Patient Health Questionnaire-9 score=0-4). The secondary outcome was joint symptom reduction (mean scores on the Patient Health Questionnaire Anxiety and Depression Scale) at 3 and 12 months after randomization.

RESULTS: As reported previously, 3-month outcomes were significantly better with guided wb-CBT than self-guided wb-CBT (P=.02) or TAU (P=.02). However, subsequent follow-up showed that 12-month joint remission (adjusted risk differences=6.0-6.5, SE 0.4-0.5, and P<.001 to P=.007; adjusted mean differences=2.70-2.69, SE 0.7-0.8, and P<.001 to P=.001) was significantly better with self-guided wb-CBT than with the other interventions. Participants randomly assigned to the guided wb-CBT arm spent twice as many minutes logged on as those in the self-guided wb-CBT arm in the first 12 weeks (mean 12.5, SD 36.9 vs 5.9, SD 27.7; χ[2]1=107.1, P<.001), whereas participants in the self-guided wb-CBT arm spent twice as many minutes logged on as those in the guided wb-CBT arm in weeks 13 to 52 (mean 0.4, SD 7.5 vs 0.2, SD 4.4; χ[2]1=10.5, P=.001). Subgroup analysis showed that this longer-term superiority of self-guided wb-CBT was confined to the 40% (528/1319) of participants with high predicted self-guided wb-CBT compliance beyond 3 months based on a counterfactual nested cross-validated machine learning model. The 12-month outcome differences were nonsignificant across arms among other participants (all P>.05).

CONCLUSIONS: The results have important practical implications for precision intervention targeting to maximize longer-term wb-CBT benefits. Future research needs to investigate strategies to increase sustained guided wb-CBT use once guidance ends.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04780542; https://www.clinicaltrials.gov/study/NCT04780542.

RR2-10.1186/s13063-022-06255-3.},
}

Humans
Female
Male
*Students/psychology
Universities
*Cognitive Behavioral Therapy/methods
*Internet-Based Intervention
Young Adult
Adult
*Depression/therapy
Anxiety/therapy
Patient Compliance
Colombia
Mexico
Adolescent

@article {pmid40034763,
year = {2025},
author = {Orchard, P and Blackwell, TW and Kachuri, L and Castaldi, PJ and Cho, MH and Christenson, SA and Durda, P and Gabriel, S and Hersh, CP and Huntsman, S and Hwang, S and Joehanes, R and Johnson, M and Li, X and Lin, H and Liu, CT and Liu, Y and Mak, ACY and Manichaikul, AW and Paik, D and Saferali, A and Smith, JD and Taylor, KD and Tracy, RP and Wang, J and Wang, M and Weinstock, JS and Weiss, J and Wheeler, HE and Zhou, Y and Zoellner, S and Wu, JC and Mestroni, L and Graw, S and Taylor, MRG and Ortega, VE and Johnson, CW and Gan, W and Abecasis, G and Nickerson, DA and Gupta, N and Ardlie, K and Woodruff, PG and Zheng, Y and Bowler, RP and Meyers, DA and Reiner, A and Kooperberg, C and Ziv, E and Ramachandran, VS and Larson, MG and Cupples, LA and Burchard, EG and Silverman, EK and Rich, SS and Heard-Costa, N and Tang, H and Rotter, JI and Smith, AV and Levy, D and , and , and Aguet, F and Scott, L and Raffield, LM and Parker, SCJ},
title = {Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40034763},
abstract = {Most genetic variants associated with complex traits and diseases occur in non-coding genomic regions and are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterize 14,324 ancestrally diverse RNA-sequencing samples from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and integrate whole genome sequencing data to perform cis and trans expression and splicing quantitative trait locus (cis-/trans-e/sQTL) analyses in six tissues and cell types, most notably whole blood (N=6,454) and lung (N=1,291). We show this dataset enables greater detection of secondary cis-e/sQTL signals than was achieved in previous studies, and that secondary cis-eQTL and primary trans-eQTL signal discovery is not saturated even though eGene discovery is. Most TOPMed trans-eQTL signals colocalize with cis-e/sQTL signals, suggesting many trans signals are mediated by cis signals. We fine-map European UK BioBank GWAS signals from 164 traits and colocalize the resulting 34,107 fine-mapped GWAS signals with TOPMed e/sQTL signals, finding that of 10,611 GWAS signals with a colocalization, 7,096 GWAS signals colocalize with at least one secondary e/sQTL signal. These results demonstrate that larger e/sQTL analyses will continue to uncover secondary e/sQTL signals, and that these new signals will benefit GWAS interpretation.},
}

@article {pmid40053601,
year = {2025},
author = {Binkowski, B and Klamer, Z and Gao, C and Staal, B and Repesh, A and Tran, HL and Brass, DM and Bartlett, P and Gallinger, S and Blomqvist, M and Morrow, JB and Allen, P and Shi, C and Singhi, A and Brand, R and Huang, Y and Hostetter, G and Haab, BB},
title = {Multiplexed glycan immunofluorescence identification of pancreatic cancer cell subpopulations in both tumor and blood samples.},
journal = {Science advances},
volume = {11},
number = {10},
pages = {eadt0029},
doi = {10.1126/sciadv.adt0029},
pmid = {40053601},
issn = {2375-2548},
mesh = {Humans ; *Polysaccharides/metabolism/blood ; *Pancreatic Neoplasms/blood/metabolism/pathology/diagnosis ; *Carcinoma, Pancreatic Ductal/blood/metabolism/diagnosis/pathology ; *Biomarkers, Tumor/blood/metabolism ; *Fluorescent Antibody Technique ; Cell Line, Tumor ; },
abstract = {Pancreatic ductal adenocarcinoma (PDAC) tumor heterogeneity impedes the development of biomarker assays for early disease detection. We hypothesized that PDAC cell subpopulations could be identified by aberrant glycan signatures in both tumor tissue and blood samples. We used multiplexed glycan immunofluorescence to distinguish between PDAC and noncancer cell subpopulations within tumor tissue, and we developed hybrid glycan sandwich assays to determine whether the aberrant glycan signatures could be detected in blood samples. We found that PDAC cells were identified by signatures of glycans detected by four glycan-binding proteins (VVL, CA19-9, sTRA, and GM2) and that there are three types of glycan-defined PDAC tumors: sTRA type, CA19-9 type, and intermixed. In patient-matched tumor and blood samples, the PDAC tumor type could be determined by the aberrant glycans in the blood. As a result, the combined assays of aberrant glycan signatures were more sensitive and specific than any individual assay. Our results demonstrate a methodology to detect and stratify PDAC.},
}

Humans
*Polysaccharides/metabolism/blood
*Pancreatic Neoplasms/blood/metabolism/pathology/diagnosis
*Carcinoma, Pancreatic Ductal/blood/metabolism/diagnosis/pathology
*Biomarkers, Tumor/blood/metabolism
*Fluorescent Antibody Technique
Cell Line, Tumor

@article {pmid40051480,
year = {2024},
author = {Back, A and Myers, S and Guy, J and Perez, J and Lazar Thorn, L and McGregor, B},
title = {Evolving Guidelines for the Use of Touch During a Clinical Trial of Group Psilocybin-Assisted Therapy.},
journal = {Psychedelic medicine (New Rochelle, N.Y.)},
volume = {2},
number = {4},
pages = {187-191},
pmid = {40051480},
issn = {2831-4433},
abstract = {For a new clinical trial testing a group retreat-based format of psilocybin-assisted therapy, our research team created an initial set of practice guidelines that aimed to describe facilitator use of touch in a way that is ethical, supportive, and minimizes harm. In our first three retreats, however, we had two unexpected experiences with touch that led us to iterate our initial guidelines into a new version of guidelines. In this Technical Report, we describe our evolving guidelines specifying acceptable practices for facilitator use of touch to ensure a safe, supportive, and therapeutic participant experience. Our primary goal with these guidelines is to create a haptic experience during the psilocybin session that reinforces the participants' sense of safety and supports their own experience during the psilocybin session. Our secondary goal is to allow the facilitator team to notice and maintain therapeutic boundaries and to respond to participant experiences with empathy and openness in the context of those boundaries (Clinical Trials No: NCT05847686).},
}

@article {pmid40049206,
year = {2025},
author = {Morris, ZS and Demaria, S and Monjazeb, AM and Formenti, SC and Weichselbaum, RR and Welsh, J and Enderling, H and Schoenfeld, JD and Brody, JD and McGee, HM and Mondini, M and Kent, MS and Young, KH and Galluzzi, L and Karam, SD and Theelen, WSME and Chang, JY and Huynh, MA and Daib, A and Pitroda, S and Chung, C and Serre, R and Grassberger, C and Deng, J and Sodji, QH and Nguyen, AT and Patel, RB and Krebs, S and Kalbasi, A and Kerr, C and Vanpouille-Box, C and Vick, L and Aguilera, TA and Ong, IM and Herrera, F and Menon, H and Smart, D and Ahmed, J and Gartrell, RD and Roland, CL and Fekrmandi, F and Chakraborty, B and Bent, EH and Berg, TJ and Hutson, A and Khleif, S and Sikora, AG and Fong, L},
title = {Proceedings of the National Cancer Institute Workshop on combining immunotherapy with radiotherapy: challenges and opportunities for clinical translation.},
journal = {The Lancet. Oncology},
volume = {26},
number = {3},
pages = {e152-e170},
doi = {10.1016/S1470-2045(24)00656-9},
pmid = {40049206},
issn = {1474-5488},
support = {R37 CA262557/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Immunotherapy/methods ; *Neoplasms/radiotherapy/immunology/therapy ; United States ; *National Cancer Institute (U.S.) ; *Translational Research, Biomedical ; Animals ; Combined Modality Therapy ; },
abstract = {Radiotherapy both promotes and antagonises tumour immune recognition. Some clinical studies show improved patient outcomes when immunotherapies are integrated with radiotherapy. Safe, greater than additive, clinical response to the combination is limited to a subset of patients, however, and how radiotherapy can best be combined with immunotherapies remains unclear. The National Cancer Institute-Immuno-Oncology Translational Network-Society for Immunotherapy of Cancer-American Association of Immunology Workshop on Combining Immunotherapy with Radiotherapy was convened to identify and prioritise opportunities and challenges for radiotherapy and immunotherapy combinations. Sessions examined the immune effects of radiation, barriers to anti-tumour immune response, previous clinical trial data, immunological and computational assessment of response, and next-generation radiotherapy-immunotherapy combinations. Panel recommendations included: developing and implementing patient selection and biomarker-guided approaches; applying mechanistic understanding to optimise delivery of radiotherapy and selection of immunotherapies; using rigorous preclinical models including companion animal studies; embracing data sharing and standardisation, advanced modelling, and multidisciplinary cross-institution collaboration; interrogating clinical data, including negative trials; and incorporating novel clinical endpoints and trial designs.},
}

Humans
*Immunotherapy/methods
*Neoplasms/radiotherapy/immunology/therapy
United States
*National Cancer Institute (U.S.)
*Translational Research, Biomedical
Animals
Combined Modality Therapy

@article {pmid40048931,
year = {2025},
author = {Moore, M and Anderson, L and Schiffer, JT and Matrajt, L and Dimitrov, D},
title = {Durability of COVID-19 vaccine and infection induced immunity: A systematic review and meta-regression analysis.},
journal = {Vaccine},
volume = {54},
number = {},
pages = {126966},
doi = {10.1016/j.vaccine.2025.126966},
pmid = {40048931},
issn = {1873-2518},
abstract = {BACKGROUND: Despite the success of mRNA vaccines, COVID-19 remains a significant public health threat. Waning of immune memory and the emergence of new variants can degrade population-level protection and contribute to ongoing morbidity.

METHODS: In this systematic review and meta-regression, we searched for studies in PubMed, medRxiv and bioRxiv published January 1, 2020 - January 1, 2023 measuring vaccine effectiveness as the reduction in infection, symptomatic disease, and severe disease (resulting in hospitalization and/or death) conferred by mRNA-based vaccination and prior SARS-CoV-2 infections relative to naïve individuals. We excluded studies that did not distinguish between mRNA and non-mRNA vaccines or had less than 1000 participants. Using a multi-level model, we quantified the initial effectiveness and change over four to six months following vaccination or infection. Model covariates were COVID variant, number of vaccine doses, and the number and variant of prior infection. Our estimates were adjusted for the age of the study population.

FINDINGS: Of 828 screened, we included 123 studies in our analysis. Vaccine effectiveness against infection and disease declined both over time and with the emergence of Omicron, regardless of booster doses, though protection against severe outcomes was more durable. Booster doses reduced severe Omicron infections by 90.5 % (95 % confidence interval 87.1-93.8) and 77.6 % (70.5-84.7) at two and 26 weeks post-vaccination, respectively. Protection conferred by hybrid immunity was more durable than that from either vaccination or prior infection alone, but protection against Omicron reinfection was only 50.1 % (32.5-67.8) at 26 weeks following vaccination. Individuals with hybrid immunity had 80.6 % protection (70.0-91.2) following booster doses declining to 36.9 % (19.3-54.6) after 16 weeks.

INTERPRETATION: Our results suggest that timely deployment of pre-existing boosters can greatly mitigate seasonal COVID outbreaks even in populations with prior infection and vaccination.

FUNDING: Centers for Disease Control and Prevention (NU38OT000297-03).},
}

@article {pmid40048743,
year = {2025},
author = {Nath, K and Zhang, MJ and Bye, M and Abid, MB and Benjamin, C and Betts, BC and Bhatt, NS and Arrieta-Bolaños, E and Bolon, YT and Gadalla, SM and Grunwald, MR and Krem, MM and Lee, SJ and Marsh, SGE and Martino, R and Mehta, PA and Milano, F and Prestidge, T and Saultz, JN and Shaw, BE and Spellman, SR and Choe, HK and Shaffer, BC},
title = {Transplant Outcomes Using Older Matched Sibling Donors Compared to Young Alternative Donors: A CIBMTR Analysis.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014858},
pmid = {40048743},
issn = {2473-9537},
abstract = {Whether younger donors should be prioritized over HLA-matching for allogeneic hematopoietic cell transplantation (allo-HCT) when using post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis is unclear. To address this, we compared outcomes of allo-HCT recipients aged ≥50-years using PTCy-based GvHD prophylaxis from an older (≥50-years) matched sibling donor (MSD) to those of younger alternative donors ≤35-years: HLA-matched unrelated donors (MUD), HLA-mismatched unrelated donors (MMUD), and haploidentical (haplo)-related donors reported to the Center for International Blood & Marrow Transplant Research between 2014-2021. Young MUD and older MSD receiving calcineurin inhibitor (CNI)-based allo-HCT that met study criteria were concurrently examined. The primary endpoint was overall survival (OS). Among 14,662 HCT recipients, 3,746 received PTCy- and 10,916 CNI-based GvHD prophylaxis. The median follow-up was 47 months. In patients treated with PTCy, the adjusted 5-year OS was not significantly different at 44% for MSD compared with 52% for MUD (multivariable hazard ratio [HR]: 1.20, 95%CI: 1.03-1.41, p=0.09), 45% for haplo (HR: 1.02, 0.88-1.18, p=1.00) and 46% for MMUD (HR: 1.00, 0.83-1.21, p=1.00). Compared to MSDs, receipt of younger MUD associated with improved disease-free survival (DFS) both with PTCy (HR: 1.21, 1.05-1.40, p=0.048) and CNI (HR 1.09, 1.04-1.15, p<0.01) based prophylaxis. Haplo-donor recipients associated with similar OS to MSD, but worse OS compared to MUD recipients with PTCy (HR: 1.18, 1.05-1.33, p=0.04). These data suggest that older MSDs result in similar OS compared to younger alternative donors in older-aged recipients. Younger MUDs may be preferred for older patients due to improved DFS when available.},
}

@article {pmid40048671,
year = {2025},
author = {Rajdev, L and King, GG and Lieu, CH and Cohen, SA and Pant, S and Uboha, NV and Deming, D and Malla, M and Kasi, A and Klute, K and Spencer, KR and Dasari, A and Morris, VK and Botta, G and Lowy, AM and O'Hara, MH and Eads, J and King, D and Shah, MA and Hong, TS and Parikh, A and Klempner, SJ and Jabbour, SK and Chawla, A and Molena, D and George, TJ and Gibson, MK and Allegra, C and Goodman, K and Eng, C and Philip, PA},
title = {Incorporating Circulating Tumor DNA Testing Into Clinical Trials: A Position Paper by the National Cancer Institute GI Oncology Circulating Tumor DNA Working Group.},
journal = {JCO precision oncology},
volume = {9},
number = {},
pages = {e2400489},
doi = {10.1200/PO-24-00489},
pmid = {40048671},
issn = {2473-4284},
mesh = {Humans ; *Circulating Tumor DNA/blood/genetics ; *Gastrointestinal Neoplasms/genetics/blood ; United States ; *National Cancer Institute (U.S.) ; *Clinical Trials as Topic ; },
abstract = {PURPOSE: Circulating tumor DNA (ctDNA) is an emerging tool in the evaluation of GI cancers. Challenges remain in defining its utility and role as a primary end point in therapeutic trials. The National Cancer Institute (NCI) ctDNA GI working group was created to evaluate current data and provide guidance on the inclusion of ctDNA in GI cancer trials.

METHODS: The NCI GI steering committee assigned four task force members to serve as co-chairs for the working group. Co-chairs identified experts within each GI disease group to form a panel that convened to review data and provide recommendations. The group focused on ctDNA's role as a potential surrogate for assessing prognosis and guiding treatment decisions that may enhance GI cancer trials. A manuscript was drafted, circulated, revised, and voted on by the panel. The final draft was reviewed by the Cancer Therapy Evaluation Program.

RESULTS: Further data are required to support ctDNA as a primary end point for late-phase therapeutic trials, particularly in studies that could change the standard-of-care. However, the group supports ctDNA as a primary efficacy end point for phase II studies and as a noninvasive evaluation strategy for new drug development. Incorporation of ctDNA as a biomarker in trial design must consider the specific context of disease biology of the GI cancer subtypes. ctDNA should be incorporated as an exploratory end point across a variety of disease settings and indications. Several practical considerations were identified to optimize the incorporation of ctDNA in future trial design.

CONCLUSION: Prospective trials are required to clarify the role of ctDNA as a valid surrogate end point for progression-free or overall survival in GI cancers.},
}

Humans
*Circulating Tumor DNA/blood/genetics
*Gastrointestinal Neoplasms/genetics/blood
United States
*National Cancer Institute (U.S.)
*Clinical Trials as Topic

@article {pmid40045233,
year = {2025},
author = {Yilmaz, S and Aryal, K and King, J and Bischof, JJ and Hong, AS and Wood, N and Gould Rothberg, BE and Hudson, MF and Heinert, SW and Wattana, MK and Coyne, CJ and Reyes-Gibby, C and Todd, K and Lyman, G and Klotz, A and Abar, B and Grudzen, C and Bastani, A and Baugh, CW and Henning, DJ and Bernstein, S and Rico, JF and Ryan, RJ and Yeung, SJ and Qdaisat, A and Padela, A and Madsen, TE and Liu, R and Adler, D},
title = {Understanding oncologic emergencies and related emergency department visits and hospitalizations: a systematic review.},
journal = {BMC emergency medicine},
volume = {25},
number = {1},
pages = {40},
pmid = {40045233},
issn = {1471-227X},
mesh = {Humans ; *Emergency Service, Hospital/statistics & numerical data ; *Neoplasms/therapy/epidemiology ; *Hospitalization/statistics & numerical data ; Emergencies/epidemiology ; Emergency Room Visits ; },
abstract = {BACKGROUND: Patients with cancer frequently visit the emergency department (ED) and are at high risk for hospitalization due to severe illness from cancer progression or treatment side effects. With an aging population and rising cancer incidence rates worldwide, it is crucial to understand how EDs and other acute care venues manage oncologic emergencies. Insights from other nations and health systems may inform resources necessary for optimal ED management and novel care delivery pathways. We described clinical management of oncologic emergencies and their contribution to ED visits and hospitalizations worldwide.

METHODS: We performed a systematic review of peer-reviewed original research studies published in the English language between January 1st, 2003, to December 31st, 2022, garnered from PubMed, Web of Science, and EMBASE. We included all studies investigating adult (≥ 18 years) cancer patients with emergency visits. We examined chief complaints or predictors of ED use that explicitly defined oncologic emergencies.

RESULTS: The search strategy yielded 49 articles addressing cancer-related emergency visits. Most publications reported single-site studies (n = 34/49), with approximately even distribution across clinical settings- ED (n = 22/49) and acute care hospital/ICU (n = 27/49). The number of patient observations varied widely among the published studies (range: 9 - 87,555 patients), with most studies not specifying the cancer type (n = 33/49), stage (n = 41/49), or treatment type (n = 36/49). Most studies (n = 31/49) examined patients aged ≥ 60 years. Infection was the most common oncologic emergency documented (n = 22/49), followed by pain (n = 20/49), dyspnea (n = 19/49), and gastrointestinal (GI) symptoms (n = 17/49). Interventions within the ED or hospital ranged from pharmacological management with opioids (n = 11/49), antibiotics (n = 9/49), corticosteroids (n = 5/49), and invasive procedures (e.g., palliative stenting; n = 13/49) or surgical interventions (n = 2/49).

CONCLUSION: Limited research specifically addresses oncologic emergencies despite the international prevalence of ED presentations among cancer patients. Patients with cancer presenting to the ED appear to have a variety of complaints which could result from their cancers and thus may require tailored diagnostic and intervention pathways to provide optimal acute care. Further acute geriatric oncology research may clarify the optimal management strategies to improve the outcomes for this vulnerable patient population.},
}

Humans
*Emergency Service, Hospital/statistics & numerical data
*Neoplasms/therapy/epidemiology
*Hospitalization/statistics & numerical data
Emergencies/epidemiology
Emergency Room Visits

@article {pmid40044856,
year = {2025},
author = {Tran-Kiem, C and Paredes, MI and Perofsky, AC and Frisbie, LA and Xie, H and Kong, K and Weixler, A and Greninger, AL and Roychoudhury, P and Peterson, JM and Delgado, A and Halstead, H and MacKellar, D and Dykema, P and Gamboa, L and Frazar, CD and Ryke, E and Stone, J and Reinhart, D and Starita, L and Thibodeau, A and Yun, C and Aragona, F and Black, A and Viboud, C and Bedford, T},
title = {Fine-scale patterns of SARS-CoV-2 spread from identical pathogen sequences.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40044856},
issn = {1476-4687},
abstract = {Pathogen genomics can provide insights into underlying infectious disease transmission patterns[1,2], but new methods are needed to handle modern large-scale pathogen genome datasets and realize this full potential[3-5]. In particular, genetically proximal viruses should be highly informative about transmission events as genetic proximity indicates epidemiological linkage. Here we use pairs of identical sequences to characterize fine-scale transmission patterns using 114,298 SARS-CoV-2 genomes collected through Washington State (USA) genomic sentinel surveillance with associated age and residence location information between March 2021 and December 2022. This corresponds to 59,660 sequences with another identical sequence in the dataset. We find that the location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postcodes with male prisons, consistent with transmission between prison facilities. We find that transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. Overall, this study improves our ability to use large pathogen genome datasets to understand the determinants of infectious disease spread.},
}

@article {pmid40043139,
year = {2025},
author = {Rubio, AA and Baharani, VA and Dadonaite, B and Parada, M and Abernathy, ME and Wang, Z and Lee, YE and Eso, MR and Phung, J and Ramos, I and Chen, T and El Nesr, G and Bloom, JD and Bieniasz, PD and Nussenzweig, MC and Barnes, CO},
title = {Bispecific antibodies targeting the N-terminal and receptor binding domains potently neutralize SARS-CoV-2 variants of concern.},
journal = {Science translational medicine},
volume = {17},
number = {788},
pages = {eadq5720},
doi = {10.1126/scitranslmed.adq5720},
pmid = {40043139},
issn = {1946-6242},
mesh = {*Antibodies, Bispecific/immunology/pharmacology ; *SARS-CoV-2/immunology ; Animals ; Humans ; *Antibodies, Neutralizing/immunology ; *COVID-19/virology/immunology ; Mice ; Spike Glycoprotein, Coronavirus/immunology/chemistry/metabolism ; Antibodies, Viral/immunology ; Protein Domains ; Epitopes/immunology ; Protein Binding ; Neutralization Tests ; Female ; Binding Sites ; Cryoelectron Microscopy ; },
abstract = {The ongoing emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that reduce the effectiveness of antibody therapeutics necessitates development of next-generation antibody modalities that are resilient to viral evolution. Here, we characterized amino-terminal domain (NTD)- and receptor binding domain (RBD)-specific monoclonal antibodies previously isolated from coronavirus disease 2019 (COVID-19) convalescent donors for their activity against emergent SARS-CoV-2 VOCs. Among these, the NTD-specific antibody C1596 displayed the greatest breadth of binding to VOCs, with cryo-electron microscopy structural analysis revealing recognition of a distinct NTD epitope outside of the site i antigenic supersite. Given C1596's favorable binding profile, we designed a series of bispecific antibodies (bsAbs), termed CoV2-biRNs, that featured both NTD and RBD specificities. Two of the C1596-inclusive bsAbs, CoV2-biRN5 and CoV2-biRN7, retained potent in vitro neutralization activity against all Omicron variants tested, including XBB.1.5, BA.2.86, and JN.1, contrasting the diminished potency of parental antibodies delivered as monotherapies or as a cocktail. Furthermore, prophylactic delivery of CoV2-biRN5 reduced the viral load within the lungs of K18-hACE2 mice after challenge with SARS-CoV-2 XBB.1.5. In conclusion, NTD-RBD bsAbs offer promising potential for the design of resilient, next-generation antibody therapeutics against SARS-CoV-2 VOCs.},
}

*Antibodies, Bispecific/immunology/pharmacology
*SARS-CoV-2/immunology
Animals
Humans
*Antibodies, Neutralizing/immunology
*COVID-19/virology/immunology
Mice
Spike Glycoprotein, Coronavirus/immunology/chemistry/metabolism
Antibodies, Viral/immunology
Protein Domains
Epitopes/immunology
Protein Binding
Neutralization Tests
Female
Binding Sites
Cryoelectron Microscopy

@article {pmid40042432,
year = {2025},
author = {Gao, F and Janes, H and Buchbinder, S and Donnell, D},
title = {Active-Controlled Trial Design for HIV Prevention Trials With a Counterfactual Placebo.},
journal = {Statistics in medicine},
volume = {44},
number = {6},
pages = {e70022},
doi = {10.1002/sim.70022},
pmid = {40042432},
issn = {1097-0258},
support = {R37AI029168/NH/NIH HHS/United States ; R01AI177078/NH/NIH HHS/United States ; S10OD028685/NH/NIH HHS/United States ; UM1AI068617/NH/NIH HHS/United States ; },
mesh = {Humans ; *HIV Infections/prevention & control/drug therapy ; *Pre-Exposure Prophylaxis/methods ; Placebos ; Research Design ; Anti-HIV Agents/therapeutic use ; Models, Statistical ; Controlled Clinical Trials as Topic/ethics/methods ; },
abstract = {In the quest for enhanced HIV prevention methods, the advent of antiretroviral drugs as pre-exposure prophylaxis (PrEP) has marked a significant stride forward. However, the ethical challenges in conducting placebo-controlled trials for new PrEP agents against a backdrop of highly effective existing PrEP options necessitate innovative approaches. This manuscript delves into the design and implementation of active-controlled trials that incorporate a counterfactual placebo estimate-a theoretical estimate of what HIV incidence would have been without effective prevention. We introduce a novel statistical framework for regulatory approval of new PrEP agents, predicated on the assumption of an available and consistent counterfactual placebo estimate. Our approach aims to assess the absolute efficacy (i.e., against placebo) of the new PrEP agent relative to the absolute efficacy of the active control. We propose a two-step procedure for hypothesis testing and further develop an approach that addresses potential biases inherent in non-randomized comparisons to counterfactual placebos. By exploring different scenarios with moderately and highly effective active controls and counterfactual placebo estimates from various sources, we demonstrate how our design can significantly reduce sample sizes compared to traditional non-inferiority trials and offer a robust framework for evaluating new PrEP agents. This work contributes to the methodological repertoire for HIV prevention trials and underscores the importance of adaptability in the face of ethical and practical challenges.},
}

Humans
*HIV Infections/prevention & control/drug therapy
*Pre-Exposure Prophylaxis/methods
Placebos
Research Design
Anti-HIV Agents/therapeutic use
Models, Statistical
Controlled Clinical Trials as Topic/ethics/methods

@article {pmid40027810,
year = {2025},
author = {Newsom, OJ and Sullivan, LB},
title = {Defined media reveals the essential role of lipid scavenging to support cancer cell proliferation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40027810},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R35 GM147118/GM/NIGMS NIH HHS/United States ; },
abstract = {Fetal bovine serum (FBS) is a nearly ubiquitous, yet undefined additive in mammalian cell culture media whose functional contributions to promoting cell proliferation remain poorly understood. Efforts to replace serum supplementation in culture media have been hindered by an incomplete understanding of the environmental requirements fulfilled by FBS in culture. Here, we use a combination of live-cell imaging and liquid chromatography-mass spectrometry to elucidate the role of serum in supporting proliferation. We show that serum provides consumed factors that enable proliferation and demonstrate that the serum metal and lipid components are crucial to sustaining proliferation in culture. Importantly, despite access to a wide range of lipid classes, albumin-bound lipids are the primary species consumed during cancer cell proliferation. Furthermore, we find that combinations of the additive ITS, containing necessary metals, and albumin-associated lipid classes are sufficient to replace FBS in culture media. We show that serum-free media enables sensitive quantification of lipid consumption dynamics during cell proliferation, which indicate that fatty acids (FA) are consumed through a mass-action mechanism, with minimal competition from other lipid classes. Finally, we find that pharmacologic disruption of FA activation and incorporation into the cellular lipidome reduces uptake from the environment and impairs cell proliferation. This work therefore identifies metabolic contributions of serum in cell culture settings and provides a framework for building cell culture systems that sustain cell proliferation without the variable and undefined contributions of FBS.},
}

@article {pmid40027790,
year = {2025},
author = {Li, S and Song, K and Sun, H and Tao, Y and Huang, A and Bhatia, V and Hanratty, B and Patel, RA and Long, HW and Morrissey, C and Haffner, MC and Nelson, PS and Graeber, TG and Lee, JK},
title = {Defined cellular reprogramming of androgen receptor-active prostate cancer to neuroendocrine prostate cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40027790},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; P50 CA092131/CA/NCI NIH HHS/United States ; DP2 CA271301/CA/NCI NIH HHS/United States ; R01 CA266452/CA/NCI NIH HHS/United States ; P01 CA163227/CA/NCI NIH HHS/United States ; R01 CA222877/CA/NCI NIH HHS/United States ; },
abstract = {Neuroendocrine prostate cancer (NEPC) arises primarily through neuroendocrine transdifferentiation (NEtD) as an adaptive mechanism of therapeutic resistance. Models to define the functional effects of putative drivers of this process on androgen receptor (AR) signaling and NE cancer lineage programs are lacking. We adapted a genetically defined strategy from the field of cellular reprogramming to directly convert AR-active prostate cancer (ARPC) to AR-independent NEPC using candidate factors. We delineated critical roles of the pioneer factors ASCL1 and NeuroD1 in NEtD and uncovered their abilities to silence AR expression and signaling by remodeling chromatin at the somatically acquired AR enhancer and global AR binding sites with enhancer activity. We also elucidated the dynamic temporal changes in the transcriptomic and epigenomic landscapes of cells undergoing acute lineage conversion from ARPC to NEPC which should inform future therapeutic development. Further, we distinguished the activities of ASCL1 and NeuroD1 from the inactivation of RE-1 silencing transcription factor (REST), a master suppressor of a major neuronal gene program, in establishing a NEPC lineage state and in modulating the expression of genes associated with major histocompatibility complex class I (MHC I) antigen processing and presentation. These findings provide important, clinically relevant insights into the biological processes driving NEtD of prostate cancer.},
}

@article {pmid40046543,
year = {2023},
author = {Nayak, S and Waters, A and Warsi, M and Hegde, A and Chu, ES},
title = {Inpatient Physician and Nurse Experience During the COVID-19 Crisis at a Public Safety Net Hospital.},
journal = {The Brown journal of hospital medicine},
volume = {2},
number = {1},
pages = {57694},
pmid = {40046543},
issn = {2831-5553},
abstract = {BACKGROUND: The COVID-19 pandemic has been associated with front line health care provider burnout, depression, and post-traumatic stress disorder. We sought to better understand how nurses and physicians of differing genders may have been affected differently by the COVID-19 crisis.

METHODS: Between July 17, 2020, and October 31, 2020, we surveyed nurses and physicians caring for COVID-19 patients at a large, academic, public safety net hospital in the southern United States. Survey questions were adapted from validated questionnaires used to determine quality of life, assess levels of anxiety, and determine how COVID-19 may have affected our nurses' and physicians' work, home and social lives.

RESULTS: Overall, 120 (41.7%) providers responded, including 39 (50%) physicians and 81 (38.6%) nurses. 69.3% reported disruption to their home/family, 76.3% to their social lives, and 29.8% worried about financial strain. More nurses than physicians worried about being excluded from social gatherings (59.7% v 35.1%, p=0.01). Similarly, 70.1% of nurses and 46.0% of physicians expressed concern of exposing others to COVID-19 (p=0.01). Nurses also expressed greater concern about being treated differently by others when compared to physicians (64.5% v 37.8%, p= 0.01). Female physicians reported greater difficulty separating their personal lives from their professional lives than male physicians and either male or female nurses (84.6%% vs 35% vs 33.3% vs 35.9%, p <0.05). Most physicians (89.7%) and nurses (93.8%) reported some level of anxiety, with 31.5% of respondents experiencing moderate or severe anxiety.

CONCLUSION: Healthcare workers on the frontline of COVID-19 pandemic, regardless of profession, reported increased anxiety that extended beyond the hospital into their homes and social lives. Physicians and nurses, as well as men and women, reported different sources and degrees of stress and disruption to their work, home and social lives.},
}

@article {pmid40041932,
year = {2025},
author = {Yuan, JM and Kensler, TW and Dacic, S and Hartman, DJ and Wang, R and Balogh, PA and Sufka, P and Turner, MA and Fuhrer, K and Seigh, L and Pham, YT and Adams-Haduch, J and Valacchi, G and Singh, SV and Herman, JG and Wilson, DO},
title = {Randomized phase II clinical trial of sulforaphane in former smokers at high risk for lung cancer.},
journal = {Cancer prevention research (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1158/1940-6207.CAPR-24-0386},
pmid = {40041932},
issn = {1940-6215},
abstract = {Experimental studies have shown dietary isothiocyanates reduced cellular proliferative marker Ki-67 and increased apoptotic markers Caspase-3 and TUNEL in animals, but human data are lacking. The present study was to assess whether sulforaphane would stop/reverse the progression of bronchial histopathology, reduce Ki-67 index and/or increase Caspase-3 and TUNEL indices in humans. A randomized clinical trial (NCT03232138) was conducted in former smokers. Forty-three subjects were randomly assigned to the placebo or the treatment with a potential daily dose of 95 µmol sulforaphane for 12 months. The endpoints were the changes of histopathology scores, and Ki-67, Caspase-3 and TUNEL indices in post- vs. pre-treatment bronchial biopsies. Thirty-seven participants (17 in the sulforaphane and 20 in the placebo group) completed the study. Supplementation of sulforaphane did not show significant impact on bronchial histopathology, but significantly reduced Ki-67 index with a 20% decrease in the sulforaphane group and a 65% increase in the placebo (p = 0.014). The difference was even greater in high-density (3+) positive Ki-67, with a 44% decrease in the sulforaphane group compared with a 71% increase in the placebo (p = 0.004). Higher bioavailability of sulforaphane was correlated with greater reduction of Ki-67 index (P for trend = 0.019). Sulforaphane treatment had no impact on Caspase-3 or TUNEL index in bronchial biopsies. No severe adverse event was observed in the study participants. The findings of oral sulforaphane that significantly reduced Ki-67 index in bronchial tissue support further development as a potential chemopreventive agent against lung cancer development.},
}

@article {pmid40040586,
year = {2025},
author = {Owens, L and Fung, A and Shuhendler, J and Glick, J and Ryser, MD and Gulati, R and Etzioni, R},
title = {Trends in Young-Onset Cancer Incidence: A Modeling Perspective.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf050},
pmid = {40040586},
issn = {1460-2105},
abstract = {BACKGROUND: Recent increases in the diagnosis of certain cancers among younger individuals are generating intense concern. Many studies attribute the increase in so-called "young-onset" cancer to an etiologic cause but questions have also arisen about the role of earlier diagnosis.

METHODS: We simulate incidence trends from a natural history model that includes healthy, preclinical, and clinical disease states, where transitions from a healthy to a preclinical state represent disease onset and transitions from the preclinical to the clinical state represent diagnosis. We superimpose birth cohort effects on the rate of disease onset and period effects on the rate of disease diagnosis to identify those that match patterns of relative incidence by age group and five-year calendar interval from 2000-2019 for six "young-onset" cancers (colon, rectum, female breast, gastric, pancreas, kidney).

RESULTS: Two types of effects are broadly consistent with the observed increasing incidence trends in younger individuals: (1) A birth-cohort effect on disease onset that begins around 1970 and becomes more pronounced in later birth years, or (2) A period effect consistent with progressive reduction over time in the duration of preclinical disease. An earlier, protective birth cohort effect is consistent with recent declining trends in incidence in older individuals for colon, rectal, and gastric cancers.

DISCUSSION: A disease model provides clues about the possible drivers of cancer incidence trends, suggests constraints on the patterns of exposures that might be implicated etiologically, and indicates that the role of diagnostic changes warrants consideration alongside potential etiologic explanations.},
}

@article {pmid40038837,
year = {2025},
author = {Yousefiasl, M and Soltanattar, A and Ezzatollahi Tanha, A and Azami, P and Alaei, M and Alamdari, AA and Esmailsorkh, F and Habibzadeh, A and Khanmohammadi, S},
title = {Association of triglyceride-glucose index with bone mineral density and fracture: a systematic review.},
journal = {Diabetology & metabolic syndrome},
volume = {17},
number = {1},
pages = {77},
pmid = {40038837},
issn = {1758-5996},
abstract = {BACKGROUND AND AIM: Studies have found inconsistent results regarding triglyceride-glucose (TyG) index and bone health. This systematic review aims to synthesize the existing evidence on the association between the (TyG) index, bone mineral density (BMD), and bone fractures.

METHOD: A comprehensive search of PubMed, Scopus, Web of Science, and Embase databases was performed for studies published up to December 26, 2024. Inclusion criteria encompassed human studies examining the TyG index in relation to BMD or fractures. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Data synthesis included both qualitative and descriptive statistical analyses.

RESULTS: From 201 studies identified, 12 met the inclusion criteria comprising 817,242 participants. Most studies reported a significant association between TyG index and bone fractures. The studies reported inconsistent findings regarding the association between the TyG index and BMD. While some studies found no correlation between the TyG index and BMD in individuals aged ≥ 50 years, studies on the general population aged ≥ 18 years demonstrated a significant correlation between the TyG index and BMD. Variations in the age of study populations, the presence of diabetes, BMI, and adjustment factors likely contributed to these discrepancies. Further research is needed to clarify the role of the TyG index in bone health and its potential utility as a surrogate marker.

CONCLUSION: The TyG index is associated with bone fractures and can serve as a surrogate marker for osteoporosis in the general populations rather than exclusively for the elderly.},
}

@article {pmid40038122,
year = {2025},
author = {Javid, SH and Kilgore, MR and Austin, EJ and Parker, EU and Alvarez, R and Flanagan, MR and Brewer, EG and Gibbons, C and Holt, SK and Lee, JM and Donlan, AW and DeStefano, LM and Gore, JL},
title = {The development and comparative effectiveness of a patient-centered pathology report for breast cancer care: a randomized clinical trial.},
journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer},
volume = {33},
number = {3},
pages = {248},
pmid = {40038122},
issn = {1433-7339},
mesh = {Humans ; *Breast Neoplasms/pathology/therapy/psychology ; Female ; Middle Aged ; *Patient-Centered Care ; Adult ; *Self Efficacy ; Aged ; Health Knowledge, Attitudes, Practice ; Decision Making ; Surveys and Questionnaires ; Comparative Effectiveness Research ; },
abstract = {PURPOSE: Pathology reports contain complex medical terminology that may be confusing or overwhelming for patients newly diagnosed with breast cancer. We evaluated the effectiveness of patient-centered pathology reports (PCPRs), which translate pathology results into patient-friendly language.

METHODS: Sixty-six participants newly diagnosed with breast cancer were randomized to receive either a PCPR and standard pathology report (intervention arm) or a standard pathology report alone (control arm). Patients were surveyed at initial pathology disclosure and 1 month later to assess breast cancer knowledge and ratings of decisional confidence, conflict, and self-efficacy for treatment decision-making. Knowledge was assessed for four pathology domains independently.

RESULTS: Accuracy of breast cancer knowledge across all domains trended higher for the intervention group compared with the control group (66% vs. 50%, p = 0.11); cancer type and surgical margin status knowledge domains exceeded 75% accuracy for the intervention group. No significant differences between groups were observed for patient-reported ratings of communication, decisional conflict, and decision self-efficacy.

CONCLUSIONS: PCPRs in lay language appeared to improve patients' knowledge of their breast cancer diagnosis, were acceptable to patients and providers, and have the potential to be broadly applied in an effort to improve patient knowledge and improve the patient experience surrounding a breast cancer diagnosis.},
}

Humans
*Breast Neoplasms/pathology/therapy/psychology
Female
Middle Aged
*Patient-Centered Care
Adult
*Self Efficacy
Aged
Health Knowledge, Attitudes, Practice
Decision Making
Surveys and Questionnaires
Comparative Effectiveness Research

@article {pmid40037704,
year = {2025},
author = {Wang, MF and Li, MY and Yang, YC and Chuang, YC and Tsai, CY and Binder, MN and Ma, L and Lin, SW and Li, HW and Smith, GR and Chi, P},
title = {Mug20-Rec25-Rec27 binds DNA and enhances meiotic DNA break formation via phase-separated condensates.},
journal = {Nucleic acids research},
volume = {53},
number = {5},
pages = {},
pmid = {40037704},
issn = {1362-4962},
support = {MOST 111-2311-B-002-006-MY3//Ministry of Science and Technology/ ; //National Science and Technology Council/ ; NIH R35 GM118120/NH/NIH HHS/United States ; R35 GM118120/GM/NIGMS NIH HHS/United States ; //Cellular Imaging Shared Resource/ ; },
mesh = {*Meiosis/genetics ; *DNA Breaks, Double-Stranded ; *Schizosaccharomyces/genetics/metabolism ; *Schizosaccharomyces pombe Proteins/metabolism/chemistry ; *DNA, Fungal/metabolism/genetics/chemistry ; DNA-Binding Proteins/metabolism/chemistry ; Protein Binding ; Nuclear Proteins/metabolism/chemistry ; Homologous Recombination ; },
abstract = {During meiosis, programmed DNA double-strand breaks (DSBs) are formed at hotspots to initiate homologous recombination, which is vital for reassorting genetic material. In fission yeast, the linear element (LinE) proteins Mug20, Rec25, and Rec27 interdependently bind chromosomal hotspots with high specificity and are necessary for high-level DSB formation. However, their mechanistic role in regulating the meiotic DSB machinery remains unknown. Here, using purified Mug20-Rec25-Rec27 (MRR) complex and functional intracellular analyses, we reveal that the MRR-DNA nucleoprotein complex assembles phase-separated condensates that compact the DNA. Notably, MRR complex formation is a prerequisite for DNA binding and condensate assembly, with Rec27 playing a pivotal role in directly binding DNA. Consistent with this finding, failure to form MRR-DNA condensates results in defective intracellular meiotic DSB formation and recombination. Our results provide mechanistic insights into how LinEs enhance meiotic DSB formation and provide a paradigm for studies in other species.},
}

*Meiosis/genetics
*DNA Breaks, Double-Stranded
*Schizosaccharomyces/genetics/metabolism
*Schizosaccharomyces pombe Proteins/metabolism/chemistry
*DNA, Fungal/metabolism/genetics/chemistry
DNA-Binding Proteins/metabolism/chemistry
Protein Binding
Nuclear Proteins/metabolism/chemistry
Homologous Recombination

@article {pmid40036963,
year = {2025},
author = {Coronado, G and Rutter, C},
title = {Response to McElroy and Everett.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf042},
pmid = {40036963},
issn = {1460-2105},
}

@article {pmid40036318,
year = {2025},
author = {Alagoz, O and Caswell-Jin, JL and de Koning, HJ and Huang, H and Huang, X and Lee, SJ and Li, Y and Plevritis, SK and Sarkar, S and Schechter, CB and Stout, NK and Trentham-Dietz, A and van Ravesteyn, N and Lowry, KP and , },
title = {Mathematical Modeling to Address Questions in Breast Cancer Screening: An Overview of the Breast Cancer Models of the Cancer Intervention and Surveillance Modeling Network.},
journal = {Journal of breast imaging},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbi/wbaf003},
pmid = {40036318},
issn = {2631-6129},
support = {U01CA253911, P30CA014520/NH/NIH HHS/United States ; 21-078-01-CPSH//American Cancer Society/ ; },
abstract = {The National Cancer Institute-funded Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer mathematical models have been increasingly utilized by policymakers to address breast cancer screening policy decisions and influence clinical practice. These well-established and validated models have a successful track record of use in collaborations spanning over 2 decades. While mathematical modeling is a valuable approach to translate short-term screening performance data into long-term breast cancer outcomes, it is inherently complex and requires numerous inputs to approximate the impacts of breast cancer screening. This review article describes the 6 independently developed CISNET breast cancer models, with a particular focus on how they represent breast cancer screening and estimate the contribution of screening to breast cancer mortality reduction and improvements in life expectancy. We also describe differences in structures and assumptions across the models and how variation in model results can highlight areas of uncertainty. Finally, we offer insight into how the results generated by the models can be used to aid decision-making regarding breast cancer screening policy.},
}

@article {pmid40036070,
year = {2025},
author = {Zhao, LP and Papadopoulos, GK and Skyler, JS and Kwok, WW and Bondinas, GP and Moustakas, AK and Wang, R and Pyo, CW and Nelson, WC and Geraghty, DE and Lernmark, Å},
title = {Two DRB3 residues predictively associate with the progression to type 1 diabetes among DR3 carriers.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.184348},
pmid = {40036070},
issn = {2379-3708},
abstract = {HLA-DR genes are associated with the progression from stage 1 and stage 2 to onset of stage 3 type 1 diabetes (T1D), after accounting HLA-DQ genes with which they are in high linkage-disequilibrium. Based on an integrated cohort of participants from two completed clinical trials, this investigation finds that sharing a haplotype with the DRB1*03:01 (DR3) allele, DRB3*01:01:02 and *02:02:01 have respectively negative and positive associations with the progression. Further, we uncovered two residues (β11, β26, participating in pockets 6 and 4, respectively) on the DRB3 molecule responsible for the progression among DR3 carriers, i.e. motif RY and LF respectively delay and promote the progression (Hazard Ratio = 0.73 and 2.38, p-value = 0.039 and 0.017, respectively). Two anchoring pockets 6 and 4 probably bind differential autoantigenic epitopes. We further investigated the progression association with the motifs RY and LF among carriers of DR3 and found that carriers of the motif LF have significantly faster progression than carriers of RY (HR = 1.48 and p = 0.019 in unadjusted analysis; HR = 1.39, p = 0.047 in adjusted analysis). New insights provide an impetus to examine the possible role of specific DRB3-binding peptides in the progression to T1D.},
}

@article {pmid40035770,
year = {2025},
author = {Haberman, M and Kamyshinsky, R and Reznik, N and Yeshaya, N and Khmelnitsky, L and Plender, EG and Eichler, EE and Fass, D},
title = {MUC5AC filaments illuminate the structural diversification of respiratory and intestinal mucins.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {10},
pages = {e2419717122},
doi = {10.1073/pnas.2419717122},
pmid = {40035770},
issn = {1091-6490},
support = {2660/20//Israel Science Foundation (ISF)/ ; 101097867//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; },
mesh = {*Mucin 5AC/metabolism/genetics/chemistry ; Humans ; Mucin-2/metabolism/chemistry/genetics ; Mucin-5B/metabolism/genetics/chemistry ; Intestinal Mucosa/metabolism ; Models, Molecular ; Mucins/metabolism/chemistry ; Amino Acid Sequence ; von Willebrand Factor/metabolism/chemistry/genetics ; Respiratory Mucosa/metabolism ; },
abstract = {Secreted mucins are multimegadalton glycoprotein polymers that share the function of protecting mucosal tissues but diversified for activities in different organs of the body. Structural studies of secreted mucins are complicated by the enormous sizes, flexibility, and complex supramolecular assembly modes of these glycoproteins. The two major respiratory mucins are MUC5AC and MUC5B. Here, we present structures of a large amino-terminal segment of MUC5AC in the form of helical filaments. These filaments differ from filamentous and tubular structures observed previously for the intestinal mucin MUC2 and the partial mucin homolog VWF. Nevertheless, the MUC5AC helical filaments support the proposed mechanism, based on MUC2 and VWF, for how noncovalent interactions between mucin monomers guide disulfide crosslinking to form polymers. The high-resolution MUC5AC structures show how local and limited changes in amino acid sequence can profoundly affect higher-order assembly while preserving the overall folds and polymerization activity of mucin glycoproteins. Differences in supramolecular assembly are likely to be functionally significant considering the divergence of mechanical properties and physiological requirements between respiratory and intestinal mucins. Determining the high-resolution structures of respiratory mucins provides a foundation for understanding the mechanisms by which they clean and protect the lungs. Moreover, the MUC5AC structure enables visualization of the sites of human amino acid sequence variation and disease-associated mutations.},
}

*Mucin 5AC/metabolism/genetics/chemistry
Humans
Mucin-2/metabolism/chemistry/genetics
Mucin-5B/metabolism/genetics/chemistry
Intestinal Mucosa/metabolism
Models, Molecular
Mucins/metabolism/chemistry
Amino Acid Sequence
von Willebrand Factor/metabolism/chemistry/genetics
Respiratory Mucosa/metabolism

@article {pmid40027747,
year = {2025},
author = {Hart, ML and Davidsen, K and Danquah, S and Zheng, E and Sokolov, D and Sullivan, LB},
title = {Succinate Dehydrogenase loss causes cascading metabolic effects that impair pyrimidine biosynthesis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40027747},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R35 GM147118/GM/NIGMS NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; U54 CA132381/CA/NCI NIH HHS/United States ; },
abstract = {Impaired availability of the amino acid aspartate can be a metabolic constraint of cell proliferation in diverse biological contexts. However, the kinetics of aspartate depletion, and its ramifications on downstream metabolism and cell proliferation, remain poorly understood. Here, we deploy the aspartate biosensor jAspSnFR3 with live cell imaging to resolve temporal relationships between aspartate and cell proliferation from genetic, pharmacological, and nutritional manipulations. In cells with impaired aspartate acquisition from mitochondrial complex I inhibition or constrained uptake in aspartate auxotrophs, we find that the proliferation defects lag changes in aspartate levels and only manifest once aspartate levels fall below a critical threshold, supporting the functional link between aspartate levels and cell proliferation in these contexts. In another context of aspartate synthesis inhibition, impairing succinate dehydrogenase (SDH), we find a more complex metabolic interaction, with initial aspartate depletion followed by a rebound of aspartate levels over time. We find that this aspartate rebound effect results from SDH inhibition disproportionately impairing pyrimidine synthesis by inhibiting aspartate transcarbamoylase (ATCase) through the dual effect of diminishing aspartate substrate availability while accumulating succinate, which functions as a competitive inhibitor of aspartate utilization. Finally, we uncover that the nucleotide imbalance from SDH inhibition causes replication stress and introduces a vulnerability to ATR kinase inhibition. Altogether, these findings identify a mechanistic role for succinate in modulating nucleotide synthesis and demonstrate how cascading metabolic interactions can unfold to impact cell function.},
}

@article {pmid39989965,
year = {2025},
author = {Nicholas, JC and Katz, DH and Tahir, UA and Debban, CL and Aguet, F and Blackwell, T and Bowler, RP and Broadaway, KA and Chen, J and Clish, CB and Coresh, J and Cornell, E and Cruz, DE and Deo, R and Doyle, MF and Durda, P and Ekunwe, L and Floyd, JS and Gill, D and Guo, X and Hoogeveen, RC and Johnson, C and Lange, LA and Li, Y and Manning, A and Meigs, JB and Mi, MY and Mychaleckyj, JC and Olson, NC and Pratte, KA and Psaty, BM and Reiner, AP and Ruan, P and Sevilla-Gonzalez, M and Shah, AM and Sun, Q and Tracy, RP and Wen, J and Wood, AC and Wilson, JG and Young, KL and Yu, B and Rooney, MR and Manichaikul, A and Dubin, R and Mohlke, KL and Rich, SS and Rotter, JI and Ganz, P and Gerszten, RE and Taylor, KD and Raffield, LM},
title = {Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {39989965},
issn = {2693-5015},
support = {U54 HG003067/HG/NHGRI NIH HHS/United States ; UL1 TR001079/TR/NCATS NIH HHS/United States ; T32 ES007018/ES/NIEHS NIH HHS/United States ; R01 HL071250/HL/NHLBI NIH HHS/United States ; N01HC95159/HL/NHLBI NIH HHS/United States ; N01HC95167/HL/NHLBI NIH HHS/United States ; R01 HL071205/HL/NHLBI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R01 HL071258/HL/NHLBI NIH HHS/United States ; OT3 HL142478/HL/NHLBI NIH HHS/United States ; UL1 RR033176/RR/NCRR NIH HHS/United States ; 75N92020D00002/HL/NHLBI NIH HHS/United States ; HHSN268201500003C/HL/NHLBI NIH HHS/United States ; T32 GM135128/GM/NIGMS NIH HHS/United States ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; N01HC95160/HL/NHLBI NIH HHS/United States ; R01 HL071251/HL/NHLBI NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; R01 HL071259/HL/NHLBI NIH HHS/United States ; N01HC95163/HL/NHLBI NIH HHS/United States ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; N01HC95169/HL/NHLBI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; R01 DK072193/DK/NIDDK NIH HHS/United States ; N01HC95164/HL/NHLBI NIH HHS/United States ; OT3 HL142481/HL/NHLBI NIH HHS/United States ; N01HC95162/HL/NHLBI NIH HHS/United States ; OT3 HL147154/HL/NHLBI NIH HHS/United States ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; N01HC95168/HL/NHLBI NIH HHS/United States ; R01 HL146860/HL/NHLBI NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; R01 HL071051/HL/NHLBI NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; U01 AG082042/AG/NIA NIH HHS/United States ; R01 HL159081/HL/NHLBI NIH HHS/United States ; N01HC95165/HL/NHLBI NIH HHS/United States ; N01HC95161/HL/NHLBI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; OT3 HL142480/HL/NHLBI NIH HHS/United States ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; HHSN268201500014C/HL/NHLBI NIH HHS/United States ; R01 HL133870/HL/NHLBI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; OT3 HL142479/HL/NHLBI NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; R01 HL151855/HL/NHLBI NIH HHS/United States ; UM1 DK078616/DK/NIDDK NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; N01HC95166/HL/NHLBI NIH HHS/United States ; },
abstract = {Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants (pQTL) and phenotypes. Here, we examined 2,157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1,930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2,157 proteins followed a bimodal distribution (median r=0.30). Protein measures from each platform were associated with genetic variants (pQTLs), and one-third of the pQTL signals were driven by protein-altering variants (PAVs). We highlight 80 proteins that correlate differently across ancestry groups likely due to differing PAV frequencies by ancestry. Furthermore, adjustment for PAVs with opposite directions of effect by platform improved inter-platform protein measure correlation and resulted in more concordant genetic and phenotypic associations. Hence, PAVs need to be accounted for across ancestries to facilitate platform-concordant and accurate protein measurement.},
}

@article {pmid39989958,
year = {2025},
author = {von Delft, F and Ni, X and Richardson, R and Godoy, A and Ferla, M and Kikawa, C and Scheen, J and Hannon, W and Capkin, E and Lahav, N and Balcomb, B and Marples, P and Fairhead, M and Wang, S and Williams, E and Tomlinson, C and Aschenbrenner, J and Lithgo, R and Winokan, M and Giroud, C and Chandran, A and Walsh, M and Thompson, W and Bloom, J and Barr, H and Kirkegaard, K and Koekemoer, L and Fearon, D and Evans, M},
title = {Crystallographic fragment screening and deep mutational scanning of Zika virus NS2B-NS3 protease enable development of resistance-resilient inhibitors.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {39989958},
issn = {2693-5015},
support = {U19 AI171399/AI/NIAID NIH HHS/United States ; },
abstract = {The Zika viral protease NS2B-NS3 is essential for the cleavage of viral polyprotein precursor into individual structural and non-structural (NS) proteins and is therefore an attractive drug target. Generation of a robust crystal system of co-expressed NS2B-NS3 protease has enabled us to perform a crystallographic fragment screening campaign with 1076 fragments. 47 fragments with diverse scaffolds were identified to bind in the active site of the protease, with another 6 fragments observed in a potential allosteric site. To identify binding sites that are intolerant to mutation and thus suppress the outgrowth of viruses resistant to inhibitors developed from bound fragments, we performed deep mutational scanning of NS2B-NS3 protease. Merging fragment hits yields an extensive set of 'mergers', defined as synthetically accessible compounds that recapitulate constellations of observed fragment-protein interactions. In addition, the highly sociable fragment hits enable rapid exploration of chemical space via algorithmic calculation and thus yield diverse possible starting points that maximally explore the binding opportunities to NS2B-NS3 protease, facilitating its resistance-resilient antiviral development.},
}

@article {pmid40034245,
year = {2025},
author = {Apolo, A and Baumann, BC and Al-Ahmadie, H and Ballas, L and Bangs, R and Brothers, K and Greenberg, SC and Delacroix, S and Dignam, JJ and Efstathiou, JA and Feldman, AS and Foster, JC and Hahn, NM and Hall, E and Hansel, DE and Hoffman-Censits, J and Kamat, AM and Kamran, SC and Khani, F and Lerner, SP and Lipman, R and Mann, B and McConkey, D and McKiernan, J and Rose, TL and Smith, AB and Tangen, C and Amiri, AT and Weinstock, C and West, PJ and Milowsky, MI and Black, PC},
title = {Summary from the NCI clinical trials planning meeting on next generation of clinical trials in non-muscle invasive bladder cancer.},
journal = {Bladder cancer (Amsterdam, Netherlands)},
volume = {11},
number = {1},
pages = {23523735251319185},
pmid = {40034245},
issn = {2352-3735},
abstract = {The National Cancer Institute organized a virtual Clinical Trials Planning Meeting (CTPM) on 'Defining the next generation of clinical trials with combination therapies in non-muscle invasive bladder cancer (NMIBC)' led by the Bladder Cancer Task Force of the NCI Genitourinary Cancers Steering Committee. The purpose of this meeting was to accelerate advances in clinical trials for patients with high-risk NMIBC. The meeting delivered a multidisciplinary expert consensus on optimal strategies for next-generation clinical trial designs in NMIBC with prioritization of combination therapies. Two clinical trial concepts were developed for potential implementation within the National Clinical Trials Network.},
}

@article {pmid40032074,
year = {2025},
author = {Kinoshita, H and Walti, CS and Webber, K and Pezzella, G and Jensen-Wachspress, M and Lang, H and Shuey, K and Boonyaratanakornkit, J and Pergam, SA and Chu, HY and Bollard, CM and Keller, MD and Hill, JA},
title = {T cell immune response to influenza vaccination when administered prior to and following autologous CAR-T cell therapy.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.02.019},
pmid = {40032074},
issn = {2666-6367},
abstract = {BACKGROUND: Chimeric antigen receptor-modified T (CAR-T) cell therapies are gaining wider use in relapsed and refractory malignancies. However, data on vaccination in this population is lacking. We evaluated T cell responses in an established cohort of CAR-T recipients and healthy controls before and after 2019-2020 influenza vaccination.

METHODS: Peripheral blood mononuclear cells were isolated from healthy controls and patients who received the 2019-2020 influenza vaccine pre- or post-CD19, CD20 or B cell maturation antigen (BCMA) CAR-T. T cells were expanded in vitro for 10 days with peptide libraries for hemagglutinin (HA) and nucleoprotein (NP) from the 2019-2020 vaccine influenza A strains and analyzed by flow cytometry following IFNγ/TNFα intracellular staining. Antibody response was evaluated by a hemagglutination-inhibition (HAI) assay.

RESULTS: Twenty-nine participants, including eight immunocompetent adults, seven pre-CAR-T and 14 post-CAR-T patients, were evaluated. IFNγ[+]/TNFα[+] T cell responses after influenza vaccination in healthy controls varied with an increased response to HA-Kansas after vaccination in 7/8 individuals. In the pre-CAR-T cohort, there was a rise in CD4+ T cell response to HA-Brisbane in 6/7 patients after vaccination that remained detectable in 3/4 evaluable patients 90 days post-CAR-T. Five of six patients who lacked an antibody response nonetheless demonstrated a T cell response to HA-Brisbane. There was no association between time since CAR-T administration, baseline IgG or absolute lymphocyte count and change in CD4+ T cell IFNγ[+]/TNFα[+] response pre- to post-vaccine for the post-CART cohort.

CONCLUSION: These data demonstrate that cell-mediated immunity to the influenza vaccine can be elicited in patients vaccinated pre-CAR-T and sustained post-CAR-T, filling an important gap from lack of humoral responses.},
}

@article {pmid40030014,
year = {2025},
author = {Torgbor, C and Sohn, H and Dizon, BLP and Mutic, EC and George, R and Kwak, K and Akkaya, M and Ulker, EB and Traver, M and Brzostowski, J and Galloway, DA and Thompson, CD and Çuburu, N and Schiller, JT and Pierce, SK},
title = {In the activation of HPV-specific human B cells HPV-VLP vaccines mimic membrane-associated antigens.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {10},
pages = {e2414514122},
doi = {10.1073/pnas.2414514122},
pmid = {40030014},
issn = {1091-6490},
mesh = {Humans ; *Papillomavirus Vaccines/immunology ; *B-Lymphocytes/immunology/metabolism ; *Ion Channels/metabolism/immunology ; Cell Membrane/metabolism ; Papillomavirus Infections/immunology/prevention & control/virology ; Antigen Presentation/immunology ; Papillomaviridae/immunology ; Lymphocyte Activation/immunology ; Antigens, Viral/immunology ; },
abstract = {B cell responses to membrane-presented antigens appear to be strongly favored over soluble antigens in vivo suggesting that vaccines that mimic membrane-presented antigens may be highly efficacious. We recently demonstrated that human B cell responses to membrane-associated but not to soluble antigens in vitro depended on the expression and activity of the plasma membrane mechanosensitive ion channel, Piezo1. Here, we provide evidence that the efficacy of the current human papillomavirus virus-like particle (HPV VLP) vaccines may be due in part to their inherent ability to mimic Piezo1-dependent membrane presentation of antigens to B cells. We compared HPV-specific human B cell responses to HPV VLPs versus soluble HPV pentameric capsomeres and showed that although both induced calcium responses, only HPV VLP-induced responses were blocked by Piezo1 inhibitors. The kinetics of internalization of HPV-VLP and capsomeres into HPV-specific B cells were similar and neither required Piezo1 function as shown by small interfering RNA (siRNA)-mediated knockdown of Piezo. However, trafficking of HPV-VLPs into intracellular major histocompatibility complex (MHC) class II, lysosomal associated membrane protein 1 (LAMP1)[+] antigen-processing compartments was Piezo1-dependent, whereas trafficking of capsomeres was not. In addition, a time course of intracellular trafficking suggested that colocalization of HPV-VLP with MHC classII was more stable over time as compared to capsomeres. Taken together these findings suggest that the ability of HPV-VLP vaccines to mimic Piezo1-dependent membrane antigen presentation may be exploited in the design of highly effective human vaccines.},
}

Humans
*Papillomavirus Vaccines/immunology
*B-Lymphocytes/immunology/metabolism
*Ion Channels/metabolism/immunology
Cell Membrane/metabolism
Papillomavirus Infections/immunology/prevention & control/virology
Antigen Presentation/immunology
Papillomaviridae/immunology
Lymphocyte Activation/immunology
Antigens, Viral/immunology

@article {pmid40029972,
year = {2025},
author = {Sommers, J and Dizon, DS and Lewis, MA and Stone, E and Andreoli, R and Henderson, V},
title = {Assessing Health Information Seeking Behaviors Among Targeted Social Media Users Using an Infotainment Video About a Cancer Clinical Trial: Population-Based Descriptive Study.},
journal = {JMIR cancer},
volume = {11},
number = {},
pages = {e56098},
doi = {10.2196/56098},
pmid = {40029972},
issn = {2369-1999},
mesh = {Humans ; *Social Media ; *Information Seeking Behavior ; Female ; *Clinical Trials as Topic ; Breast Neoplasms/psychology ; Adult ; Middle Aged ; Video Recording ; Neoplasms ; },
abstract = {BACKGROUND: The lack of information and awareness about clinical trials, as well as misconceptions about them, are major barriers to cancer clinical trial participation. Digital and social media are dominant sources of health information and offer optimal opportunities to improve public medical awareness and education by providing accurate and trustworthy health information from reliable sources. Infotainment, material intended to both entertain and inform, is an effective strategy for engaging and educating audiences that can be easily disseminated using social media and may be a novel way to improve awareness of and recruitment in clinical trials.

OBJECTIVE: The purpose of this study was to evaluate whether an infotainment video promoting a clinical trial, disseminated using social media, could drive health information seeking behaviors.

METHODS: As part of a video series, we created an infotainment video focused on the promotion of a specific cancer clinical trial. We instituted a dissemination and marketing process on Facebook to measure video engagement and health information seeking behaviors among targeted audiences who expressed interest in breast cancer research and organizations. To evaluate video engagement, we measured reach, retention, outbound clicks, and outbound click-through rate. Frequencies and descriptive statistics were used to summarize each measure.

RESULTS: The video substantially increased health information seeking behavior by increasing viewership from 1 visitor one month prior to launch to 414 outbound clicks from the video to the clinical trial web page during the 21-day social media campaign period.

CONCLUSIONS: Our study shows that digital and social media tools can be tailored for specific target audiences, are scalable, and can be disseminated at low cost, making it an accessible educational, recruitment, and retention strategy focused on improving the awareness of clinical trials.},
}

Humans
*Social Media
*Information Seeking Behavior
Female
*Clinical Trials as Topic
Breast Neoplasms/psychology
Adult
Middle Aged
Video Recording
Neoplasms

@article {pmid40029708,
year = {2025},
author = {Johnson, ACM and Zager, RA},
title = {Veverimer, a Non-Absorbed Gastrointestinal Tract HCl Binder, Decreases Renal Ammoniagenesis and Mitigates Nephrotoxic Serum Nephritis.},
journal = {Kidney360},
volume = {},
number = {},
pages = {},
doi = {10.34067/KID.0000000743},
pmid = {40029708},
issn = {2641-7650},
abstract = {BACKGROUND: Increased tubular ammoniagenesis is an adaptive response to progressive kidney disease, facilitating net acid excretion. However, excess ammonia production can also exacerbate kidney disease progression, in part, by activating the alternative complement cascade. Oral Na bicarbonate therapy can decrease the systemic H+ burden, limiting ammonia production. However, poor compliance limits bicarbonate's efficacy. Veverimer is an oral, Na+ free, non-absorbed polymer that binds H+ within the gastrointestinal (GI) tract. This stimulates GI carbonic anhydrase-mediated bicarbonate production and systemic bicarbonate uptake. Hence, the goals of this study were to: test whether GI HCl binding decreases renal tubular ammoniagenesis; assess whether decreased complement activation results; and determine whether these changes can mitigate nephrotoxic serum (NTS) nephritis in which complement activation may play a role.

METHODS: A normal diet ± veverimer (4.5% w/w) was fed to normal mice for ∼1 week. Veverimer's impact on plasma bicarbonate, blood/urinary pH, urinary ammonia excretion, and tubular H+ transporter, NHE3, density were assessed. Additional mice were fed the normal or veverimer diet following NTS injection. Urine protein, albumin, ammonia, C5b-9 excretion, and plasma C3a levels were measured at 1 and/or 2 weeks post NTS injection. Renal histologic changes (H/E stain; C5b-9, CD45 immunohistochemistry), and selected injury mediators/biomarkers (NGAL, IL-6, MCP-1, TGF beta 1, endothelin-1 mRNAs) were also assessed.

RESULTS: Veverimer increased plasma bicarbonate/urinary pH, reduced urinary ammonia, and decreased NHE3 in normal mice. Veverimer also reduced NTS-induced proteinuria/albuminura, urinary ammonia, and C5b-9 excretion (by ∼60%, ∼75%, ∼50%, respectively). Significant reductions in NTS-induced glomerular/ tubulointerstitial injury, inflammatory/profibrotic gene expression, renal C5b-9 deposition, and suppressed plasma C3a levels were observed. Oral bicarbonate also conferred protection, implicating bicarbonate in veverimer's beneficial effect.

CONCLUSIONS: Veverimer-mediated bicarbonate generation can suppress renal ammoniagenesis and complement activation. These findings suggest a potential benefit of veverimer/ bicarbonate therapy in selected complement-mediated renal diseases.},
}

@article {pmid40029702,
year = {2025},
author = {Lee, CI and Elmore, JG},
title = {FDA Breast Density Reporting Requirements and Evidence-Based Medical Practice.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2025.0001},
pmid = {40029702},
issn = {1538-3598},
}

@article {pmid40028765,
year = {2025},
author = {Henikoff, S and Levens, DL},
title = {The plusses and minuses of DNA torsion.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {40028765},
issn = {2050-084X},
mesh = {*RNA Polymerase II/metabolism/genetics ; *DNA/genetics ; Humans ; Nucleic Acid Conformation ; },
abstract = {A new method for mapping torsion provides insights into the ways that the genome responds to the torsion generated by RNA polymerase II.},
}

*RNA Polymerase II/metabolism/genetics
*DNA/genetics
Humans
Nucleic Acid Conformation

@article {pmid39990346,
year = {2025},
author = {Prodanov, T and Plender, EG and Seebohm, G and Meuth, SG and Eichler, EE and Marschall, T},
title = {Locityper: targeted genotyping of complex polymorphic genes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39990346},
issn = {2692-8205},
support = {R01 HG002385/HG/NHGRI NIH HHS/United States ; },
abstract = {The human genome contains numerous structurally-variable polymorphic loci, including several hundred disease-associated genes, almost inaccessible for accurate variant calling. Here we present Locityper, a tool capable of genotyping such challenging genes using short and long-read whole genome sequencing. For each target, Locityper recruits and aligns reads to locus haplotypes, for instance extracted from a pangenome, and finds the likeliest haplotype pair by optimizing read alignment, insert size and read depth profiles. Locityper accurately genotypes up to 194 of 256 challenging medically relevant loci (95% haplotypes at QV33), an 8.8-fold gain compared to 22 genes achieved with standard variant calling pipelines. Furthermore, Locityper provides access to hyperpolymorphic HLA genes and other gene families, including KIR, MUC and FCGR. With its low running time of 1h10m per sample at 8 threads, Locityper is scalable to biobank-sized cohorts, enabling association studies for previously intractable disease-relevant genes.},
}

@article {pmid40028346,
year = {2025},
author = {Weinfurtner, K and Tischfield, D and McClung, G and Crainic, J and Gordan, J and Jiao, J and Furth, EE and Li, W and Supan, ET and Nadolski, GJ and Hunt, SJ and Kaplan, DE and Gade, TPF},
title = {Human GM-CSF/IL-3 enhance tumor immune infiltration in humanized HCC patient-derived xenografts.},
journal = {JHEP reports : innovation in hepatology},
volume = {7},
number = {3},
pages = {101264},
pmid = {40028346},
issn = {2589-5559},
abstract = {BACKGROUND & AIMS: Response to immunotherapy in hepatocellular carcinoma (HCC) is suboptimal with no biomarkers to guide patient selection. "Humanized" mice represent promising models to address this deficiency but are limited by variable chimerism and underdeveloped myeloid compartments. We hypothesized that expression of human GM-CSF and IL-3 increases tumor immune cell infiltration, especially myeloid-derived cells, in humanized HCC patient-derived xenografts.

MATERIAL AND METHODS: NOG (NOD/Shi-scid/IL-2Rγ[null]) and NOG-EXL (huGM-CSF/huIL-3 NOG) mice conditioned with busulfan underwent i.v. injection of human CD34+ cells. HCC patient-derived xenograft tumors were then implanted subcutaneously or orthotopically. Following serial blood sampling, mice were euthanized at defined tumor sizes. Tumor, blood, liver, and spleen were analyzed by flow cytometry and immunohistochemistry.

RESULTS: Humanized NOG-EXL mice demonstrated earlier and higher levels of human chimerism compared to humanized NOG mice (82.1% vs. 43.8%, p <0.0001) with a greater proportion of human monocytes (3.2% vs. 1.1%, p = 0.001) and neutrophils (0.8% vs. 0.3%, p = 0.02) in circulation. HCC tumors in humanized NOG-EXL mice exhibited greater human immune cell infiltration (57.6% vs. 30.2%, p = 0.04) with higher proportions of regulatory T cells (14.6% vs. 6.8%, p = 0.04), CD4+ PD-1 expression (84.7% vs. 32.0%, p <0.01), macrophages (1.2% vs. 0.6%, p = 0.02), and neutrophils (0.5% vs. 0.1%, p <0.0001). No differences were observed in tumor engraftment or growth latency in subcutaneous tumors, but orthotopic tumors required implantation at 2 rather than 4 weeks post-humanization for successful engraftment. Finally, utilizing adult bone marrow instead of fetal livers enabled partial HLA-matching to HCC tumors but required more CD34+ cells.

CONCLUSIONS: Human GM-CSF and IL-3 expression in humanized mice resulted in features more closely approximating the immune microenvironment of human disease, providing a promising model for investigating critical questions in immunotherapy for HCC.

IMPACT AND IMPLICATIONS: This study introduces a unique mouse model at a critical point in the evolution of treatment paradigms for patients with hepatocellular carcinoma (HCC). Immunotherapies have become the first-line treatment for advanced HCC; however, response rates remain low with no clear predictors of response to guide patient selection. In this context, animal models that recapitulate human disease are greatly needed. Leveraging xenograft tumors derived from patients with unresectable HCCs and a commercially available immunodeficient mouse strain that expresses human GM-CSF and IL-3, we demonstrate a novel but accessible approach for modeling the HCC tumor microenvironment.},
}

@article {pmid40027237,
year = {2025},
author = {Le, C and Tatunay, K and Liu, W and Lu, H and Rodis, NA and Nam, T and Laurino, MY and Dubard-Gault, ME},
title = {Lessons learned in migrating from one commercial genetics clinical decision-making tool to another: Assessment of data integrity and utilization.},
journal = {Genetics in medicine open},
volume = {3},
number = {},
pages = {101913},
pmid = {40027237},
issn = {2949-7744},
abstract = {PURPOSE: Rapid advancements in information technology have greatly influenced clinicians' engagement with patient data for health maintenance. The electronic health record often contains multiple ways to record risk factors and to identify patients at an elevated genetic risk for cancer. However, these variables exist in multiple forms and disparate locations in each commercial electronic health record solution resulting in significant variations in how family history or genetic data is codified. Furthermore, there is pressure to migrate from one commercial solution to another at times, prompting the need for a process ensuring data integrity during such a transition.

METHODS: Between July and December 2023, the genetics team migrated a family history database from one commercial software solution to another. After the data migration of 13,000 patient records, we reviewed 500 randomly selected charts in both support tools to measure the rate of concordance of information transferred.

RESULTS: A total of 461 patient charts were reviewed. Of these, 425 (92.2%) were noted to be concordant. Of the 36 charts that were discordant, 9 had incorrect genetic testing results entered, 19 had missing information, 5 charts contained data recorded on paper before 2017 (legacy data), and 3 had additional information transferred.

CONCLUSION: There was high data integrity after migration from one commercial software solution to another. Although these results can ease clinicians' concerns after such support tool transitions, our effort also highlights areas for improvement in how family and patient genetic data are recorded and utilized for clinical care and research within an institution.},
}

@article {pmid40026777,
year = {2025},
author = {Hartlage, W and Castillo, AY and Kassamali Escobar, Z and Bajenov, M and Martinez-Paz, N and Lynch, JB and Bryson-Cahn, C and Chan, JD},
title = {Stewarding the inappropriate diagnosis and treatment of urinary tract infection: leveraging the urinalysis to understand true antibiotic overuse.},
journal = {Antimicrobial stewardship & healthcare epidemiology : ASHE},
volume = {5},
number = {1},
pages = {e49},
pmid = {40026777},
issn = {2732-494X},
abstract = {We evaluated 249 asymptomatic patients receiving antibiotics for urinary infection: 222 had asymptomatic pyuria and/or nitrituria (ASPN) and 133 had asymptomatic bacteriuria (ASB, growth ≥10[5] colony forming units/ml). ASPN identified 40% more cases of unnecessary antibiotics compared to ASB and may be a more comprehensive measure of unnecessary antibiotic use.},
}

@article {pmid40025499,
year = {2025},
author = {Fang, H and Tronco, AR and Bonora, G and Nguyen, T and Thakur, J and Berletch, JB and Filippova, GN and Henikoff, S and Shendure, J and Noble, WS and Duan, Z and Disteche, CM and Deng, X},
title = {CTCF-mediated insulation and chromatin environment modulate Car5b escape from X inactivation.},
journal = {BMC biology},
volume = {23},
number = {1},
pages = {68},
pmid = {40025499},
issn = {1741-7007},
support = {U54DK107979/GF/NIH HHS/United States ; UM1HG011586/GF/NIH HHS/United States ; UM1 HG011586/HG/NHGRI NIH HHS/United States ; GM131745/GF/NIH HHS/United States ; GM1273727/GF/NIH HHS/United States ; },
mesh = {*CCCTC-Binding Factor/metabolism/genetics ; Animals ; *X Chromosome Inactivation/genetics ; Mice ; *Chromatin/metabolism ; Female ; Binding Sites ; Repressor Proteins/metabolism/genetics ; },
abstract = {BACKGROUND: Genes that escape X-chromosome inactivation (XCI) in female somatic cells vary in number and levels of escape among mammalian species and tissues, potentially contributing to species- and tissue-specific sex differences. CTCF, a master chromatin conformation regulator, is enriched at escape regions and may play an important role in regulating escape, but the molecular mechanisms remain elusive.

RESULTS: CTCF binding profiles and epigenetic features were systematically examined at escape genes (escapees) using mouse allelic systems with skewed XCI to distinguish the inactive X (Xi) and active X (Xa) chromosomes. We found that six constitutive and two facultative escapees are located inside 30-800 kb domains marked by convergent arrays of CTCF binding sites, consistent with the formation of chromatin loops. Facultative escapees show clear differences in CTCF binding depending on their XCI status in specific cell types/tissues. In addition, sets of strong and in some cases divergent CTCF binding sites located at the boundary between an escapee and its adjacent neighbors subject to XCI would also help insulate domains. Indeed, deletion but not inversion of a CTCF binding site at the boundary between the facultative escapee Car5b and its silent neighbor Siah1b results in a dramatic reduction of Car5b escape. This is associated with reduced CTCF and cohesin binding, which indicates loss of looping and insulation and is supported by 3C combined with Hi-C analysis. In addition, enrichment in the repressive mark H3K27me3 invades the Car5b domain in deleted cells, consistent with loss of expression from the Xi. In contrast, cells with an inversion of the CTCF binding site retain CTCF and cohesin binding, as well as looping, in line with persistence of escape. Interestingly, the levels of escape increase in cells with deletion of either Dxz4, which disrupts the Xi-specific compact 3D structure, or Firre, which results in lower H3K27me3 enrichment on the Xi, indicating that the structural and epigenetic features of the Xi constrain escape from XCI in wild type conditions.

CONCLUSIONS: Taken together, our findings support the idea that escape from XCI in female somatic cells is modulated by both the topological insulation of domains via CTCF binding and the surrounding heterochromatin environment.},
}

*CCCTC-Binding Factor/metabolism/genetics
Animals
*X Chromosome Inactivation/genetics
Mice
*Chromatin/metabolism
Female
Binding Sites
Repressor Proteins/metabolism/genetics

@article {pmid39990799,
year = {2025},
author = {Chen, KY and Toro-Moreno, M and Subramaniam, AR},
title = {GitHub is an effective platform for collaborative and reproducible laboratory research.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {39990799},
issn = {2331-8422},
support = {R01 AT012826/AT/NCCIH NIH HHS/United States ; R35 GM119835/GM/NIGMS NIH HHS/United States ; },
abstract = {Laboratory research is a complex, collaborative process that involves several stages, including hypothesis formulation, experimental design, data generation and analysis, and manuscript writing. Although reproducibility and data sharing are increasingly prioritized at the publication stage, integrating these principles at earlier stages of laboratory research has been hampered by the lack of broadly applicable solutions. Here, we propose that the workflow used in modern software development offers a robust framework for enhancing reproducibility and collaboration in laboratory research. In particular, we show that GitHub, a platform widely used for collaborative software projects, can be effectively adapted to organize and document all aspects of a research project's lifecycle in a molecular biology laboratory. We outline a three-step approach for incorporating the GitHub ecosystem into laboratory research workflows: 1. designing and organizing experiments using issues and project boards, 2. documenting experiments and data analyses with a version control system, and 3. ensuring reproducible software environments for data analyses and writing tasks with containerized packages. The versatility, scalability, and affordability of this approach make it suitable for various scenarios, ranging from small research groups to large, cross-institutional collaborations. Adopting this framework from a project's outset can increase the efficiency and fidelity of knowledge transfer within and across research laboratories. An example GitHub repository based on this approach is available at https://github.com/rasilab/github_demo and a template repository that can be copied is available at https://github.com/rasilab/github_template.},
}

@article {pmid40025364,
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 = {Correction: Preoperative MRI to Predict Upstaging of DCIS to Invasive Cancer at Surgery.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1245/s10434-025-17029-x},
pmid = {40025364},
issn = {1534-4681},
}

@article {pmid40023656,
year = {2025},
author = {Sullivan, KM and Sanders, JE},
title = {The Cure of Thalassemia and the Angst of a Junior Attending.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {3},
pages = {113-117},
doi = {10.1016/j.jtct.2025.02.006},
pmid = {40023656},
issn = {2666-6367},
}

@article {pmid40022306,
year = {2025},
author = {Zhou, P and Yeshoua, BJ and Konuthula, N and Pan, CJ and Ferrandino, RM and Holte, SE and Rizvi, Z and Marchiano, EM and Futran, ND and Barber, BR},
title = {Association of Oral Health Determinants With Oral Squamous Cell Carcinoma in Never-Smoking Adults.},
journal = {Head & neck},
volume = {},
number = {},
pages = {},
doi = {10.1002/hed.28119},
pmid = {40022306},
issn = {1097-0347},
support = {//RFPU-NW research award/ ; },
abstract = {BACKGROUND: The incidence of oral cavity squamous cell carcinoma (OCSCC) is increasing among non-smokers. This study investigates the association between local and systemic oral health determinants and OCSCC in never-smoking adults.

METHODS: A case-control study using the National Institutes of Health All of Us database was conducted. Lifetime exposures to periodontal disease, acquired absence of teeth, hyperlipidemia, hyperglycemia, HIV, oral-related autoimmune diseases, depression, and eating disorders were analyzed. Multivariate logistic regression estimated odds ratios (ORs) and 95% confidence intervals to identify independent OCSCC risk factors.

RESULTS: Several risk factors were independently associated with OCSCC: periodontal disease (OR 4.99), hyperlipidemia (OR 1.53), HIV infection (OR 2.96), oral-related autoimmune diseases (OR 2.40), depression (OR 1.51), and eating disorders (OR 8.46). Acquired absence of teeth and hyperglycemia did not show statistical significance.

CONCLUSIONS: This study highlights the complex pathophysiology of OCSCC in never-smoking adults and underscores the need for comprehensive risk assessment and prevention strategies.},
}

@article {pmid40022201,
year = {2025},
author = {Jennings-Shaffer, C and Rich, DH and Macaulay, M and Karcher, MD and Ganapathy, T and Kiami, S and Kooperberg, A and Zhang, C and Suchard, MA and Matsen, FA},
title = {Finding high posterior density phylogenies by systematically extending a directed acyclic graph.},
journal = {Algorithms for molecular biology : AMB},
volume = {20},
number = {1},
pages = {2},
pmid = {40022201},
issn = {1748-7188},
support = {R01 AI162611/AI/NIAID NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; S10OD028685/RI/ORIP NIH HHS/United States ; AI162611/NH/NIH HHS/United States ; },
abstract = {Bayesian phylogenetics typically estimates a posterior distribution, or aspects thereof, using Markov chain Monte Carlo methods. These methods integrate over tree space by applying local rearrangements to move a tree through its space as a random walk. Previous work explored the possibility of replacing this random walk with a systematic search, but was quickly overwhelmed by the large number of probable trees in the posterior distribution. In this paper we develop methods to sidestep this problem using a recently introduced structure called the subsplit directed acyclic graph (sDAG). This structure can represent many trees at once, and local rearrangements of trees translate to methods of enlarging the sDAG. Here we propose two methods of introducing, ranking, and selecting local rearrangements on sDAGs to produce a collection of trees with high posterior density. One of these methods successfully recovers the set of high posterior density trees across a range of data sets. However, we find that a simpler strategy of aggregating trees into an sDAG in fact is computationally faster and returns a higher fraction of probable trees.},
}

@article {pmid40019842,
year = {2025},
author = {Kronenberger, DW and Zimmers, TA and Ralston, RK and Runco, DV},
title = {Circulating Growth Differentiation Factor 15 (GDF15) in Paediatric Disease: A Systematic Review.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {16},
number = {2},
pages = {e13712},
pmid = {40019842},
issn = {2190-6009},
mesh = {*Growth Differentiation Factor 15/blood ; Humans ; Child ; *Biomarkers/blood ; Child, Preschool ; Infant, Newborn ; Infant ; Adolescent ; },
abstract = {BACKGROUND: Growth Differentiation Factor 15 (GDF15), a nonspecific inflammatory marker and member of the TGF-β superfamily, has a well-established role in both inflammation and metabolic modulation, but lacks a comprehensive paediatric literature review. In several adult disease states, including cancer cachexia and pregnancy, circulation and expression of GDF15 has been of clinical and scientific interest, but little published paediatric data exists. As such, we aim to summarize existing paediatric studies.

METHODS: This review follows the PRISMA-ScR guidelines for reporting and aims to summarize existing paediatric studies including GDF15, describe disease entities in which GDF15 has been investigated including existing reference ranges, and identify literature gaps to present future clinical and research direction. Our search strategy queried Ovid MEDLINE, Ovid Embase, Cochrane Library and Scopus databases to find original scientific articles measuring GDF15 from birth through children up to age 18. Data relating to study participant demographic and disease pathology, GDF15 measurement methods and clinical outcomes of interest were extracted.

RESULTS: Sixty-two studies were included, classified as cardiac, endocrine, mitochondrial, hematologic, neonatal, oncologic, infectious, rheumatologic, renal, neurologic or healthy. While several entities demonstrated elevated GDF15, the highest median GDF15 levels were observed in cardiac arrest 7089 pg/mL (interquartile range 3805-13 306) and mitochondrial diseases 4640 pg/mL (1896-14 064). In certain conditions, including cardiac stress, polycystic ovarian syndrome (PCOS), Kawasaki Disease (KD) and certain mitochondrial myopathies GDF15 can normalize with disease treatment or resolution. Of healthy children studied, GDF15 levels were highest in healthy neonates and followed a predictable pattern, decreasing over time. Mean and standard deviation values of GDF15 in healthy children were 343.8 ± 221.0 pg/mL, with a range of 90-1134 pg/mL for study averages.

CONCLUSIONS: Circulating GDF15 has been studied in a variety of paediatric diseases. However, variable evaluated outcome measures and GDF15 measurement methodologies prevent generalizability and direct comparison of these published studies. Validating normal GDF15 levels in children with standardized and reproducible methodology will help clarify GDF15's utility as a diagnostic marker of disease, a necessary step to elucidate clinical implications of GDF15 over expression and its potential as a therapeutic target.},
}

*Growth Differentiation Factor 15/blood
Humans
Child
*Biomarkers/blood
Child, Preschool
Infant, Newborn
Infant
Adolescent

@article {pmid40019493,
year = {2025},
author = {Fasching, PA and Slamon, D and Nowecki, Z and Kukielka-Budny, B and Stroyakovskiy, D and Yardley, DA and Huang, CS and Chan, A and Chia, S and Martín, M and Rugo, HS and Loi, S and Hurvitz, S and Untch, M and Afenjar, K and Fresco, R and Danyliv, A and Ferrusi, I and Li, Z and Hortobagyi, G},
title = {Health-related quality of life in patients with HR+/HER2- early breast cancer treated with ribociclib plus a nonsteroidal aromatase inhibitor: results from the NATALEE trial.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-24-1724},
pmid = {40019493},
issn = {1557-3265},
abstract = {PURPOSE: The phase 3 NATALEE trial reported a statistically significant invasive disease-free survival benefit with ribociclib plus nonsteroidal aromatase inhibitor (NSAI) versus an NSAI alone in stage II/III hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC). Here we report health-related quality of life (HRQOL) data from NATALEE.

PATIENTS AND METHODS: Patients were randomized to receive ribociclib plus NSAI or NSAI alone. Patient-reported outcome scores (EORTC QLQ-C30 global health status and physical, social, and emotional functioning domains; EORTC QLQ-BR23 breast-symptoms scale; health on a visual analog scale of EQ-5D-5L; and the Hospital Anxiety and Depression Scale) were assessed. The prespecified primary HRQOL endpoint was physical functioning. Mean scores and time-categorical and prespecified linear-time repeated-measure models were used to evaluate HRQOL changes during treatment.

RESULTS: HRQOL was evaluated in all patients in the ribociclib plus NSAI (n = 2549) and NSAI alone (n = 2552) arms. Compliance was high in both arms (≈93%-97%). Mean scores did not differ meaningfully from baseline for any analyzed domain. Likewise, neither a meaningful change from baseline (in either treatment arm) nor a difference between arms was observed during treatment in the time-categorical, model-adjusted mean scores for any HRQOL domains-using published thresholds for interpreting longitudinal and between-group differences, with all values being within 0.5 SD of their baseline values. Linear-time regression analysis confirmed these findings.

CONCLUSIONS: These analyses of NATALEE show that adding adjuvant ribociclib to an NSAI does not negatively impact HRQOL in patients with HR+/HER2- EBC.},
}

@article {pmid40019453,
year = {2025},
author = {Di, M and Maurer, MJ and Flowers, CR},
title = {End points and Outcomes in Follicular Lymphoma: What should we measure, how, and why?.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024026978},
pmid = {40019453},
issn = {1528-0020},
abstract = {Overall survival (OS) and quality of life (QoL) are clinically relevant outcomes/endpoints during examination of therapies. However, with median OS approaching 20 years for patients with follicular lymphoma (FL), it is often not feasible to use OS as a primary endpoint in clinical studies. While validated tools for assessing QoL in patient with lymphoma exist, QoL data are rarely the sole basis for drug approvals in FL. Therefore, other survival endpoints, surrogates, and intermediate clinical endpoints have all been used to measure outcomes in FL trials. In this review, we discuss the strengths and limitations of these commonly used traditional endpoints in FL trials and examine the current gaps, including delayed availability of results and suboptimal sensitivity in distinguishing difference in therapeutic effects. To help address the gaps identified, well-validated surrogates, such as complete remission 30 months after starting frontline immunochemotherapy (CR30), may be used as the primary or co-primary endpoint in confirmatory randomized trials. Emerging intermediate endpoints like minimal residual disease, may be useful in early phase trials and in guiding accelerated approvals after appropriate validation. As patient preference plays a crucial role in treatment decisions in FL, it is critical to include QoL as an important secondary trial endpoint and to measure non-medical burdens, including time and financial toxicities. Endpoints that are clinically relevant, timely, and patient-centered may identify new drugs that help patients with FL live longer and better lives.},
}

@article {pmid40016020,
year = {2025},
author = {Indorf, A and Kwok, M and Jao, M and Chen, A and Baek, GT and Banerjee, R and Cicero, KI and Cowan, AJ and Portuguese, AJ and Yoon, L and Segal, EM},
title = {Enhancing Multiple Myeloma Care: Implementation of Pharmacist-Led Prescribing of Immunomodulatory Drugs in an Academic Medical Setting.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.01.013},
pmid = {40016020},
issn = {2152-2669},
abstract = {BACKGROUND: The oncology healthcare landscape has transformed and has demonstrated the need for efficient care delivery models due to improved survival resulting in larger patient panels. Pharmacists can prescribe oral anticancer agents (OAA), laboratory orders, and supportive care treatments as licensed independent practitioners (LIP) under their pharmacist license. Using immunomodulators (IMiDs) for patients with multiple myeloma (MM) has complexities with regulatory requirements for prescribing. At our institution, the care team was spending about 240 hours per month satisfying regulatory activities. We aim to characterize the effectiveness of pharmacist LIPs for patients with MM receiving IMiD treatment.

METHODS: A multidisciplinary quality improvement team implemented a model for OAA management with pharmacist LIPs. Patients were evaluated for IMiD adherence. Medication possession ratios (MPR) were collected using fill history for patients with 6 months of fill history pre and postpharmacist LIPs involvement, and paired McNemar's Test assessed differences in adherence. A care team survey gauged satisfaction.

RESULTS: The pharmacist patient panel comprised 246 patients. There were similar adherence rates, with an MPR of 96% preintervention and 96.55% postintervention. All survey participants recommended the pharmacist prescriber for IMiDs and reported positive reviews of pharmacist involvement.

CONCLUSION: Management of OAAs by pharmacist LIPs is viable clinical model. The care team reduced their administrative burden while empowering pharmacists to practice at the top of their license. This framework serves as a guide for institutions to adapt and optimize OAA management in an increasingly complex therapeutic landscape.},
}

@article {pmid40015292,
year = {2025},
author = {Haidar, G and Thomas, S and Loubet, P and Baker, RI and Benfield, T and Boonyaratanakornkit, J and Kiertiburanakul, S and Kim, AHJ and Longbrake, EE and Molina, JM and Paredes, R and Tucker, D and Uriel, A and Weinmann-Menke, J and Aksyuk, AA and Clegg, LE and Currie, A and Yang, H and Flyrin, K and Gibbs, M and Shroff, M and Perez, JL and Chang, LJ and Cohen, TS and , },
title = {Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(24)00804-1},
pmid = {40015292},
issn = {1474-4457},
abstract = {BACKGROUND: Sipavibart is an anti-spike monoclonal antibody that neutralises SARS-CoV-2 with exceptions, including Phe456Leu-containing variants (eg, KP.2* and KP.3*). This trial assessed sipavibart efficacy and safety for prevention of symptomatic COVID-19 in participants who are immunocompromised.

METHODS: In this ongoing, double-blind, international, phase 3 trial, we enrolled participants who were immunocompromised and aged 12 years or older at 197 hospitals, university health centres, and clinical trial units in 18 countries. Participants were randomly allocated 1:1 to a sipavibart group (intramuscular sipavibart 300 mg on days 1 and 181) or a comparator group (tixagevimab 300 mg-cilgavimab 300 mg on day 1 and placebo on day 181 or placebo on days 1 and 181), stratified by previous COVID-19 vaccination and infection status and use of tixagevimab-cilgavimab. The primary efficacy outcomes were symptomatic COVID-19 caused by any variant or symptomatic COVID-19 caused by non-Phe456Leu-containing variants within 181 days of dosing, assessed in the SARS-CoV-2-negative set, comprising all participants without a positive RT-PCR test for SARS-CoV-2 at baseline and who received at least one trial intervention dose. Safety outcomes for adverse events were assessed 90 days following the first dose and for serious adverse events throughout the study in the safety analysis set (ie, all participants who received at least one injection of sipavibart or comparator). This study is registered with ClinicalTrials.gov, NCT05648110.

FINDINGS: Participants were screened from March 31 to Oct 27, 2023; 3349 participants (56·8% female) were randomly assigned: 1674 to the sipavibart group (five no first dose; 1669 sipavibart) and 1675 to the comparator group (nine no first dose; 1105 tixagevimab-cilgavimab and 561 placebo). Within 181 days of dosing, 122 (7·4%) of 1649 participants in the sipavibart group and 178 (10·9%) of 1631 participants in the comparator group had symptomatic COVID-19 due to any variant (relative risk reduction [RRR] 34·9% [97·5% CI 15·0 to 50·1]; p=0·0006), 54 (3·3%) participants in the sipavibart group and 90 (5·5%) participants in the comparator group had symptomatic COVID-19 due to non-Phe456Leu-containing variants (RRR 42·9% [95% CI 19·9 to 59·3]; p=0·0012), and 47 (2·9%) participants in the sipavibart group and 64 (3·9%) participants in the comparator group had symptomatic COVID-19 due to Phe456Leu-containing variants (30·4% [-1·8 to 52·5]). Adverse events occurred in 833 (49·9%) of 1671 participants in the sipavibart group and 857 (51·5%) of 1663 participants in the comparator group within 3 months of the first dose. One COVID-19-related death occurred in the comparator group. Serious adverse events considered related to trial intervention occurred in two (0·1%) of 1671 participants in the sipavibart group and seven (0·4%) of 1663 participants in the comparator group (none fatal). No serious cardiovascular or thrombotic events were considered to be related to sipavibart.

INTERPRETATION: The primary analysis showed efficacy and safety of sipavibart in preventing symptomatic COVID-19 in participants who are immunocompromised when susceptible (ie, non-Phe456Leu-containing) variants dominated, although no efficacy was shown against resistant (ie, Phe456Leu-containing) variants that dominate as of November, 2024.

FUNDING: AstraZeneca.},
}

@article {pmid40014858,
year = {2025},
author = {Nudy, M and Aragaki, AK and Jiang, X and Manson, JE and Shadyab, AH and Jung, SY and Martin, LW and Wild, RA and Womack, C and Mouton, CP and Rossouw, JE and Schnatz, PF},
title = {Long-Term Changes to Cardiovascular Biomarkers After Hormone Therapy in the Women's Health Initiative Hormone Therapy Clinical Trials.},
journal = {Obstetrics and gynecology},
volume = {},
number = {},
pages = {},
pmid = {40014858},
issn = {1873-233X},
abstract = {OBJECTIVE: To assess the long-term changes in cardiovascular biomarkers during the WHI (Women's Health Initiative) hormone therapy (HT) clinical trials of conjugated equine estrogens (CEE) alone and CEE plus medroxyprogesterone acetate (MPA).

METHODS: HT trial participants from the CEE alone (n=1,188, 0.625 mg/d CEE or placebo) and the CEE+MPA (n=1,508, 0.625 mg/d CEE plus continuous 2.5 mg/d MPA or placebo) trials provided blood samples at baseline and after 1, 3, and 6 years. Low-density lipoprotein cholesterol (LDL-C; primary endpoint), high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol, lipoprotein(a), glucose, insulin, and homeostatic model assessment for insulin resistance were measured. Repeated-measures regression models estimated the geometric means of each log-transformed biomarker by restricted maximum likelihood. A constant treatment effect across visits was used to estimate the overall effect, expressed as a ratio of geometric means, and was complemented with geometric means (95% CIs) by randomization group and corresponding ratios of geometric means (95% CI; HT vs placebo) at each visit.

RESULTS: During the intervention phase of the CEE-alone trial, randomization to CEE reduced LDL-C by 11% over 6 years (ratio of geometric means 0.89, 95% CI, 0.88-0.91, P<.001). The overall reduction in LDL-C was similar for CEE+MPA relative to placebo (ratio of geometric means 0.88, 95% CI, 0.86-0.89, P<.001). Relative to placebo, HDL-C and triglycerides were 13.0% and 7.0% higher with CEE and CEE+MPA, respectively. The homeostatic model assessment for insulin resistance decreased by 14.0% and 8.0% for CEE-alone and CEE+MPA trial participants, respectively. Relative to placebo, lipoprotein(a) decreased by 15.0% and 20.0% for participants randomized to CEE alone and CEE+MPA, respectively.

CONCLUSION: Lipoprotein(a), LDL-C, and homeostatic model assessment for insulin resistance were lower and HDL-C levels were higher for HT compared with placebo. Triglycerides increased in both the CEE and CEE+MPA trials, however. Future research should assess whether other progestogens attenuate the effect of estrogen on HDL-C. These results may be used to counsel younger menopausal women with bothersome symptoms who are deciding whether to initiate oral HT within the context of published effects of oral HT on rates of cardiovascular events.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00000611.},
}

@article {pmid40014323,
year = {2025},
author = {Hirayama, AV and Bleakley, M},
title = {Competition for CD19 binding may accelerate CAR efficacy.},
journal = {Blood},
volume = {145},
number = {9},
pages = {902-903},
doi = {10.1182/blood.2024027469},
pmid = {40014323},
issn = {1528-0020},
}

@article {pmid40013681,
year = {2025},
author = {Childers, CP and Petty, AM and Selzer, DJ and Senkowski, CK},
title = {Obesity and Work in Abdominal Surgery.},
journal = {Journal of the American College of Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1097/XCS.0000000000001367},
pmid = {40013681},
issn = {1879-1190},
abstract = {BACKGROUND: Recent analyses have shown that Modifier 22 does not reimburse surgeons for the increased work required to care for the most complex patients. New strategies are needed to identify patients that require additional work to create a financial system that ensures equitable access. Obesity has been identified as a growing and potentially reliable patient risk factor that could be used to identify cases that require additional work.

STUDY DESIGN: Using 2022 ACS NSQIP data, this study evaluated 10 common general surgery operations (appendectomy, cholecystectomy, colon/rectal operations, hernia repairs). The primary predictor was BMI category (Normal: 18.5-25, overweight: 25-29.9, class I obesity: 30-34.9, class II obesity: 35-39.9, class III obesity 40-49.9, extreme obesity >=50). Primary outcomes were operative time and composite measures of complications.

RESULTS: The final sample included 158,692 operations. Across the entire cohort, 22.2% were normal weight and 76.3% were overweight or obese. Overall, operative time was increased by 5.6% (95% CI 4.8-6.3%) for overweight, by 10.6% (CI 9.8-11.5%) for class I obesity, by 14.7% (CI 13.6-15.8%) for class II obesity, by 18.9% (CI 17.6-20.2%) for class III obesity, and by 26.8% (CI 14.1-29.6%) for extreme obesity compared to those with normal BMI. Obesity was associated with higher odds of any complication or serious complication, driven by wound complications, pulmonary emboli, and renal insufficiency.

CONCLUSION: Obesity is a growing challenge in abdominal surgery and is associated with increase operative time and risk of complications. The consistency of the magnitude of effect makes it an ideal target for a modifier or add-on code that could identify cases requiring additional work.},
}

@article {pmid40013392,
year = {2025},
author = {Haney, M and Ashraf, A and Lake, KE and Strecker, L and Myers, KC and Towe, C and Walkup, L and Woods, J and Edwards, SL and Cooper, R and Lehmann, LE and Cisneros, GS and Freedman, JL and Baker, KS and Doherty, E and MacMillan, ML and Goldfarb, SB and Davies, SM and Koo, J and Groups, T},
title = {Community respiratory viruses are generally well-tolerated in hematopoietic stem cell transplant recipients: a brief report from the TRANSPIRE study.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.287107},
pmid = {40013392},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid40009771,
year = {2025},
author = {Collin, LJ and Cushing-Haugen, KL and Terry, KL and Goode, EL and Wu, AH and Harris, HR and Sasamoto, N and Cramer, DW and Modugno, F and Elishaev, E and Fu, Z and Moysich, KB and Fasching, PA and Pearce, CL and Menon, U and Gentry-Maharaj, A and Gayther, SA and Wentzensen, N and Goodman, MT and George, J and Talhouk, A and Anglesio, MS and Ramus, SJ and Bowtell, DD and Tworoger, SS and Schildkraut, JM and Webb, PM and Doherty, JA},
title = {Patterns of associations with epidemiologic factors by high grade serous ovarian cancer gene expression subtypes.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-1143},
pmid = {40009771},
issn = {1538-7755},
abstract = {BACKGROUND: Ovarian high-grade serous carcinomas (HGSC) comprise four distinct molecular subtypes based on mRNA expression patterns, with differential survival. Understanding risk factor associations is important to elucidate the etiology of HGSC. We investigated associations between different epidemiologic risk factors and HGSC molecular subtypes.

METHODS: We pooled data from 11 case-control studies with epidemiologic and tumor gene expression data from custom NanoString CodeSets developed through a collaboration within the Ovarian Tumor Tissue Analysis Consortium. The PrOTYPE validated NanoString-based 55 gene classifier was used to assign HGSC gene expression subtypes. We examined associations between epidemiologic factors and HGSC subtypes in 2,070 cases and 16,633 controls using multivariable-adjusted polytomous regression models.

RESULTS: Among the 2,070 HGSC cases, 556 (27%) were classified as C1.MES, 340 (16%) as C5.PRO, 538 (26%) as C2.IMM, and 636 (31%) as C4.DIF. Key factors, including oral contraceptive use, parity, breastfeeding, and family history of ovarian cancer, were similarly associated with all subtypes. Heterogeneity was observed for several factors. Former smoking (OR=1.25, 95%CI: 1.03, 1.51) and genital powder use (OR=1.42, 95%CI: 1.08, 1.86) were uniquely associated with C2.IMM. History of endometriosis was associated with C5.PRO (OR=1.46, 95%CI: 0.98, 2.16) and C4.DIF (OR=1.27, 95%CI: 0.94, 1.71) only. Family history of breast cancer (OR=1.44, 95%CI: 1.16, 1.78) and current smoking (OR=1.40, 95%CI: 1.11, 1.76) were associated with C4.DIF only.

CONCLUSIONS: This study observed heterogeneous associations of epidemiologic and modifiable factors with HGSC molecular subtypes.

IMPACT: The different patterns of associations may provide key information about the etiology of the four subtypes.},
}

@article {pmid40007996,
year = {2025},
author = {Crotty, EE and Sato, AA and Abdelbaki, MS},
title = {Integrating MAPK pathway inhibition into standard-of-care therapy for pediatric low-grade glioma.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1520316},
pmid = {40007996},
issn = {2234-943X},
abstract = {Pediatric low-grade gliomas (pLGG) are a group of tumors largely driven by alterations in a single genetic pathway, known as the RAS-RAF-mitogen-activated protein kinase (MAPK) pathway. Recent biologic insights and therapeutic targeting of MAPK-alterations have dramatically shifted the treatment approach in pLGG. While chemotherapy remains front-line therapy for unresectable pLGG in most scenarios (with the notable exception of BRAF [V600E]-altered tumors), many patients recur following cytotoxic agents and require further treatment. Inhibitors of the MAPK pathway, primarily MEK and RAF kinase inhibitors, have emerged as effective and tolerable second-line or later therapy for pLGG. As familiarity with these targeted agents increases, their indications for use continue to expand and Phase 3 clinical trials investigating their utility in the front-line setting are ongoing. We have adopted mitigation strategies for their associated toxicities; skin toxicity, in particular, is now managed by prevention strategies and early dermatologic intervention. This review highlights current approaches for the clinical implementation of MEK and RAF kinase inhibitors for pLGG, focusing on the practical aspects of drug administration, toxicity management, response monitoring, and distribution to patients experiencing geographic or financial barriers to care. Additionally, we review important considerations for the off-label use of these agents while contemporaneous clinical trials assessing front-line efficacy are ongoing. We discuss the potential for more expansive or histology-agnostic tumor targeting using MEK inhibitors, harnessing their biologic relevance for other RAS-altered conditions.},
}

@article {pmid40006680,
year = {2025},
author = {Shen, X and Korber, B and Spreng, RL and Sawant, SS and deCamp, A and McMillan, AS and Mathura, R and Zolla-Pazner, S and Pinter, A and Parks, R and Bowman, C and Sutherland, L and Scearce, R and Yates, NL and Montefiori, DC and Haynes, BF and Tomaras, GD},
title = {A Pentavalent HIV-1 Subtype C Vaccine Containing Computationally Selected gp120 Strains Improves the Breadth of V1V2 Region Responses.},
journal = {Vaccines},
volume = {13},
number = {2},
pages = {},
pmid = {40006680},
issn = {2076-393X},
support = {HHSN27201100016C/AI/NIAID NIH HHS/United States ; AI067854//Center for HIV/AIDS Vaccine Immunology/ ; AI100645//Duke Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery/ ; P30AI064518//Duke Center for AIDS Research/ ; },
abstract = {BACKGROUND: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for HIV-1 vaccine candidates. The V1V2 region's highly variable nature and the extensive diversity of subtype C HIV-1 Envelopes (Envs) make the V1V2 response breadth a high priority for HIV-1 vaccine regimens aiming for V1V2-mediated protection in Southern Africa. Here, we determined whether the breadth of the anti-V1V2 vaccine response can be broadened by including HIV-1 Env strains computationally designed to enhance the coverage of subtype C V1V2 sequence diversity.

METHODS: Three subtype C Env strains were selected to maximize antibody binding coverage while complementing subtype C vaccine gp120s that were given in human clinical trials in South Africa, as well as to improve epitope accessibility. Humoral immunogenicity of a novel trivalent gp120 vaccine immunogen, a bivalent gp120 boost already in clinical trials (1086C and TV1), and a pentavalent (all five gp120s combined) were evaluated in a preclinical immunization study in guinea pigs. The pentavalent combination was further evaluated with alum versus glucopyranosyl lipid adjuvants formulated in squalene-in-water emulsion (GLA-SE) adjuvants in non-human primates. The breadth of the anti-V1V2 response was assessed using an array of cross-subtype variable loops 1&2 (V1V2) scaffold proteins and linear V2 peptides.

RESULTS: The breadth of the IgG response against V1V2 antigens of the trivalent and pentavalent groups was comparable, and both were greater than the breadth of the bivalent group. Linear epitope mapping showed that two linear epitopes in V2 were targeted by the vaccinated animals: the V2 hotspot focused at [169]K that potentially correlated with decreased HIV-1 risk in RV144 and the V2.2 site ([179]LDV/I[181]) that is part of the integrin α4β7 binding site. The bivalent vaccine elicited a significantly higher magnitude of binding to the V2 hotspot compared to the trivalent vaccine whereas the trivalent vaccine elicited significantly higher binding to the V2.2 epitope compared to the bivalent vaccine, while the pentavalent recognized both regions.

CONCLUSIONS: These results demonstrate that the three new computationally selected subtype C Envs successfully complemented 1086C and TV1 for broader V1V2 antibody responses, and, in concert with adjuvants that stimulate V1V2 responses, can be considered as part of a rationale immunogen design to improve V1V2 IgG coverage in future vaccine trials in South Africa.},
}

@article {pmid39990376,
year = {2025},
author = {Wang, Y and Gornalusse, GG and Siegel, DA and Barbehenn, A and Hoh, R and Martin, J and Hecht, F and Pilcher, C and Semenova, L and Murdoch, DM and Margolis, DM and Levy, CN and Jerome, KR and Rudin, CD and Hladik, F and Deeks, SG and Lee, SA and Browne, EP},
title = {NF-κB dependent gene expression and plasma IL-1β, TNFα and GCSF drive transcriptomic diversity and CD4:CD8 ratio in people with HIV on ART.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39990376},
issn = {2692-8205},
support = {R01 DA054994/DA/NIDA NIH HHS/United States ; K23 GM112526/GM/NIGMS NIH HHS/United States ; R01 AI143381/AI/NIAID NIH HHS/United States ; R01 AI184122/AI/NIAID NIH HHS/United States ; KL2 TR002317/TR/NCATS NIH HHS/United States ; P30 AI027757/AI/NIAID NIH HHS/United States ; UM1 AI164567/AI/NIAID NIH HHS/United States ; UM1 AI126623/AI/NIAID NIH HHS/United States ; },
abstract = {Despite antiretroviral therapy (ART), people with HIV (PWH) on ART experience higher rates of morbidity and mortality vs. age-matched HIV negative controls, which may be driven by chronic inflammation due to persistent virus. We performed bulk RNA sequencing (RNA-seq) on peripheral CD4+ T cells, as well as quantified plasma immune marker levels from 154 PWH on ART to identify host immune signatures associated with immune recovery (CD4:CD8) and HIV persistence (cell-associated HIV DNA and RNA). Using a novel dimension reduction tool - Pairwise Controlled Manifold Approximation (PaCMAP), we defined three distinct participant transcriptomic clusters. We found that these three clusters were largely defined by differential expression of genes regulated by the transcription factor NF-κB. While clustering was not associated with HIV reservoir size, we observed an association with CD4:CD8 ratio, a marker of immune recovery and prognostic factor for mortality in PWH on ART. Furthermore, distinct patterns of plasma IL-1β, TNF-α and GCSF were also strongly associated with the clusters, suggesting that these immune markers play a key role in CD4+ T cell transcriptomic diversity and immune recovery in PWH on ART. These findings reveal novel subgroups of PWH on ART with distinct immunological characteristics, and define a transcriptional signature associated with clinically significant immune parameters for PWH. A deeper understanding of these subgroups could advance clinical strategies to treat HIV-associated immune dysfunction.},
}

@article {pmid39975454,
year = {2025},
author = {Xie, T and Richman, H and Gao, J and Matsen, FA and Zhang, C},
title = {PhyloVAE: Unsupervised Learning of Phylogenetic Trees via Variational Autoencoders.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {39975454},
issn = {2331-8422},
support = {R01 AI162611/AI/NIAID NIH HHS/United States ; },
abstract = {Learning informative representations of phylogenetic tree structures is essential for analyzing evolutionary relationships. Classical distance-based methods have been widely used to project phylogenetic trees into Euclidean space, but they are often sensitive to the choice of distance metric and may lack sufficient resolution. In this paper, we introduce phylogenetic variational autoencoders (PhyloVAEs), an unsupervissed learning framework designed for representation learning and generative modeling of tree topologies. Leveraging an efficient encoding mechanism inspired by autoregressive tree topology generation, we develop a deep latent-variable generative model that facilitates fast, parallelized topology generation. PhyloVAE combines this generative model with a collaborative inference model based on learnable topological features, allowing for high-resolution representations of phylogenetic tree samples. Extensive experiments demonstrate PhyloVAE's robust representation learning capabilities and fast generation of phylogenetic tree topologies.},
}

@article {pmid39975229,
year = {2025},
author = {Shi, Z and Tsuge, M and Collier, N and Takeuchi, Y and Uchida, T and Rutter, CM and Teraoka, Y and Uprichard, S and Ishida, Y and Tateno, C and Ozik, J and Dahari, H and Chayama, K},
title = {Modeling of hepatitis B virus infection spread in primary human hepatocytes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975229},
issn = {2692-8205},
support = {R01 AI144112/AI/NIAID NIH HHS/United States ; R01 AI146917/AI/NIAID NIH HHS/United States ; },
abstract = {Chronic hepatitis B virus (HBV) infection poses a significant global health threat, causing severe liver diseases including cirrhosis and hepatocellular carcinoma. We characterized HBV DNA kinetics in primary human hepatocytes (PHH) over 32 days post-inoculation (pi) and used agent-based modeling (ABM) to gain insights into HBV lifecycle and spread. Parallel PHH cultures were mock-treated or HBV entry inhibitor Myr-preS1 (6.25 μg/mL) was initiated 24h pi. In untreated PHH, 3 viral DNA kinetic patterns were identified: (1) an initial decline, followed by (2) rapid amplification, and (3) slower amplification/accumulation. In the presence of Myr-preS1, viral DNA and infected cell numbers in phase 3 were effectively blocked, with minimal to no increase. This suggests that phase 2 represents viral amplification in initially infected cells, while phase 3 corresponds to viral spread to naïve cells. The ABM reproduced well the HBV kinetic patterns observed and predicted that the viral eclipse phase lasts between 18 and 38 hours. After the eclipse phase, the viral production rate increases over time, starting with a slow production cycle of 1 virion per day, which gradually accelerates to 1 virion per hour after 3 days. Approximately 4 days later, virion production reaches a steady state production rate of 4 virions/hour. The estimated median efficacy of Myr-preS1 in blocking HBV spread was 91% (range: 90-92%). The HBV kinetics and the predicted estimates of the HBV eclipse phase duration and HBV production cycles in PHH are similar of those predicted in uPA/SCID mice with human livers.},
}

@article {pmid39975131,
year = {2025},
author = {Barrero, DJ and Hedouin, S and Mao, Y and Asbury, CL and Stergachis, A and O'Toole, E and Biggins, S},
title = {Centromeres in the thermotolerant yeast K. marxianus mediate attachment to a single microtubule.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975131},
issn = {2692-8205},
support = {DP5 OD029630/OD/NIH HHS/United States ; R35 GM134842/GM/NIGMS NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; },
abstract = {Eukaryotic chromosome segregation requires spindle microtubules to attach to chromosomes through kinetochores. The chromosomal locus that mediates kinetochore assembly is the centromere and is epigenetically specified in most organisms by a centromeric histone H3 variant called CENP-A. An exception to this is budding yeast which have short, sequenced-defined point centromeres. In S. cerevisiae, a single CENP-A nucleosome is formed at the centromere and is sufficient for kinetochore assembly. The thermophilic budding yeast Kluyveromyces marxianus also has a point centromere but its length is nearly double the S. cerevisiae centromere and the number of centromeric nucleosomes and kinetochore attachment sites is unknown. Purification of native kinetochores from K. marxianus yielded a mixed population, with one subpopulation that appeared to consist of doublets, making it unclear whether K. marxianus shares the same attachment architecture as S. cerevisiae. Here, we demonstrate that though the doublet kinetochores have a functional impact on kinetochore strength, kinetochore localization throughout the cell cycle appears conserved between these two yeasts. In addition, whole spindle electron tomography demonstrates that a single microtubule binds to each chromosome. Single-molecule nucleosome mapping analysis suggests the presence of a single centromeric nucleosome. Taken together, we propose that the K. marxianus point centromere assembles a single centromeric nucleosome that mediates attachment to one microtubule.},
}

@article {pmid39973981,
year = {2025},
author = {Gustav, M and van Treeck, M and Reitsam, NG and Carrero, ZI and Loeffler, CML and Meneghetti, AR and Märkl, B and Boardman, LA and French, AJ and Goode, EL and Gsur, A and Brezina, S and Gunter, MJ and Murphy, N and Hönscheid, P and Sperling, C and Foersch, S and Steinfelder, R and Harrison, T and Peters, U and Phipps, A and Kather, JN},
title = {Assessing Genotype-Phenotype Correlations with Deep Learning in Colorectal Cancer: A Multi-Centric Study.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39973981},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA107333/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; U01 CA137088/CA/NCI NIH HHS/United States ; P20 CA252733/CA/NCI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; HHSN268201700006C/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; HHSN261201000032C/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Deep Learning (DL) has emerged as a powerful tool to predict genetic biomarkers directly from digitized Hematoxylin and Eosin (H&E) slides in colorectal cancer (CRC). However, few studies have systematically investigated the predictability of biomarkers beyond routinely available alterations such as microsatellite instability (MSI), and BRAF and KRAS mutations.

METHODS: Our primary dataset comprised H&E slides of CRC tumors across five cohorts totaling 1,376 patients who underwent comprehensive panel sequencing, with an additional 536 patients from two public datasets for validation. We developed a DL model using a single transformer model to predict multiple genetic alterations directly from the slides. The model's performance was compared against conventional single-target models, and potential confounders were analyzed.

FINDINGS: The multi-target model was able to predict numerous biomarkers from pathology slides, matching and partly exceeding single-target transformers. The Area Under the Receiver Operating Characteristic curve (AUROC, mean ± std) on the primary external validation cohorts was: BRAF (0·78 ± 0·01), hypermutation (0·88 ± 0·01), MSI (0·93 ± 0·01), RNF43 (0·86 ± 0·01); this biomarker predictability was mirrored across metrics and co-occurrence analyses. However, biomarkers with high AUROCs largely correlated with MSI, with model predictions depending considerably on MSI-associated morphology upon pathological examination.

INTERPRETATION: Our study demonstrates that multi-target transformers can predict the biomarker status for numerous genetic alterations in CRC directly from H&E slides. However, their predictability is mainly associated with MSI phenotype, despite indications of slight biomarker-inherent contributions to a phenotype. Our findings underscore the need to analyze confounders in AI-based oncology biomarkers. To enable this, we developed a validated model applicable to other cancers and larger, diverse datasets.

FUNDING: The German Federal Ministry of Health, the Max-Eder-Programme of German Cancer Aid, the German Federal Ministry of Education and Research, the German Academic Exchange Service, and the EU.},
}

@article {pmid39786430,
year = {2025},
author = {Lee, SM and Hamid, O and Jotte, R and Zakharia, Y and Medina, T and Gillespie-Twardy, A and Mehmi, I and Chandra, S and Watson, G and Ward, P and Chaney, M and Lu, H and Berndt, J and O'Connor, BP and Rathi, K and Shaikh, E and Cowey, CL},
title = {Phase II Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1-Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {31},
number = {5},
pages = {848-859},
doi = {10.1158/1078-0432.CCR-24-1478},
pmid = {39786430},
issn = {1557-3265},
support = {//Pfizer Foundation/ ; },
mesh = {Humans ; *Antibodies, Monoclonal, Humanized/administration & dosage/therapeutic use/adverse effects ; Female ; Male ; Middle Aged ; *Melanoma/drug therapy/pathology/mortality ; Aged ; *Carcinoma, Non-Small-Cell Lung/drug therapy/pathology/mortality ; Adult ; *Skin Neoplasms/drug therapy/pathology/mortality ; *Lung Neoplasms/drug therapy/pathology/secondary/mortality ; Aged, 80 and over ; *Brentuximab Vedotin/therapeutic use/administration & dosage ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Melanoma, Cutaneous Malignant ; },
abstract = {PURPOSE: Brentuximab vedotin (BV) is hypothesized to selectively deplete T regulatory cells that express CD30 and resensitize tumors to anti-PD-1 therapy. This study evaluated responses to BV + pembrolizumab after PD-1 therapy and explored corresponding biomarkers.

PATIENTS AND METHODS: A total of 55 patients with metastatic non-small cell lung cancer and 58 patients with metastatic cutaneous melanoma received ≥1 dose of BV + pembrolizumab. Patients had received a median of 2.0 prior lines of systemic therapies (range, 1-7). The primary endpoint was confirmed objective response rate (ORR). Exploratory endpoints included overall survival (OS) and biomarker analysis in blood and tumor.

RESULTS: For the secondary refractory metastatic non-small cell lung cancer cohort (RECIST v1.1), the ORR was 14%, median progression-free survival (PFS) was 5.85 months, and median OS was 14.4 months. For the secondary refractory metastatic cutaneous melanoma cohort (immune RECIST), the ORR was 24%, median PFS was 4.44 months, and median OS was 21.9 months. Overall, the median duration of OS follow-up was 17.2 months (95% confidence interval, 14.62-22.87). No new safety signals were identified. No treatment-related grade 5 toxicity was seen. Longitudinal immune phenotyping in peripheral blood demonstrated a transient decrease in T regulatory cells. Paired tumor biopsies from baseline and cycle 3 day 1 showed a trend of increased CD8 T-cell infiltration, especially in responding patients.

CONCLUSIONS: BV + pembrolizumab in solid tumor malignancies resulted in clinically meaningful, durable responses with encouraging OS and PFS rates supportive of the immunomodulatory activity of this combination. Stronger antitumor activity was observed in secondary refractory cohorts. The safety profile of this combination was consistent with the individual drug risk profiles.},
}

Humans
*Antibodies, Monoclonal, Humanized/administration & dosage/therapeutic use/adverse effects
Female
Male
Middle Aged
*Melanoma/drug therapy/pathology/mortality
Aged
*Carcinoma, Non-Small-Cell Lung/drug therapy/pathology/mortality
Adult
*Skin Neoplasms/drug therapy/pathology/mortality
*Lung Neoplasms/drug therapy/pathology/secondary/mortality
Aged, 80 and over
*Brentuximab Vedotin/therapeutic use/administration & dosage
*Programmed Cell Death 1 Receptor/antagonists & inhibitors
Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Melanoma, Cutaneous Malignant

@article {pmid40006664,
year = {2025},
author = {Gwin, WR and Salazar, LG and Dai, JY and Higgins, D and Coveler, AL and Childs, JS and Blancas, R and Dang, Y and Reichow, J and Slota, M and Lu, H and Disis, ML},
title = {A Phase II Study of Denileukin Diftitox in Patients with Advanced Treatment Refractory Breast Cancer.},
journal = {Vaccines},
volume = {13},
number = {2},
pages = {},
pmid = {40006664},
issn = {2076-393X},
abstract = {Background/Objectives: Regulatory T cells (Treg) suppress immunity in the tumor microenvironment, are linked to poor prognosis across breast cancer subtypes, and suppress the cytolytic function of cytotoxic CD8+ T cells. Denileukin diftitox, a diphtheria toxin (DT)/IL-2 fusion protein, targets and depletes Tregs. This Phase II study aimed to assess the safety of denileukin diftitox and its effect on Tregs and tumor growth in patients with advanced breast cancer. Methods: This single-arm Phase II study of denileukin diftitox enrolled patients with refractory stage IV breast cancer. Patients received denileukin diftitox 18 mcg/kg/day IV for Days 1-5 every 21 days for up to six cycles. Toxicity was assessed using CTCAE v3.0 and tumor response was evaluated per RECIST criteria. Blood samples were collected to analyze Tregs by flow cytometry and anti-DT antibodies by ELISA. Results: Fifteen patients with stage IV breast cancer were enrolled. Four patients completed all planned denileukin diftitox infusions and achieved stable disease (27%, 95% CI [0.08, 0.55]). Two patients (13%) discontinued due to toxicity, and nine patients (60%) discontinued due to progressive disease. Eleven patients experienced at least one grade 3 or 4 adverse event. Although there was a general reduction in peripheral blood Tregs, the difference in CD4+CD25+FOXP3+ Tregs levels post-treatment was not statistically significant (p = 0.10). Six patients (40%) achieved ≥25% reductions in Tregs. A significant increase in anti-DT IgG antibodies was observed post-treatment (p < 0.005). Conclusions: Denileukin diftitox demonstrated moderate toxicity in this advanced breast cancer cohort. Denileukin diftitox modulated regulatory T cells. However, the majority of patients experienced disease progression in the study.},
}

@article {pmid40004846,
year = {2025},
author = {Costa, BA and Dima, D and Mark, T and Sadek, NL and Ijioma, S and Ray, D and Goel, U and Dranitsaris, G and Sheng, T and Moshier, E and Mouhieddine, TH and Khouri, J and Rossi, A},
title = {Impact of Prior Selinexor Exposure on Outcomes of Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma: An Exploratory Analysis.},
journal = {Journal of clinical medicine},
volume = {14},
number = {4},
pages = {},
pmid = {40004846},
issn = {2077-0383},
support = {NA//Karyopharm Therapeutics/ ; },
abstract = {Background/Objectives: Chimeric antigen receptor T-cell therapy (CAR-T) has become a key treatment option for relapsed/refractory multiple myeloma (RRMM), but factors impairing T-cell fitness may diminish efficacy. Our exploratory analysis aimed to evaluate the impact of prior treatment with a selinexor-containing regimen on CAR-T outcomes for RRMM patients. Methods: Data for this retrospective cohort study were sourced from electronic medical records at two US academic centers. Kaplan-Meier estimates assessed duration of response (DOR), progression-free survival (PFS), and overall survival (OS), reported as medians with interquartile ranges (IQRs). Cox proportional hazards regression analyzed factors potentially associated with PFS and OS, reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Among 45 patients exposed to selinexor before undergoing BCMA-directed CAR-T, median therapy line numbers for selinexor use and CAR-T were 7 and 9, respectively, with 24.4% receiving selinexor as part of bridging. At median follow-up of 68 months, median PFS and OS post CAR-T were 8.0 (IQR 3.1-39.5) and 35.9 (IQR 14.2-NR) months, respectively. Overall response rate to CAR-T was 89%, with a median DOR of 8.1 months (IQR 2.9-39.0). In our multivariable model, patients who received a selinexor-based regimen in the line of therapy preceding CAR-T showed a trend toward reduced risk of death (HR = 0.08; 95% CI 0.02-0.46) and/or disease progression (HR = 0.40; 95% CI 0.14-1.09). Conclusions: Prior selinexor exposure does not appear to compromise CAR-T outcomes in heavily pretreated RRMM, suggesting potential T-cell sparing. Our findings warrant larger, prospective studies to determine whether preemptive selinexor treatment can optimize CAR-T efficacy.},
}

@article {pmid40000903,
year = {2025},
author = {Itkin, T and Houghton, S and Schreiner, R and Lin, Y and Badwe, CR and Voisin, V and Murison, A and Seyedhassantehrani, N and Kaufmann, KB and Garcia-Prat, L and Booth, GT and Geng, F and Liu, Y and Gomez-Salinero, JM and Shieh, JH and Redmond, D and Xiang, JZ and Josefowicz, SZ and Trapnell, C and Pietras, EM and Spencer, JA and Levine, R and Xiao, W and Zangi, L and Hadland, B and Dick, JE and Xie, SZ and Rafii, S},
title = {Transcriptional activation of regenerative hematopoiesis via microenvironmental sensing.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {40000903},
issn = {1529-2916},
abstract = {Transition between activation and quiescence states in hematopoietic stem and progenitor cells (HSPCs) is tightly governed by cell-intrinsic means and microenvironmental co-adaptation. Although this balance is fundamental for lifelong hematopoiesis and immunity, the underlying molecular mechanisms remain poorly defined. Multimodal analysis divulging differential transcriptional activity between distinct HSPC states indicates the presence of Fli-1 transcription factor binding motif in activated hematopoietic stem cells. We reveal that Fli-1 activity is essential during regenerative hematopoiesis in mice. Fli-1 directs activation programs while priming cellular sensory and output machineries, enabling HSPCs co-adoptability with a stimulated vascular niche through propagation of niche-derived angiocrine Notch1 signaling. Constitutively induced Notch1 signaling is sufficient to recuperate functional hematopoietic stem cells impairments in the absence of Fli-1, without leukemic transformation. Applying FLI-1 transient modified-mRNA transduction into latent adult human mobilized HSPCs, enables their niche-mediated expansion and superior engraftment capacities. Thus, decryption of stem cell activation programs offers valuable insights for immunological regenerative medicine.},
}

@article {pmid39999848,
year = {2025},
author = {Ugalde-Morales, E and Wilf, R and Pluta, J and Ploner, A and Fan, M and Damra, M and Aben, KK and Anson-Cartwright, L and Chen, C and Cortessis, VK and Daneshmand, S and Ferlin, A and Gamulin, M and Gietema, JA and Gonzalez-Niera, A and Grotmol, T and Hamilton, RJ and Harland, M and Haugen, TB and Hauser, R and Hildebrandt, MAT and Karlsson, R and Kiemeney, LA and Kim, J and Lessel, D and Lothe, RA and Loveday, C and Chanock, SJ and McGlynn, KA and Meijer, C and Nead, KT and Nsengimana, J and Popovic, M and Rafnar, T and Richiardi, L and Rocca, MS and Schwartz, SM and Skotheim, RI and Stefansson, K and Stewart, DR and Turnbull, C and Vaughn, DJ and Winge, SB and Zheng, T and Monteiro, AN and Almstrup, K and Kanetsky, PA and Nathanson, KL and Wiklund, F and , },
title = {Identification of genes associated with testicular germ cell tumor susceptibility through a transcriptome-wide association study.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2025.01.022},
pmid = {39999848},
issn = {1537-6605},
abstract = {Transcriptome-wide association studies (TWASs) have the potential to identify susceptibility genes associated with testicular germ cell tumors (TGCTs). We conducted a comprehensive TGCT TWAS by integrating genome-wide association study (GWAS) summary data with predicted expression models from normal testis, TGCT tissues, and a cross-tissue panel that encompasses shared regulatory features across 22 normal tissues, including the testis. Gene associations were evaluated while accounting for variant-level effects from GWASs, followed by fine-mapping analyses in regions exhibiting multiple TWAS signals, and finally supplemented by colocalization analysis. Expression and protein patterns of identified TWAS genes were further examined in relevant tissues. Our analysis tested 19,805 gene-disease links, revealing 165 TGCT-associated genes with a false discovery rate of less than 0.01. We prioritized 46 candidate genes by considering GWAS-inflated signals, correlations between neighboring genes, and evidence of colocalization. Among these, 23 genes overlap with 22 GWAS loci, with 7 being associations not previously implicated in TGCT risk. Additionally, 23 genes located within 21 loci are at least 1 Mb away from published GWAS index variants. The 46 prioritized genes display expression levels consistent with expected expression levels in human gonadal cell types and precursor tumor cells and significant enrichment in TGCTs. Additionally, immunohistochemistry revealed protein-level accumulation of two candidate genes, ARID3B and GINM1, in both precursor and tumor cells. These findings enhance our understanding of the genetic predisposition to TGCTs and underscore the importance of further functional investigations into these candidate genes.},
}

@article {pmid39996762,
year = {2025},
author = {Gang, M and Othus, M and Walter, RB},
title = {Significance of Measurable Residual Disease in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia.},
journal = {Cells},
volume = {14},
number = {4},
pages = {},
pmid = {39996762},
issn = {2073-4409},
support = {T32-HL007093//NIH/NHLBI/ ; },
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods ; *Leukemia, Myeloid, Acute/therapy ; *Neoplasm, Residual ; *Transplantation, Homologous ; },
abstract = {Allogeneic hematopoietic cell transplantation (HCT) remains an important curative-intent treatment for many patients with acute myeloid leukemia (AML), but AML recurrence after allografting is common. Many factors associated with relapse after allogeneic HCT have been identified over the years. Central among these is measurable ("minimal") residual disease (MRD) as detected by multiparameter flow cytometry, quantitative polymerase chain reaction, and/or next-generation sequencing. Demonstration of a strong, independent prognostic role of pre- and early post-HCT MRD has raised hopes MRD could also serve as a predictive biomarker to inform treatment decision-making, with emerging data indicating the potential value to guide candidacy assessment for allografting as a post-remission treatment strategy, the selection of conditioning intensity, use of small molecule inhibitors as post-HCT maintenance therapy, and preemptive infusion of donor lymphocytes. Monitoring for leukemia recurrence after HCT and surrogacy for treatment response are other considerations for the clinical use of MRD data. In this review, we will outline the current landscape of MRD as a biomarker for patients with AML undergoing HCT and discuss areas of uncertainty and ongoing research.},
}

Humans
*Hematopoietic Stem Cell Transplantation/methods
*Leukemia, Myeloid, Acute/therapy
*Neoplasm, Residual
*Transplantation, Homologous

@article {pmid39996711,
year = {2025},
author = {Morishita, T and Martin, PJ and Inamoto, Y},
title = {Treatment Response in Individual Organs Affected by Chronic Graft-Versus-Host Disease.},
journal = {Cells},
volume = {14},
number = {4},
pages = {},
pmid = {39996711},
issn = {2073-4409},
support = {22K08517//Japan Society for the Promotion of Science/ ; },
mesh = {*Graft vs Host Disease/therapy ; Humans ; Chronic Disease ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Treatment Outcome ; Organ Specificity ; },
abstract = {Chronic graft-versus-host disease (GVHD) occurs in 30-70% of patients after allogeneic hematopoietic cell transplantation (HCT) and increases the risks of morbidity and mortality. Systemic corticosteroids are the standard initial treatment, but one-third of patients require subsequent treatment with other systemic agents. Treatment decisions are often based on physicians' experience. The expected treatment response rates in specific organs affected by chronic GVHD may inform such decisions. In this review, we identify 20 studies reporting treatment response rates in individual organs according to objective criteria, summarize the results, discuss the caveats in data interpretation, identify the unmet needs, and suggest future directions in the field. For cutaneous sclerosis, we observed large discrepancies in organ response rates according to the current NIH criteria and patient-reported improvement, highlighting the need for better measurement tools. High response rates for lung involvement with certain novel drugs deserve further investigation.},
}

*Graft vs Host Disease/therapy
Humans
Chronic Disease
*Hematopoietic Stem Cell Transplantation/adverse effects
Treatment Outcome
Organ Specificity

@article {pmid39994463,
year = {2025},
author = {Banerjee, R and Fritz, AR and Akhtar, OS and Freeman, CL and Cowan, AJ and Shah, N and Landau, HJ and Kumar, SK and Vogl, DT and Efebera, YA and McCarthy, PL and Vesole, DH and Mendizabal, A and Krishnan, AY and Somlo, G and Stadtmauer, EA and Pasquini, MC},
title = {Urine-free response criteria predict progression-free survival in multiple myeloma: a post hoc analysis of BMT CTN 0702.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {39994463},
issn = {1476-5551},
}

@article {pmid39992626,
year = {2025},
author = {Krishnamoorthy, GP and Glover, AR and Untch, BR and Sigcha-Coello, N and Xu, B and Vukel, D and Liu, Y and Tiedje, V and Pineda, JMB and Berman, K and Tamarapu, PP and Acuña-Ruiz, A and Saqcena, M and de Stanchina, E and Boucai, L and Ghossein, RA and Knauf, JA and Abdel-Wahab, O and Bradley, RK and Fagin, JA},
title = {RBM10 loss promotes metastases by aberrant splicing of cytoskeletal and extracellular matrix mRNAs.},
journal = {The Journal of experimental medicine},
volume = {222},
number = {5},
pages = {},
pmid = {39992626},
issn = {1540-9538},
support = {R01 CA50706-31/NH/NIH HHS/United States ; R01 CA255211/CA/NCI NIH HHS/United States ; RG183080//National Health and Medical Research Council/ ; //Marie-Josée and Henry R. Kravis Center for Molecular Oncology/ ; R01 CA050706/CA/NCI NIH HHS/United States ; P30 CA008748-58/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA249663/CA/NCI NIH HHS/United States ; //Cycle for Survival/ ; //Royal Australasian College of Surgeons Foundation/ ; },
mesh = {Animals ; Humans ; Mice ; *Extracellular Matrix/metabolism ; *RNA-Binding Proteins/metabolism/genetics ; *rac1 GTP-Binding Protein/metabolism/genetics ; *Neoplasm Metastasis ; *Hyaluronan Receptors/metabolism/genetics ; *RNA, Messenger/genetics/metabolism ; Cytoskeleton/metabolism ; Thyroid Neoplasms/genetics/pathology/metabolism ; Cell Line, Tumor ; RNA Splicing/genetics ; Exons/genetics ; Alternative Splicing/genetics ; Gene Expression Regulation, Neoplastic ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Cell Movement/genetics ; },
abstract = {RBM10 modulates transcriptome-wide cassette exon splicing. Loss-of-function RBM10 mutations are enriched in thyroid cancers with distant metastases. Analysis of transcriptomes and genes mis-spliced by RBM10 loss showed pro-migratory and RHO/RAC signaling signatures. RBM10 loss increases cell velocity. Cytoskeletal and ECM transcripts subject to exon inclusion events included vinculin (VCL), tenascin C (TNC), and CD44. Knockdown of the VCL exon inclusion transcript in RBM10-null cells reduced cell velocity, whereas knockdown of TNC and CD44 exon inclusion isoforms reduced invasiveness. RAC1-GTP levels were increased in RBM10-null cells. Mouse HrasG12V/Rbm1OKO thyrocytes develop metastases that are reversed by RBM10 expression or by combined knockdown of VCL, CD44, and TNC inclusion isoforms. Thus, RBM10 loss generates exon inclusion in transcripts regulating ECM-cytoskeletal interactions, leading to RAC1 activation and metastatic competency. Moreover, a CRISPR-Cas9 screen for synthetic lethality with RBM10 loss identified NFκB effectors as central to viability, providing a therapeutic target for these lethal thyroid cancers.},
}

Animals
Humans
Mice
*Extracellular Matrix/metabolism
*RNA-Binding Proteins/metabolism/genetics
*rac1 GTP-Binding Protein/metabolism/genetics
*Neoplasm Metastasis
*Hyaluronan Receptors/metabolism/genetics
*RNA, Messenger/genetics/metabolism
Cytoskeleton/metabolism
Thyroid Neoplasms/genetics/pathology/metabolism
Cell Line, Tumor
RNA Splicing/genetics
Exons/genetics
Alternative Splicing/genetics
Gene Expression Regulation, Neoplastic
Proto-Oncogene Proteins p21(ras)/genetics/metabolism
Cell Movement/genetics

@article {pmid39991196,
year = {2025},
author = {Jefferson, JA and Chen, K and Hingorani, S and Malik, AB and Tykodi, SS and Keller, KH and Huang, Y and Smith, KD and Reed, RC and Weins, A and Akilesh, S},
title = {Genetic and Iatrogenic Defects in Peripheral Tolerance Associated with Anti-Nephrin Antibody-Associated Minimal Change Disease.},
journal = {Glomerular diseases},
volume = {5},
number = {1},
pages = {74-83},
pmid = {39991196},
issn = {2673-3633},
abstract = {INTRODUCTION: Minimal change disease (MCD) is a common cause of nephrotic syndrome in children and adults. Immune dysregulation is a contributor, but the relative roles of individual components of the immune system in MCD pathogenesis remain unclear.

CASE PRESENTATION: Here, we present 2 patients with defects in immune tolerance mechanisms that developed MCD associated with anti-nephrin antibodies. The first patient had a pathogenic deletion in FOXP3, leading to reduced regulatory T cells. Serum could not be obtained from this patient during the active phase of MCD to directly establish the presence of anti-nephrin antibodies. However, this patient demonstrated IgG dusting over podocyte cell bodies by immunofluorescence microscopy, as well as colocalization of IgG with nephrin in confocal microscopy. The second patient developed MCD in the context of immune checkpoint inhibitor treatment for metastatic carcinoma. Anti-nephrin antibodies were detected in this patient during active disease. The patient's kidney biopsy also showed evidence of binding of anti-nephrin antibodies within the glomeruli.

CONCLUSION: These cases demonstrate that genetic and iatrogenic mechanisms of breakdown in peripheral tolerance can lead to MCD.},
}

@article {pmid39990276,
year = {2025},
author = {Goel, U and Zanwar, S and Cowan, AJ and Banerjee, R and Khouri, J and Dima, D},
title = {Ciltacabtagene Autoleucel for the Treatment of Relapsed/Refractory Multiple Myeloma: Efficacy, Safety, and Place in Therapy.},
journal = {Cancer management and research},
volume = {17},
number = {},
pages = {357-372},
pmid = {39990276},
issn = {1179-1322},
abstract = {Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are two chimeric antigen receptor T cell (CAR T) therapies approved for use in patients with relapsed/refractory multiple myeloma (MM). Initially approved for late line MM (>4 prior lines), these were recently approved for use in MM with 1-2 prior lines of therapy in April 2024. As their use outside of the pivotal clinical trials continues to expand, it is important to critically evaluate the safety and efficacy of these therapies. Further, it is important to identify patients that would be most likely to benefit from the use of CAR T in earlier lines of therapy. Cilta-cel was initially studied in the phase-I LEGEND-2 study, followed by CARTITUDE-1 and CARTITUDE-4 trials, demonstrating remarkable efficacy. A recent large real-world study also demonstrated similar efficacy, in a mostly pivotal trial ineligible patient population. Based on these impressive results, cilta-cel is currently being studied in trials for newly diagnosed as well as smoldering multiple myeloma. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) are known toxicities of cilta-cel (and other CAR Ts), however movement and cognitive disorders (delayed neurotoxicity) and second primary malignancies are an evolving concern. In this article we discuss safety and efficacy data from existing cilta-cel studies. We propose that all patients with MM who have received ≥4 prior lines of therapy should be considered for CAR T. Earlier line use of CAR T should be restricted to patients with a high-risk disease phenotype (eg, functional high-risk disease). This disease phenotype has historically shown poor outcomes with standard triplet regimens and would be most likely to benefit from earlier use of CAR T: considering the availability of other safe and highly effective therapies, and potential high-risk toxicities of CAR T.},
}

@article {pmid39975072,
year = {2025},
author = {Radford, CE and Bloom, JD},
title = {Comprehensive maps of escape mutations from antibodies 10-1074 and 3BNC117 for Envs from two divergent HIV strains.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975072},
issn = {2692-8205},
support = {R01 AI140891/AI/NIAID NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; U01 AI169385/AI/NIAID NIH HHS/United States ; },
abstract = {Antibodies capable of neutralizing many strains of HIV are being explored as prophylactic and therapeutic agents, but viral escape mutations pose a major challenge. Efforts have been made to experimentally define the escape mutations from specific antibodies in specific viral strains, but it remains unclear how much the effects of mutations on neutralization differ among HIV strains. Here, we use pseudovirus deep mutational scanning to comprehensively map escape mutations from the V3 loop targeting antibody 10-1074 and the CD4-binding site targeting antibody 3BNC117 for both a clade A (BF520) and a clade B (TRO.11) HIV Envelope (Env). Mutations that escape neutralization by antibody 10-1074 are largely similar for the two Envs, but mutations that escape 3BNC117 differ greatly between Envs. Some differences in the effects of mutations on escape between Envs can be explained by strain-to-strain variation in mutational tolerance or glycosylation patterns, but other mutations have different effects on escape for unclear reasons. Overall, the extent that measurements of mutational effects on antibody neutralization can be generalized across HIV strains differs among antibodies.},
}

@article {pmid39974143,
year = {2025},
author = {Park, MS and Kumar, RD and Ovadiuc, C and Folta, A and McEwen, AE and Snyder, A and Fowler, DM and Rubin, AF and Shirts, BH and Starita, LM and Stergachis, AB},
title = {Insights on improving accessibility and usability of functional data to unlock its potential for variant interpretation.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39974143},
support = {R01 HG013025/HG/NHGRI NIH HHS/United States ; UM1 HG011969/HG/NHGRI NIH HHS/United States ; },
abstract = {INTRODUCTION: Variant-level functional data is a core component of clinical variant classification and can aid in reinterpreting variants of uncertain significance (VUS). However, the usage of functional data by genetics professionals is currently unknown.

METHODS: An online survey was developed and distributed in spring of 2024 to individuals actively engaged in variant interpretation. Quantitative and qualitative methods were used to assess responses.

RESULTS: 190 eligible individuals responded, with 93% reporting interpreting 26 or more variants per year. The median respondent reported 11-20 years of experience. The most common professional roles were laboratory medical geneticists (23%) and variant review scientists (23%). 77% reported using functional data for variant interpretation in a clinical setting and overall respondents felt confident in assessing functional data. However, 67% indicated that functional data for variants of interest was rarely or never available, and 91% considered insufficient quality metrics or confidence in the accuracy of data as barriers to its use. 94% of respondents noted that better access to primary functional data and standardized interpretation of functional data would improve usage. Respondents also indicated that handling conflicting functional data is a common challenge in variant interpretation that is not performed in a systematic manner across institutions.

DISCUSSION: The results from this survey showed a demand for a comprehensive database with reliable quality metrics to support use of functional evidence in clinical variant interpretation. The results also highlight a need for guidelines regarding how putatively conflicting functional data should be used for variant classification.},
}

@article {pmid39990199,
year = {2025},
author = {Meehan, KA and Waters, AR and Wangen, M and Odebunmi, OO and Ferrari, RM and Marciniak, MW and Brenner, AT and Wheeler, SB and Shah, PD},
title = {Not just about pills: Findings from a national survey of pharmacists to understand their views on addressing social determinants of health.},
journal = {Preventive medicine reports},
volume = {51},
number = {},
pages = {102991},
pmid = {39990199},
issn = {2211-3355},
abstract = {OBJECTIVE: We evaluated community pharmacists' perspectives on addressing social determinants of health for their patients in the United States.

METHODS: From 9/2022-1/2023, we conducted a national, online survey of 578 pharmacists to evaluate their perspectives on social barriers affecting their patients, their pharmacy staff's ability to address these social barriers, and resources available or needed to address barriers.

RESULTS: Healthcare access and quality was perceived as the most addressable social barrier (59 %), while education (24 %) and neighborhood/built environment were perceived as the least addressable (14 %). Staff capacity to address social needs was significantly associated with increases in the pharmacy's ability to address social determinants of health across all five domains. Pharmacists were more likely to report adequate staff capacity if they practiced in independent community pharmacies.

CONCLUSIONS: Pharmacists commonly address social determinants of health of their patients, but most lack adequate staff capacity to address patient social barriers. Pharmacies with capacity can only address a portion of the social needs of their patient population. Greater access to resources and staffing support are needed to improve pharmacy's role in addressing patient unmet social needs.},
}

@article {pmid39989044,
year = {2025},
author = {Unger, JM and Mazza, GL and Elsaid, MI and Duan, F and Dressler, EV and Snavely, AC and Enserro, DM and Pugh, SL},
title = {When to adjust for multiplicity in cancer clinical trials.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {2025},
number = {68},
pages = {3-9},
pmid = {39989044},
issn = {1745-6614},
support = {UG1 CA189974/CA/NCI NIH HHS/United States ; //ECOG/ ; UG1CA189961//University of Rochester/ ; UG1 CA189823/CA/NCI NIH HHS/United States ; UG1CA189974/NH/NIH HHS/United States ; UG1CA189824//Wake Forest University/ ; UG1CA189961//Alliance NCORP Research Base/ ; U10 CA180794/CA/NCI NIH HHS/United States ; UG1CA189828//ACRIN/ ; U10 CA180819/CA/NCI NIH HHS/United States ; UG1CA189828//NRG Oncology/ ; 5UG1CA189955-11//Children's Oncology Group/ ; UG1 CA189867/CA/NCI NIH HHS/United States ; P30 CA016058-47S1//ACRIN/ ; UG1CA189974//SWOG/ ; UG1 CA189828/CA/NCI NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; UG1CA189823//SWOG Cancer Research Network/ ; U10CA180822//Wake Fores NCORP Research Base/ ; P30 CA016058/CA/NCI NIH HHS/United States ; UG1 CA189961/CA/NCI NIH HHS/United States ; UG1CA189867//NCI Community Oncology Research Program/ ; UG1 CA189824/CA/NCI NIH HHS/United States ; UG1CA189824//URCC NCORP Research Base/ ; },
mesh = {Humans ; *Neoplasms/therapy ; *Clinical Trials as Topic ; Research Design ; United States ; National Cancer Institute (U.S.) ; Data Interpretation, Statistical ; False Positive Reactions ; },
abstract = {Interpreting cancer clinical trial results often depends on addressing issues of multiplicity. When testing multiple hypotheses, unreliable findings can occur by chance due to the inflation of the type I error rate, the probability of mistakenly rejecting the null hypothesis when the null hypothesis is true. In this setting, researchers may often set the type I error rate (or the alpha level) low to limit false positive findings and the interpretation of a causal relationship where none exists. Conversely, overly conservative type I error control may result in declaring findings, that do not meet multiplicity-adjusted alpha levels, as false when they are actually true, reducing opportunities for new discovery. This presentation focuses on multiplicity adjustment in the context of clinical trials conducted within the NCI's Community Oncology Research Program (NCORP). Because federally sponsored trials often require long-term participation from patients and represent a substantial investment by taxpayers, striking the right balance between optimizing what is learned from these trials, while avoiding false positive results, should be a priority.},
}

Humans
*Neoplasms/therapy
*Clinical Trials as Topic
Research Design
United States
National Cancer Institute (U.S.)
Data Interpretation, Statistical
False Positive Reactions

@article {pmid39989043,
year = {2025},
author = {Mazza, GL and Culakova, E and Enserro, DM and Dignam, JJ and Unger, JM},
title = {Design and analysis considerations for investigating patient subgroups of interest within cancer clinical trials.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {2025},
number = {68},
pages = {22-29},
pmid = {39989043},
issn = {1745-6614},
support = {UG1CA189823/NH/NIH HHS/United States ; 5UG1CA189955-11//Children's Oncology Group/ ; //NCI Community Oncology Research Program/ ; UG1 CA189974/CA/NCI NIH HHS/United States ; //ECOG/ ; UG1CA189974//SWOG/ ; UG1CA189961//University of Rochester/ ; UG1 CA189823/CA/NCI NIH HHS/United States ; UG1 CA189961/CA/NCI NIH HHS/United States ; UG1 CA189824/CA/NCI NIH HHS/United States ; UG1CA189828//ACRIN/ ; U10 CA180822/CA/NCI NIH HHS/United States ; UG1 CA189828/CA/NCI NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; UG1CA189824//Wake Forest University/ ; UG1CA189867//NRG Oncology/ ; },
mesh = {Humans ; *Neoplasms/therapy ; *Clinical Trials as Topic ; *Research Design ; Precision Medicine/methods ; United States ; Patient Selection ; National Cancer Institute (U.S.) ; },
abstract = {Examining treatment effects in subgroups of patients defined by demographic, genetic, or clinical characteristics is increasingly of interest given the pursuit of personalized medicine and the importance of representation and equity in treatment decisions. The magnitude or even the direction of the treatment effect may vary across subgroups, and these differential treatment effects could have clinical implications. Subgroup analyses require caution in their interpretation, however, because of the high probability of a false-positive or false-negative conclusion. We outline study design and analysis considerations for responsibly investigating and reporting differential treatment effects across subgroups in oncology trials, with examples from the National Cancer Institute's National Clinical Trials Network and Community Oncology Research Program. Recommendations include ensuring appropriate representation of patients from subgroups of interest, recognizing power and multiplicity limitations, and treating exploratory subgroup analyses as hypothesis generating rather than practice changing.},
}

Humans
*Neoplasms/therapy
*Clinical Trials as Topic
*Research Design
Precision Medicine/methods
United States
Patient Selection
National Cancer Institute (U.S.)

@article {pmid39989038,
year = {2025},
author = {Bandos, H and Torres-Saavedra, PA and Culakova, E and Gunn, HJ and Lee, MK and Duan, F and Cecchini, RS and Unger, JM and Dueck, AC and Steingrimsson, JA},
title = {Best practices and pragmatic approaches for patient-reported outcomes and quality of life measures in cancer clinical trials.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {2025},
number = {68},
pages = {14-21},
pmid = {39989038},
issn = {1745-6614},
support = {5UG1CA189955-11//Children's Oncology Group/ ; //Community Oncology Research Program/ ; UG1 CA189974/CA/NCI NIH HHS/United States ; UG1CA189974//SWOG/ ; UG1CA189961//University of Rochester/ ; UG1 CA189823/CA/NCI NIH HHS/United States ; UG1 CA189824/CA/NCI NIH HHS/United States ; UG1CA189828//ACRIN/ ; U10 CA180819/CA/NCI NIH HHS/United States ; //ECOG/ ; U10CA180822/BC/NCI NIH HHS/United States ; UG1 CA189828/CA/NCI NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; UG1CA189824//Wake Forest University/ ; UG1CA189867//NRG Oncology/ ; /NH/NIH HHS/United States ; UG1 CA189961/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Quality of Life ; *Neoplasms/therapy/psychology ; *Patient Reported Outcome Measures ; *Clinical Trials as Topic ; Research Design ; },
abstract = {Patient-reported outcomes (PROs) are often collected in cancer clinical trials. Data obtained from trials with PROs are essential in evaluating participant experiences relating to symptoms, financial toxicity, or health-related quality of life. Although most features of clinical trial design, implementation, and analyses apply to trials with PROs, several considerations are unique. In this paper, we focus on specific issues such as selection of the tool, timing and frequency of assessments, and data collection methods. We discuss how the estimand framework can be used in connection with PROs, properties of common estimation methods, and handling of missing outcomes. With a plethora of literature available, we aim to summarize best practices and pragmatic approaches to the design and analysis of the studies incorporating PROs.},
}

Humans
*Quality of Life
*Neoplasms/therapy/psychology
*Patient Reported Outcome Measures
*Clinical Trials as Topic
Research Design

@article {pmid39989035,
year = {2025},
author = {Dressler, EV and Pugh, SL and Gunn, HJ and Unger, JM and Zahrieh, DM and Snavely, AC},
title = {Practical design considerations for cluster randomized controlled trials: lessons learned in community oncology research.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {2025},
number = {68},
pages = {56-64},
pmid = {39989035},
issn = {1745-6614},
support = {UG1 CA189974/CA/NCI NIH HHS/United States ; //ECOG/ ; R01CA207158/CA/NCI NIH HHS/United States ; UG1CA189824/CA/NCI NIH HHS/United States ; UG1CA189961//University of Rochester/ ; UG1 CA189823/CA/NCI NIH HHS/United States ; U10CA180822//Wake Forest NCORP/ ; //SWOG NCORP RB/ ; U10 CA180819/CA/NCI NIH HHS/United States ; 5UG1CA189955-11//Children's Oncology Group/ ; UG1 CA189867/CA/NCI NIH HHS/United States ; UG1 CA189828/CA/NCI NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; R01HS025194//Agency for Healthcare Research and Quality/ ; U10CA180882//NRG Oncology/ ; UG1CA189974//Alliance for Clinical Trials in Oncology/ ; UG1CA189824//Wake Forest University/ ; /NH/NIH HHS/United States ; UG1 CA189961/CA/NCI NIH HHS/United States ; UG1CA189867//NCI Community Oncology Research Program/ ; UG1 CA189824/CA/NCI NIH HHS/United States ; UG1CA189828//ACRIN/ ; R01 CA207158/CA/NCI NIH HHS/United States ; R01 HS025194/HS/AHRQ HHS/United States ; },
mesh = {Humans ; *Randomized Controlled Trials as Topic ; *Research Design ; *Medical Oncology/methods/standards ; *Neoplasms/therapy ; United States ; Cluster Analysis ; National Cancer Institute (U.S.) ; Sample Size ; Patient Selection ; },
abstract = {Cancer care delivery research trials conducted within the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) routinely implement interventions at the practice or provider level, necessitating the use of cluster randomized controlled trials (cRCTs). The intervention delivery requires cluster-level randomization instead of participant-level, affecting sample size calculation and statistical analyses to incorporate correlation between participants within a practice. Practical challenges exist in the conduct of these cRCTs due to unique trial network infrastructures, including the possibility of unequal participant accrual totals and rates and staggered study initiation by clusters, potentially with differences between randomized arms. Execution of cRCT designs can be complex, ie, if some clusters do not accrue participants, unintended cluster-level crossover occurs, how best to identify appropriate cluster-level stratification, timing of randomization, and multilevel eligibility criteria considerations. This article shares lessons learned with potential mitigation strategies from 3 NCORP cRCTs.},
}

Humans
*Randomized Controlled Trials as Topic
*Research Design
*Medical Oncology/methods/standards
*Neoplasms/therapy
United States
Cluster Analysis
National Cancer Institute (U.S.)
Sample Size
Patient Selection

@article {pmid39988778,
year = {2025},
author = {Stamatatos, L},
title = {The Germline Targeting Vaccine Concept: Overview and Updates from HIV Pre-Clinical and Clinical Trials.},
journal = {Current HIV research},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570162X358302250206074255},
pmid = {39988778},
issn = {1873-4251},
abstract = {An effective HIV-1 vaccine should elicit diverse immune responses, including broadly neutralizing antibodies (bNAbs). Such antibodies recognize regions of the viral envelope glyco-protein (Env) that are conserved among the diverse HIV-1 clades and strains. They are isolated from people living with HIV-1 to protect animals from experimental viral exposure and reduce HIV-1 acquisition in clinical settings. However, despite efforts spanning several decades, bNAbs have not been elicited through immunization. The HIV Env efficiently binds bNAbs, but not their unmutated (germline, gl) precursors. In contrast, Env readily engages the germline precursors of antibodies with no, or very narrow, cross-neutralizing activities (non-neutralizing antibodies, nnAbs). That, in part, explains why Env-based immunogens consistently elicit nnAbs, but not bNAbs. In the past decade, Env-derived proteins have been specifically designed to engage the germline precursors of diverse bNAbs. These 'germline-targeting' Env immunogens activate the corresponding naive B cells in vivo, but are unable to guide their proper maturation towards their broadly neutralizing forms. For this, immunizations with currently not well-defined heterologous Envs are required. Here, we discuss the development of germline-targeting Env immunogens, their in vivo evaluation, and the strategies currently under evaluation that aim to rapidly guide the mat-uration of germline-precursor BCRs into their broadly neutralizing forms.},
}

@article {pmid39975340,
year = {2025},
author = {Jochim, BE and Topalidou, I and Lehrbach, NJ},
title = {Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975340},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R35 GM142728/GM/NIGMS NIH HHS/United States ; },
abstract = {The Nrf/NFE2L family of transcription factors regulates redox balance, xenobiotic detoxification, metabolism, proteostasis, and aging. Nrf1/NFE2L1 is primarily responsible for stress-responsive upregulation of proteasome subunit genes and is essential for adaptation to proteotoxic stress. Nrf2/NFE2L2 is mainly involved in activating oxidative stress responses and promoting xenobiotic detoxification. Nrf1 and Nrf2 contain very similar DNA binding domains and can drive similar transcriptional responses. In C. elegans, a single gene, skn-1, encodes distinct protein isoforms, SKN-1A and SKN-1C, that function analogously to mammalian Nrf1 and Nrf2, respectively, and share an identical DNA binding domain. Thus, the extent to which SKN-1A/Nrf1 and SKN-1C/Nrf2 functions are distinct or overlapping has been unclear. Regulation of the proteasome by SKN-1A/Nrf1 requires post-translational conversion of N-glycosylated asparagine residues to aspartate by the PNG-1/NGLY1 peptide:N-glycanase, a process we term 'sequence editing'. Here, we reveal the consequences of sequence editing for the transcriptomic output of activated SKN-1A. We confirm that activation of proteasome subunit genes is strictly dependent on sequence editing. In addition, we find that sequence edited SKN-1A can also activate genes linked to redox homeostasis and xenobiotic detoxification that are also regulated by SKN-1C, but the extent of these genes' activation is antagonized by sequence editing. Using mutant alleles that selectively inactivate either SKN-1A or SKN-1C, we show that both isoforms promote optimal oxidative stress resistance, acting as effectors for distinct signaling pathways. These findings suggest that sequence editing governs SKN-1/Nrf functions by tuning the SKN-1A/Nrf1 regulated transcriptome.},
}

@article {pmid39987960,
year = {2025},
author = {Ross, WL and Santiago-Rivera, Y and Tan, MT and Roy, MM and Bryant, S and Appel, BE and Casillas, J and Demedis, J and Smitherman, AB and Horwitz, LI and Hurtado-de-Mendoza, A and Mendoza, JA and Santacroce, SJ and Kadan-Lottick, NS},
title = {Design and methods of a multi-level intervention to improve adherence to childhood cancer survivorship care by partnering with primary care providers: The BRIDGES randomized controlled trial.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {107859},
doi = {10.1016/j.cct.2025.107859},
pmid = {39987960},
issn = {1559-2030},
abstract = {BACKGROUND: Despite heightened risk of chronic health conditions, <20 % of childhood cancer survivors (CCS) receive guideline-recommended surveillance for late effects. Barriers include avoidance of reminders, lack of knowledge, and costs. The goal of the BRIDGES Study is to evaluate the effects of a multi-level, remote intervention on adherence to guideline-recommended surveillance among CCS by partnering with primary care providers (PCPs).

METHODS: This ongoing study is a multi-site, two-arm, prospective, parallel design, 1:1 randomized controlled non-inferiority trial (N = 240; n = 120/group). Eligibility criteria are: cancer diagnosis at age < 21 years, 2.0-4.0 years post-cancer therapy, and no previous specialty survivorship clinic care. The intervention includes: 1) patient survivorship education via telehealth with a cancer center nurse, including discussion of patient's individualized survivorship care plan (SCP), 2) ongoing patient-tailored health education within the electronic health record's patient portal, 3) a structured interactive phone call between the cancer center nurse and PCP, including discussion of patient's SCP, and 4) an in-person PCP visit for survivorship care. Patients randomized to the comparison group are contacted to schedule an in-person visit at their cancer center-based survivorship clinic. Adherence to guideline-recommended surveillance tests (primary outcome) is assessed at 1-year post-randomization (primary follow-up time point) and 2-years post-randomization (for durability). Patient knowledge, self-efficacy, and activation; PCP knowledge and self-efficacy; and process outcomes are also assessed.

CONCLUSION: Models of survivorship care that overcome existing barriers are needed. If efficacious, this scalable, remote intervention would be a valuable strategy to address barriers and bridge gaps in care to reach more CCS.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05448560.},
}

@article {pmid39986828,
year = {2025},
author = {Lange, PH and Schellhammer, PF},
title = {Tribute to Michael Droller MD.},
journal = {Urologic oncology},
volume = {43},
number = {2},
pages = {94},
doi = {10.1016/j.urolonc.2024.05.008},
pmid = {39986828},
issn = {1873-2496},
}

@article {pmid39985691,
year = {2025},
author = {Viskochil, RH and Lin, T and Gigic, B and Himbert, C and Bandera, VM and Skender, S and Holowatyj, AN and Schrotz-King, P and Steindorf, K and Strehli, I and Mutch, MG and Chao, D and Toriola, AT and Shibata, D and Siegel, EM and Li, CI and Hardikar, S and Peoples, AR and Figueiredo, JC and Schneider, M and Ulrich, CM and Ose, J},
title = {Sedentary behavior and physical activity one year after colorectal cancer diagnosis: results from the ColoCare Study.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {39985691},
issn = {1932-2267},
abstract = {PURPOSE: Physical activity plays key roles in colorectal cancer survivorship; however, the impact of different clinicodemographic outcomes on cross-sectional and longitudinal objectively measured physical activity 12 and 24 months post-diagnosis are unclear.

METHODS: ColoCare study participants (n = 165) wore an Actigraph GT3x accelerometer for 4-10 consecutive days to objectively assess activity levels 12 and 24 months after colorectal cancer diagnosis and resection. Associations between these clinical/demographic exposures and physical activity outcomes and longitudinal changes were determined using t-test, ANOVA F-test, and linear regression modeling, adjusting for common confounders (e.g., sex, age, stage).

RESULTS: Key physical activity and sedentary behavior variables significantly differed by demographic status, including minutes of weekly exercise by sex and age (age < 50: 364 min ± 303 min; age 50-70: 232 min ± 263 min; age > 70: 93 min ± 135 min, p < 0.001) and (%) daily sedentary time by age (age < 50: 64 ± 10%; age 50-70: 67 ± 7%; age > 70: 71 ± 7%, p = 0.003). Within the multivariate model, age was the primary measure consistently associated with activity differences. Participants who wore accelerometers 12- and 24-month post-resection (n = 52) significantly increased weekly exercise minutes (214 min ± 208 min vs. 288 min ± 316 min, p = 0.04).

CONCLUSION: Age is the primary clinicodemographic determinant separating physical activity levels in colorectal cancer survivors, and increases in exercise from 12 to 24 months are likely due to consolidation of sporadic daily physical activity into bouts of exercise.

Colorectal cancer survivors experience different volumes and changes in accelerometer-derived physical activity based on some (e.g., age) but not all (e.g., stage) clinicodemographic variables.},
}

@article {pmid39984572,
year = {2025},
author = {Ahmed, SR and Befano, B and Egemen, D and Rodriguez, AC and Desai, KT and Jeronimo, J and Ajenifuja, KO and Clark, C and Perkins, R and Campos, NG and Inturrisi, F and Wentzensen, N and Han, P and Guillen, D and Norman, J and Goldstein, AT and Madeleine, MM and Donastorg, Y and Schiffman, M and de Sanjose, S and Kalpathy-Cramer, J and , },
title = {Generalizable deep neural networks for image quality classification of cervical images.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {6312},
pmid = {39984572},
issn = {2045-2322},
mesh = {Humans ; Female ; *Uterine Cervical Neoplasms/diagnostic imaging/diagnosis/pathology ; *Neural Networks, Computer ; *Cervix Uteri/diagnostic imaging/pathology ; Image Processing, Computer-Assisted/methods ; Image Interpretation, Computer-Assisted/methods ; Deep Learning ; Artificial Intelligence ; },
abstract = {Successful translation of artificial intelligence (AI) models into clinical practice, across clinical domains, is frequently hindered by the lack of image quality control. Diagnostic models are often trained on images with no denotation of image quality in the training data; this, in turn, can lead to misclassifications by these models when implemented in the clinical setting. In the case of cervical images, quality classification is a crucial task to ensure accurate detection of precancerous lesions or cancer; this is true for both gynecologic-oncologists' (manual) and diagnostic AI models' (automated) predictions. Factors that impact the quality of a cervical image include but are not limited to blur, poor focus, poor light, noise, obscured view of the cervix due to mucus and/or blood, improper position, and over- and/or under-exposure. Utilizing a multi-level image quality ground truth denoted by providers, we generated an image quality classifier following a multi-stage model selection process that investigated several key design choices on a multi-heterogenous "SEED" dataset of 40,534 images. We subsequently validated the best model on an external dataset ("EXT"), comprising 1,340 images captured using a different device and acquired in different geographies from "SEED". We assessed the relative impact of various axes of data heterogeneity, including device, geography, and ground-truth rater on model performance. Our best performing model achieved an area under the receiver operating characteristics curve (AUROC) of 0.92 (low quality, LQ vs. rest) and 0.93 (high quality, HQ vs. rest), and a minimal total %extreme misclassification (%EM) of 2.8% on the internal validation set. Our model also generalized well externally, achieving corresponding AUROCs of 0.83 and 0.82, and %EM of 3.9% when tested out-of-the-box on the external validation ("EXT") set. Additionally, our model was geography agnostic with no meaningful difference in performance across geographies, did not exhibit catastrophic forgetting upon retraining with new data, and mimicked the overall/average ground truth rater behavior well. Our work represents one of the first efforts at generating and externally validating an image quality classifier across multiple axes of data heterogeneity to aid in visual diagnosis of cervical precancer and cancer. We hope that this will motivate the accompaniment of adequate guardrails for AI-based pipelines to account for image quality and generalizability concerns.},
}

Humans
Female
*Uterine Cervical Neoplasms/diagnostic imaging/diagnosis/pathology
*Neural Networks, Computer
*Cervix Uteri/diagnostic imaging/pathology
Image Processing, Computer-Assisted/methods
Image Interpretation, Computer-Assisted/methods
Deep Learning
Artificial Intelligence

@article {pmid39983446,
year = {2025},
author = {Ficarra, S and Kang, DW and Wilson, RL and Gonzalo-Encabo, P and Christopher, CN and Normann, AJ and Lopez, P and Lakićević, N and Dieli-Conwright, CM},
title = {Exercise medicine for individuals diagnosed with Lung Cancer: A systematic review and meta-analysis of health outcomes.},
journal = {Lung cancer (Amsterdam, Netherlands)},
volume = {201},
number = {},
pages = {108413},
doi = {10.1016/j.lungcan.2025.108413},
pmid = {39983446},
issn = {1872-8332},
abstract = {Consensus exists regarding the need to provide exercise interventions to individuals diagnosed with lung cancer (LC). Exercise interventions for this populations usually include multidisciplinary approaches, making the attempt to understand the effects of exercise a real challenge. Therefore, we designed a systematic review to identify the effects of exercise interventions among individuals with a LC diagnosis. Following the PRISMA guidelines, studies across 5 different databases were systematically screened. Eligible studies were randomised and non-randomised trials, including individuals with a LC diagnosis, administering exercise-only interventions. Three-level meta-analyses were performed for cardiorespiratory fitness, strength, physical function, anxiety, depression, and health-related quality of life. Differences between exercise types were also explored. The Cochrane Risk of Bias (RoB) II tool for randomised controlled trials and the RoB in non-randomised studies - of interventions were used to assess study quality. A total of 36,304 records were screened and 13 studies, including 547 LC survivors, were considered eligible. Randomised and non-randomised trials were mainly judged as "some concern" and at "serious" RoB, respectively. Meta-analyses reported significant improvements on physical function among exercise groups compared to control (ES = 0.62; 95 % CI: 0.10 to 1.15; p = 0.03), and no significant changes for all other variables. There is moderate evidence that exercise interventions appear to be an effective tool to improve physical function among individuals diagnosed with LC. Further studies are still needed to determine exercise prescription effectiveness on health outcomes, differences across exercise types and enhance individualized interventions.},
}

@article {pmid39982694,
year = {2025},
author = {Alduhayh, S and Laskar, RS and Jiang, X and Zhu, Z and Vincent, EE and Constantinescu, AE and Buchanan, DD and Grant, RC and Phipps, AI and Brenner, H and Huang, WY and Kweon, SS and Li, L and Pearlman, R and Castellví-Bel, S and Gruber, SB and Li, CI and Pellatt, A and Platz, EA and Van Guelpen, B and Zheng, W and Chan, AT and Figueiredo, JC and Ogino, S and Ulrich, CM and Gunter, MJ and Haycock, P and Severi, G and Murphy, N and Dimou, N},
title = {Association of genetic liability to allergic diseases with overall and early-onset colorectal cancer risk: a Mendelian randomization study.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-0970},
pmid = {39982694},
issn = {1538-7755},
abstract = {BACKGROUND: Tumor immunosurveillance theory supports that allergic conditions could decrease cancer risk. However, observational evidence yielded inconsistent results for the association between allergic diseases and colorectal cancer risk. We used Mendelian randomization (MR) to examine potential causal associations of allergies with risk of overall and early-onset colorectal cancer.

METHODS: Genome-wide association study summary statistic data were used to identify genetic variants associated with allergic diseases (Nvariants=65) and individual allergic conditions (asthma, hay fever/allergic rhinitis, eczema). Using two-sample MR, we examined these variants in relation to incident overall (Ncases=52,775 cases) and early-onset colorectal cancer (Ncases=6,176). The mediating role of white blood cells was examined using multivariable MR.

RESULTS: In inverse-variance weighted models, genetic liability to allergic diseases was inversely associated with overall (ORper log(odds)= 0.90 [95% CI= 0.85-0.96]; P< 0.01) and early-onset colorectal cancer (OR= 0.83 [95% CI= 0.73-0.95]; P= 0.01). Similar inverse associations were found for hay fever/allergic rhinitis or eczema, while no evidence of association was found between liability to asthma-related phenotypes and colorectal cancer risk. Multivariable MR adjustment for eosinophils weakened the inverse associations for liability to allergic diseases for overall (OR= 0.96 [95% CI= 0.89-1.03]; P= 0.26) and early-onset colorectal cancer (OR= 0.86 [95% CI= 0.73-1.01]; P= 0.06).

CONCLUSIONS: Our study supports a potential causal association between liability to allergic diseases, specifically hay fever/allergic rhinitis or eczema, and colorectal cancer, possibly at least in part mediated via eosinophil counts.

IMPACT: Our results provide evidence that allergic responses may also have a role in immunosurveillance against colorectal cancer.},
}

@article {pmid39982410,
year = {2025},
author = {Burfeind, KG and Funahashi, Y and Su, XT and Lackey, AE and Hagen, MW and Blanche, S and Emathinger, JM and Hebert, JF and McDonough, AA and Gurley, SB and Nelson, JW and Hutchens, MP},
title = {Kidney cell response to acute cardiorenal and isolated kidney ischemia-reperfusion injury.},
journal = {Physiological genomics},
volume = {},
number = {},
pages = {},
doi = {10.1152/physiolgenomics.00161.2024},
pmid = {39982410},
issn = {1531-2267},
support = {I01BX004288//U.S. Department of Veterans Affairs (VA)/ ; W81XWH2010196/PR191304//U.S. Department of Defense (DOD)/ ; 20CDA35320169//American Heart Association (AHA)/ ; K01DK121737//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; //Collins Medical Trust (CMT)/ ; TL1TR002371//HHS | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; KL2TR002370//HHS | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; 24CDA1269598//American Heart Association (AHA)/ ; },
abstract = {Acute cardiorenal syndrome (CRS) represents a critical intersection of cardiac and renal dysfunction with profound clinical implications. Despite its significance, the molecular underpinnings that mediate cellular responses within the kidney during CRS remain inadequately understood. We employed single nucleus RNA sequencing (snRNAseq) to dissect the cellular transcriptomic landscape of the kidney following in a translational model of CRS, cardiac arrest/cardiopulmonary resuscitation (CA/PCR) in comparison to ischemia reperfusion injury (IRI). In each dataset, we found that proximal tubule (PT) cells of the kidney undergo significant gene expression changes, with decreased expression of genes critically important for cell identity and function, indicative of dedifferentiation. Based on this, we created a novel score to capture the dedifferentiation state of each kidney cell population and found that certain epithelial cell populations, such as the PT S1 and S2 segments, as well as the distal convoluted tubule, exhibited significant dedifferentiation response. Interestingly, the dedifferentiation response in the distal nephron differed in magnitude between IRI and CA/CPR. Gene set enrichment analysis (GSEA) of PT response to IRI and CA/CPR revealed similarities between the two models and key differences, including enrichment of immune system process genes. Transcriptional changes in both mouse models of AKI highly correlated with a dataset of human biopsies from patients diagnosed with acute kidney injury (AKI). This comprehensive single nucleus transcriptomic profiling provides valuable insights into the cellular mechanisms driving CRS.},
}

@article {pmid39981705,
year = {2025},
author = {Taylor, MR and Bradford, MC and Zhou, C and Fladeboe, KM and Wittig, JF and Baker, KS and Yi-Frazier, JP and Rosenberg, AR},
title = {Heart Rate Variability as a Digital Biomarker in Adolescents and Young Adults Receiving Hematopoietic Cell Transplantation.},
journal = {Cancer medicine},
volume = {14},
number = {4},
pages = {e70609},
pmid = {39981705},
issn = {2045-7634},
support = {//American Cancer Society/ ; },
mesh = {Humans ; Adolescent ; *Hematopoietic Stem Cell Transplantation ; *Heart Rate ; Male ; Female ; Young Adult ; *Quality of Life ; *Patient Reported Outcome Measures ; Anxiety ; Biomarkers ; Child ; Prospective Studies ; Depression ; Adult ; Autonomic Nervous System/physiopathology ; },
abstract = {INTRODUCTION: Adolescents and young adults (AYAs) receiving hematopoietic cell transplantation (HCT) are at high risk for poor psychosocial outcomes. Heart rate variability (HRV), a surrogate for autonomic nervous system activity, is a promising digital biomarker that has been linked to important outcomes. The objectives of this study were to prospectively describe the trajectory of HRV among AYAs receiving HCT and explore the association between HRV and patient-reported outcomes (PROs).

METHODS: This was a multi-site study embedded in a randomized trial among AYAs receiving HCT (NCT03640325). We collected sequential 24-h HRV metrics, including the standard deviation of normal-to-normal beats (SDNN), root-mean-square of successive differences (RMSSD), as well as frequency domain measures. PRO surveys queried anxiety, depression, quality of life, hope, and resilience at baseline and 3 months. We summarized outcomes using descriptive statistics, and Pearson correlation coefficients were used to examine the relationship between HRV and PROs.

RESULTS: Thirty-nine HRV recordings were collected from n = 16 participants aged 12-21 years. There was a moderately strong correlation between inferior baseline HRV and higher anxiety and depression (anxiety: r = -0.35 (p = 0.18) for SDNN, r = -0.47 (p = 0.07) for RMSSD; depression: r = -0.26 (p = 0.34) for SDNN, r = -0.39 (p = 0.14) for RMSSD). Among participants with elevated baseline anxiety, higher HRV suggested greater improvement in anxiety over time (r = -0.66 (p = 0.08) for SDNN, r = -0.31 (p = 0.45) for RMSSD).

CONCLUSIONS: There was a correlation between HRV and PROs in this study, and among those with elevated anxiety, HRV predicted improvement over time. Digital biomarkers may augment behavioral intervention design and implementation.},
}

Humans
Adolescent
*Hematopoietic Stem Cell Transplantation
*Heart Rate
Male
Female
Young Adult
*Quality of Life
*Patient Reported Outcome Measures
Anxiety
Biomarkers
Child
Prospective Studies
Depression
Adult
Autonomic Nervous System/physiopathology

@article {pmid39980037,
year = {2025},
author = {Nikolaienko, O and Anderson, GL and Chlebowski, RT and Jung, SY and Harris, HR and Knappskog, S and Lønning, PE},
title = {MGMT epimutations and risk of incident cancer of the colon, glioblastoma multiforme, and diffuse large B cell lymphomas.},
journal = {Clinical epigenetics},
volume = {17},
number = {1},
pages = {28},
pmid = {39980037},
issn = {1868-7083},
mesh = {Humans ; *Glioblastoma/genetics/epidemiology ; Female ; *Lymphoma, Large B-Cell, Diffuse/genetics/epidemiology ; *Tumor Suppressor Proteins/genetics ; *DNA Repair Enzymes/genetics ; *DNA Modification Methylases/genetics ; Case-Control Studies ; *DNA Methylation/genetics ; Aged ; Middle Aged ; *Promoter Regions, Genetic/genetics ; *Colonic Neoplasms/genetics/epidemiology ; Mutation ; Genetic Predisposition to Disease/genetics ; Epigenesis, Genetic/genetics ; Incidence ; },
abstract = {BACKGROUND: Constitutional BRCA1 epimutations (promoter hypermethylation) are associated with an elevated risk of triple-negative breast cancer and high-grade serous ovarian cancer. While MGMT epimutations are frequent in colon cancer, glioblastoma, and B-cell lymphoma, it remains unknown whether constitutional MGMT epimutations are associated with risk of any of these malignancies.

METHODS: We designed a nested case-control study, assessing potential associations between MGMT epimutations in blood from healthy individuals and subsequent risk of incident cancer. The study cohort was drawn from postmenopausal women, participating in the Women's Health Initiative (WHI) study, who had not been diagnosed with either colon cancer, glioblastoma, or B-cell lymphoma prior to study entry. The protocol included n = 400 women developing incident left-sided and n = 400 women developing right-sided colon cancer, n = 400 women developing diffuse large B-cell lymphomas, all matched on a 1:2 basis with cancer-free controls, and n = 195 women developing incident glioblastoma multiforme, matched on a 1:4 basis. All cancers were confirmed in centralized medical record review. Blood samples, collected at entry, were analyzed for MGMT epimutations by massive parallel sequencing. Associations between MGMT methylation and incident cancers were analyzed by Cox proportional hazards regression.

RESULTS: Analyzing epimutations affecting the key regulatory area of the MGMT promoter, the hazard ratio (HR) was 1.07 (95% CI 0.79-1.45) and 0.80 (0.59-1.08) for right- and left-sided colon cancer, respectively, 1.13 (0.78-1.64) for glioblastoma, and 1.11 (0.83-1.48) for diffuse large B-cell lymphomas. Sensitivity analyses limited to subregions of the MGMT promoter and to individuals with different genotypes of a functional SNP in the MGMT promoter (rs16906252), revealed no significant effect on HR for any of the cancer forms. Neither did we observe any effect of rs16906252 status on HR for any of the cancer forms among individuals methylated or non-methylated at the MGMT promoter.

CONCLUSIONS: Constitutional MGMT promoter methylation in normal tissue is not associated with an increased risk of developing colon cancer, glioblastoma, or B-cell lymphoma.},
}

Humans
*Glioblastoma/genetics/epidemiology
Female
*Lymphoma, Large B-Cell, Diffuse/genetics/epidemiology
*Tumor Suppressor Proteins/genetics
*DNA Repair Enzymes/genetics
*DNA Modification Methylases/genetics
Case-Control Studies
*DNA Methylation/genetics
Aged
Middle Aged
*Promoter Regions, Genetic/genetics
*Colonic Neoplasms/genetics/epidemiology
Mutation
Genetic Predisposition to Disease/genetics
Epigenesis, Genetic/genetics
Incidence

@article {pmid39979638,
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 = {Author Correction: Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.},
journal = {Nature aging},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43587-025-00837-x},
pmid = {39979638},
issn = {2662-8465},
}

@article {pmid39979464,
year = {2025},
author = {Briney, CA and Henriksen, JC and Lin, C and Jones, LA and Benner, L and Rains, AB and Gutierrez, R and Gafken, PR and Rissland, OS},
title = {Muskelin is a substrate adaptor of the highly regulated Drosophila embryonic CTLH E3 ligase.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {39979464},
issn = {1469-3178},
support = {5T32GM136444//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 5T32GM141742//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35GM128680//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 2P40OD010949//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; CAREER 2056136//National Science Foundation (NSF)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD030225/CD/ODCDC CDC HHS/United States ; },
abstract = {The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that in Drosophila the deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies because Drosophila lacks an identifiable substrate adaptor, and the mechanisms restricting the degradation of ME31B and its cofactors to the MZT are unknown. Here, we show that the developmental regulation of the CTLH complex is multi-pronged, including transcriptional control by OVO and autoinhibition of the E3 ligase. One major regulatory target is the subunit Muskelin, which we demonstrate is a substrate adaptor for the Drosophila CTLH complex. Finally, we find that Muskelin has few targets beyond the three known RNA-binding proteins, showing exquisite target specificity. Thus, multiple levels of integrated regulation restrict the activity of the embryonic CTLH complex to early embryogenesis, during which time it regulates three important RNA-binding proteins.},
}

@article {pmid38746305,
year = {2025},
author = {Ni, X and Richardson, RB and Godoy, AS and Ferla, MP and Kikawa, C and Scheen, J and Hannon, WW and Capkin, E and Lahav, N and Balcomb, BH and Marples, PG and Fairhead, M and Wang, S and Williams, EP and Tomlinson, CWE and Aschenbrenner, JC and Lithgo, RM and Winokan, M and Giroud, C and Chandran, AV and Walsh, M and Thompson, W and Bloom, JD and Barr, H and Kirkegaard, K and Koekemoer, L and Fearon, D and Evans, MJ and von Delft, F},
title = {Crystallographic fragment screening and deep mutational scanning of Zika virus NS2B-NS3 protease enable development of resistance-resilient inhibitors.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38746305},
issn = {2692-8205},
support = {U19 AI171399/AI/NIAID NIH HHS/United States ; },
abstract = {The Zika viral protease NS2B-NS3 is essential for the cleavage of viral polyprotein precursor into individual structural and non-structural (NS) proteins and is therefore an attractive drug target. Generation of a robust crystal system of co-expressed NS2B-NS3 protease has enabled us to perform a crystallographic fragment screening campaign with 1076 fragments. 47 fragments with diverse scaffolds were identified to bind in the active site of the protease, with another 6 fragments observed in a potential allosteric site. To identify binding sites that are intolerant to mutation and thus suppress the outgrowth of viruses resistant to inhibitors developed from bound fragments, we performed deep mutational scanning of NS2B-NS3 protease. Merging fragment hits yields an extensive set of 'mergers', defined as synthetically accessible compounds that recapitulate constellations of observed fragment-protein interactions. In addition, the highly sociable fragment hits enable rapid exploration of chemical space via algorithmic calculation and thus yield diverse possible starting points that maximally explore the binding opportunities to NS2B-NS3 protease, facilitating its resistance-resilient antiviral development.},
}

@article {pmid39977705,
year = {2025},
author = {Boiko, JR and Ensbey, KS and Waltner, OG and Jenkins, IC and Bhise, SS and MacDonald, KP and Blazar, BR and Hall, AM and Gooley, TA and Minnie, SA and Lee, SJ and Furlan, SN and Hill, GR},
title = {Defining pathogenic IL-17 and CSF-1 gene expression signatures in chronic graft-versus-host disease.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025337},
pmid = {39977705},
issn = {1528-0020},
abstract = {Chronic graft-versus-host disease (cGVHD) remains the leading cause of non-relapse morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Effective therapeutics agents targeting dysregulated cytokines including IL-17 and CSF-1 have been defined in preclinical models of cGVHD, and efficacy in subsequent clinical trials has led to their recent FDA approval. Despite this, these agents are effective in only a subset of patients, expensive, difficult to access outside the US, and used in a trial-and-error fashion. The ability to readily discern druggable, dysregulated immunity in these patients is desperately needed to facilitate the selection of appropriate treatment and to potentially identify high-risk individuals for preemptive therapy. We used single cell sequencing-based approaches in our informative preclinical cGVHD models to "reverse engineer" temporal IL-17 and CSF-1 signatures in mouse blood that could be used to interrogate patients. We defined distinct, non-intuitive IL-17 and CSF-1 signatures in mouse blood monocytes that could be identified in relevant monocytes within 70% of patients at diagnosis of cGVHD and in half of patients at day +100 post-HCT who subsequently developed cGVHD. These signatures can now be evaluated prospectively in clinical studies to help delineate potential responder and non-responders to relevant therapeutics targeting these pathways.},
}

@article {pmid39976968,
year = {2025},
author = {Umoren, RA and Ezeaka, C and Berkelhamer, SK and Hippe, DS and Asangansi, IE and Cook, MW and Fajolu, IB and Olawuyi, O and Adeboboye, C and Ekhalufoh, OO and Fashola, OS and Feltner, J and Fisher, JD and James, JM and Imoukhuede, OM and Park, N and Quach, V and Stiffler, AK and Engmann, CM},
title = {Essential Newborn Care Virtual Simulations for Skills Retention in Newborn Care.},
journal = {JAMA network open},
volume = {8},
number = {2},
pages = {e2460565},
pmid = {39976968},
issn = {2574-3805},
mesh = {Humans ; Infant, Newborn ; Female ; *Clinical Competence/statistics & numerical data ; Nigeria ; *Simulation Training/methods ; Male ; Adult ; Infant Care/methods ; Cohort Studies ; Health Personnel/education ; },
abstract = {IMPORTANCE: Newborn mortality accounts for approximately 47% of all mortality of children under the age of 5 years. Virtual simulation may be a viable approach to support retention of essential newborn care knowledge and skills among health care professionals in low- and middle-income countries.

OBJECTIVE: To evaluate the association between mobile virtual simulation using Virtual Essential Newborn Care (vENC) and knowledge and skills retention in early newborn care in low-resource settings and to propose a frequency of virtual simulation use for among health care professionals who care for newborns in low-resource settings.

This cohort study was conducted at 23 primary, secondary, and tertiary health care facilities in Lagos, Nigeria, for 6 months between December 1, 2022, and June 30, 2023. Participants included nurses and midwives who participated in deliveries and provided newborn care. Potential participants who attended a Helping Babies Breathe or Essential Newborn Care (ENC) course within the past 1 year were excluded.

EXPOSURES: All participants received in-person training using the World Health Organization ENC 1 and ENC 2 curricula along with virtual simulation practice at variable recommended frequencies for 6 months after course completion.

MAIN OUTCOMES AND MEASURES: Primary outcomes included assessments of bag-valve-mask (BVM) ventilation skills, and performance on ENC 1 and ENC 2 case A and B scenarios conducted by trained research assistants before, immediately after, and 6 months after the in-person course. All scores ranged from 0% to 100%, with higher scores indicating better performance.

RESULTS: Of 70 enrolled participants (67 of 69 [97%] female), 62 (89%) completed the 6-month follow-up. Immediate posttraining performance (median [IQR] scores: BVM ventilation skills, 93% [86%-100%]; ENC 1 case scenario A, 72% [61%-78%]; ENC 1 case scenario B, 76% [68%-88%]; ENC 2 case scenario A, 80% [73%-87%]; and ENC 2 case scenario B, 88% [70%-95%]) improved compared with pretraining performance for all skill assessments (median [IQR] scores: BVM ventilation skills, 57% [29%-64%]; ENC 1 case scenario A, 39% [28%-50%]); ENC 2 case scenario A, 33% [20%-45%]) (all P < .001). There were further gains in performance at the 6-month follow-up assessment for BVM ventilation (median [IQR], 100% [86%-100%]; P = .04) and the ENC1 and ENC2 assessments by case scenario (case scenario A: ENC 1 median [IQR] score, 78% [72%-83%]; P = .001 and ENC 2 median [IQR] score, 87% [80%-93%]; P = .008; and case scenario B: ENC 1 median [IQR] score, 88% [76%-92%]; P = .009 and ENC 2 median [IQR] score, 93% [80%-100%]; P = .004) relative to the immediate postcourse assessment scores.

CONCLUSIONS AND RELEVANCE: Findings of this cohort study suggest that the app-based simulations may be effective in supporting the retention of knowledge and skills following ENC training and may contribute to further performance gains for health care professionals in low- and middle-income countries. More clinical and implementation research is needed to explore the impact of virtual simulations on health professionals' clinical practices and neonatal outcomes.},
}

Humans
Infant, Newborn
Female
*Clinical Competence/statistics & numerical data
Nigeria
*Simulation Training/methods
Male
Adult
Infant Care/methods
Cohort Studies
Health Personnel/education

@article {pmid39976936,
year = {2025},
author = {DeVine, A and Landier, W and Hudson, MM and Constine, LS and Bhatia, S and Armenian, SH and Gramatges, MM and Chow, EJ and Friedman, DN and Ehrhardt, MJ},
title = {The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers: A Review.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2024.6812},
pmid = {39976936},
issn = {2374-2445},
abstract = {IMPORTANCE: Since 2003, the Children's Oncology Group (COG) has developed and disseminated the Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. These guidelines have benchmarked the standard of care for long-term survivors of childhood cancer in North America and beyond. Since their inception, they have evolved in depth, scope, and contributors to maintain fidelity toward continually emerging evidence related to cancer survivorship. They are intended to inform care for individuals who survived 2 or more years from completion of childhood, adolescent, and young adult cancer-directed therapy and receiving care in either specialty or primary care environments. The guidelines are updated on a 5-year cycle, during which comprehensive literature searches pertaining to guideline-specific questions are performed, evidence abstracted from pertinent publications, and recommendations determined and scored following expert deliberation.

OBSERVATIONS: Version 6.0 of the guidelines, released in October 2023, comprised 165 sections and 45 health links and represents the cooperative efforts of 220 individuals. Major changes include the addition of recommendations regarding surveillance for genetic cancer predisposition, surveillance following the use of novel cancer treatment modalities, and routine vaccination practices during long-term follow-up. In addition, surveillance echocardiograms were omitted for those at low risk of cardiomyopathy.

CONCLUSIONS AND RELEVANCE: This narrative review outlines the historical evolution of the COG Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, current methods guiding their development, and key recommendations from version 6.0. The guidelines are publicly available in their entirety online. The COG guidelines continue to set the standard for surveillance practices for long-term survivors of childhood, adolescent, and young adult cancer. The growing body of evidence supporting these recommendations will continue to guide their evolution to inform optimal survivorship care practices.},
}

@article {pmid39976415,
year = {2025},
author = {Dumm, W and Ralph, D and DeWitt, W and Vora, A and Araki, T and Victora, GD and Matsen Iv, FA},
title = {Leveraging DAGs to improve context-sensitive and abundance-aware tree estimation.},
journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences},
volume = {380},
number = {1919},
pages = {20230315},
doi = {10.1098/rstb.2023.0315},
pmid = {39976415},
issn = {1471-2970},
support = {/NH/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; //James S. McDonnell Foundation/ ; /RI/ORIP NIH HHS/United States ; },
mesh = {*Phylogeny ; Models, Genetic ; Receptors, Antigen, B-Cell/genetics ; Software ; Likelihood Functions ; },
abstract = {The phylogenetic inference package GCtree uses abundance of sampled sequences to improve the performance of parsimony-based inference, using a branching process model. Our previous work showed that GCtree performs competitively on B-cell receptor data, compared with other similar tools. In this article, we describe recent enhancements to GCtree, including an efficient tree storage data structure that discovers additional diversity of parsimonious trees with negligible additional computational cost. We also describe a suite of new objective functions that can be used to rank these trees, including a Poisson context likelihood function that models sequence evolution in a context-sensitive way. We validate these additions to GCtree with simulated B-cell receptor data, and benchmark performance against other phylogenetic inference tools.This article is part of the theme issue '"A mathematical theory of evolution": phylogenetic models dating back 100 years'.},
}

*Phylogeny
Models, Genetic
Receptors, Antigen, B-Cell/genetics
Software
Likelihood Functions

@article {pmid39974149,
year = {2025},
author = {Bhardwaj, S and Galanter, N and Berenbrok, LA and Shah, PD and Bacci, JL},
title = {Pediatric vaccination in pharmacies is not associated with delayed well-child visits among commercially insured children.},
journal = {Health affairs scholar},
volume = {3},
number = {2},
pages = {qxaf028},
pmid = {39974149},
issn = {2976-5390},
abstract = {Pediatric vaccination rates in the United States lag national goals. Policies that expand pharmacy-based vaccinations among children could help improve vaccination rates. Opponents argue, however, that such policies will result in delayed or missed well-child visits as most children receive routine vaccinations in primary care settings. We evaluated the likelihood of having a timely well-child visit following a routine vaccination in pharmacies and primary care settings among children aged 4-17 years. We conducted a retrospective cohort analysis with commercial claims data from 2016-2019, using conditional logistic regression models. A timely well-child visit was defined as one within 12 months after a preceding well-child visit for primary analysis and 15 months for secondary analysis. Approximately 95% of the sample consisted of children with influenza among their index vaccine(s). The odds of having a timely well-child visit were similar between children who received vaccines in pharmacies and those who received them in primary care settings. Findings suggest that guardians or parents who choose pharmacy-based pediatric vaccinations for their commercially insured children do not forgo well-child visits and may actually be more likely to obtain a timely well-child visit. Extending pharmacy-based vaccinations to patients of all ages can help improve pediatric vaccination rates.},
}

@article {pmid39973814,
year = {2025},
author = {Landi, D and Navai, SA and Brock, RM and Fousek, K and Nawas, Z and Sanber, K and Chauvin-Fleurence, C and Bhat, RR and Xu, S and Krishnamurthy, P and Choe, M and Campbell, M and Morris, JS and Gad, AZ and Shree, A and Echeandia, A and Saadeldin, A and Matthew, PR and Mullikin, D and Bielamowicz, K and Kurenbekova, L and Major, AM and Salsman, VS and Byrd, TT and Hicks, MJ and Zhang, YJ and Yustein, J and Carisey, AF and Joseph, SK and Ahmed, N and Hegde, M},
title = {A checkpoint reversal receptor mediates bipartite activation and enhances CAR T-cell function.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-24-0125},
pmid = {39973814},
issn = {2767-9764},
abstract = {The efficacy of CAR T-cells (CART) in solid tumors is limited by immune inhibition. In our study, we observed that effector cytokines mediated the upregulation of the PD-L1 immune-checkpoint in primary glioblastoma (GBM). To offset the PD-L1 inhibitory signal, we engineered PD-1 checkpoint reversal receptors (CPR) with a CD28 or 41BB co-stimulatory endodomain and co-expressed them with a first-generation or a CD28-containing second-generation HER2-specific CAR (CPR/CART) using bicistronic vectors. We found that bipartite T-cell activation, by CAR-generated signal 1 and CPR co-stimulation (signal 2), fine-tuned pro-inflammatory cytokine release and sustained antitumor activity. While both CPR28 and CPR41BB effectively counteracted the PD-1 signal in vitro, CPR41BB, when co-expressed with a first-generation CAR (CARζ/CPR41BB), promoted central memory differentiation following repeat antigenic stimulation. CARζ/CPR41BB T-cells formed a robust immune synapse with tumor targets, similar to a 4-1BB-containing second-generation CART, maintained the favorable metabolic parameters associated with 4-1BB co-stimulation, and demonstrated superior antitumor function after adoptive transfer in xenograft models of GBM and metastatic osteosarcoma. Thus, a CPR molecule with 4-1BB co-stimulation that curtails PD-1 inhibition and complements CAR signaling to optimize T-cell activation could enhance CART efficacy against solid tumors.},
}

@article {pmid39973220,
year = {2025},
author = {Meanley, S and Rodriguez Garcia, L and Lisha, NE and Ahmed, A and Korolkova, A and Figueroa, T and Nguyen, E and J Peluso, M and Cohn, LB and Deeks, S and Dubé, K and Sauceda, J},
title = {Exploring Stigma and Self-Image: Mixed-Methods Insights from HIV Cure-Related Research Participants Undergoing Analytical Treatment Interruptions.},
journal = {AIDS patient care and STDs},
volume = {},
number = {},
pages = {},
doi = {10.1089/apc.2024.0254},
pmid = {39973220},
issn = {1557-7449},
abstract = {This mixed-methods study explored self-image among people with HIV participating in an HIV cure-related study involving analytical treatment interruptions (ATIs). Using both quantitative and qualitative approaches, we described how self-image emerged across study participation, focusing on internalized stigma, emotional strengths, and the psychosocial dimensions of study participation. Data come from the SCOPE-ATI substudy (NCT00187512) of the University of California San Francisco SCOPE cohort (NCT04359186). Quantitative data were collected at three timepoints: pre-ATI (n = 15), post-ATI (n = 12), and end of the study (n = 14). We observed a general decline in self-image scores over time. However, participants maintained a moderately high agreement with statements about contributing to reducing HIV stigma through their involvement in the study. Qualitative interviews were collected pre-ATI (n = 11), during ATI (n = 8), and post-ATI (n = 6). Qualitative findings revealed two major themes shaping self-image: (1) experiencing and reconciling internalized HIV stigma and (2) self-evaluations in relation to life purpose. Many participants expressed disappointment at having to resume antiretroviral therapy, viewing it as a reminder of their HIV status and its associated stigma. Nevertheless, some found purpose and pride in their participation, motivated by altruistic contributions to improving future HIV control options. The findings highlight the emotional complexities of participating in HIV cure research and underscore the need for psychosocial support throughout ATI studies. While most participants experienced a decline in self-image, some derived meaning and empowerment from their involvement. This study suggests that addressing emotional well-being and reinforcing participants' contributions to science can enhance their experience in future research.},
}