@article {pmid40580948,
year = {2025},
author = {Khor, S and Carlson, JJ and Basu, A and Bansal, A and Yu, K and Fedorenko, CR and Ramsey, S and Shankaran, V},
title = {The association between new cancer therapy innovations and financial toxicity.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf152},
pmid = {40580948},
issn = {1460-2105},
abstract = {BACKGROUND: Recent advancements in cancer treatments have improved survival rates, but rising costs associated with these innovations raise concerns about their financial impact on patients. This study investigates the trade-off between improved survival and the financial toxicity over time in advanced non-small cell lung cancer (NSCLC).

METHODS: We conducted a retrospective cohort study using linked data from the Western Washington SEER cancer registry and TransUnion credit records, focusing on adults diagnosed with advanced NSCLC, bladder, uterine, head and neck, and liver cancers between 2013 and 2017. Financial toxicity was assessed through major adverse financial events (AFEs), including collections, charge offs, liens, delinquent payments, foreclosures, repossessions, and bankruptcies. Multivariable multinomial logistic regression evaluated trends in a composite outcome of survival and AFEs for NSCLC patients within two years post-diagnosis. A falsification test evaluated a negative control group of advanced cancers lacking new therapies.

RESULTS: Our study included 6548 patients (mean age 69; 42% female; 86% non-Hispanic White). Two-year survival for NSCLC patients increased from 15.2% to 19.2% between 2013 and 2017 (mean change 4.0%pt, 95%CI 0.7, 7.3). The proportion of survivors without AFEs increased by 2.2%pt (95%CI -0.6, 5.1), while those alive with major AFEs increased by 1.9%pt (95%CI 0.02, 3.6). This trend was absent in the negative control group.

CONCLUSIONS AND RELEVANCE: The trade-off between survival gains and increased economic hardships linked to treatment innovations underscores the need to expand our focus beyond clinical outcomes and implement protective measures that ensure healthcare advancements promote population health without inducing financial distress.},
}

@article {pmid40579877,
year = {2025},
author = {Dudakov, JA and van den Brink, MRM},
title = {Burning Down the House: Thymic Repair and Regeneration After Acute Damage.},
journal = {Immunological reviews},
volume = {332},
number = {1},
pages = {e70050},
doi = {10.1111/imr.70050},
pmid = {40579877},
issn = {1600-065X},
support = {R01-HL123340/HL/NHLBI NIH HHS/United States ; R01-HL145276/HL/NHLBI NIH HHS/United States ; R01-HL147584/HL/NHLBI NIH HHS/United States ; R01-HL165673/HL/NHLBI NIH HHS/United States ; R35-HL-171556/HL/NHLBI NIH HHS/United States ; P01-CA023766/CA/NCI NIH HHS/United States ; R01-CA228308/CA/NCI NIH HHS/United States ; R01-CA228358/CA/NCI NIH HHS/United States ; P01-AG052359/AG/NIA NIH HHS/United States ; U01-AI70035//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Thymus Gland/physiology/immunology/radiation effects ; *Regeneration ; Animals ; Signal Transduction ; Cytokines/metabolism ; },
abstract = {The thymus is extremely sensitive to insult but also has a remarkable capacity for endogenous repair. However, even though there is continual thymic involution and regeneration in response to everyday insults like stress and infection, profound thymic damage such as ionizing radiation leads to prolonged T cell lymphopenia for which there is currently no therapeutic treatment. We and others have been focusing in recent years on untangling the cellular and molecular mechanisms underlying endogenous thymic regeneration in the hope of being able to exploit them for clinical benefit. To date, multiple molecular mechanisms have been identified that are centered on several distinct cell axes, including interleukin-22 produced by innate lymphoid cells, BMP4 by endothelial cells, and type 2 cytokines from eosinophils, ILCs, and Tregs. Notably, one of the uniting triggers for these pathways of repair centers on the balance of cell death detection. In this review, we will highlight the current state of play with regard to cellular and molecular pathways of regeneration as well as the mechanisms triggering them. We will also highlight recent work that sheds light on the limitations of thymus repair and speculate as to what will be needed for an effective thymus-boosting therapy.},
}

Humans
*Thymus Gland/physiology/immunology/radiation effects
*Regeneration
Animals
Signal Transduction
Cytokines/metabolism

@article {pmid40578716,
year = {2025},
author = {Morrell, ED and Cheng, GS},
title = {Lumpers vs. Splitters: The Search for Treatable Traits in Post-Transplant BOS.},
journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.healun.2025.06.010},
pmid = {40578716},
issn = {1557-3117},
}

@article {pmid40578660,
year = {2025},
author = {Mitsunami, M and Soria-Contreras, DC and Ortiz-Panozo, E and Harris, HR and Missmer, SA and Chavarro, JE},
title = {Soy consumption and the risk of laparoscopically confirmed endometriosis in a prospective cohort study.},
journal = {Fertility and sterility},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.fertnstert.2025.06.028},
pmid = {40578660},
issn = {1556-5653},
abstract = {OBJECTIVE: To investigate the association of soy and isoflavone intake with the risk of laparoscopically confirmed endometriosis.

DESIGN: The Nurses' Health Study II, a prospective cohort study from 1991 to 2021.

SUBJECTS: 82,084 premenopausal participants aged 27-44 years in 1991 EXPOSURE: Soy and isoflavone intake was evaluated from 1991 and every 4 years using a food frequency questionnaire.

MAIN OUTCOME MEASURES: Self-reported laparoscopically confirmed endometriosis in biennial follow-up questionnaires. Cox proportional hazard models with age in months were used to calculate hazard ratios and 95% confidence intervals for laparoscopically-confirmed endometriosis. Restricted cubic splines were used to examine the possibility of non-linear relations between isoflavone intake and the risk of endometriosis.

RESULTS: 3,829 incident cases of laparoscopically confirmed endometriosis were reported over 1,038,888 person-years of follow-up (incidence rate = 369 per 100 000 person-years). Increasing soy intake by 1 serving per week was associated with a 8% lower risk of laparoscopically confirmed endometriosis (Hazard ratio=0.92, 95% confidence interval [0.87-0.98]). This association was present among participants without a concurrent report of infertility (Hazard ratio=0.92, 95% confidence interval [0.86, 0.99]) although not among participants with a concurrent infertility diagnosis (Hazard ratio=0.97, 95% confidence interval [0.83, 1.13], Test for heterogeneity 1.00). There was evidence of a non-linear inverse association of isoflavones intake with the risk of laparoscopically confirmed endometriosis (P, non-linearity = 0.02), in which the inverse association between isoflavones and endometriosis was approximately linear up until an intake of 4mg/day (∼95[th] percentile of intake), which plateaued thereafter.

CONCLUSION: In a population with a modest intake of soy products, consistent with levels seen in other Western populations, soy intake is associated with a lower risk of laparoscopically confirmed endometriosis.},
}

@article {pmid40578047,
year = {2025},
author = {Ssenyonga, N and Stiller, CA and Marcos-Gragera, R and Kuehni, CE and Saint-Jacques, N and Bulliard, JL and Redaniel, MT and Nakata, K and Schwartz, S and De, P and Ragusa, R and Troussard, X and Curado, MP and Girardi, F and Maynadié, M and Valkov, M and Guilloteau, A and Lima, C and Coleman, MP and Allemani, C and , },
title = {Conditional survival of children, adolescents and young adults (0-24 years) diagnosed with leukaemia during 2000-2014 world-wide: (CONCORD-3).},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {225},
number = {},
pages = {115445},
doi = {10.1016/j.ejca.2025.115445},
pmid = {40578047},
issn = {1879-0852},
abstract = {BACKGROUND: Population-based survival estimates provide valuable insights into cancer care patterns world-wide. Access to optimal treatment leads to better outcomes, however, treatment pathways vary globally. Conditional survival is the probability that patients who have already survived for a given number of years since diagnosis will live for an additional number of years. It is a useful proxy to assess the success of initial treatment or remission of leukaemia.

METHODS: We analysed data for 164,563 patients aged 0-24 years diagnosed during 2000-2014, from 258 population-based cancer registries in 61 countries. Using the Pohar-Perme estimator, we estimated net survival at five years, conditional on surviving at least one year, and at 10 years conditional on surviving five years. To control for background mortality, we used life tables of all-cause mortality by single year of age, sex, country and calendar year. All-ages survival estimates were standardised to the marginal age distribution.

FINDINGS: During 2010-2014, age-standardised five-year conditional net survival ranged from 61.8 % in Mexico to 90 % or more in 20 countries. By 2010-2014, five-year conditional survival in most high-income countries exceeded 90 % for children, but not for older patients, and for acute myeloid leukaemia it was typically 5-10 % lower than for lymphoid leukaemia. Ten-year conditional survival was 90 % or higher in most countries, with less variation world-wide.

INTERPRETATION: World-wide variation in survival was less marked for patients who survived the first year(s) after diagnosis. Notable gains occurred in countries with initially lower five-year survival (e.g., China or Mexico), where legislative changes contributed to improved access to treatment for young patients with cancer. Nonetheless, inequalities persisted between high-income and low- and middle-income countries. Population-based cancer registry data remain essential to monitor further improvements.

FUNDING: Children with Cancer UK; the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute and the American Cancer Society.},
}

@article {pmid40577227,
year = {2025},
author = {Perazzolo, S and Flexner, CW and Stephen, ZR and Acosta, EP and Bender Ignacio, RA and Ho, RJY},
title = {Long-acting Injectable Containing Lopinavir Eliminates Reliance on Ritonavir Pharmacokinetic Enhancement.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiaf319},
pmid = {40577227},
issn = {1537-6613},
abstract = {High-extraction protease inhibitors (e.g., for HIV and COVID-19) typically require ritonavir to enhance bioavailability by overcoming first-pass metabolism. However, in the long-acting subcutaneous injectable dosage form TLC-ART 101, lopinavir persisted in plasma for 57 days, while ritonavir was detectable for only 3-7 days. The remarkable duration of lopinavir suggests that ritonavir may be unnecessary in long-acting injectable products, potentially reducing side effects and drug-drug interactions.},
}

@article {pmid40576898,
year = {2025},
author = {Goodsell, KE and Chauhan, SSB and Pillarisetty, VG and Sham, JG},
title = {Somatostatin Analogs for Preventing Postoperative Pancreatic Fistula: Past Evidence Reveals New Opportunities.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {40576898},
issn = {1534-4681},
abstract = {Postoperative pancreatic fistula (POPF) is the defining complication following pancreatectomy. The incidence of POPF after pancreatic resection remains high even at experienced centers, with associated patient morbidity, increased healthcare costs, and poorer oncologic outcomes. There is evidence that POPF is more frequent after distal pancreatectomy. On the basis of the premise that reduction in pancreatic exocrine secretion reduces the risk of fistula formation, somatostatin analogs (SSA) to prevent POPF and its sequelae have been studied for more than 30 years. However, evidence regarding their efficacy remains mixed. Early multicenter randomized control trials demonstrated a benefit of octreotide in reducing POPF, although subsequent single-center studies failed to confirm these results. Despite additional studies demonstrating a significant reduction in POPF with the use of newer SSAs including pasireotide and lanreotide, surgical practices in the use of somatostatin analogs in preventing POPF are highly variable. Herein, we review three decades of available data on SSA for POPF prophylaxis and highlight the need for pragmatic, focused, and data-driven design for future trials with modern agents.},
}

@article {pmid40576840,
year = {2025},
author = {Mayer, J and Blanco-Melo, D and Coffin, JM and Gifford, RJ and Johnson, WE and Lindemann, D and Peeters, M and Sato, K and Stoye, J and Tachedjian, G and Hatziioannou, T},
title = {2024 taxonomy update for the family Retroviridae.},
journal = {Archives of virology},
volume = {170},
number = {8},
pages = {164},
pmid = {40576840},
issn = {1432-8798},
mesh = {*Retroviridae/classification/genetics ; Genome, Viral ; Phylogeny ; Terminology as Topic ; Humans ; },
abstract = {The Retroviridae are a family of viruses that reverse transcribe their RNA genome and integrate the resulting double-stranded DNA copy into the genome of the host cell. Retroviruses are well-documented pathogens that have been associated with a variety of diseases. The International Committee on Taxonomy of Viruses (ICTV) currently lists 65 species of retroviruses. As required by the ICTV, we have converted the species nomenclature to a binomial format comprised of the genus and a freeform epithet. Assigning binomial species names to classify new retroviruses will be facilitated when following the epithet rules described herein.},
}

*Retroviridae/classification/genetics
Genome, Viral
Phylogeny
Terminology as Topic
Humans

@article {pmid40576634,
year = {2025},
author = {Figueiredo, JC and Redwood, D and Li, L and Donato, E and Fort, D and Fox, EE and Grady, WM and Green, H and Harrison, TA and Haupt, C and Hsu, L and Hullar, MAJ and Huyghe, JR and Johnson, W and Koehne, AL and LaBrie, SD and Lakey, MA and Lin, M and Loroña, NC and Maresh, GA and Matrana, M and Mizrahi, JD and Nash, SH and Nguyen, NT and Paruch, JL and Phipps, AI and Qu, C and Randolph, TW and Romo, S and Thomas, CE and Thomas, S and Tiesinga, J and Whitlow, C and Yeung, CCS and Yin, H and Zibilich, CM and Li, CI and Thomas, TK and Peters, U},
title = {The Translational Research Program in Cancer Differences across Populations.},
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-24-1711},
pmid = {40576634},
issn = {1538-7755},
abstract = {BACKGROUND: Colorectal cancer (CRC) incidence and mortality vary substantially across populations. The Translational Research Program in Cancer Differences across Populations (TRPCDP) was established in 2020 to address differences in CRC incidence and mortality rates within the United States.

METHODS: TRPCDP centralized data acquisition and harmonization across three sites in the U.S. to create a well-annotated resource of CRC tumors across four populations: African American/Black, Alaska Native, Hispanic/Latino/a, and non-Hispanic White. Using a case-control framework, patients with lethal CRC were matched to two controls with non-lethal CRC. Formalin-fixed paraffin-embedded tumor and normal tissue were retrieved and sent for centralized pathology review, followed by DNA and RNA extraction and tissue microarray development. Multi-omics and spatial profiling are underway to evaluate the transcriptome, proteome, and microbiome. Patient demographic and clinical data were obtained by medical record review, patient self-report, or linkage to cancer registries. Additional health-related factors were assessed using geospatial linkage.

RESULTS: The virtual biorepository includes 7,181 patients [African American (n=1,345), Alaska Native (n=1,640), Hispanic (n=1,659), and non-Hispanic White (n=2,537)]. Tissue blocks (1,594 tumor, 728 normal colon) were selected for 938 patients. To date, DNA and RNA have been extracted (n=831) and tissue microarrays have been constructed (n=414). Transcriptomic, spatial tumor profiling (multiplex immunofluorescence, PhenoCycler, GeoMx) and microbiome data (16S rRNAseq, ddPCR) are available.

CONCLUSION: The TRPCDP has developed a clinically annotated biorepository for future molecular epidemiology studies.

IMPACT: TRPCDP is a unique program that supports collaborative research, community engagement, and pipeline development for the next generation of scientists.},
}

@article {pmid40576334,
year = {2025},
author = {Lee, EM and Srinivasan, S and Purvine, SO and Fiedler, TL and Leiser, OP and Proll, SC and Minot, SS and Djukovic, D and Raftery, D and Johnston, C and Fredricks, DN and Deatherage Kaiser, BL},
title = {Syntrophic bacterial and host-microbe interactions in bacterial vaginosis.},
journal = {The ISME journal},
volume = {19},
number = {1},
pages = {},
pmid = {40576334},
issn = {1751-7370},
support = {S10OD021562/RI/ORIP NIH HHS/United States ; GM103493/GM/NIGMS NIH HHS/United States ; U19 AI113173/NH/NIH HHS/United States ; R01AI061628/NH/NIH HHS/United States ; },
mesh = {Female ; *Vaginosis, Bacterial/microbiology ; Humans ; Vagina/microbiology ; *Host Microbial Interactions ; *Bacteria/metabolism/classification/genetics/isolation & purification ; Formates/metabolism ; Adult ; Putrescine/metabolism ; Proteomics ; Microbiota ; Bacterial Proteins/metabolism ; },
abstract = {Bacterial vaginosis (BV) is a common, polymicrobial condition of the vaginal microbiota that is associated with symptoms such as malodor and excessive discharge, along with increased risk of various adverse sequelae. Host-bacteria and bacteria-bacteria interactions are thought to contribute to the condition, but many of these functions have yet to be elucidated. Using untargeted metaproteomics, we identified 1068 host and 1418 bacterial proteins in a set of cervicovaginal lavage samples collected from 20 participants with BV and 9 who were negative for the condition. We identified Dialister micraerophilus as a major producer of malodorous polyamines and identified a syntrophic interaction between this organism and Fannyhessea vaginae that leads to increased production of putrescine, a metabolite characteristic of BV. Although formate synthesis has not previously been noted in BV, we discovered diverse bacteria associated with the condition express pyruvate formate-lyase enzymes in vivo and confirm these organisms secrete formic acid in vitro. Sodium hypophosphite efficiently inhibited this function in multiple taxa. We also found that the fastidious organism Coriobacteriales bacterium DNF00809 can metabolize formic acid secreted by Gardnerella vaginalis, representing another syntrophic interaction. We noted an increased abundance of the host epithelial repair protein transglutaminase 3 in the metaproteomic data, which we confirmed by enzyme-linked immunosorbent assay. Other proteins identified in our samples implicate Finegoldia magna and Parvimonas micra in the production of malodorous trimethylamine. Some bacterial proteins identified represent novel targets for future therapeutics to disrupt BV communities and promote vaginal colonization by commensal lactobacilli.},
}

Female
*Vaginosis, Bacterial/microbiology
Humans
Vagina/microbiology
*Host Microbial Interactions
*Bacteria/metabolism/classification/genetics/isolation & purification
Formates/metabolism
Adult
Putrescine/metabolism
Proteomics
Microbiota
Bacterial Proteins/metabolism

@article {pmid40571676,
year = {2025},
author = {Muskara, A and Parthasarathy, PB and Oyarbide, U and Ma, Y and Ganguly, S and Imamura, J and Liao, R and Rubin, BP and Macaskill, A and Murphy, ES and Anderson, PM and Gryder, BE and Scott, JG and Zahler, SG and Mian, OY},
title = {Transcriptomic Profiling of Relapsed Rhabdomyosarcoma: Pre- and Post-Treatment Tissue Analysis Reveals Molecular Characteristics of Treatment Failure.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e31864},
doi = {10.1002/pbc.31864},
pmid = {40571676},
issn = {1545-5017},
support = {//VeloSano Foundation Research/ ; P30CA043703//Case Comprehensive Cancer Center NIH/ ; P30CA043703//Case Comprehensive Cancer Center NIH/ ; //Case Comprehensive Cancer Center, Case Western Reserve University/ ; L30CA220908//NIH/NCI/ ; },
abstract = {BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Historically classified based on histology, advances in molecular profiling have allowed further sub-classification, which has improved risk stratification. Although molecular profiling has improved our understanding of disease progression and risk, the molecular evolution of therapy resistance in RMS remains poorly characterized. Transcriptomic profiling of patients with high-risk, relapsed RMS was undertaken with the goal of uncovering insights into the biology of RMS treatment failure.

PROCEDURE: Formalin-fixed, paraffin-embedded (FFPE) tissue samples from patients with relapsed RMS who had samples archived at diagnosis and relapse were obtained. Histologic subtype and PAX3/7::FOXO1 fusion status were confirmed. Transcriptomic profiling of the FFPE tissue samples was performed using the high-throughput genomics (HTG) whole transcriptome panel.

RESULTS: We identified 11 patients with relapsed RMS who had FFPE tissue samples archived at diagnosis and relapse following multimodality therapy. All patients were stratified as high risk, including five with PAX3/7::FOXO1 fusion-positive RMS (FP-RMS) and six with PAX3/7::FOXO1 fusion-negative RMS (FN-RMS). The transcriptomic analysis revealed that the myogenesis pathway and markers associated with myogenic differentiation were enriched pre-treatment in patients with FP-RMS and enriched post-treatment in patients with FN-RMS. Post-treatment enrichment of the inflammatory response pathway was observed in both FP-RMS and FN-RMS samples.

CONCLUSIONS: Using a probe-based transcriptome panel to characterize matched pre- and post-treatment tissue samples from patients with RMS, we report that relapsed RMS follows a fusion status-dependent evolutionary trajectory, marked by differential expression of myogenesis-associated genes, myogenic differentiation markers, and inflammatory response pathways.},
}

@article {pmid40570746,
year = {2025},
author = {Giacani, L and Romeis, E and Haynes, A and Molini, BJ and Tantalo, LC and Xu, LH and Trejos, AT and Keane, J and Mohamed, Z and Armstrong, TD and Wieland, BA and Phung, Q and Vyshenska, D and Campbell, VL and Godornes, C and Koelle, DM and Reid, TB and Wang, Y and Vorobieva, AA and Wald, A and Lieberman, NAP and Greninger, AL},
title = {Immunization with full-length TprC variants induces a broad response to surface-exposed epitopes of the Treponema pallidum repeat protein family and is partially protective in the rabbit model of syphilis.},
journal = {Vaccine},
volume = {61},
number = {},
pages = {127406},
doi = {10.1016/j.vaccine.2025.127406},
pmid = {40570746},
issn = {1873-2518},
abstract = {An effective vaccine against syphilis could aid current control measures to reduce the incidence of infection. Protective immunity from the syphilis agent, Treponema pallidum subsp. pallidum (T. pallidum), is associated with pathogen clearance by phagocytosis, supporting that immunization with an effective vaccine candidate should elicit opsonic antibodies to key epitopes at the host-pathogen interface. The T. pallidumrepeat (Tpr) proteins are putative β-barrel outer membrane porins with ten predicted extracellular loops. Here, we immunized three groups of eight rabbits with either a combination of three recombinant variants of the full-length TprC antigen, the TprD2 protein, or the conserved NH2-terminal region of TprK, with the latter antigen already known to induce incomplete protection in immunized rabbits. Compared to unimmunized controls, rabbits immunized with the three TprC variants or the TprK fragment exhibited attenuated primary chancres, reduced treponemal burden at the challenge sites, and limited pathogen dissemination to lymph nodes. Immunization with TprD2, alone did not produce comparable results. Strong humoral and cellular responses against TprC and TprK were elicited by immunization, and functional analyses supported the induction of opsonizing antibodies. Epitope mapping performed using TprC- and TprK-specific synthetic peptides and phage immunoprecipitation-sequencing identified a subset of highly reactive sequences and demonstrated immunity to predicted surface-exposed epitopes across multiple Tpr paralogs, which explained the significant, albeit incomplete protection measured post-challenge. These data advance TprC and TprK as syphilis vaccine candidates and highlight several correlates of their protection that deserve further examination.},
}

@article {pmid40569916,
year = {2025},
author = {Ortblad, KF and Brown, ER and Heffron, R and Ngure, K and Mujugira, A and Donnell, D},
title = {Research designs to generate evidence of HIV post-exposure prophylaxis effectiveness for new long-acting agents.},
journal = {Journal of the International AIDS Society},
volume = {28 Suppl 1},
number = {},
pages = {e26475},
doi = {10.1002/jia2.26475},
pmid = {40569916},
issn = {1758-2652},
support = {R00 MH121166/MH/NIMH NIH HHS/United States ; K24 MH123371/MH/NIMH NIH HHS/United States ; K24 MH123371/NH/NIH HHS/United States ; R00 MH121166/NH/NIH HHS/United States ; },
mesh = {Humans ; *HIV Infections/prevention & control/drug therapy ; *Post-Exposure Prophylaxis/methods ; *Research Design ; *Anti-HIV Agents/administration & dosage/therapeutic use ; Treatment Outcome ; Pre-Exposure Prophylaxis ; },
abstract = {INTRODUCTION: New longer-acting antiretroviral (ARV) drugs-that is single doses with antiviral activity for at least a month-are being utilized for HIV treatment and pre-exposure prophylaxis (PrEP) but have not been explored for post-exposure prophylaxis (PEP). A "one-and-done" simplification of PEP has the potential to serve the HIV prevention needs of individuals not being met with traditional services and expand overall biomedical HIV prevention coverage. We discuss challenges with the assessment of PEP effectiveness in human trials and potential study designs that could generate evidence needed to inform the use of new, single-administered, long-acting ARVs for PEP.

DISCUSSION: Challenges with determining the effectiveness of new long-acting PEP agents in human trials include the low likelihood of observing an HIV acquisition and the short period for outcome assessment (likely 1 month) following PEP administration. Additional challenges include recruiting individuals in the brief window in which they could benefit (<72 hours of a potential HIV exposure) and ethics of conducting informed consent during a period of high stress/vulnerability. Consequently, design approaches where the efficacy goal is to establish that the HIV incidence rate following PEP administration (of the standard or a novel agent) approaches zero should be considered. HIV RNA testing conducted within 5 days of a potential exposure could define prevention per exposure. Novel recruitment venues-such as community-based retail or online pharmacies-could be used to reach individuals after a potential exposure. Potential study designs include one- or two-arm individual-level product assignment aimed at demonstration of short-course efficacy or longer-term effectiveness compared to a background rate; cluster-randomized controlled trials of recruitment venues; and novel individual-level approaches that either do not or do utilize randomization in combination with choice, enabling assessment of preferences and effectiveness.

CONCLUSIONS: Over the past decade, multiple new HIV PrEP products-but no new PEP products-have been developed to meet the diverse needs of individuals seeking HIV prevention services. Challenges exist with generating PEP effectiveness evidence, but they are not insurmountable. Effectiveness research on new PEP products could advance the number of HIV prevention options available.},
}

Humans
*HIV Infections/prevention & control/drug therapy
*Post-Exposure Prophylaxis/methods
*Research Design
*Anti-HIV Agents/administration & dosage/therapeutic use
Treatment Outcome
Pre-Exposure Prophylaxis

@article {pmid40569884,
year = {2025},
author = {Roche, SD and Omollo, V and Mogere, P and Asewe, M and Gakuo, S and Banerjee, P and Harkey, K and Sharma, M and Pintye, J and Mugambi, ML and Shah, P and Odoyo, J and Ong'wen, P and Were, D and Bukusi, EA and Ngure, K and Ortblad, KF},
title = {A modified pharmacy provider-led delivery model of oral HIV pre- and post-exposure prophylaxis in Kenya: a pilot study extension.},
journal = {Journal of the International AIDS Society},
volume = {28 Suppl 1},
number = {},
pages = {e26467},
doi = {10.1002/jia2.26467},
pmid = {40569884},
issn = {1758-2652},
support = {INV-033052/GATES/Gates Foundation/United States ; R34 MH120106/MH/NIMH NIH HHS/United States ; R00MH121166/MH/NIMH NIH HHS/United States ; R01HD108041//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Anti-HIV Agents/administration & dosage/therapeutic use ; *HIV Infections/prevention & control ; Kenya/epidemiology ; Pharmacies ; Pilot Projects ; *Post-Exposure Prophylaxis/methods ; *Pre-Exposure Prophylaxis/methods ; },
abstract = {INTRODUCTION: Private pharmacies in Africa reach individuals with ongoing and periodic HIV risk, yet few countries currently leverage pharmacies as an HIV service delivery platform. We conducted a 6-month pilot to evaluate a model for pharmacy provider-led delivery of HIV pre- and post-exposure prophylaxis (PrEP and PEP) in Kenya.

METHODS: At 12 private pharmacies in Kisumu and Kiambu Counties, licensed pharmacy providers initiated and managed eligible clients ≥18 years on PrEP and PEP under remote clinician supervision (NCT04558554); four of these pharmacies additionally offered sextually transmitted infection (STI) testing. PrEP/PEP clients were scheduled for follow-up 1 month later and then quarterly (PrEP clients only). Primary outcomes included PrEP and PEP initiation and continuation during the pilot period. Client and providers rated the model across multiple constructs of acceptability and feasibility from established frameworks.

RESULTS: From January to July 2022, 1028 clients interested in PrEP, PEP and/or STI testing were screened and 829 initiated one or more service: 661 PrEP, 162 PEP and 52 STI testing. About half of clients (48%, 398/829) were male, most were unmarried (78%, 644/829) and PrEP-naïve (89%, 737/829), and the median age was 25 years (IQR 22-31). Most PrEP clients reported inconsistent condom use (88%, 581/661) or sex with partners of unknown HIV status (70%, 460/661) in the past 6 months. Most PEP clients reported condomless sex (48%, 78/162) or a condom break (46%, 75/162) in the past 72 hours; 4% (6/162) reported sexual assault. Among PrEP clients eligible for a refill, 73% (479/658) refilled at least once and 60% (197/328) twice. Among PEP clients eligible for follow-up, 44% (65/148) completed follow-up HIV testing and 20% (30/148) transitioned to PrEP. Among STI clients, 19% (10/52) tested positive for gonorrhoea (n = 7) and/or chlamydia (n = 5). Most clients and providers (≥92%) found the delivery model and its implementation strategies acceptable. All providers (n = 12) thought it was possible to deliver PrEP and PEP at pharmacies in Kenya.

CONCLUSIONS: Pharmacy PrEP/PEP delivery achieved high uptake, continuation and acceptability among eligible clients that could benefit, highlighting the potential of pharmacies to expand HIV prevention service coverage in Kenya, particularly to individuals not accessing these services at clinics.},
}

Adolescent
Adult
Female
Humans
Male
Middle Aged
Young Adult
*Anti-HIV Agents/administration & dosage/therapeutic use
*HIV Infections/prevention & control
Kenya/epidemiology
Pharmacies
Pilot Projects
*Post-Exposure Prophylaxis/methods
*Pre-Exposure Prophylaxis/methods

@article {pmid40569864,
year = {2025},
author = {Kiptinness, C and Naik, P and Kareithi, T and Thuo, N and Okello, P and Culquichicon, C and Rafferty, M and Abdulrashid, S and Jomo, E and Nyamasyo, N and Wood, T and Mendonca, R and Malen, RC and Dettinger, JC and Pintye, J and Mwangi, J and Stergachis, A and Onentia, J and Curran, K and Mugambi, ML and Were, D and Ngure, K and Sharma, M and Ortblad, KF and , },
title = {Online delivery of oral HIV pre- and post-exposure prophylaxis: findings from the ePrEP Kenya pilot.},
journal = {Journal of the International AIDS Society},
volume = {28 Suppl 1},
number = {},
pages = {e26468},
doi = {10.1002/jia2.26468},
pmid = {40569864},
issn = {1758-2652},
support = {INV-037646/GATES/Gates Foundation/United States ; R00 MH121166/MH/NIMH NIH HHS/United States ; K01 MH115789/MH/NIMH NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Administration, Oral ; *Anti-HIV Agents/administration & dosage/therapeutic use ; *HIV Infections/prevention & control ; Kenya ; Pilot Projects ; *Post-Exposure Prophylaxis/methods ; *Pre-Exposure Prophylaxis/methods ; *Telemedicine ; },
abstract = {INTRODUCTION: The expansion of telecommunication networks and smartphones in many African countries could be leveraged to deliver HIV prevention products directly to consumers. In collaboration with a private e-commerce platform and online pharmacy in Kenya, MYDAWA, we piloted a new model of HIV pre- and post-exposure prophylaxis (PrEP/PEP) delivery.

METHODS: In the ePrEP Kenya pilot (NCT05377138), individuals living in Nairobi and Mombasa Counties could complete a free telehealth visit with a remote clinician to assess eligibility for online PrEP/PEP (i.e. ≥18 years; no medical contraindications). Eligible individuals could order HIV testing services-courier delivered to clients' choice location-for a fee of 250 KES (∼$2 USD) for self-testing or 150 KES (∼$1 USD) for provider-administered rapid diagnostic testing. Following confirmation of clients' HIV-negative status (via an uploaded test result image), free PrEP/PEP drugs from government supply were courier delivered with or separately from HIV testing services. Clients paid a delivery fee ≤149 KES (∼$1 USD) per courier visit.

RESULTS: From October 2022 to December 2023, we screened 2257 individuals and enrolled 1915. Most PrEP/PEP clients were men (63%, 1428/1915), ≥25 years (72%, 1631/1915) and never married (80%, 1796/1915); few had ever used PrEP (3%, 48/1915) or PEP (14%, 263/1915). At enrolment, 227 (12%) were preliminarily eligible for PrEP and 1688 (88%) for PEP. Among PrEP-eligible clients, 89% (203/227) completed HIV testing and 92% (208/227) received PrEP; among PEP-eligible clients, 92% (1551/1688) completed HIV testing and 92% (1549/1688) received PEP. Most PrEP/PEP clients completed HIV testing within 6 hours of their telehealth visit (53%, 927/1757) and had drugs delivered with testing services (88%, 1546/1757). Among PrEP clients eligible for follow-up, 47% (120/256) continued PrEP and 4% (10/256) initiated PEP following PrEP discontinuation. Among PEP clients eligible for follow-up, 7% (99/1428) repeated PEP use and 6% (83/1428) transitioned from PEP to PrEP.).

CONCLUSIONS: Online PrEP/PEP delivery could expand access to prevention services by reaching individuals not engaged in existing delivery platforms. The uptake of online PEP was five times greater than PrEP, underscoring an unmet demand for PEP and highlighting the potential for online pharmacies to deliver time-sensitive PEP services.},
}

Adolescent
Adult
Female
Humans
Male
Middle Aged
Young Adult
Administration, Oral
*Anti-HIV Agents/administration & dosage/therapeutic use
*HIV Infections/prevention & control
Kenya
Pilot Projects
*Post-Exposure Prophylaxis/methods
*Pre-Exposure Prophylaxis/methods
*Telemedicine

@article {pmid40575114,
year = {2023},
author = {Vannier, D and Torok-Storb, B and Stromholt, S and Chowning, JT},
title = {The Pathways Undergraduate Researchers Program: Fostering Career Interests, Sense of Belonging, and Student Confidence in Pursuing Science.},
journal = {Journal of STEM outreach},
volume = {6},
number = {2},
pages = {},
pmid = {40575114},
issn = {2576-6767},
support = {R25 CA221770/CA/NCI NIH HHS/United States ; },
abstract = {The Pathways Undergraduate Researchers Program is a paid, nine-week summer internship at the Fred Hutchinson Cancer Center. It targets rising first-, second-, and third-year college students from backgrounds underrepresented in biomedical research. This paper describes how the internship impacted students' awareness of biomedical careers, scientific identification, and sense of belonging in research. Interns reported an increased awareness of biomedical careers and how to attain them. The experience also challenged interns' career ideas. Interns described a mix of feelings on sense of belonging. All felt welcomed and confident in their abilities. Nonetheless, some noted they were different from the other researchers. A number were motivated by being in the minority and ready to become leaders in diversifying the workforce. Data gathered during the COVID-19 pandemic shed a different light on the internship's impact. The interns reported becoming 'credible resources' on public health issues for their families and communities. The program supported this by building their confidence to understand and communicate science. This undergraduate program developed out of a longer running high school internship effort and many of the strategies described herein are used in both. These findings have implications for programs for underrepresented students at the high school and college level.},
}

@article {pmid40569643,
year = {2025},
author = {Rashidi, A},
title = {Microbiota and chronic GVHD: a plasmablast link.},
journal = {Blood},
volume = {145},
number = {26},
pages = {3073-3075},
doi = {10.1182/blood.2025029521},
pmid = {40569643},
issn = {1528-0020},
}

@article {pmid40569290,
year = {2025},
author = {Biernacki, MA and Lok, J and Foster, KA and Cummings, C and Busch, S and Black, RG and Ray, S and Baquero Galvis, L and Monahan, T and Oh, ST and Oehler, VG and Stirewalt, DL and Wu, D and Deeg, HJ and Doulatov, S and Bleakley, M},
title = {SF3B1K700E neoantigen is a CD8+ T-cell target shared across human myeloid neoplasms.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
doi = {10.1158/2326-6066.CIR-24-0091},
pmid = {40569290},
issn = {2326-6074},
abstract = {Acquired mutations in spliceosome genes in early hematopoietic stem/progenitor cells are common events in myelodysplastic neoplasms (MDS) and related myeloid malignancies. Mutations in the spliceosome factor subunit B1 (SF3B1) gene occur in ≥20% of MDS cases at conserved hotspots and in early neoplastic clones as driver events. Neoantigens from aberrant SF3B1 proteins could serve as shared T-cell therapy targets for SF3B1-mutated myeloid neoplasms. We identified a candidate neoantigen from the prevalent SF3B1K700E variant using in silico predictions of epitope processing and presentation, then validated presentation and immunogenicity in vitro. CD8+ T cells recognizing SF3B1K700E demonstrated high functional avidity and killed neoplastic myeloid cell lines and primary cells in an antigen-specific manner. We then sequenced, cloned, and transduced a SF3B1K700E-specific T-cell receptor (TCR) into 3rd-party T cells and confirmed that TCR transfer conferred antigen specificity and killing of neoplastic myeloid cells in vitro and in vivo. The data indicate that the SF3B1K700E neoantigen represents a promising T-cell target for patients with SF3B1-mutated MDS and acute myeloid leukemia.},
}

@article {pmid40569102,
year = {2025},
author = {Cheng, GS and Sheshadri, A and Turner, J and Williams, KM and Hsu, JL and Agoritsas, T and Ali, MH and Bondeelle, L and Bouguet, G and Chanez, P and Cooke, KR and Galban, CJ and Goldfarb, S and Hallstrand, TS and Johnson, S and Lam, DCL and Michonneau, D and O'Dwyer, DN and Paczesny, S and Sharifi, H and Todd, JL and Wolff, D and Yadav, H and Yanik, GA and Bergeron, A},
title = {Addressing Knowledge Gaps in the Early Detection of Bronchiolitis Obliterans Syndrome After Hematopoietic Cell Transplantation. An Official American Thoracic Society Research Statement.},
journal = {American journal of respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
doi = {10.1164/rccm.202506-1352ST},
pmid = {40569102},
issn = {1535-4970},
abstract = {BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a late onset noninfectious pulmonary complication of allogeneic hematopoietic cell transplantation (HCT) that is often diagnosed in advanced stage with severe lung impairment. Increasing utilization of HCT for the treatment of hematologic diseases worldwide translates to an increasing burden of BOS, particularly for the community pulmonologist. Early recognition of BOS, which offers the best opportunity to mitigate morbidity and mortality, is hampered by incomplete knowledge of the clinical course and disease process. The goal of this research statement is to survey our current understanding of BOS and to define the research agenda for the early detection of BOS.

METHODS: We convened a multidisciplinary panel that included community representatives for an in-depth survey of the published literature followed by an online workshop.

RESULTS: Major knowledge gaps were identified within interrelated themes of natural history and pathogenesis, risk factors, and the clinical diagnostic approach.

CONCLUSIONS: This statement reflects the detailed assessment of identified knowledge gaps with associated key research questions, as well as a proposed research roadmap to stimulate cross-disciplinary collaborations from pre-clinical to clinical investigations.},
}

@article {pmid40568722,
year = {2025},
author = {Hogan, LE and Bhatla, T and Xu, X and Gore, L and Raetz, EA and Bhojwani, D and Teachey, DT and Hunger, SP and Loh, ML and Brown, PA and Ji, L},
title = {Severe toxicity and poor efficacy of reinduction chemotherapy are associated with overall poor outcomes in relapsed B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group AALL1331 trial.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.287386},
pmid = {40568722},
issn = {1592-8721},
abstract = {Children's Oncology Group AALL1331 utilized an intensive chemotherapy induction (Block 1) based on UK ALLR3 induction for children, adolescents, and young adults with acute lymphoblastic leukemia in first relapse, followed by risk-stratified therapy. High/intermediate risk patients were subsequently randomized to receive 2 blocks of chemotherapy or 2 blocks of blinatumomab followed by hematopoietic stem cell transplant. Low risk patients were randomized to chemotherapy or chemotherapy cycles intercalated with three blinatumomab blocks. Patients who had an early treatment failure were eligible to receive blinatumomab for up to 2 salvage cycles. We reviewed Block 1 responses, risk stratification, randomization rates, adverse events (AE), and event-free survival and overall survival for all enrolled patients. AALL1331 enrolled 661 patients: 24 died during Block 1 and 42 experienced early treatment failure. Overall, 531/661 (80.3%) attained complete remission with 586 risk-assigned and only 471 were randomized. Of 532 patients with marrow involvement, 290 (54.5%) were minimal residual disease positive (≥0.01%) after Block 1. Grade 3/4/5 AE occurred in Block 1 in 44.9, 24.1, and 3.6% patients respectively, with febrile neutropenia, infections, and sepsis most frequent. Notably, 190 enrolled patients (28.7%) did not proceed with post-induction therapy, including 115 (17.4%) risk stratified but not randomized. These patients had dismal survival. More effective and less toxic reinduction strategies are needed for B-ALL in first relapse. Trial Registration Number: NCT02101853.},
}

@article {pmid40568668,
year = {2025},
author = {Mendez, JS and Queme, B and Fu, Y and Morrison, J and Lewinger, JP and Kawaguchi, E and Mi, H and Obón-Santacana, M and Moratalla-Navarro, F and Martín, V and Moreno, V and Lin, Y and Bien, SA and Qu, C and Su, YR and White, E and Harrison, TA and Huyghe, JR and Tangen, CM and Newcomb, PA and Phipps, AI and Thomas, CE and Conti, DV and Wang, J and Platz, EA and Keku, TO and Newton, CC and Um, CY and Kundaje, A and Shcherbina, A and Murphy, N and Gunter, MJ and Dimou, N and Papadimitriou, N and Bézieau, S and van Duijnhoven, FJ and Männistö, S and Rennert, G and Wolk, A and Hoffmeister, M and Brenner, H and Chang-Claude, J and Tian, Y and Le Marchand, L and Cotterchio, M and Tsilidis, KK and Bishop, DT and Melaku, YA and Lynch, BM and Buchanan, DD and Ulrich, CM and Ose, J and Peoples, AR and Pellatt, AJ and Li, L and Devall, MA and Campbell, PT and Albanes, D and Weinstein, SJ and Berndt, SI and Gruber, SB and Ruiz-Narvaez, E and Song, M and Joshi, AD and Drew, DA and Petrick, JL and Chan, AT and Giannakis, M and Hsu, L and Peters, U and Gauderman, WJ and Stern, MC},
title = {Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40568668},
support = {U01 HG004438/HG/NHGRI NIH HHS/United States ; U01 HG004446/HG/NHGRI NIH HHS/United States ; K05 CA154337/CA/NCI NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; U01 CA164930/CA/NCI NIH HHS/United States ; R01 CA066635/CA/NCI NIH HHS/United States ; U01 CA167551/CA/NCI NIH HHS/United States ; R01 CA042182/CA/NCI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; U01 CA122839/CA/NCI NIH HHS/United States ; R01 CA059045/CA/NCI NIH HHS/United States ; R01 CA197350/CA/NCI NIH HHS/United States ; R35 CA197735/CA/NCI NIH HHS/United States ; U2C CA252971/CA/NCI NIH HHS/United States ; U10 CA037429/CA/NCI NIH HHS/United States ; U54 CA233465/CA/NCI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; Z01 CP010200/ImNIH/Intramural NIH HHS/United States ; P01 CA055075/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; R01 CA151993/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; R01 CA048998/CA/NCI NIH HHS/United States ; U01 CA137088/CA/NCI NIH HHS/United States ; R01 CA242218/CA/NCI NIH HHS/United States ; R01 CA137178/CA/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; R01 CA081488/CA/NCI NIH HHS/United States ; R01 CA143237/CA/NCI NIH HHS/United States ; R01 CA201407/CA/NCI NIH HHS/United States ; R01 CA063464/CA/NCI NIH HHS/United States ; P01 CA033619/CA/NCI NIH HHS/United States ; U01 CA086308/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R01 CA060987/CA/NCI NIH HHS/United States ; R01 CA136726/CA/NCI NIH HHS/United States ; UM1 CA182883/CA/NCI NIH HHS/United States ; R37 CA054281/CA/NCI NIH HHS/United States ; U19 CA148107/CA/NCI NIH HHS/United States ; U01 AG018033/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: High intake of red and/or processed meat are established colorectal cancer (CRC) risk factors. Genome-wide association studies (GWAS) have reported 204 variants (G) associated with CRC risk. We used functional annotation data to identify subsets of variants within known pathways and constructed pathway-based Polygenic Risk Scores (pPRS) to model pPRS x environment (E) interactions.

METHODS: A pooled sample of 30,812 cases and 40,504 CRC controls of European ancestry from 27 studies were analyzed. Quantiles for red and processed meat intake were constructed. The 204 GWAS variants were annotated to genes with AnnoQ and assessed for overrepresentation in PANTHER-reported pathways. pPRS's were constructed from significantly overrepresented pathways. Covariate-adjusted logistic regression models evaluated pPRSxE interactions with red or processed meat intake in relation to CRC risk.

RESULTS: A total of 30 variants were overrepresented in four pathways: Alzheimer disease-presenilin, Cadherin/WNT-signaling, Gonadotropin-releasing hormone receptor, and TGF-β signaling. We found a significant interaction between TGF-β-pPRS and red meat intake (p = 0.003). When variants in the TGF-β pathway were assessed, significant interactions with red meat for rs2337113 (intron SMAD7 gene, Chr18), and rs2208603 (intergenic region BMP5, Chr6) (p = 0.013 & 0.011, respectively) were observed. We did not find evidence of pPRS x red meat interactions for other pathways or with processed meat.

CONCLUSIONS: This pathway-based interaction analysis revealed a significant interaction between variants in the TGF-β pathway and red meat consumption that impacts CRC risk.

IMPACT: These findings shed light into the possible mechanistic link between CRC risk and red meat consumption.},
}

@article {pmid40564099,
year = {2025},
author = {Wang, H and Wang, C and Qin, R and He, J and Zhang, X and Ma, C and Li, S and Fan, L and Wang, L and Cao, L},
title = {Integrative Analysis of Plasma Proteomics and Transcriptomics Reveals Potential Therapeutic Targets for Psoriasis.},
journal = {Biomedicines},
volume = {13},
number = {6},
pages = {},
pmid = {40564099},
issn = {2227-9059},
support = {82304250//National Natural Science Foundation of China/ ; 82273734//National Natural Science Foundation of China/ ; YQ2022H005//Heilongjiang Province Natural Science Foundation/ ; },
abstract = {Background Psoriasis (PsO): is an immune-mediated inflammatory disease that imposes a significant burden on patients. Many patients experience relapse or inadequate responses, and PsO subtypes also lack effective therapies, highlighting the need for new therapeutic targets. Methods: We performed a proteome-wide Mendelian randomization (MR) to explore potential therapeutic targets for PsO. Protein quantitative trait loci (pQTLs) data were obtained from the Pharma Proteomics Project (54,219 UK Biobank participants, 2923 proteins), and PsO phenotype and subtype data were sourced from FinnGen (10,312 cases; 397,564 controls) for discovery. Replication MR utilized integrated protein data (Iceland and Norfolk) and phenotype data from multiple databases (UK Biobank and GWAS Catalog). Reverse MR and colocalization were used to support causal relationships. Single-cell RNA-seq analysis revealed distinct expression patterns of protein-coding genes across different cell types in PsO biopsy samples and normal skin tissues. Protein-protein interactions (PPI) and molecular docking were used to evaluate druggability. Results: MR analysis identified 13 proteins significantly associated with PsO risk (p < 2.56×10-5), including 10 proteins associated with PsO subtypes. Decreased levels of eight proteins (IFNLR1, APOF, TDRKH, DDR1, HLA-E, LTA, MOG, and ICAM3) and increased levels of five proteins (IFNGR2, HCG22, IL12B, BTN3A2, and TRIM40) showed protective effects against PsO progression. Robust colocalization (PPH4 > 0.9) identified IFNLR1, IFNGR2, APOF, and TDRKH as top candidates. Single-cell RNA sequencing analysis revealed that IFNLR1, IFNGR2, LTA, TDRKH, and DDR1 were specifically expressed in T cells of psoriatic biopsy specimens compared to healthy controls. Molecular docking indicated the druggability of IFNLR1 and IFNGR2. Conclusions: We identified several potential therapeutic targets for PsO, with IFNLR1, IFNGR2, APOF, and TDRKH emerging as promising candidates, particularly IFNLR1 and IFNGR2, which are associated with the IFN family. These findings may provide new perspectives on PsO therapy and pathogenesis.},
}

@article {pmid40562770,
year = {2025},
author = {Dima, D and Vazquez-Martinez, MA and Davis, JA and Goel, U and Afrough, A and Sannareddy, A and Pasvolsky, O and Razzo, B and Banerjee, R and Khouri, J and Grajales-Cruz, A and Lieberman-Cribbin, A and Rana, MS and Julian, K and DeJarnette, S and Portuguese, AJ and Gaballa, MR and De Avila, G and Susaniba Adaniya, S and Raza, S and Herr, MM and Ouchveridze, E and Richards, T and Hosoya, H and Mikkilineni, L and Kaur, G and Castaneda Puglianini, O and Rossi, A and Lin, Y and Atrash, S and Sborov, D and Shain, KH and Voorhees, PM and Richard, S and Garfall, AL and Hansen, DK and Sidana, S and Patel, KK and Cowan, AJ and Anderson, LD and Lee, HC and Anwer, F and Ferreri, CJ and Shune, L},
title = {Outcomes of teclistamab in patients with relapsed/refractory multiple myeloma with prior exposure to BCMA-directed therapy: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {111},
pmid = {40562770},
issn = {2044-5385},
mesh = {Humans ; *Multiple Myeloma/drug therapy/mortality/pathology ; Male ; Female ; Middle Aged ; Aged ; *B-Cell Maturation Antigen/antagonists & inhibitors ; Retrospective Studies ; Adult ; Aged, 80 and over ; Treatment Outcome ; United States ; *Antineoplastic Agents, Immunological/therapeutic use/adverse effects ; },
abstract = {Data describing outcomes of teclistamab in multiple myeloma patients with prior exposure to BCMA-directed therapy (BCMA-DT) are limited. The goal of this multicenter retrospective analysis was to report the efficacy and safety of standard-of-care teclistamab in patients with prior BCMA-DT. A total of 385 patients were included, of whom 193 (50%) had received prior BCMA-DT, including 47 (24%) patients with prior antibody-drug conjugate (ADC)-only, 99 (51%) with chimeric antigen receptor T-cell therapy (CAR T)-only, 36 (19%) with both ADC and CAR T, 6 (3%) with bispecific antibody-only, and 5 (3%) with other combinations. Most safety parameters between cohorts were comparable. The prior BCMA-DT cohort had a lower overall response rate (ORR: 48.7% versus 61.5%; p = 0.012), and median progression-free survival (PFS: 4.6 versus 8.2 months; p = 0.017) compared to the cohort without prior BCMA-DT. However, in multivariable analysis, despite a clear trend, ultimately receipt of a prior BCMA-DT was not independently associated with ORR or PFS (p = 0.057 and p = 0.1, respectively). No significant differences in PFS were noted when stratifying patients by number of prior BCMA-DTs, types of all prior BCMA-DTs received, type of most recent prior BCMA-DT, or depth of response to most recent BCMA-DT. Using the maximally selected rank statistics method, the optimal cut-off for time from the last BCMA-DT exposure to teclistamab initiation was identified as 8.7 months. Patients with >8.7 months between their last exposure to prior BCMA-DT and teclistamab initiation had a significantly improved median PFS with teclistamab (8.1 months, 95% CI: 4.6-11.7) compared to patients with <8.7 months (2.5 months, 95% CI: 1.1-5.7), p = 0.001. Altogether, our findings support the use of teclistamab as a viable treatment option in patients previously exposed to BCMA-DT.},
}

Humans
*Multiple Myeloma/drug therapy/mortality/pathology
Male
Female
Middle Aged
Aged
*B-Cell Maturation Antigen/antagonists & inhibitors
Retrospective Studies
Adult
Aged, 80 and over
Treatment Outcome
United States
*Antineoplastic Agents, Immunological/therapeutic use/adverse effects

@article {pmid40562030,
year = {2025},
author = {Banerjee, R and Yamshon, S},
title = {Double trouble: Non-relapse mortality with bispecific antibodies in lymphoma and myeloma.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2025.06.014},
pmid = {40562030},
issn = {1525-0024},
}

@article {pmid40561681,
year = {2025},
author = {Coleman, RL and Fleming, GF and Brady, MF and Swisher, EM and Steffensen, KD and Friedlander, M and Okamoto, A and Moore, KN and Leath, CA and Cella, D and Sun, Z and Patel, S and Tang, Z and Ratajczak, CK and Aghajanian, C and Bookman, MA},
title = {Veliparib concomitant with first-line chemotherapy and as maintenance therapy in ovarian cancer: Final overall survival and disease-related symptoms results.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {225},
number = {},
pages = {115587},
doi = {10.1016/j.ejca.2025.115587},
pmid = {40561681},
issn = {1879-0852},
abstract = {INTRODUCTION: In the VELIA trial, the addition of veliparib to standard first-line platinum-based chemotherapy and continued as maintenance resulted in significantly longer median progression-free survival (PFS) compared with carboplatin plus paclitaxel induction therapy alone (23.5 vs 17.3 months; p < 0.001) in patients with ovarian cancer. We now report final overall survival (OS) and updated safety and disease-related symptoms (DRS) from patient-reported outcomes of the trial.

METHODS: This randomized, placebo-controlled, double-blind, multicenter, phase 3 study enrolled adult women with an initial diagnosis of stage III/IV high-grade serous ovarian cancer undergoing primary or interval cytoreductive surgery. Patients were randomized 1:1:1 to chemotherapy plus veliparib followed by veliparib maintenance (veliparib-throughout), chemotherapy plus veliparib followed by placebo maintenance (veliparib-combination-only), or chemotherapy plus placebo followed by placebo maintenance (placebo-throughout). PFS was the primary endpoint; OS and DRS were secondary endpoints.

RESULTS: In the intention-to-treat population (N = 1140), median OS was 59.2 months (95 % confidence interval: 52.1, 68.2) for the veliparib-throughout group, 58.0 (50.6, 64.1) months for veliparib-combination-only, and 57.8 (52.3, 63.8) months for placebo-throughout. OS outcomes were not significantly different between arms overall or in the BRCA-deficient and homologous recombination-deficient cohorts. No new safety signals were identified during the longer follow-up period and DRS analyses indicated there was no significant additional symptom-related burden overall when veliparib was added to chemotherapy or used for maintenance.

CONCLUSION: No OS or DRS benefit of addition of veliparib to platinum-based chemotherapy and continued as maintenance therapy was detected in this study, despite an observed benefit over chemotherapy alone in PFS.},
}

@article {pmid40561385,
year = {2025},
author = {Zeiser, R and Russo, D and Ram, R and Hashmi, SK and Chakraverty, R and Middeke, JM and Musso, M and Giebel, S and Uzay, A and Langmuir, P and Hamad, N and Burock, K and Gowda, M and Stefanelli, T and Lee, SJ and Teshima, T and Locatelli, F},
title = {Ruxolitinib in Patients With Corticosteroid-Refractory or Corticosteroid-Dependent Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of the Phase III REACH3 Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2402477},
doi = {10.1200/JCO-24-02477},
pmid = {40561385},
issn = {1527-7755},
abstract = {In REACH3 (ClinicalTrials.gov identifier: NCT03112603), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (weeks 24-156), patients continued randomized treatment, entered long-term survival follow-up, or crossed over from BAT to ruxolitinib. In 329 randomly assigned patients (ruxolitinib: 165; BAT: 164), the median failure-free survival (FFS) was 38.4 months for ruxolitinib versus 5.7 months for BAT (hazard ratio, 0.36 [95% CI, 0.27 to 0.49]). Median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months for BAT. Ruxolitinib-treated patients had a higher probability of FFS (ruxolitinib: 56.5%; BAT: 18.2%) and maintaining a response (ruxolitinib: 59.6%; BAT: 26.7%) at 36 months. Median overall survival was not reached. Nonrelapse mortality and malignancy relapse/recurrence events were low. In 70 patients who crossed over to ruxolitinib, the overall response rate (50.0%) at week 24 and best overall response (81.4%) during the crossover period were consistent with the primary analysis of randomly assigned patients. No new safety signals were observed. Ruxolitinib provided longer FFS and DOR than BAT, demonstrating sustained efficacy and manageable safety over 3 years of follow-up in patients with SR/D-cGVHD.},
}

@article {pmid40561376,
year = {2025},
author = {Bardia, A and Rugo, HS and Sedrak, MS and Loibl, S and Tolaney, SM and Punie, K and Hurvitz, SA and Kalinsky, KM and Cortés, J and O'Shaughnessy, JA and Dieras, V and Piccart-Gebhart, MJ and Dasgupta, A and Kaushik, A and Lai, C and Shi, L and Brufsky, A},
title = {Q-TWiST Analysis to Assess Benefit-Risk of Sacituzumab Govitecan in Previously Treated Patients With Metastatic Triple-Negative Breast Cancer.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2400806},
doi = {10.1200/OP-24-00806},
pmid = {40561376},
issn = {2688-1535},
abstract = {PURPOSE: In ASCENT, sacituzumab govitecan (SG) showed significantly longer overall survival and progression-free survival than chemotherapy of physician's choice with similar rates of treatment-emergent adverse events (TEAEs) in previously treated patients with metastatic triple-negative breast cancer (mTNBC). We assessed the benefit-risk of SG versus chemotherapy by integrating patient preferences (health utilities) with clinical benefits in this analysis.

METHODS: Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) methodology was used to compare treatments where survival was partitioned into three health states using the intention-to-treat ASCENT population: (1) toxicity (grade ≥3 TEAE after random assignment and before disease progression), (2) TWiST (progression-free period without grade ≥3 TEAE), and (3) relapse (disease progression until death or end of follow-up, whichever came first). Health state utilities were derived from published literature. Q-TWiST was calculated as utility-weighted sum of mean health state durations. The established threshold for relative Q-TWiST improvement considered clinically important is 10% and clearly clinically important is 15%.

RESULTS: SG had significantly longer Q-TWiST (8.3 months; 95% CI, 7.6 to 9.1 months) than chemotherapy (4.8 months; 95% CI, 4.3 to 5.4 months) in patients with mTNBC, a difference of 3.5 months (95% CI, 2.6 to 4.4 months; P < .0001). Relative Q-TWiST improvement with SG was 39.5%, exceeding the clearly clinically important threshold. Q-TWiST benefits of SG over chemotherapy increased over the available 31-month follow-up. Restricted mean time with toxicity was numerically higher with SG versus chemotherapy; this difference stabilized with longer follow-up.

CONCLUSION: The Q-TWiST analysis supports a positive benefit-risk ratio for SG versus chemotherapy in patients with previously treated mTNBC. Net benefits of SG continued to accrue over time.},
}

@article {pmid40561372,
year = {2025},
author = {Calverley, DC and Leader, A and Cheong, MA and Sanfilippo, KM and Mason, G and Lyman, GH and Kuderer, NM},
title = {Inconsistent and Inaccurate Cancer Clinical Trial Reporting of Venous and Arterial Thrombotic Events: An Urgent Call to Action.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500489},
doi = {10.1200/JCO-25-00489},
pmid = {40561372},
issn = {1527-7755},
}

@article {pmid40558267,
year = {2025},
author = {Terashima, M and Nakayama, K and Ugai, S and Lee, HY and Tsukumo, Y and Suzuki, E and Mizuno, H and Song, M and Sasamoto, N and Kawachi, I and Ugai, T},
title = {Global Incidence Trend of Early-Onset Obesity-Related and Non-Obesity-Related Cancers.},
journal = {Current oncology (Toronto, Ont.)},
volume = {32},
number = {6},
pages = {},
pmid = {40558267},
issn = {1718-7729},
support = {R50 CA274122/NH/NIH HHS/United States ; },
mesh = {Humans ; *Neoplasms/epidemiology/etiology ; *Obesity/complications/epidemiology ; Incidence ; Female ; Male ; Adult ; Age of Onset ; Middle Aged ; Global Health ; Young Adult ; },
abstract = {The global rise in obesity prevalence and the incidence of early-onset cancer (diagnosed between 20 and 49 years of age) is a serious public health concern. We, therefore, evaluated the recent global trends in the incidence of early-onset obesity-related cancers and compared them to those of non-obesity-related cancers. We obtained age-standardized incidence rates of early-onset cancers diagnosed between 2000 and 2012 in 44 countries from the Cancer Incidence in Five Continents database. Using joinpoint regression models, we calculated the average annual percentage changes (AAPCs) and their corresponding 95% confidence intervals (95% CIs) for combined and individual categories of obesity-related cancers (11 and 9 cancer types in females and males, respectively) and non-obesity-related cancers (12 cancer types in both females and males). Differences in the AAPC were assessed by comparing 95% CIs, where nonoverlapping 95% CIs were considered statistically significantly different. We observed statistically significant positive AAPCs for early-onset obesity-related cancers in all available countries combined among females (global AAPC, 4.3%; 95% CI, 4.1-4.6%) and males (global AAPC, 1.4%; 95% CI, 1.2-1.7%). When analyzed by countries, we observed statistically significant positive AAPCs in 26 countries among females and 11 countries among males. AAPCs for early-onset obesity-related cancers were statistically significantly higher than those of non-obesity-related cancers in several regions, especially North America and Oceania. In conclusion, this study indicates that the incidence of early-onset obesity-related cancers exhibited a more pronounced increasing trend than non-obesity-related cancers among both sexes in many countries and regions.},
}

Humans
*Neoplasms/epidemiology/etiology
*Obesity/complications/epidemiology
Incidence
Female
Male
Adult
Age of Onset
Middle Aged
Global Health
Young Adult

@article {pmid40556953,
year = {2025},
author = {Mda, P and Mngadi, K and Zhang, B and Burnham, R and Juraska, M and Hyrien, O and Garrett, N and Dubula, T and Toni, S and Joseph, S and Kotze, P and Buchbinder, S and Takalani, A and Tomaka, F and Luedtke, A and Willems, W and Swann, E and Hutter, J and Gelderblom, H and McElrath, MJ and Lavreys, L and Stranix-Chibanda, L and Roxby, AC and Bekker, LG and Gray, GE},
title = {Pregnancy and contraceptive use among participants of childbearing potential in the HVTN 705 HIV vaccine trial in Southern Africa.},
journal = {Frontiers in reproductive health},
volume = {7},
number = {},
pages = {1565933},
pmid = {40556953},
issn = {2673-3153},
abstract = {BACKGROUND: HIV vaccine trial participants include sexually active cisgender females who agree to avoid pregnancy during the active vaccination period. Nevertheless, some pregnancies occur in almost all studies. We examined contraceptive use, pregnancy incidence, and the relationship between pregnancy and HIV seroconversion in one HIV vaccine trial.

METHODS: We performed an exploratory analysis of data collected for HVTN 705/HPX2008, a phase IIb HIV vaccine trial enrolling cisgender women across 23 sites in five southern African countries. Baseline characteristics and contraceptive use were assessed among participants who became pregnant and those who did not during the active vaccination phase (months 0-15). Pregnancy incidence rates were calculated for this phase and the duration of follow up (36 months). Cox regression analysis was used to assess factors associated with incident pregnancy.

RESULTS: There were 2,636 participants who received at least one vaccine or placebo dose (mean age: 23 years, standard deviation: 3 years). At enrolment, when contraception was required, 62.9% reported using injectable contraceptives. Overall pregnancy rate was 2.95 per 100 person-years (95% CI: 2.40, 3.58), with 101 pregnancies reported by month 15. Cumulative incidence of pregnancy at month 15 was similar between trial arms (log-rank p = 0.688). Each additional year of age was associated with an 8% decrease in pregnancy incidence (p = 0.014). Women aged 31-35 years had the lowest pregnancy incidence [1.75 (0.48, 4.48) per 100 person-years]. In a Cox regression analysis covering months 0-15, all contraceptive methods significantly reduced the incidence of pregnancy compared to no contraceptive use. Oral contraception was associated with the least reduction in pregnancy risk; implants were associated with the most reduction in pregnancy risk (p < 0.001).

CONCLUSIONS: In HVTN 705/HPX2008, higher incidence of pregnancy was associated with younger age and oral contraception (compared to other methods). These data may inform future designs of HIV prevention or vaccine trials.},
}

@article {pmid40555394,
year = {2025},
author = {Iqbal, M and Kumar, A and Dreger, P and Chavez, J and Sauter, CS and Sureda, AM and Bachanova, V and Maziarz, RT and Dreyling, M and Smith, SM and Jacobson, C and Glass, B and Casulo, C and Oluwole, OO and Montoto, S and Advani, R and Cohen, J and Salles, G and Hamad, N and Kuruvilla, J and Kahl, BS and Shadman, M and Kanate, AS and Budde, LE and Kamdar, M and Flowers, C and Hamadani, M and Kharfan-Dabaja, MA},
title = {Corrigendum to 'Clinical Practice Recommendations for Hematopoietic Cell Transplantation.' Transplant Cell Ther. 2024 Sep;30(9):832-843.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.022},
pmid = {40555394},
issn = {2666-6367},
}

@article {pmid40554677,
year = {2025},
author = {Venkataraman, V and Abrams, HR and Shulman, DS and Loggers, ET and Pollack, SM and Paulson, KG and Wagner, MJ},
title = {Effect of HLA restriction on racial and ethnic disparities in access to immune therapies for advanced synovial sarcoma.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyaf193},
pmid = {40554677},
issn = {1549-490X},
abstract = {PURPOSE: Synovial sarcoma (SS) is aggressive with poor outcomes. Cellular therapies are now FDA approved for advanced disease, but are restricted to certain HLA-A*02 alleles. We estimate eligibility to cellular therapies by race and ethnicity.

MATERIALS AND METHODS: Demographic and clinical features of SS cases from 2001 to 2020 were obtained from the United States Cancer Statistics (USCS; NPCR-SEER). Survival analyses were performed overall and by races/ethnicity. The proportion eligible for cellular therapy was estimated by races/ethnicity using previously published data on HLA-A*02 status and MAGE-A4 positivity.

RESULTS: From 2001 to 2020, 10,605 patients (48% female, 64% Non-Hispanic White, 17% Hispanic) with SS were identified. The incidence rate was 1.5-1.8/million/person-years and was stable over time, corresponding to an average 530 new cases annually. The most common primary site was the extremity (n = 5,877; 58%), and most patients presented with localized disease (n = 5,753; 54%). The 5-year cause-specific survival was 60% across all races/ethnicities and 79% for localized, 57% for regional, 12% for distant disease. Differences by race and ethnicity were found in the proportions of patients expected to be eligible for HLA-restricted cellular therapies targeting MAGE-A4. People of European/European descent had the highest estimated proportion (25-39%), and people of Asian/Pacific Islander descent had the lowest (11-17%).

CONCLUSION: Engineered T-cells targeting MAGE-A4 have shown encouraging safety and efficacy in advanced SS; however, eligibility restrictions will lead to racial and ethnic disparities. HLA-independent solutions must be developed to counter disparities and ensure all patients have access.},
}

@article {pmid40554428,
year = {2025},
author = {Bhatt, NS and Borogovac, A and Efebera, YA and DeSalvo, AM and Devine, SM and Foley, A and Stewart, V and Hamilton, BK and Heuer, M and Molfenter, T and Plastaras, JP and Ragon, BK and Wall, SA and Broglie, L and Juckett, MB and Khera, N and Horowitz, MM and DeZern, AE},
title = {Upfront Alternative Donor HCT in Severe Aplastic Anemia: Gaps and Opportunities to Translate Evidence into Practice.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015405},
pmid = {40554428},
issn = {2473-9537},
abstract = {Severe aplastic anemia (SAA) is a rare and life-threatening bone marrow failure disorder. Immunosuppressive therapy (IST) with anti-thymocyte globulin and cyclosporine has long been a frontline treatment option in SAA; however, its limited durability and risk of long-term complications such as secondary malignancies remain a drawback in this treatment modality. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option with significantly improved outcomes over the long term, particularly with HLA-matched related donors. However, the use of alternative donors such as haploidentical, mismatched, or matched unrelated donors, has previously been limited due to increased transplant-related morbidity, particularly graft-versus-host disease (GVHD). HCTs have therefore been limited to young recipients and those with HLA-matched related donors, creating significant disparity for older adults and those who lack matched donor options. Nevertheless, more recent advances in HCT, such as post-transplant cyclophosphamide for GVHD prophylaxis, have led to improved outcomes of HCT with alternative donors; however, alternative donor HCT remains underutilized as upfront therapy, in part because of limited multicenter trial data. This review discusses current SAA treatment approaches, including both IST and HCT, and highlights where gaps remain. It also discusses how ongoing clinical trials such as CureAA and TransIT could help address these gaps. Furthermore, we discuss the importance of stakeholder engagement and implementation science in the integration of research-based evidence into clinical practice. Bridging these gaps is necessary for achieving equitable access for patients historically excluded from frontline HCT, including older adults and racially or ethnically diverse populations.},
}

@article {pmid40554417,
year = {2025},
author = {Sharifi, H and Moss, CT and Musa, Z and Bell, A and O'Donnell, C and Borges, C and Matthaiou, EI and Johnston, L and Galban, C and Sheshadri, A and Yanik, GA and Cheng, GS and Hsu, JL},
title = {Pirfenidone for the treatment of bronchiolitis obliterans syndrome related to chronic graft-versus-host disease.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016122},
pmid = {40554417},
issn = {2473-9537},
abstract = {Bronchiolitis obliterans syndrome (BOS) is a severe form of chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic cell transplantation (HCT) with five-year survival of 40%. Currently, there is no curative therapy for BOS. Pre-clinical data suggest that pirfenidone, an anti-fibrotic drug, may benefit small airway fibrosis in HCT-associated BOS. A single-arm, open-label, 56-week phase 1 trial with 56-month extension evaluated pirfenidone's tolerability, safety, and efficacy in BOS patients. Efficacy was measured using pulmonary function tests (PFT), quantitative CT (qCT) scans, patient reported outcomes (PRO), cGVHD indices, and laboratory tests. Lung function trajectory was assessed by change in regression slopes before and during treatment. Baseline qCT metrics, including percentage normal lung, air trapping, volume change (Jacobian), and heterogeneity of volume change (Jacobian variance) were analyzed by participant response. Among 30 participants, 25 completed the 56-week trial, and 10 continued into the extension. Overall, 63% tolerated the recommended dose without safety concerns. There was significant improvement in the percent predicted forced expiratory volume in 1 second (P=0.00267) when analyzing all participants and improvement in individual PFT trend for 41.3% of participants. Quantitative CT analysis by lobe showed healthier lungs in the upper lobes of responders. Significant improvements were noted in liver function tests, PRO related to physical functioning and shortness of breath, and cGVHD skin indices. These findings indicate that pirfenidone is safe and tolerable in BOS patients post-HCT and may improve lung function and symptoms. Further trials are warranted to evaluate the efficacy of pirfenidone as a treatment for BOS after HCT. (NCT03315741).},
}

@article {pmid40502094,
year = {2025},
author = {Hurlburt, NK and Lubow, J and Goo, L and Pancera, M},
title = {Structural basis for antibody cross-neutralization of dengue and Zika viruses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40502094},
issn = {2692-8205},
abstract = {Safe and effective vaccines against co-circulating mosquito-borne orthoflaviviruses such as Zika virus (ZikV) and the four serotypes of dengue virus (DenV1-4) must elicit broadly neutralizing antibodies (bnAbs) to prevent the risk of enhancement of infection by non-neutralizing antibodies. We recently discovered new orthoflavivirus-directed bnAbs, including F25.S02, which neutralizes DenV1-4 and ZikV with comparable or superior potency to the previously characterized E dimer epitope (EDE) bnAbs. Mutagenesis studies of viral envelope proteins showed that the epitope specificity of F25.S02 is distinct from EDE1 bnAbs. Here, we used cryoEM and X-ray crystallography to understand the basis of cross-neutralization of F25.S02 at the molecular level. We obtained a ~4.2 Å cryoEM structure of F25.S02 Fab bound to a stabilized DenV3 soluble E protein dimer and a 2.3 Å crystal structure of F25.S02 Fab bound to ZikV soluble E protein dimer. Like previously described EDE1 bnAbs, the structural epitope of F25.S02 is at the E dimer interface, encompassing predominantly conserved regions in domain II, including the fusion loop. However, unlike EDE1 bnAbs, F25.S02 binding is almost entirely dependent on the heavy chain and is shifted slightly away from the dimer symmetry axis. Our findings emphasize the importance of this cross-neutralizing site of vulnerability for DenV and ZikV that can facilitate rational design of vaccines and therapeutics.},
}

@article {pmid40501932,
year = {2025},
author = {Otto, DJ and Arriaga-Gomez, E and Thieme, E and Yang, R and Lee, SC and Setty, M},
title = {Comparing phenotypic manifolds with Kompot: Detecting differential abundance and gene expression at single-cell resolution.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40501932},
issn = {2692-8205},
abstract = {Kompot is a statistical framework for holistic comparison of multi-condition single-cell datasets, supporting both differential abundance and differential expression. Differential abundance captures changes in how cells populate the phenotypic manifold across conditions, while differential expression identifies condition-specific changes in gene regulation that may be localized to particular regions of that manifold. Kompot models the distribution of cells and gene expression as continuous functions over a low-dimensional representation of cell states, enabling single-cell resolution inference with calibrated uncertainty estimates. Applying Kompot to aging murine bone marrow, we identified a continuum of shifts in hematopoietic stem cell and mature cell states, transcriptional remodeling of monocytes independent of compositional changes, and divergent regulation of oxidative stress response genes across cell types. By capturing both global and cell-state-specific effects of perturbation, Kompot reveals how aging reshapes cellular identity and regulatory programs across the hematopoietic landscape. This framework is broadly applicable to dissecting condition-specific effects in complex single-cell landscapes.},
}

@article {pmid40553813,
year = {2025},
author = {Barta, JA and Arenberg, D and Backhus, L and Detterbeck, F and Gould, MK and Nair, VS and Pasquinelli, M and Powell, CA and Sandler, K and Silvestri, G and Triplette, M and Vachani, A and Wiener, RS and Mazzone, PJ},
title = {Components Necessary for High-Quality Lung Cancer Screening: A 10-Year Update.},
journal = {Chest},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chest.2025.06.006},
pmid = {40553813},
issn = {1931-3543},
abstract = {Lung cancer screening (LCS) has evolved over the past decade with research advances and clinical experience helping to define target populations for screening, improve lung nodule detection and management, and identify structural components of programs that improve the quality of screening delivery. The 2015 American College of Chest Physicians and American Thoracic Society Policy Statement, Components Necessary for High-Quality Lung Cancer Screening, identified nine essential components for high-quality LCS. Ten years later, optimizing the balance between the benefits and harms of LCS and ensuring equitable screening among all population groups remain fundamental objectives. In this 2025 update we aim to summarize new knowledge and highlight critical components that are needed for providing high-quality LCS. A multidisciplinary group of LCS experts was assembled to review evidence from the past ten years. The original components were reviewed and updated to develop eight refined components that should be considered essential structural elements of screening programs. Each component recommended by the authors is supported by an evidence update. Applying this framework will allow screening programs across the country to ensure implementation of high-quality, net-benefit LCS.},
}

@article {pmid40550509,
year = {2025},
author = {Munoz, FM and Parameswaran, L and Gundacker, H and Posavad, CM and Badell, ML and Bunge, K and Mulligan, MJ and Olson-Chen, C and Novak, RM and Brady, RC and DeFranco, E and Gerber, JS and Pasetti, M and Shriver, MC and Coler, RN and Larsen, SE and Suthar, MS and Moreno, A and Miedema, J and Sui, Y and Richardson, BA and Piper, J and Beigi, R and Neuzil, KM and Brown, ER and Cardemil, CV and , },
title = {Infant Antibodies After Maternal COVID-19 Vaccination During Pregnancy or Postpartum.},
journal = {Pediatrics},
volume = {},
number = {},
pages = {},
doi = {10.1542/peds.2024-070175},
pmid = {40550509},
issn = {1098-4275},
abstract = {BACKGROUND AND OBJECTIVE: We describe the kinetics of maternally derived antibodies in infants in the first 6 months of life following 2- or 3-dose maternal vaccination during pregnancy or postpartum.

METHODS: This prospective, multicenter cohort study enrolled infants born to mothers vaccinated with 2- (n = 280) or 3-dose (boosted) monovalent messenger RNA vaccines in pregnancy (n = 202) or to mothers vaccinated postpartum (n = 36) from July 2021 to January 2022. Binding (immunoglobulin G to S and receptor-binding domain), pseudovirus, and live neutralizing antibody (nAb) geometric mean titers (GMTs) to vaccine and Omicron BA.1/BA.5 strains were measured at birth and 2 and 6 months of age. Antibody half-life and the effect of maternal or infant COVID-19 infection were assessed.

RESULTS: Significantly higher GMTs of binding antibody and nAb to all antigens were present at birth and 2 months in infants of boosted mothers (P < .01) and higher titers to the vaccine strain, but not Omicron BA.1 and BA.5, persisted up to 6 months of age in infants of boosted mothers compared with the other groups (P < .01). Higher infant antibody titers at delivery and 6 months of age were associated with a booster dose during pregnancy and maternal prenatal and infant COVID-19 infection. Maternal infection status or vaccine regimen did not influence the half-life of infant antibodies.

CONCLUSIONS: A maternal COVID-19 booster in pregnancy results in significantly higher functional antibody titers in infants compared with 2 doses in pregnancy or postpartum. High titers at birth and maternal hybrid immunity result in persistently elevated titers in infants for 6 months.},
}

@article {pmid40549982,
year = {2025},
author = {El-Jawahri, A and LeBlanc, TW and Kavanaugh, A and Webb, J and Fausto, J and Traeger, L and Greer, JA and Jackson, V and Horick, N and Rabideau, DJ and Fenech, A and Newcomb, R and Ufere, NN and Caruso, E and Pepper, J and DeFilipp, Z and Chen, YB and Lee, SJ and Temel, JS},
title = {Multisite Randomized Trial of Inpatient Palliative Care Intervention for Patients Undergoing Hematopoietic Stem Cell Transplantation.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500378},
doi = {10.1200/JCO-25-00378},
pmid = {40549982},
issn = {1527-7755},
abstract = {PURPOSE: Patients undergoing hematopoietic stem cell transplantation (HSCT) and their caregivers endure immense physical and psychological symptoms, which result in quality-of-life (QOL) impairments during HSCT.

METHODS: We conducted a multisite randomized trial among adults undergoing autologous or allogeneic HSCT at three academic institutions. Patients were randomly assigned to an inpatient palliative care (PC) intervention or usual care. Intervention patients met with PC clinicians twice weekly during the HSCT hospitalization. Patients assigned to usual care could be referred to PC as per standard of care. We assessed QOL (patient: Functional Assessment of Cancer Therapy-Bone Marrow Transplant; caregiver: Caregiver-Oncology-QOL), depression and anxiety symptoms (Hospital-Anxiety-and-Depression-Scale), and patients' post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist) at baseline, week 2, and 3 and 6 months post-HSCT. The primary end point was patients' QOL at week 2 during hospitalization when patients experience their QOL nadir. We used linear regression, adjusting for baseline scores, to evaluate the effect of the intervention on patient-reported outcomes at week 2. We used linear mixed-effect models to assess the effect of the intervention on study outcomes longitudinally.

RESULTS: We enrolled 68.7% (360/524) of eligible patients between October 2018 and July 2022. Compared with those receiving usual care, patients receiving the intervention reported better QOL (adjusted mean difference [B], 6.3; SE, 0.1; P < .001), lower depression (B, -1; SE, 0.4; P = .026), and fewer PTSD symptoms (B, -1.9; SE, 0.9; P = .046) at week 2. Patient-reported anxiety did not differ significantly between groups at week 2. In longitudinal analyses, patients receiving the intervention reported a steeper decline in PTSD symptoms over 6 months post-HSCT (slope difference, -0.9; SE, 0.7; P = .012). All other patient-reported outcomes did not differ longitudinally between the groups.

CONCLUSION: PC led to substantial improvements in patients' QOL, depression, and PTSD symptoms with sustained effects on PTSD symptoms up to 6 months post-HSCT.},
}

@article {pmid40549387,
year = {2025},
author = {Marrero, RJ and Shastri, VM and Nicolet, D and Mrózek, K and Walker, CJ and Blum, WG and Powell, BL and Kolitz, JE and Moore, JO and Uy, GL and Stock, W and Carroll, AJ and Byrd, JC and Aplenc, R and Cooper, TM and Gamis, AS and Wu, H and Pounds, S and Wang, YC and Alonzo, TA and Meshinchi, S and Eisfeld, AK and Kolb, EA and Lamba, JK},
title = {Cytarabine Pharmacogenomics and Outcomes Among Children and Young Adults With Acute Myeloid Leukemia.},
journal = {JAMA network open},
volume = {8},
number = {6},
pages = {e2516296},
pmid = {40549387},
issn = {2574-3805},
mesh = {Humans ; *Leukemia, Myeloid, Acute/genetics/drug therapy/mortality ; Adolescent ; Male ; Female ; Child ; Young Adult ; Adult ; Child, Preschool ; *Cytarabine/therapeutic use ; *Antimetabolites, Antineoplastic/therapeutic use ; Infant ; *Pharmacogenetics ; Treatment Outcome ; Cohort Studies ; Infant, Newborn ; },
abstract = {IMPORTANCE: Therapeutic responses in acute myeloid leukemia (AML) demonstrate considerable variability both across and within established risk stratifications and age groups. Moreover, significant racial disparities persist, with Black patients experiencing inferior survival outcomes compared with their White counterparts.

OBJECTIVE: To validate the association of the previously reported 10 single nucleotide variant (SNV)-based ara-C pharmacogenomics score (ACS10) with survival outcomes in a large cohort of pediatric AML patients; to evaluate whether ACS10 remains relevant in an adolescent and young adult (AYA) population of patients with AML treated with similar intensive induction chemotherapy protocols; and to assess the association of ACS10 with race and treatment outcomes in both cohorts.

This cohort study included patients from the Children's Oncology Group's AAML1031 trial, a multicenter, open-label randomized clinical trial that enrolled pediatric patients with newly diagnosed, treatment-naive primary AML from June 2011 to July 2017 (aged 0 to 29.5 years) and from the Alliance for Clinical Trials in Oncology frontline protocols, which included AYA patients from 9 different trials that enrolled patients with newly diagnosed AML from 1992 to 2010. Data were analyzed from September 2022 to March 2025.

EXPOSURES: Patients in the AAML1031 trial were randomized to 2 arms, standard chemotherapy alone or standard chemotherapy with the addition of bortezomib. Patients in the Alliance for Clinical Trials in Oncology cohorts were treated with similar intensive induction chemotherapy protocols.

MAIN OUTCOMES AND MEASURES: ACS10 scores were evaluated for association with outcomes according to race, treatment arm, and hematopoietic stem cell transplant (HSCT) status.

RESULTS: The study included 1086 patients with AML. There were 717 patients from the pediatric AML cohort (median [range] age, 9.6 [0.04-29.2 years]; 379 [53%] male; 33 [5%] Asian, 84 [12%] Black, and 522 [73%] White) and 369 AYA patients with AML from the Alliance for Clinical Trials in Oncology group (median [range] age, 30 [17-39] years; 196 [53%] male; 7 [2%] Asian, 32 [9%] Black, and 288 [78%] White). Within the standard treatment arm of AAML1031, patients in the low ACS10 group had significantly worse event-free survival (EFS) compared with those in the high ACS10 group (all patients: hazard ratio [HR], 1.42; 95% CI, 1.05-1.95; P = .02; non-HSCT cohort: HR, 1.48; 95% CI, 1.06-2.07; P = .02). The ACS10 score remained significantly associated with EFS in multivariable analysis after adjusting for age, race, risk group and white blood cell count, within the standard treatment arm (HR, 1.44; 95% CI, 1.03-2.02; P = .03). In the Alliance for Clinical Trials in Oncology AYA non-HSCT cohort, the low ACS10 score group had significantly inferior overall survival (OS) and a higher point estimate for EFS compared with patients with a high ACS10 score (OS: HR, 1.50; 95% CI, 1.05-2.14; P = .03; EFS: HR, 1.32; 95% CI, 0.95-1.83; P = .10). A higher number of early deaths was observed in the low ACS10 group compared with the high ACS10 group, but the difference was not statistically significant (death within 30 days of treatment initiation: 6 of 112 [5%] vs 2 of 257 [1%]; P = .07). Across both cohorts, a low ACS10 score was significantly more abundant in Black patients compared with White patients (eg, in Alliance for Clinical Trials in Oncology cohort, 27 of 32 Black patients [84%] had low ACS10 scores compared with 64 of 288 White patients [22%]; P < .001) and inferior survival was observed in Black patients (eg, OS of Black compared with White patients in AAML1031 cohort: HR, 1.47; 95% CI, 1.02-2.13; P = .04). In the AAML1031 cohort, there were no significant differences in EFS or OS between Black and White patients receiving augmented treatment, suggesting that the addition of bortezomib was associated with benefit for Black patients.

CONCLUSIONS AND RELEVANCE: In this study of 717 pediatric and 369 AYA patients with AML, the ACS10 score was associated with EFS in pediatric and AYA patients when treated with a standard induction regimen. There was a higher abundance of low ACS10 scores in Black patients, and Black patients treated with augmented therapy (ie, the addition of bortezomib) seemed to have improved outcomes. Integrating the ACS10 score into a prospective clinical trial to personalize induction therapy based on an individual's genetic profile has the potential to improve treatment outcomes.},
}

Humans
*Leukemia, Myeloid, Acute/genetics/drug therapy/mortality
Adolescent
Male
Female
Child
Young Adult
Adult
Child, Preschool
*Cytarabine/therapeutic use
*Antimetabolites, Antineoplastic/therapeutic use
Infant
*Pharmacogenetics
Treatment Outcome
Cohort Studies
Infant, Newborn

@article {pmid40549281,
year = {2025},
author = {Yi, JC and Walsh, CA and Chow, EJ and Baker, KS and Mendoza, JA and Cole, A},
title = {Primary care providers and their needs caring for cancer survivors: a qualitative study.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {40549281},
issn = {1932-2267},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; },
abstract = {PURPOSE: To enhance survivorship care, we explored primary care providers' (PCPs) preferences and needs related to treatment summary and survivorship care plans (TS/SCPs) as a communication tool and PCPs' general thoughts related to barriers in managing the care of cancer survivors.

METHODS: We conducted semi-structured qualitative interviews via video with PCPs within primary care practice networks in the Pacific Northwest. A codebook was developed with the interview guide as a template. Directed content analysis was used to analyze PCP reported challenges, supports needed, and TS/SCP feedback.

RESULTS: Qualitative interviews were conducted with 18 PCPs. The majority were female (72%) and non-Hispanic White (94%), with 56% from urban areas and with varied amounts of time in clinical practice (median 4.5 years, range 0.5-47). PCPs reported common challenges caring for cancer survivors (e.g., unsure what surveillance is needed) and supports needed to improve care (e.g., further PCP education). PCPs also described preferred information to include in TS/SCPs (e.g., surveillance schedule) and format (e.g., in the electronic health record). They also reported that e-consultation could be useful in communication with other health care providers about any questions, CONCLUSIONS: PCPs want further education and support about cancer surveillance guidelines and managing long-term effects in survivors. Having TS/SCP information easy to find in the EHR was mentioned by the PCPs as something that would improve their care of cancer survivors.

Providing PCPs with more education and tools in the EHR could lead to improved care of cancer survivors.},
}

@article {pmid40549085,
year = {2025},
author = {Goodsell, KE and Sham, JG},
title = {ASO Author Reflections: Reasonable Doubt: The Case for Somatostatin Analogs in Pancreas Surgery Remains Unsettled.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {40549085},
issn = {1534-4681},
}

@article {pmid40549080,
year = {2025},
author = {Fernandez, M and Todeschini, L and Keenan, BP and Rosenberg, D and Hernandez, S and Zampese, M and Qiao, G and Pollini, T and Maker, AV},
title = {ASO Visual Abstract: Novel Computational Analysis Identifies Cytotoxic Lymphocyte-to-Monocyte Balance in Tumors as a Predictor of Recurrence-Free Survival in Colorectal Carcinoma.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1245/s10434-025-17700-3},
pmid = {40549080},
issn = {1534-4681},
}

@article {pmid40548935,
year = {2025},
author = {Readshaw, JJ and Doyle, LA and Puiu, M and Kelly, A and Nelson, A and Kaiser, AJ and McGuire, SF and Peralta Acosta, J and Smith, DL and Stoddard, BL and Kaiser, BK and Blower, TR},
title = {PglZ from Type I BREX phage defence systems is a metal-dependent nuclease that forms a sub-complex with BrxB.},
journal = {Nucleic acids research},
volume = {53},
number = {12},
pages = {},
doi = {10.1093/nar/gkaf540},
pmid = {40548935},
issn = {1362-4962},
support = {BB/T008695/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/Y003659/1//responsive mode/ ; //Lister Institute Prize Fellowship to A.K. and T.R.B./ ; //New England Biolabs/ ; //Fred Hutchinson Cancer Center/ ; R01GM105691/GF/NIH HHS/United States ; R35GM148166/GF/NIH HHS/United States ; R15GM140375//BKK/ ; },
mesh = {*Bacteriophages/genetics ; *Bacterial Proteins/metabolism/chemistry/genetics ; Models, Molecular ; *Viral Proteins/metabolism/chemistry ; Metals/metabolism ; *DNA-Binding Proteins/metabolism/chemistry/genetics ; },
abstract = {BREX (Bacteriophage Exclusion) systems, identified through shared identity with Pgl (Phage Growth Limitation) systems, are a widespread, highly diverse group of phage defence systems found throughout bacteria and archaea. The varied BREX Types harbour multiple protein subunits (between four and eight) and all encode a conserved putative phosphatase, PglZ, and an equally conserved, putative ATPase, BrxC. Almost all BREX systems also contain a site-specific methyltransferase, PglX. Despite having determined the structure and fundamental biophysical and biochemical behaviours of several BREX factors (including the PglX methyltransferase, the BrxL effector, the BrxA DNA-binding protein, and a commonly-associated transcriptional regulator, BrxR), the mechanism by which BREX impedes phage replication remains largely undetermined. In this study, we identified a stable BREX sub-complex of PglZ:BrxB, generated and validated a structural model of that protein complex, and assessed the biochemical activity of PglZ from BREX, revealing it to be a metal-dependent nuclease. PglZ can cleave cyclic oligonucleotides, linear oligonucleotides, plasmid DNA and both non-modified and modified linear phage genomes. PglZ nuclease activity has no obvious role in BREX-dependent methylation, but does contribute to BREX phage defence. BrxB binding does not impact PglZ nuclease activity. These data contribute to our growing understanding of BREX phage defence.},
}

*Bacteriophages/genetics
*Bacterial Proteins/metabolism/chemistry/genetics
Models, Molecular
*Viral Proteins/metabolism/chemistry
Metals/metabolism
*DNA-Binding Proteins/metabolism/chemistry/genetics

@article {pmid40548549,
year = {2025},
author = {Chao, ST and Berkowitz, A and Harris, EER and Henderson, MA and Lo, SS and Pacella, M and Palmer, J and Saeed, H and Simone, CB and Ziemer, BP and Small, W and Schechter, NR},
title = {ACR-ARS Practice Parameter for the Performance of Stereotactic Body Radiation Therapy.},
journal = {American journal of clinical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1097/COC.0000000000001224},
pmid = {40548549},
issn = {1537-453X},
abstract = {OBJECTIVES: This practice parameter was revised collaboratively by the American College of Radiology (ACR) and American Radium Society (ARS). Stereotactic body radiation therapy (SBRT) precisely delivers higher dose(s) of radiation in 5 of fewer fractions, compared with conventional radiation. Given the complexity and technical nature of this treatment technique, practice parameters are needed to provide guidance to physicians and physicists.

METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS.

RESULTS: Workflow, qualifications/responsibilities of personnel, quality control, and treatment delivery/verification are reviewed. Notable elements of SBRT include image guidance, immobilization, and motion management, with the treatment planning goal of minimizing the volume of normal tissue exposed to medium and high dose levels and maximizing dose safely to the target. Specialized training is encouraged, as some technologies are not used in standard treatments.

CONCLUSIONS: This practice parameter provides direction on key components recommended for SBRT and may be used as a guide to physicians and physicists wanting to provide this treatment to their patients.},
}

@article {pmid40546794,
year = {2025},
author = {Unger, JM and Andrews, HS and Levit, LA and McKelvey, BA and Stewart, M and Canin, B and Flaherty, K and Kimball, D and Miller, T and Onitilo, A and Bruinooge, S and Garrett-Mayer, E and Schenkel, C},
title = {Impact of the COVID-19 Pandemic Mitigation Strategies on Cancer Treatment Trials: A Meta-Analysis of Industry and National Cancer Institute Studies.},
journal = {JCO oncology advances},
volume = {2},
number = {1},
pages = {e2500021},
pmid = {40546794},
issn = {2994-9750},
abstract = {PURPOSE: The onset of the COVID-19 pandemic in early 2020 disrupted the conduct of cancer clinical trials. In response, federal agencies allowed more flexibility for trial recruitment and patient follow-up. A key question is whether the benefits of adopting these strategies outweigh the potential detriments to quality metrics.

METHODS: A joint ASCO and Friends of Cancer Research task force invited industry and National Cancer Institute trial sponsors to contribute deidentified trial-level aggregate data on enrollment, major protocol deviations, dropouts, and severe adverse events (Common Terminology Criteria for Adverse Events grade 3-5). These quality metrics were examined as proportions of participants at risk during the pre-COVID-19 (January 2017-February, 2020), initial wave (March-April, 2020), initial recovery (May-December, 2020), and secondary recovery (January 2021-December 2022) periods. Multilevel beta-regression was used, adjusting for phase; study and sponsor were treated as random effects. Indicator variables were used with pre-COVID-19 as the reference.

RESULTS: Ten sponsors contributed 67 analyzable trials with N = 12,000 US-based participants. Enrollment odds decreased 49% in the initial wave (odds ratio [OR], 0.51 [95% CI, 0.30 to 0.86], P = .01) but recovered to pre-COVID-19 levels by 2021-2022 (OR, 1.01 [95% CI, 0.56 to 1.81], P = .97). Major protocol deviations, dropouts, and severe toxicity all had a lower incidence in the initial wave compared with pre-COVID-19; these outcomes were also less frequent (P < .05) in the initial recovery period but returned to pre-COVID-19 levels by 2021-2022.

CONCLUSION: In this multicollaborator evaluation, large declines in enrollment, major protocol deviations, dropouts, and severe toxicity during the acute phase of the pandemic all returned to pre-COVID-19 levels by 2021-2022. These findings highlight the impact of the temporary disruption to trial conduct during the pandemic's peak, but suggest that pandemic-related procedural flexibility did not result in long-term reduced data quality. Sponsors and regulators should consider broader adaptation of trial flexibilities moving forward.},
}

@article {pmid40546726,
year = {2025},
author = {Iyer, SP and Dakhil, S and Shinohara, MM and Zain, J and Acosta, M and Foss, F},
title = {Pralatrexate injection combined with oral leucovorin for mucositis management in PTCL/CTCL treatment: a multicenter phase 2 trial.},
journal = {Blood neoplasia},
volume = {2},
number = {1},
pages = {100055},
pmid = {40546726},
issn = {2950-3280},
abstract = {Pralatrexate (Folotyn) is an antifolate indicated for the treatment of relapsed/refractory peripheral T-cell lymphoma (PTCL), and although durable clinical benefit has been demonstrated, oral and gastrointestinal mucositis and/or skin reactions are frequent toxicity complications associated with pralatrexate treatment. Leucovorin (d,l-folinic acid) administration has been used as a standard rescue for patients receiving high-dose methotrexate therapy and has recently been studied in patients with PTCL and cutaneous T-cell lymphoma receiving pralatrexate. We describe results from a multicenter, phase 2, single-arm, open-label trial, conducted with the primary objective of evaluating the effect of leucovorin in preventing or reducing the incidence of grade 2 or higher oral mucositis associated with pralatrexate treatment in cycle 1. Patients were administered pralatrexate, 30 mg/m[2] as an IV push, once weekly for 6 weeks in each cycle, followed by a week of rest (no treatment). Leucovorin 25 mg tablets were administered 3 times daily for 2 days (a total of 6 doses [150 mg cumulative weekly dose]), initiated 24 hours (±2 hours) after each pralatrexate dose. The evaluable population included 34 patients, with a mean age of 63.7 years and 60% males, of whom 2 (5.9%) developed grade 2 oral mucositis during the study period (P < .0001) and there were no reports of grade 3 or higher oral mucositis. Dose modifications, including omissions, delays, or reductions, due to oral mucositis were limited to 1 patient. Coadministration of leucovorin resulted in a significant reduction in mucositis and can be considered a prophylactic therapy in patients receiving pralatrexate treatment. This trial was registered at www.clinicaltrials.gov as #NCT02106650.},
}

@article {pmid40501893,
year = {2025},
author = {Robertson, AJ and Kerr, B and Feder, AF},
title = {Social interactions shape antiviral resistance outcomes in poliovirus via eco-evolutionary feedback.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40501893},
issn = {2692-8205},
abstract = {Antiviral resistance evolution poses a major obstacle for controlling viral infections. A promising strategy is to target shared viral proteins that allow drug susceptible viruses to sensitize resistant ones during cellular coinfection, muting selection for resistance. Pocapavir, a poliovirus capsid inhibitor, employs this sociovirological strategy. While susceptible viruses significantly suppressed resistance in the presence of pocapavir in cell culture, a pocapavir clinical trial observed widespread resistance evolution and limited improvements to clearance times. To reconcile these findings, we present an intra-host eco-evolutionary model of poliovirus in the presence of pocapavir, which reproduces both the potent interference observed in vitro and the resistance emergence seen in patients. In the short term, our model predicts that a high density of susceptible viruses sensitizes resistant ones to pocapavir, mirroring cell culture results. However, over multiple replication cycles, pocapavir's high potency collapses viral density, which reduces coinfection and allows resistance to evolve as observed in the clinical trial. Since coinfection is essential to suppress resistance, enabling greater survival of susceptible viruses could offer therapeutic advantages. Counterintuitively, we demonstrate that this can be achieved by lessening antiviral potency, which can limit resistance evolution while also maintaining a low viral load. These findings suggest that antivirals that rely on viral social interaction must balance immediate neutralization with the preservation of future coinfection, yielding more sustained inhibition. Explicitly considering the eco-evolutionary feedback encompassing viral density, social phenotypes and absolute fitness not only provides new insights into designing effective therapies but also illuminates viral evolutionary dynamics more broadly.},
}

@article {pmid40501778,
year = {2025},
author = {Schattgen, S and Vegesana, K and Hazelton, WD and Minervina, A and Valkiers, S and Slowikowski, K and Smith, N and , and Villani, AC and Thomas, PG and Bradley, P},
title = {Diverse modes of T cell receptor sequence convergence define unique functional and cellular phenotypes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40501778},
issn = {2692-8205},
abstract = {Single-cell techniques allow concurrent study of gene activity and T cell receptor (TCR) sequences, identifying connections between TCR structure and cell traits. Expanding on our CoNGA software, we present a "metaCoNGA" analysis of 6 million T cells from 91 diverse studies, mapping TCR sequence similarity across tissues and diseases. This approach exposes shared TCR features within specific T cell subsets, including those associated with infection, cancer, and autoimmunity. We introduce a method to identify T cell groups with similar gene expression and biased TCR amino acid composition, providing a systematic framework for classifying diverse unconventional T cells, including KIR+ CD8+ T cells, CD4+ regulatory T cells, and subsets of NKT and MAIT cells. A new TCR clustering approach identifies thousands of convergent TCR sequence clusters hypothesized to target shared antigens. These clusters show coherent gene expression, highlighting the role of antigen exposure in shaping T cell behavior. Finally, we provide a tool for users to merge new data with this resource and rapidly identify T cell features in their data sets. This resource empowers investigations into the complex relationship between TCR sequence and T cell function in human health.},
}

@article {pmid40339678,
year = {2025},
author = {Dontchos, BN and Dodelzon, K and Bhole, S and Edmonds, CE and Mullen, LA and Parikh, JR and Daly, CP and Epling, JA and Christensen, S and Grimm, LJ},
title = {Opinions and Preferences Regarding Artificial Intelligence Use in Health Care Delivery: Results From a National Multisite Survey of Breast Imaging Patients.},
journal = {Journal of the American College of Radiology : JACR},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacr.2025.05.001},
pmid = {40339678},
issn = {1558-349X},
abstract = {OBJECTIVE: Artificial intelligence (AI) utilization is growing, but patient perceptions of AI are unclear. Our objective was to understand patient perceptions of AI through a multisite survey of breast imaging patients.

METHODS: A 36-question survey was distributed to eight US practices (six academic, two nonacademic) from October 2023 through October 2024. This article analyzes a subset of questions from the survey addressing digital health literacy and attitudes toward AI in medicine and breast imaging specifically. Multivariable analysis compared responses by respondent demographics.

RESULTS: A total of 3,532 surveys were collected (response rate: 69.9%, 3,532 of 5,053). Median respondent age was 55 years (interquartile range 20). Most respondents were White (73.0%, 2,579 of 3,532) and had completed college (77.3%, 2,732 of 3,532). Overall, respondents were undecided (range: 43.2%-50.8%) regarding questions about general perceptions of AI in health care. Respondents with higher electronic health literacy, more education, and younger age were significantly more likely to consider it useful to use AI for aiding medical tasks (all P < .001). In contrast, respondents with lower electronic health literacy and less education were significantly more likely to indicate it was a bad idea for AI to perform medical tasks (P < .001). Non-White patients were more likely to express concerns that AI will not work as well for some groups compared with others (P < .05). Overall, favorable opinions of AI use for medical tasks were associated with younger age, more education, and higher electronic health literacy.

DISCUSSION: As AI is increasingly implemented into clinical workflows, it is important to educate patients and provide transparency to build patient understanding and trust.},
}

@article {pmid40546723,
year = {2025},
author = {Davids, MS and Ambrose, J and de Nigris, E and Prescott, J and Leng, S and Farooqui, MZH and Gandra, SR and Zettler, CM and Fernandes, LL and Wang, CK and Shadman, M},
title = {Real-world characteristics, treatment patterns, and outcomes of patients with 2 or more LOTs for CLL/SLL in the United States.},
journal = {Blood neoplasia},
volume = {2},
number = {1},
pages = {100047},
pmid = {40546723},
issn = {2950-3280},
abstract = {The development of targeted agents for chronic lymphocytic leukemia (CLL) has transformed the treatment paradigm for patients with CLL. Because of this evolving treatment landscape, contemporaneous evidence was needed related to US treatment patterns and outcomes among patients treated in the real-world. Using COTA's electronic health records-based database, we examined characteristics, treatment patterns, and outcomes of patients receiving ≥2 lines of therapy (LOTs). A total of 1283 adult patients with CLL were identified who initiated second LOT (2L) between 1 January 2014 and 30 June 2022. Of those patients, 542 (42.2%) later received third-line (3L) therapy, of whom 228 (42.1%) went on to receive fourth-line (4L) therapy. Overall, >18% of patients died after 2L initiation and before 3L initiation, and more than a quarter died before 4L initiation. Most patients were White (77.7%), male (60.6%), aged ≥65 years (68.8%), and treated in a community practice setting (87.8%). From 2014 to 2023, the use of chemoimmunotherapy in any ≥2L LOT decreased, whereas use of Bruton tyrosine kinase inhibitor and B-cell lymphoma 2 inhibitor therapy increased. Across endpoints, median times to event(s) were generally shorter with each subsequent LOT received, both in the overall population and among patients receiving a given therapy in different LOTs. With a median follow-up time from 2L initiation of 38.0 months, median real-world time to next treatment, progression-free survival, and overall survival was 31.9, 33.8, and 80.1 months, respectively. Despite great advancements in CLL treatments since 2014, unmet need persists for patients receiving late LOT.},
}

@article {pmid40545568,
year = {2025},
author = {Gupta, M and Schoettler, ML and Brazauskas, R and Bo-Subait, S and Orozco, G and Battiwalla, M and Buchbinder, D and Hamilton, BK and Savani, BN and Schoemans, H and Sorror, ML and Ahmed, S and Badawy, SM and Bhushan, V and Birdsey, K and Couriel, D and Doherty, EE and Donato, M and Farag, SS and Gutman, J and Horwitz, M and El Jurdi, N and Maakaron, JE and Maziarz, RT and Pineiro, L and Schiller, G and Weisdorf, DJ and William, BM and Shaw, BE and Phelan, R and Porter, DL and Abt, PL and Levine, M},
title = {Risk Factors for Solid Organ Graft Failure and Death in Hematopoietic Cell Transplant Recipients Undergoing Solid Organ Transplantation: A Retrospective Center for International Blood and Marrow Transplant Research and Organ Procurement and Transplantation Network Study.},
journal = {Transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1097/TP.0000000000005397},
pmid = {40545568},
issn = {1534-6080},
abstract = {BACKGROUND: There is a growing population of hematopoietic cell transplantation (HCT) survivors who later require a solid organ transplant (SOT). However, there are limited data on survival, risk factors (RFs) for SOT graft loss, and death.

METHODS: This is a retrospective Center for International Blood and Marrow Transplant Research study that included recipients of HCT followed by SOT between 2001 and 2017. HCT data were merged with data from the Organ Procurement and Transplantation Network.

RESULTS: Eighty patients underwent autologous (45%) or allogeneic (55%) HCT followed by single SOT. Common indications for HCT included leukemia/myelodysplastic syndrome (45%) and plasma cell disorders (38.8%). The median time from HCT to SOT was 47.7 mo. There were 49 kidney, 26 thoracic, and 5 liver transplants. Overall survival from SOT was significantly different by organ (P = 0.01). Three-year overall survival by organ type was 85% among kidney, 70.7% among thoracic, and 30% among liver SOT recipients. Significant RFs for death included lymphoma versus plasma cell disorders and SOT type; thoracic and liver SOT carried a greater risk of death than kidney SOT. There was no significant difference in SOT failure incidence by SOT type; 3-y overall incidence was 27.8%. RFs for SOT graft loss included lymphoma, liver SOT, and positive recipient cytomegalovirus status at SOT.

CONCLUSIONS: In this study, liver SOT recipients had inferior outcomes. However, renal and thoracic SOT recipients after HCT have acceptable outcomes compared with those of the general SOT population, and thus, SOT should be considered a viable treatment option in these patients.},
}

@article {pmid40545567,
year = {2025},
author = {Gupta, M and Schoettler, ML and Orozco, G and Brazauskas, R and Bo-Subait, S and Battiwalla, M and Buchbinder, D and Hamilton, BK and Savani, BN and Schoemans, H and Sorror, ML and Ahmed, S and Badawy, SM and Bhushan, V and Birdsey, K and Couriel, D and Doherty, EE and Donato, M and Farag, SS and Gutman, J and Horwitz, M and El Jurdi, N and Maakaron, JE and Maziarz, RT and Pineiro, L and Schiller, G and Weisdorf, DJ and William, BM and Shaw, BE and Phelan, R and Porter, DL and Levine, M and Abt, PL},
title = {Risk Factors for Solid Organ Graft Failure and Death in Solid Organ Transplant Recipients Undergoing Hematopoietic Cell Transplantation: A Retrospective Center for International Blood and Marrow Transplant Research (CIBMTR) and Organ Procurement and Transplantation Network (OPTN) Study.},
journal = {Transplantation},
volume = {},
number = {},
pages = {},
doi = {10.1097/TP.0000000000005377},
pmid = {40545567},
issn = {1534-6080},
abstract = {BACKGROUND: There is a growing population of solid organ transplant (SOT) survivors who subsequently require a hematopoietic cell transplant (HCT), although there are limited data on survival, risk factors for SOT graft loss, and death in this cohort.

METHODS: This retrospective Center for International Blood and Marrow Transplant Research study included recipients of SOT followed by HCT between 1989 and 2017. HCT data were merged with organ transplant data from the Organ Procurement and Transplantation Network.

RESULTS: Eighty-three patients with an SOT underwent an HCT. Organs transplanted included heart/lung (thoracic, n = 15), kidney (n = 42), and liver (n = 26); 24 patients (29%) received a living donor graft and 59 (71%) a deceased graft. Forty-one patients (49.4%) received an allogeneic HCT and 42 (50.6%) an autologous HCT. Three-year overall survival (OS) from HCT in the entire cohort was 38.6%. There were no significant differences in OS by SOT type, although 3-y OS appeared lowest in the kidney SOT group at 29.9%, compared with liver SOT at 40.6% and thoracic SOT at 58.2%. The incidence of SOT graft failure 3 y post-HCT was 59.1%. There were no significant differences in SOT graft failure by organ type: 3-y failure probability 67.2% for kidney, 56.5% for liver, and 46.2% for thoracic. Shared risk factors for death and graft failure included HCT indication (leukemia, lymphoma, and nonmalignant diseases), HCT type (allogeneic), and SOT type (kidney).

CONCLUSIONS: Although some SOT recipients may benefit from HCT, the incidence of SOT graft failure was high and OS was poor, particularly after allogeneic HCT.},
}

@article {pmid40545000,
year = {2025},
author = {Farhan, S and Kennedy, VE and Espinoza-Gutarra, MR and Lust, H and Bobillo, MSO and Lin, AY and Olin, RL and Lin, RJ and Rentscher, KE and Taylor, MR and Mohanraj, L and Wood, WA and Murthy, HS and Ahmed, N and Dueck, AC and Phelan, R and Kelly, DL and Yuen, C and Munshi, PN and Schoemans, H and Hamilton, BK and Lee, C and Sung, AD},
title = {Assessing Physical Function in Transplantation and CAR-T Recipients: Expert Recommendations from the Survivorship, Aging and Biobehavioral Special Interest Groups of ASTCT.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.06.017},
pmid = {40545000},
issn = {2666-6367},
abstract = {The past few decades have witnessed significant advancements in stem cell transplant and cell therapy (TCT). This allowed their expanded use in older patients and those with comorbidities with favorable outcomes. However, these procedures carry significant risks, such as graft-versus-host disease, infection, cytokine release syndrome, and immune effector cell-associated neurotoxicity. Therefore, physical function assessment is crucial to assess patient fitness and potential optimization before and after TCT. The existence of diverse assessment tools makes implementation, comparison, and sharing knowledge among centers difficult. This paper proposes a tiered approach aiming to harmonize physical assessment in TCT. This allows healthcare facilities to prioritize recommended assessments based on their current capabilities and resources. TCT patients should receive comprehensive physical assessment pre- and post-TCT using a combination of both patient-reported and objective measures. For patient-reported measures, the Patient-Reported Outcomes Measurement Information System can be considered. For objective measures, we recommend considering a physical performance assessment (e.g., gait speed) or muscle strength assessment (e.g., hand grip), if feasible. Albumin and C reactive protein are also informative in predicting the risk of non-relapse mortality. Other composite tools, questionnaire libraries, biomarkers, imaging, and wearables can be added according to research and clinic needs. A care workflow needs to be in place in case any impairment is found during the evaluation with goals of increasing physiology reserve and mitigating stressors. This tiered approach will increase awareness and adoption of these tools and hence improve patient care, facilitate data sharing, and enhance collaboration in this field.},
}

@article {pmid40544344,
year = {2024},
author = {Gilbert, PB and Peng, J and Han, L and Lange, T and Lu, Y and Nie, L and Shih, MC and Waddy, SP and Wiley, K and Yann, M and Zafari, Z and Ghosh, D and Follmann, D and Juraska, M and Díaz, I},
title = {A surrogate endpoint-based provisional approval causal roadmap, illustrated by vaccine development.},
journal = {Biostatistics (Oxford, England)},
volume = {26},
number = {1},
pages = {},
doi = {10.1093/biostatistics/kxaf018},
pmid = {40544344},
issn = {1468-4357},
support = {//National Institute of Allergy and Infectious Diseases/ ; R37AI054165/NH/NIH HHS/United States ; /NH/NIH HHS/United States ; /VA/VA/United States ; //United States Government/ ; },
mesh = {Humans ; *Biomarkers ; *Clinical Trials, Phase III as Topic/methods ; *Endpoint Determination/methods ; *Vaccines ; Randomized Controlled Trials as Topic ; Observational Studies as Topic ; Biostatistics ; },
abstract = {For many rare diseases with no approved preventive interventions, promising interventions exist. However, it has proven difficult to conduct a pivotal phase 3 trial that could provide direct evidence demonstrating a beneficial effect of the intervention on the target disease outcome. When a promising putative surrogate endpoint(s) for the target outcome is available, surrogate-based provisional approval of an intervention may be pursued. Following the general Causal Roadmap rubric, we describe a surrogate endpoint-based provisional approval causal roadmap. Based on an observational study data set and a phase 3 randomized trial data set, this roadmap defines an approach to analyze the combined data set to draw a conservative inference about the treatment effect (TE) on the target outcome in the phase 3 study population. The observational study enrolls untreated individuals and collects baseline covariates, surrogate endpoints, and the target outcome, and is used to estimate the surrogate index-the regression of the target outcome on the surrogate endpoints and baseline covariates. The phase 3 trial randomizes participants to treated vs. untreated and collects the same data but is much smaller and hence very underpowered to directly assess TE, such that inference on TE is based on the surrogate index. This inference is made conservative by specifying 2 bias functions: one that expresses an imperfection of the surrogate index as a surrogate endpoint in the phase 3 study, and the other that expresses imperfect transport of the surrogate index in the untreated from the observational to the phase 3 study. Plug-in and nonparametric efficient one-step estimators of TE, with inferential procedures, are developed. The finite-sample performance of the estimators is evaluated in simulation studies. The causal roadmap is motivated by and illustrated with contemporary Group B Streptococcus vaccine development.},
}

Humans
*Biomarkers
*Clinical Trials, Phase III as Topic/methods
*Endpoint Determination/methods
*Vaccines
Randomized Controlled Trials as Topic
Observational Studies as Topic
Biostatistics

@article {pmid40544207,
year = {2025},
author = {Fernandez, M and Todeschini, L and Keenan, BP and Rosenberg, D and Hernandez, S and Zampese, M and Qiao, G and Pollini, T and Maker, AV},
title = {Novel Computational Analysis Identifies Cytotoxic Lymphocyte-to-Monocyte Balance in Tumors as a Predictor of Recurrence-Free Survival in Colorectal Carcinoma.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {40544207},
issn = {1534-4681},
support = {R37CA238435//Basic Research Laboratory/ ; },
abstract = {The microenvironment and immune infiltrate population of colorectal tumors can serve as a stronger predictor of patient survival than microsatellite-status or traditional T- or N-staging. This study aimed to leverage transcriptomic techniques to identify specific immune cell populations and their ratios associated with cancer recurrence in colorectal cancer patients. The goal was to identify patients who could benefit from early adjuvant interventions, identify those at higher risk of recurrence for surveillance, and identify potential combinatorial immunotherapy strategies tailored to this disease. We found that a lower ratio of cytotoxic lymphocyte: monocytic lineage cells, and not microsatellite-status, was associated with cancer recurrence. Additional differential gene expression analysis of the monocytic lineage demonstrated that genes specifically associated with tumor associated macrophages and a protumoral phenotype were overexpressed in the tumor microenvironment in patients that went on to have recurrent disease. Gene Ontology analysis revealed that pathways associated with pro-tumoral extracellular matrix remodeling were suppressed in tumors exhibiting a high cytotoxic lymphocyte: monocytic lineage ratio, suggesting a diminished propensity for tumor progression. The development of these prognostic markers not only associates with colorectal cancer recurrence, aiding in risk stratification and guiding adjuvant therapy decisions for resected early-stage patients, but also suggests that effective colon cancer treatments will likely require a combination of cytotoxic T-cell-directed immunomodulation and targeted inhibition of tumor-associated macrophages.},
}

@article {pmid40543709,
year = {2025},
author = {Brehm, V and Wang, Z and Rocha, L and Jones, B and Jenq, RR and Chang, CC and Cheng, GS and Hsu, J and Sharifi, H and Yanik, G and Luna, L and Waqar, A and Zaveri, J and Dickey, BF and Bashoura, L and Shpall, EJ and Zinter, M and O'Dwyer, D and Champlin, RE and Chen, G and Alousi, A and Paczesny, S and Peterson, CB and Sheshadri, A},
title = {Inflammatory markers and microbiome dysbiosis in hematopoietic cell transplant recipients with lung graft-versus-host disease.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.06.020},
pmid = {40543709},
issn = {2666-6367},
abstract = {Bronchiolitis obliterans (BOS) is a manifestation of pulmonary chronic graft versus host disease (cGVHD) and is a devastating complication of allogenic hematopoietic stem cell transplantation (HCT). Early detection and treatment of BOS may improve outcomes, but biomarkers which accurately identify BOS early are lacking. We aimed to determine whether certain validated cGVHD markers could also accurately diagnose BOS as compared to patients without BOS and with or without extrapulmonary cGVHD. In addition, we sought to determine whether dysbiosis of gut or oral microbiomes was associated with BOS or with inflammatory biomarkers. We enrolled 43 allogenic HCT recipients, of whom 16 had BOS. For each patient, we obtained pulmonary function tests, measured the levels of nine serum biomarkers utilizing enzyme linked immunosorbent assays, and analyzed both the oral and gut microbiome using microbial DNA amplification and sequencing. We compared biomarker levels to lung function, both at baseline and over time, as well as to microbiome diversity. Higher IL1RL1 (p = 0.002) and IL-17 (p = 0.041) at enrollment were negatively correlated with FEV1% lung function over time. Increases in IL1RL1 (p = 0.035), IL-17 (p = 0.009), and WFDC2 (p = 0.045) levels over time were associated with worsened lung function/FEV1% over time. There were minimal correlations between gut microbiome diversity and lung function or serum biomarkers. Oral microbiome alpha diversity was lower in subjects with BOS than without (p = 0.00057), and oral beta diversity was associated with FEV1% and with levels of several biomarkers. Our pilot study suggests that certain serum cGVHD markers may identify allogeneic HCT recipients at higher risk for pulmonary impairment over time, and should be followed with robust, controlled studies.},
}

@article {pmid40543557,
year = {2025},
author = {Nunley, BE and Weixler, A and Kim, HG and Xie, H and Sereewit, J and Hajian, P and Ellis, S and Mills, MG and Pérez-Osorio, AC and Goya, S and Gov, J and Dewar, R and Fernandes, G and Templeton, KE and Maloney, DM and Greninger, AL and Roychoudhury, P},
title = {Clinical performance evaluation of a tiling amplicon panel for whole genome sequencing of respiratory syncytial virus.},
journal = {The Journal of molecular diagnostics : JMD},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jmoldx.2025.05.005},
pmid = {40543557},
issn = {1943-7811},
abstract = {Accurate genomic characterization of respiratory syncytial virus (RSV) is crucial for studies of epidemiology and viral evolution, including monitoring potential escape from newly authorized vaccines and prophylactic monoclonal antibodies. We adapted a viral genome tiling amplicon panel (UW-ARTIC) and developed a custom bioinformatic pipeline for high-throughput, cost-effective sequencing of both RSV-A and RSV-B subgroups. We established genome acceptability criteria and determined the performance characteristics of the panel including assay sensitivity, specificity, breadth of genome recovery, accuracy, and precision using contrived and remnant clinical specimens. High-quality genomes (>95% genome completeness; >500X and >1000X average depth for whole genome and fusion gene respectively) were recovered from samples with Ct ≤ 30 (∼594 and 2,004 copies per reaction for RSV-A and RSV-B respectively). Minor variants were accurately identified at >5% allele frequency. The assay showed high accuracy when compared to Sanger, shotgun metagenomic, and hybridization capture-based sequencing, as well as high repeatability and reproducibility. The UW-ARTIC RSV panel has utility for cost-effective RSV genome recovery in public health, clinical, and research applications. It has been used to generate FDA-reportable data for clinical trials of RSV antiviral products, with robust performance in global samples from as recently as the 2023/24 season. Continued genomic surveillance and future updates to primers will be essential for continued recovery of genomes as RSV continues to evolve.},
}

@article {pmid40542813,
year = {2025},
author = {Kouwenberg, TW and van Dalen, EC and Mulder, RL and Armenian, S and Feijen, EAM and Chow, EJ and Kosmidis, H and Vormoor-Bürger, BJ and Kiyotani, C and Nathan, PC and Kapusta, L and Grotenhuis, HB and Engels, FK and Teske, AJ and Tragiannidis, A and Slieker, MG and Ozono, S and Nohria, A and Sláma, T and Skinner, R and Hudson, MM and Kremer, LCM and Ehrhardt, MJ and Mavinkurve-Groothuis, AMC},
title = {IGHG Recommendations for Anthracycline and Anthraquinone Cardiac Dysfunction Equivalence Ratios After Childhood Cancer: JACC: CardioOncology Expert Panel.},
journal = {JACC. CardioOncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaccao.2025.05.009},
pmid = {40542813},
issn = {2666-0873},
abstract = {Anthracycline and anthraquinone agents are major contributors to cancer therapy-related cardiac dysfunction in childhood cancer. However, evidence-based equivalence ratios for estimating individual risk have not been incorporated into international surveillance guidelines. The International Late Effects of Childhood Cancer Guideline Harmonization Group systematically reviewed the literature on equivalence ratios for doxorubicin, daunorubicin, epirubicin, idarubicin, and mitoxantrone. Based on available evidence, benefit-harm considerations, and expert consensus, the panel concluded that the risk of cardiac dysfunction is lower with daunorubicin and higher with mitoxantrone compared with doxorubicin (moderate-quality evidence; strong recommendation). The panel recommends using an approximate ratio of 0.6 to convert daunorubicin to a doxorubicin-equivalent dose and a ratio of 10.5 for mitoxantrone (low-quality evidence; moderate recommendation). No recommendation was made for epirubicin or idarubicin due to inconclusive evidence.},
}

@article {pmid40542609,
year = {2025},
author = {Menz, BD and Modi, ND and Abuhelwa, AY and Kuderer, NM and Lyman, GH and Swain, SM and Kichenadasse, G and Shahnam, A and Haseloff, M and Vitry, A and Rammant, E and Ramsey, I and Chan, RJ and McKinnon, RA and Rowland, A and Sorich, MJ and Hopkins, AM},
title = {Patient-reported outcome thresholds and their associations with survival, adverse events, and quality of life in a pooled analysis of breast cancer trials.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.70020},
pmid = {40542609},
issn = {1097-0215},
support = {APP2008119//National Health and Medical Research Council/ ; APP2030913//National Health and Medical Research Council/ ; RSP-117-FY2023//Tour de Cure/ ; 2023-S-DTFA-005//Hospital Research Foundation/ ; },
abstract = {Researchers at the EORTC recently recommended clinical thresholds for the QLQ-C30 to facilitate actionable insights in clinical practice. We evaluate the distribution of these thresholds and associations with outcomes in breast cancer. Data were pooled from two early-stage and six advanced-stage breast cancer trials. EORTC thresholds were applied to available QLQ-C30 data to identify clinically important PRO domains. Associations between the number of clinically important PRO domains at baseline with overall survival (OS), invasive-disease-free survival (IDFS), progression-free survival (PFS), grade ≥3 adverse events (AEs), and serious AEs were evaluated using Cox-regression. Data from 8544 breast cancer patients, of whom 2428 (41%) of the 5893 early-stage and 1486 (56%) of the 2651 advanced-stage patients reported ≥3 clinically important PRO domains. In the early-stage, each additional clinically important PRO domain was associated with worsened grade ≥3 AEs (HR, 1.03 [95%CI, 1.01-1.04], p = 0.001) and serious AEs (1.05 [1.03-1.07], p < 0.001). In the advanced-stage, each additional clinically important PRO domain was associated with worsened OS (1.05 [1.03-1.07], p < 0.001), PFS (1.03 [1.01-1.04], p = 0.002), grade ≥3 AEs (1.04 [1.02-1.06], p < 0.001), and serious AEs (1.07 [1.04-1.11], p < 0.001). A substantial proportion of breast cancer patients report clinically important PRO domains at baseline, with increasing numbers associated with worsening AEs, survival, and quality-of-life.},
}

@article {pmid40541542,
year = {2025},
author = {Gee-Rodriguez, K and Indorf, A and Swisher, EM and Bialick, K and Banda, K},
title = {Human epidermal growth factor receptor 2 targeted agents in gynecologic cancers: an updated review.},
journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society},
volume = {},
number = {},
pages = {101948},
doi = {10.1016/j.ijgc.2025.101948},
pmid = {40541542},
issn = {1525-1438},
abstract = {Human epidermal growth factor receptor 2 (HER2) is a well-established oncogenic target across several solid tumor types and is associated with advanced disease and aggressive biology among gynecologic cancers. Experts have recommended HER2 testing algorithms to guide the treatment of advanced or recurrent endometrial cancers, but these guidelines utilize an outdated version of the recommendations for HER2 testing in breast cancers. Additionally, similar consensus guidelines do not exist for HER2 testing and reporting in ovarian or cervical cancers, leading to inconsistent HER2 measurement in clinical trials and real-world practice across all 3 gynecologic cancer types. Nonetheless, accumulating data support the efficacy of HER2-targeted treatment in gynecologic cancers, generating urgency to standardize HER2 measurement for these cancers. Practitioners also need to gain familiarity with the potential impacts on cardiac and respiratory function and the concomitant drug interactions of existing and developing HER2-targeted therapies. This review clarifies HER2 terminology and testing, discusses completed and ongoing clinical trials, and synthesizes recommendations for the use of HER2-directed agents in gynecologic cancers.},
}

@article {pmid40540800,
year = {2025},
author = {Tsilifis, C and Raedler, J and Renke, J and Medinger, M and Laberko, A and Haraldsson, Á and Patel, N and Ciznar, P and Wong, M and Keogh, SJ and Gray, PE and Mitchell, R and Bigley, V and Elcombe, SE and Hauck, F and Albert, MH and Tholouli, E and Herwadkar, A and Elkhalifa, S and Kosmidis, C and Callisti, G and Burroughs, LM and Chen, K and Carpenter, B and Fox, TA and Morris, EC and Uppuluri, R and Raj, R and Yanagimachi, M and Buddingh, EP and Oikonomopoulou, C and Gonzalez, CE and Dimitrova, D and Kanakry, JA and Arnold, DE and Pai, SY and Slatter, MA and Pearce, MS and Worth, AJ and Freeman, AF and Gennery, AR},
title = {Allogeneic haematopoietic stem cell transplantation for STAT3 hyper-IgE syndrome: a worldwide study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016158},
pmid = {40540800},
issn = {2473-9537},
abstract = {STAT3 hyper-IgE syndrome (STAT3-HIES) is a multisystem disorder causing recurrent skin and respiratory infection with bronchiectasis, pneumatocoeles, and aspergillosis; lymphoma; and extra-immune manifestations including fractures and vasculopathy. Published data on immune and extra-immune HSCT outcomes focus on case reports or small cohorts. International multicentre retrospective study of HSCT in STAT3-HIES. Primary endpoints were overall survival (OS) and event-free survival (EFS; events were death, graft failure, chronic GvHD). We identified 41 patients over a 28-year period. HSCT indication was infection (93%) or lymphoma (7%). Median age at HSCT was 14 (4-45) years. Most patients had pre-HSCT respiratory disease (93%) including parenchymal lung disease (68%) and prior suspected/confirmed pulmonary fungal infection (32%). Patients received peripheral blood stem cell (51%) or marrow (49%) from HLA 10/10-MUD (44%), MFD (44%), MMFD (10%), or one 9/10 MMUD (2%). Median CD34+ stem cell dose was 6.2 (0.05-22.0) cells x106/kg. Conditioning regimens were predominantly treosulfan-based (59%; with thiotepa, 34%); other patients received busulfan-based (24%) or melphalan-based (17%) regimens. Median follow-up for surviving patients was 5 (0.8-28) years. 5-year OS was 93% and 5-year EFS 90%. Cumulative incidence of grade II-IV acute GvHD was 22%. Median whole blood donor chimerism at latest follow up was 100%. 87% of patients have reduced or no bacterial or fungal respiratory infection. Post-HSCT, 20% developed new skeletal fractures. This worldwide study expand data on HSCT for STAT3-HIES to 41 patients. Despite significant pre-HSCT pulmonary morbidity, OS was high, and patients have improved skin and respiratory disease, though the impact on extra-immune manifestations appears limited.},
}

@article {pmid40540276,
year = {2025},
author = {Banerjee, R and Acob, YC},
title = {Telehealth and Time Burden in Patients With Advanced Cancer.},
journal = {JAMA network open},
volume = {8},
number = {6},
pages = {e2516769},
doi = {10.1001/jamanetworkopen.2025.16769},
pmid = {40540276},
issn = {2574-3805},
}

@article {pmid40540274,
year = {2025},
author = {Neupane, A and Petrykey, K and Li, K and French, J and Zhou, X and Wang, J and Im, C and Dixon, SB and Ehrhardt, MJ and Mulrooney, DA and Jefferies, JL and Gramatges, MM and Chow, EJ and Bhatia, S and Robison, LL and Ness, KK and Hudson, MM and Burridge, PW and Armstrong, GT and Yasui, Y and Sapkota, Y},
title = {TTN and BAG3 in Cancer Therapy-Related Cardiomyopathy Among Long-Term Survivors of Childhood Cancer.},
journal = {JAMA network open},
volume = {8},
number = {6},
pages = {e2515793},
pmid = {40540274},
issn = {2574-3805},
mesh = {Humans ; Male ; Female ; *Cancer Survivors/statistics & numerical data ; *Adaptor Proteins, Signal Transducing/genetics ; Retrospective Studies ; *Apoptosis Regulatory Proteins/genetics ; *Cardiomyopathies/genetics/etiology/epidemiology ; Adult ; Child ; *Neoplasms/therapy ; *Connectin/genetics ; Adolescent ; Anthracyclines/adverse effects ; Prospective Studies ; Young Adult ; },
abstract = {IMPORTANCE: Cancer therapy-related cardiomyopathy (CCM) is an important concern for childhood cancer survivors. In the general population, rare variants in TTN and BAG3 are associated with an increased risk of familial dilated cardiomyopathy, and common variants are associated with a decreased risk of sporadic dilated cardiomyopathy.

OBJECTIVES: To examine associations of common and rare protein-altering variants (PAVs) in TTN and BAG3 with late-onset CCM risk in childhood cancer survivors.

This retrospective cohort study with a prospective follow-up included childhood cancer survivors from the St Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS) with prior exposure to anthracyclines and/or chest-directed radiation. Cancer therapy-related cardiomyopathy was clinically assessed in SJLIFE and self-reported in CCSS, with severity graded using Common Terminology Criteria for Adverse Events, version 4.03. The data analysis was conducted from January 4, 2023, to March 6, 2025.

EXPOSURE: Late-onset CCM.

MAIN OUTCOME AND MEASURES: Multivariable logistic regression was used to evaluate the association of common variants in TTN and BAG3 with late-onset CCM risk, adjusting for relevant demographic and cancer treatment exposures. In SJLIFE alone, 7 echocardiographic parameters were assessed. Rare PAVs were examined using Fisher exact test. Cohort-specific results were combined using meta-analytic approaches.

RESULTS: The cohort included 1843 childhood cancer survivors from SJLIFE (median [IQR] age at CCM diagnosis, 34.9 [28.0-42.3] years; 53.2% male) and 4577 from CCSS (median [IQR] age at CCM diagnosis, 32.0 [23.0-41.0] years; 51.6% female). In the combined sample of European ancestry survivors from SJLIFE (205 with CCM grade ≥2) and CCSS (248 with CCM grade ≥2), common variants rs3829746-C in TTN (odds ratio, 0.81; 95% CI, 0.68-0.97) and rs2234962-C in BAG3 (odds ratio, 0.79; 95% CI, 0.65-0.95) were associated with a decreased risk of late-onset CCM. In SJLIFE African ancestry survivors, no association was observed with either of the common variants. Rare PAVs were not associated with late-onset CCM in European or African ancestry survivors. In European ancestry survivors, both rs3829746-C and rs2234962-C were also associated with reduced left ventricular end-systolic volume (β [SE], -1.90 [0.65] and -2.68 [0.64], respectively) and global longitudinal peak strain (β [SE], -0.31 [0.13] and -0.30 [0.12]) and with increased left ventricular ejection fraction (β [SE], 0.62 [0.27] and 0.86 [0.27], respectively).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study show that common variants in TTN and BAG3 are associated with a decreased risk of late-onset CCM among childhood cancer survivors, while rare PAVs showed no association.},
}

Humans
Male
Female
*Cancer Survivors/statistics & numerical data
*Adaptor Proteins, Signal Transducing/genetics
Retrospective Studies
*Apoptosis Regulatory Proteins/genetics
*Cardiomyopathies/genetics/etiology/epidemiology
Adult
Child
*Neoplasms/therapy
*Connectin/genetics
Adolescent
Anthracyclines/adverse effects
Prospective Studies
Young Adult

@article {pmid40539461,
year = {2025},
author = {Pandrangi, VC and Liao, JJ and de Almeida, JR and El-Sayed, IH and Hanna, G and Su, SY and Tsang, R and Won, TB and Witterick, I and Choby, G and Kuan, EC and Geltzeiler, M},
title = {Current Trends in the Management of Recurrent Nasopharyngeal Carcinoma.},
journal = {Head & neck},
volume = {},
number = {},
pages = {},
doi = {10.1002/hed.28219},
pmid = {40539461},
issn = {1097-0347},
abstract = {BACKGROUND: Recurrent nasopharyngeal carcinoma (NPC) is associated with challenges in treatment due to the complex anatomic location and impact of prior treatment modalities such as radiation therapy. The purpose of this review is to discuss modern treatment strategies for recurrent NPC, potential challenges, and outcomes.

METHODS: A narrative review was performed, evaluating management strategies of recurrent NPC, survival measures, and advancements in treatment considerations.

RESULTS: Treatment options including radiation, surgery, and chemotherapy are discussed, including data on survival outcomes and treatment-related morbidity. We review additional considerations including advances in endoscopic surgery, operative management of the internal carotid artery (ICA), novel radiation and chemotherapy protocols, and the introduction of immune checkpoint inhibitors.

CONCLUSION: This review describes contemporary management strategies for recurrent NPC, highlighting evolving management strategies that may reduce treatment-associated morbidity and improve survival.},
}

@article {pmid40537477,
year = {2025},
author = {Bentley, AR and Brown, MR and Musani, SK and Schwander, KL and Winkler, TW and Sims, M and Kilpeläinen, TO and Aschard, H and Bartz, TM and Bielak, LF and Chai, JF and Chitrala, KN and Franceschini, N and Graff, M and Guo, X and Hartwig, FP and Horimoto, ARVR and Lim, E and Liu, Y and Manning, AK and Nolte, IM and Noordam, R and Richard, MA and Smith, AV and Sung, YJ and Vojinovic, D and Wang, R and Wang, Y and Feitosa, MF and Harris, SE and Lyytikäinen, LP and Pistis, G and Rauramaa, R and van der Most, PJ and Ware, E and Weiss, S and Wen, W and Yanek, LR and Arking, DE and Arnett, DK and Ballantyne, C and Boerwinkle, E and Chen, YI and Daviglus, ML and de Las Fuentes, L and de Vries, PS and Delaney, JAC and Fretts, AM and Ekunwe, L and Faul, JD and Gallo, LC and Heikkinen, S and Homuth, G and Ikram, MA and Isasi, CR and Jonas, JB and Keltikangas-Järvinen, L and Komulainen, P and Kraja, AT and Krieger, JE and Launer, L and , and Liu, J and Lohman, K and Luik, AI and Manichaikul, AW and Marques-Vidal, P and Milaneschi, Y and Mwasongwe, SE and O'Connell, JR and Rice, K and Rich, SS and Schreiner, PJ and Schwettmann, L and Shikany, JM and Shu, XO and Smith, JA and Snieder, H and Sotoodehnia, N and Tai, ES and Taylor, KD and Tinker, L and Tsai, MY and Uitterlinden, AG and van Duijn, CM and van Heemst, D and Waldenberger, M and Wallace, RB and Wee, HL and Weir, DR and Wei, WB and Willems van Dijk, K and Wilson, G and Yao, J and Young, KL and Zhang, X and Zhao, W and Zhu, X and Zonderman, AB and Deary, IJ and Gieger, C and Grabe, HJ and Lakka, TA and Lehtimäki, T and Oldehinkel, AJ and Preisig, M and Wang, YX and Zheng, W and Evans, MK and Province, M and Gauderman, J and Gudnason, V and Hartman, CA and Horta, BL and Kardia, SLR and Kooperberg, C and Liu, CT and Mook-Kanamori, DO and Penninx, BW and Pereira, AC and Peyser, PA and Psaty, BM and Rotter, JI and Sim, X and North, KE and Rao, DC and Bierut, L and Miller, CL and Morrison, AC and Rotimi, CN and Fornage, M and Fox, ER},
title = {Multi-ancestry genome-wide association analyses incorporating SNP-by-psychosocial interactions identify novel loci for serum lipids.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {207},
pmid = {40537477},
issn = {2158-3188},
support = {Z01HG200362//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; Z01 HG200362/ImNIH/Intramural NIH HHS/United States ; R01 HL118305/HL/NHLBI NIH HHS/United States ; R01 HL156991/HL/NHLBI NIH HHS/United States ; P01 CA196569/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Male ; *Lipids/blood/genetics ; Female ; *Gene-Environment Interaction ; Adult ; Genetic Loci ; Middle Aged ; Social Support ; },
abstract = {Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of genetic loci that influence lipids. We conducted a genome-wide gene-by-psychosocial factor interaction (G×Psy) study in up to 133,157 individuals to evaluate if G×Psy influences serum lipid levels. We conducted a two-stage meta-analysis of G×Psy using both a one-degree of freedom (1df) interaction test and a joint 2df test of the main and interaction effects. In Stage 1, we performed G×Psy analyses on up to 77,413 individuals and promising associations (P < 10[-5]) were evaluated in up to 55,744 independent samples in Stage 2. Significant findings (P < 5 × 10[-8]) were identified based on meta-analyses of the two stages. There were 10,230 variants from 120 loci significantly associated with serum lipids. We identified novel associations for variants in four loci using the 1df test of interaction, and five additional loci using the 2df joint test that were independent of known lipid loci. Of these 9 loci, 7 could not have been detected without modeling the interaction as there was no evidence of association in a standard GWAS model. The genetic diversity of included samples was key in identifying these novel loci: four of the lead variants displayed very low frequency in European ancestry populations. Functional annotation highlighted promising loci for further experimental follow-up, particularly rs73597733 (MACROD2), rs59808825 (GRAMD1B), and rs11702544 (RRP1B). Notably, one of the genes in identified loci (RRP1B) was found to be a target of the approved drug Atenolol suggesting potential for drug repurposing. Overall, our findings suggest that taking interaction between genetic variants and psychosocial factors into account and including genetically diverse populations can lead to novel discoveries for serum lipids.},
}

Humans
*Genome-Wide Association Study
Polymorphism, Single Nucleotide
Male
*Lipids/blood/genetics
Female
*Gene-Environment Interaction
Adult
Genetic Loci
Middle Aged
Social Support

@article {pmid40537474,
year = {2025},
author = {Bradshaw, CS and Plummer, EL and Muzny, CA and Mitchell, CM and Fredricks, DN and Herbst-Kralovetz, MM and Vodstrcil, LA},
title = {Bacterial vaginosis.},
journal = {Nature reviews. Disease primers},
volume = {11},
number = {1},
pages = {43},
pmid = {40537474},
issn = {2056-676X},
mesh = {Humans ; Female ; *Vaginosis, Bacterial/physiopathology/epidemiology/complications/diagnosis/microbiology/therapy ; Vagina/microbiology/physiopathology ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Microbiota/physiology ; Quality of Life/psychology ; Prevalence ; },
abstract = {Bacterial vaginosis (BV) is a vaginal microbiome disorder that is associated with preterm birth and spontaneous abortion, increased risk of HIV infection and sexually transmitted infections, and has negative effects on quality of life. BV affects one in four women globally, with the highest burden in resource-limited settings. Marked alterations in vaginal microbiome composition, in pro-inflammatory cytokines and chemokines, and in the proteome and metabolome characterize BV and contribute to adverse sequelae. Despite its prevalence, the exact aetiologic agent of BV is unknown and its pathophysiology is poorly understood. These knowledge gaps impede diagnostic and management approaches, with recommended treatment strategies resulting in recurrence that exceeds 50% over 3-6 months. New data on the sexual transmission of BV, including evidence that male-partner treatment improves cure, have improved our understanding of its aetiology and pathogenesis, and provide opportunities for developing optimal diagnostic, treatment and prevention strategies. Other factors probably also contribute to the low efficacy of current treatments, including biofilm and/or antimicrobial resistance, and failure to recolonize a favourable vaginal microbiome after treatment. The complex pathophysiology of BV highlights that individualized and multifaceted management approaches will be required to manage the refractory and adverse sequelae of BV.},
}

Humans
Female
*Vaginosis, Bacterial/physiopathology/epidemiology/complications/diagnosis/microbiology/therapy
Vagina/microbiology/physiopathology
Anti-Bacterial Agents/therapeutic use/pharmacology
Microbiota/physiology
Quality of Life/psychology
Prevalence

@article {pmid40536977,
year = {2025},
author = {Sinnott-Armstrong, N and Forsythe, D and Benoit, JM and Chappell, CR and Coe, LSY and de Oliveira, BFR and Evans, N and Fagre, AC and Gilligan, JM and Hamilton, M and Henneberry, CM and Ishaq, SL and Johnston, J and Krichilsky, E and Lopez, JA and McMonigal, K and Ortiz Alvarez de la Campa, M and Rahman, R and Schwartz, NE and Talluto, L and Taylor, EJ and Vargas-Muñiz, JM and Weissman, JL},
title = {Protect transgender scientists.},
journal = {Science (New York, N.Y.)},
volume = {388},
number = {6753},
pages = {1283-1284},
doi = {10.1126/science.ady0962},
pmid = {40536977},
issn = {1095-9203},
}

@article {pmid40535475,
year = {2025},
author = {Raychaudhuri, S and Gooley, TA and Rasmussen, A and Quach, K and Gill, E and Halpern, AB and Appelbaum, JS and Ghiuzeli, CM and Hendrie, PC and Cassaday, RD and Walter, RB and Percival, MM},
title = {Phase 1 trial of venetoclax with cladribine, cytarabine, G-CSF, and mitoxantrone for AML and high-grade myeloid neoplasm.},
journal = {Blood neoplasia},
volume = {2},
number = {3},
pages = {100085},
pmid = {40535475},
issn = {2950-3280},
abstract = {Intensifying induction by combining venetoclax with a high-dose cytarabine regimen may improve outcomes for high-risk populations such as adult patients with adverse-risk newly diagnosed or relapsed acute myeloid leukemia. In a phase 1 trial testing the novel combination of venetoclax and CLAG-M (cladribine, high-dose cytarabine, granulocyte colony-stimulating factor [G-CSF], and mitoxantrone), the maximum tolerated dose was venetoclax 400 mg on days 1 through 14, combined with cladribine 5 mg/m[2] on days 1 through 5, cytarabine 1.5 g/m[2] on days 1 through 5, G-CSF 5 μg/kg on days 0 through 5, and mitoxantrone 16 or 18 mg/m[2] on days 1 through 3 (for relapsed/refractory and newly diagnosed adverse-risk patients, respectively). The 28-day mortality rate was 5%. Composite complete remission (CR) rate (CR + CR with incomplete hematologic recovery) was 65%. These findings support further phase 2 study of venetoclax in combination with CLAG-M. This trial was registered at www.ClinicalTrials.gov as #NCT04797767.},
}

@article {pmid40534994,
year = {2025},
author = {Tratt, M and Bandhlish, A and Eaton, KD and Gooley, T and Giustini, N and Deng, L},
title = {Survival Outcomes of Lung Adenocarcinoma With Intestinal Differentiation in the Era of Immunotherapy.},
journal = {JTO clinical and research reports},
volume = {6},
number = {7},
pages = {100827},
pmid = {40534994},
issn = {2666-3643},
abstract = {INTRODUCTION: Lung adenocarcinoma (LUAD) with intestinal differentiation (LAID) comprises a rare and heterogeneous NSCLC of invasive mucinous, enteric, and colloid characteristics. In the era of chemotherapy, LAID was associated with a poorer prognosis compared with other LUADs. Leveraging the National Cancer Database, we assessed survival outcomes of LAID in the era of immunotherapy.

METHODS: The National Cancer Database was queried for stage IV adenocarcinoma cases diagnosed from 2016 to 2019. LAID was defined as invasive mucinous adenocarcinoma, colloid adenocarcinoma, or enteric adenocarcinoma. An unadjusted comparison of survival distributions was performed using a log-rank test and adjusted by Cox multivariable regression.

RESULTS: A total of 40,516 patients were identified, of whom 855 had LAID and 39,661 had other LUAD. Among the cases of LAID, 593 were classified as colloid, 253 as mucinous, and nine as enteric. Patients with LAID had a higher risk of death compared with other LUAD subtypes, with a hazard ratio (HR) of 1.31 (95% confidence interval: 1.21-1.43) and a median survival of 9.19 months and 11.81 months, respectively. This was relatively consistent across all treatment subgroups (HR = 1.40: immunotherapy alone, HR = 1.29: chemoimmunotherapy; HR = 1.25: chemotherapy alone). Patients with LAID treated with chemoimmunotherapy had a median overall survival of 11.16 months, 9.19 months when treated with immunotherapy alone, and 7.09 months when treated with chemotherapy alone.

CONCLUSIONS: Compared with other LUADs, LAID remains associated with poorer survival in the era of immunotherapy. Nevertheless, exposure to immunotherapy may be associated with improved survival compared with chemotherapy alone in this rare subgroup.},
}

@article {pmid40534492,
year = {2025},
author = {Portuguese, AJ and Liang, EC and Huang, JJ and Jeon, Y and Dima, D and Banerjee, R and Kwok, M and Cicero, KI and Hirayama, AV and Basom, R and Khouderchah, C and Shadman, M and Fong, L and Cowan, AJ and Gauthier, J},
title = {Extramedullary disease is associated with severe toxicities following B-cell maturation antigen CAR T-cell therapy in multiple myeloma.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.287985},
pmid = {40534492},
issn = {1592-8721},
abstract = {Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor outcomes following B-cell maturation antigen (BCMA)-targeted CAR-T therapy, yet its impact on treatment-related toxicity remains unclear. This study evaluates the impact of active EMD on toxicity, efficacy, and survival in patients with MM treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). We conducted a retrospective cohort study of all patients with MM who received ide-cel (n=32) or cilta-cel (n=76) as standard-of-care therapy at our institution from August 2021 to October 2024. EMD was defined as the presence of soft tissue masses in extraosseous locations, and outcomes were compared based on EMD status. Among 108 patients, 26 (24%) had EMD. Patients with EMD experienced higher rates of grade (G)1+ (38% vs. 17%, p=0.022) and G3+ ICANS (19% vs. 1.2%, p=0.003), as well as G1+ (96% vs. 78%, p=0.041) and G3+ eICAHT (31% vs. 0%, p.},
}

@article {pmid40533557,
year = {2025},
author = {Li, Y and Zhang, H and Sun, C and Dong, XD and Xie, C and Liu, YT and Lin, RB and Kong, XW and Hu, ZL and Ma, XY and Dai, DL and Zhu, QY and Li, YC and Li, Y and Liu, SX and Yuan, L and Zhou, PH and Gao, S and Tang, YP and Yang, JY and Han, P and McGuire, AT and Zhao, B and Bei, JX and Robertson, E and Zeng, YX and Zhong, Q and Zeng, MS},
title = {R9AP is a common receptor for EBV infection in epithelial cells and B cells.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40533557},
issn = {1476-4687},
abstract = {Epstein-Barr virus (EBV) persistently infects more than 90% of the human population, causing infectious mononucleosis[1], susceptibility to autoimmune diseases[2] and multiple malignancies of epithelial or B cell-origin[3]. EBV infects epithelial cells and B cells through interaction between viral glycoproteins and different host receptors[4], but it has remained unknown whether a common receptor mediates infection of its two major host cell targets. Here, we establish R9AP as a crucial EBV receptor for entry into epithelial and B cells. R9AP silencing or knockout, R9AP-derived peptide and R9AP monoclonal antibody each significantly inhibit, whereas R9AP overexpression promotes, EBV uptake into both cell types. R9AP binds directly to the EBV glycoprotein gH/gL complex to initiate gH/gL-gB-mediated membrane fusion. Notably, the interaction of R9AP with gH/gL is inhibited by the highly competitive gH/gL-neutralizing antibody AMMO1, which blocks EBV epithelial and B cell entry. Moreover, R9AP mediates viral and cellular membrane fusion in cooperation with EBV gp42-human leukocyte antigen class II or gH/gL-EPHA2 complexes in B cells or epithelial cells, respectively. We propose R9AP as the crucial common receptor of B cells and epithelial cells and a potential prophylactic and vaccine target for EBV.},
}

@article {pmid40502162,
year = {2025},
author = {Bernard, MJ and Ruiz, A and Diaz, JA and Nunley, NM and Dove, RN and Heering, KY and Bopardikar, S and Gallardo, A and Hashimoto, T and Agrawal, R and Smith, CM and Wilde, BR and Matulionis, N and Richards, HM and Sharifi, MN and Lang, JM and Zhao, SG and Haffner, MC and Boutros, PC and Christofk, HR and Goldstein, AS},
title = {OGDHL regulates nucleotide metabolism, tumor growth, and neuroendocrine marker expression in prostate cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40502162},
issn = {2692-8205},
support = {T32 GM152342/GM/NIGMS NIH HHS/United States ; TL1 DK132768/DK/NIDDK NIH HHS/United States ; U2C CA271894/CA/NCI NIH HHS/United States ; U2C DK119889/DK/NIDDK NIH HHS/United States ; R01 CA270108/CA/NCI NIH HHS/United States ; R37 CA286450/CA/NCI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; U2C DK119886/DK/NIDDK NIH HHS/United States ; P50 CA092131/CA/NCI NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; T32 GM007185/GM/NIGMS NIH HHS/United States ; OT2 OD030544/OD/NIH HHS/United States ; },
abstract = {Cells regularly adapt their metabolism in response to changes in their microenvironment or biosynthetic needs. Prostate cancer cells leverage this metabolic plasticity to evade therapies targeting the androgen receptor (AR) signaling pathway. For example, nucleotide metabolism plays a critical role in treatment-resistant prostate cancer by supporting DNA replication, DNA damage response and cell fate decisions. Identifying novel regulators of nucleotide metabolism in treatment-resistant cancer that are dispensable for the health of normal cells may lead to new therapeutic approaches less toxic than commonly used chemotherapies targeting nucleotide metabolism. We identify the metabolic enzyme Oxoglutarate Dehydrogenase-Like (OGDHL), named for its structural similarity to the tricarboxylic acid (TCA) cycle enzyme Oxoglutarate Dehydrogenase (OGDH), as a regulator of nucleotide metabolism, tumor growth, and treatment-induced plasticity in prostate cancer. While OGDHL is a tumor-suppressor in various cancers, we find that its loss impairs prostate cancer cell proliferation and tumor formation while having minimal impact on TCA cycle activity. Loss of OGDHL profoundly decreases nucleotide metabolite pools, induces the DNA damage response marker Ɣ2AX, and alters androgen receptor inhibition-induced plasticity, including suppressing the neuroendocrine markers DLL3 and HES6. Finally, OGDHL is highly expressed in neuroendocrine prostate cancer (NEPC). These findings support an unexpected role of OGDHL in prostate cancer, where it functions to sustain nucleotide pools for proliferation, DNA repair, and AR inhibition-induced plasticity.},
}

@article {pmid40501795,
year = {2025},
author = {McKellar, SA and Pineda, JMB and Lattupally, R and Codd, AS and Newell, EW and Lu, SX and Bradley, RK},
title = {Chorionic Gonadotropin Beta 7 is a marker of immune evasion in cancer.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40501795},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA251138/CA/NCI NIH HHS/United States ; R01 HL128239/HL/NHLBI NIH HHS/United States ; R01 HL151651/HL/NHLBI NIH HHS/United States ; },
abstract = {Human chorionic gonadotropin beta (beta-hCG) is an oncofetal antigen expressed by trophoblast cells of the placenta, with minimal expression in adult somatic tissues. Numerous studies have demonstrated that beta-hCG-encoding genes are expressed in various cancers, but expression of these genes (CGB3, CGB5, CGB7, and CGB8) across diverse cancers has not been systematically evaluated. Here, we report that CGB genes are more widely expressed across diverse cancer types than previously appreciated and that secreted beta-hCG is readily detected. In particular, CGB genes are expressed in the majority of urothelial bladder cancers, where CGB7 is most frequently expressed and significantly associated with an immunosuppressed tumor microenvironment, including decreased CD8[+] T cell infiltration. Multiple CGB genes are associated with failure to respond to immune checkpoint inhibitor (ICI) therapy, and CGB7 is particularly strongly predictive of poor prognosis. Overall, our findings indicate that beta-hCG is a clinically accessible, predictive biomarker of immunotherapeutic response.},
}

@article {pmid40501614,
year = {2025},
author = {Singh, P and Wright, JH and Smythe, KS and Fukuda, B and Hung, LH and Yeung, CC and Yeung, KY},
title = {Graphical and Interactive Spatial Proteomics Image Analysis Workflow.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40501614},
issn = {2692-8205},
support = {R21 CA280520/CA/NCI NIH HHS/United States ; U24 HG012674/HG/NHGRI NIH HHS/United States ; },
abstract = {Spatial proteomics provides a spatially resolved view of protein expression and localization within cells and tissues by mapping the location and abundance of proteins. There is a need for containerized end-to-end imaging workflows for spatial proteomic analysis that are flexible, high-throughput, and support graphical and interactive visualizations. We present a modular and interactive spatial proteomics imaging workflow that empowers biomedical researchers to reproducibly execute and customize complex analyses. Our workflow consists of cell segmentation, unsupervised clustering, validation of clusters on the image, and cell type clustering results visualization. Users can utilize a form-based graphical interface to execute and customize multi-step workflows with a single click or interactively adjust image processing steps within the workflow, apply workflows to various datasets, and modify input parameters as needed. We illustrated the functionality of our workflow using a cancer imaging dataset consisting of a tissue microarray (TMA) stained by high-plex immunohistochemistry. This TMA contained a variety of cancer and tissue cell types to assess the broad applicability of this workflow to different biopsy types.},
}

@article {pmid40533069,
year = {2025},
author = {Shatila, M and Devalaraju, S and Takigawa, K and Catinis, C and Lee, I and Baerman, E and Ngo, S and Mittal, N and Glombicki, S and Machado, AP and Lu, L and Aleem, AS and Thompson, J and Funchain, P and Grover, S and Zhang, HC and Thomas, AS and Wang, Y},
title = {Worse Survival and Gastrointestinal Toxicity Outcomes Among Patients Receiving Proton Pump Inhibitors During Checkpoint Inhibitor Therapy.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {},
number = {},
pages = {1-7},
doi = {10.6004/jnccn.2025.7023},
pmid = {40533069},
issn = {1540-1413},
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) for cancer carry a risk of immune-related adverse events (irAEs). Upper and lower gastrointestinal tract inflammation are common toxicities. Proton pump inhibitors (PPIs) are used to treat upper gastrointestinal irAEs. Studies have suggested these agents may also worsen lower gastrointestinal irAEs. Our study evaluated the effect of PPI exposure on gastrointestinal irAE severity.

METHODS: This was a single-center retrospective chart review including all patients receiving ICIs between January 2010 and February 2024 who developed upper or lower gastrointestinal toxicity. Patients were grouped based on PPI use, defined as receiving a PPI any time from 3 months before ICI initiation until gastrointestinal toxicity diagnosis.

RESULTS: A total of 1,228 patients were included: 88 (7.2%) with upper gastrointestinal toxicity and 1,140 (92.8%) with lower toxicity. Upper gastrointestinal irAEs were more severe among PPI users (69.6% with grade 3 toxicity in the PPI group vs 29.6% in the non-PPI group; P<.05). Similarly, lower gastrointestinal irAEs were more severe among PPI users, with a higher need for multiple lines of biologic treatment, higher hospitalization rates, and longer hospital stays (P<.05 for all). PPI use was associated with significantly worse overall survival among patients receiving ICIs (P<.05).

CONCLUSIONS: Our study is the largest to date showing the impact of PPI use on immunotherapy toxicity. PPI use may predispose to more severe toxicities and worse outcomes. PPIs may also reduce immunotherapy efficacy, as reflected by worse overall survival. These findings support the judicious use of PPIs in patients receiving ICIs and call for prospective studies to validate our results.},
}

@article {pmid40532723,
year = {2025},
author = {Jabbour, E and Lussana, F and Martínez-Sánchez, P and Torrent, A and Rifón, JJ and Agrawal, V and Tormo, M and Cassaday, RD and Cluzeau, T and Huguet, F and Papayannidis, C and Hernández-Rivas, JM and Rijneveld, A and Fleming, S and Vucinic, V and Böll, B and Ikezoe, T and Abdul-Hay, M and Savoie, ML and Schuh, AC and Berthon, C and Schwartz, S and Chiaretti, S and Yuda, J and Miyazaki, T and González-Campos, J and Chen, Y and Wong, H and Choudhry, J and Zugmaier, G and Guest, E and Gordon, P and Kantarjian, H},
title = {Subcutaneous blinatumomab in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: post-hoc safety and activity analysis from a multicentre, single-arm, phase 1/2 trial.},
journal = {The Lancet. Haematology},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3026(25)00144-9},
pmid = {40532723},
issn = {2352-3026},
abstract = {BACKGROUND: Two doses of subcutaneous blinatumomab in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia were identified as preliminary recommended phase 2 doses, based on the dose-escalation phase of this multicentre single-arm, phase 1/2 trial. Here, we aim to further study the safety, activity, and pharmacokinetics of these doses in all participants who have received them, including those treated in the completed phase 1b expansion part of the study.

METHODS: We did a post-hoc analysis of data from patients enrolled in the dose-escalation and dose-expansion phases and in the pharmacokinetic evaluation cohort of this multicentre, single-arm, phase 1/2 study. Patients were recruited from 44 hospitals in 11 countries. Eligible participants were aged 18 years or older with relapsed or refractory B-cell acute lymphoblastic leukaemia, at least 5% of blasts in the bone marrow, and an Eastern Cooperative Oncology Group performance status of 2 or lower. Patients received either 250 μg subcutaneous blinatumomab once daily in week 1 of cycle 1 and then 500 μg three times weekly thereafter (250 μg/500 μg group), or 500 μg and then 1000 μg subcutaneous blinatumomab on the same schedule (500 μg/1000 μg group), previously identified as the preliminary recommended phase 2 doses. Each treatment cycle included a 4-week treatment period and a 1-week treatment-free interval. Patients received between two and five cycles. The primary endpoint for the dose-expansion phase was complete remission or complete remission with partial haematological recovery within the first two cycles, which was used as the primary outcome for this study. Data were pooled from all cohorts of the same dose level to form two dose groups. The response rates, adverse event incidence, and pharmacokinetics were summarised in each dose group separately and compared descriptively. Response was calculated with two-sided exact 80% CIs (Clopper-Pearson method). This study is registered with ClinicalTrials.gov, NCT04521231; phase 1 is complete, and phase 2 is active but not recruiting.

FINDINGS: Participants were recruited from Oct 18, 2021, to Sept 23, 2024, and median follow-up for the analyses was 5 months (IQR 3-9). Of the 88 patients included in the analysis at the data cutoff of Nov 28, 2024, 36 (41%) were treated with the 250 μg/500 μg regimen and 52 (59%) with the 500 μg/1000 μg regimen. The enrolled population comprised 55 (63%) male and 33 (38%) female participants; 56 (64%) were White, six (7%) Asian, three (3%) Black or African American, two (2%) American Indian or Alaska Native, and 20 (23%) other. Hispanic or Latino ethnicity was reported for 33 (38%) patients. 27 (75%) of 36 patients in the 250 μg/500 μg group and 41 (79%) of 52 in the 500 μg/1000 μg group showed complete remission or complete remission with partial haematological recovery. The most common grade 3-4 adverse events were neutropenia (19 [22%] patients), cytokine release syndrome (CRS; 18 [20%] patients), and immune effector cell-associated neurotoxicity syndrome (ICANS; 15 [17%] patients). Serious adverse events occurred in 70 (80%) of 88 patients and included CRS (33 [38%] patients), ICANS (20 [23%] patients), and neurotoxicity (six [7%] patients). No treatment-related deaths were reported. Consistent pharmacokinetics with dose-proportional exposures was observed following subcutaneous administration. Based on the totality of data, including efficacy, safety, and pharmacokinetic data, the subcutaneous blinatumomab dose regimen of 250 μg/500 μg was selected as the recommended phase 2 dose.

INTERPRETATION: Treatment with subcutaneous blinatumomab at the two dose regimens of 250 μg/500 μg and 500 μg/1000 μg resulted in promising preliminary activity and a manageable safety profile in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. The phase 2 part of the trial is ongoing to further evaluate subcutaneous blinatumomab activity and duration of response.

FUNDING: Amgen.},
}

@article {pmid40532705,
year = {2025},
author = {Ganesan, A and Moore, AR and Zheng, H and Toh, J and Freedman, M and Magis, AT and Heath, JR and Khatri, P},
title = {A conserved immune dysregulation signature is associated with infection severity, risk factors prior to infection, and treatment response.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2025.05.020},
pmid = {40532705},
issn = {1097-4180},
abstract = {Older age, being male, obesity, smoking, and comorbidities (e.g., diabetes, asthma) are associated with an increased risk for severe infections. We hypothesized that there is a conserved common immune dysregulation across these risk factors. We integrated single-cell and bulk transcriptomic data and proteomic data from 12,026 blood samples across 68 cohorts to test this hypothesis. We found that our previously described 42-gene Severe-or-Mild (SoM) signature was associated with each of these risk factors prior to infection. Furthermore, this conserved immune signature was modifiable using immunomodulatory drugs and lifestyle changes. The SoM score predicted the individuals with sepsis who would be harmed by hydrocortisone treatment and individuals with asthma who would not respond to monoclonal antibody treatment. Finally, the SoM score was associated with all-cause mortality. The SoM signature has the potential to redefine the immunologic framing of the baseline immune state and response to chronic, subacute, and acute illnesses.},
}

@article {pmid40532592,
year = {2025},
author = {Jeong, D and Richards, AR and Jean-Baptiste, E and Gomez, MF and Thomas, KL and Mo, Q and Gigic, B and Figueiredo, JC and Li, CI and Shibata, D and Toriola, AT and Byrd, DA and Ulrich, CM and Stewart, PA and Siegel, EM and Kresovich, JK},
title = {Comparison of volumetric and single-slice computed tomography body composition metrics for colorectal cancer survival.},
journal = {European journal of radiology},
volume = {190},
number = {},
pages = {112241},
doi = {10.1016/j.ejrad.2025.112241},
pmid = {40532592},
issn = {1872-7727},
abstract = {BACKGROUND: Body composition is associated with colorectal cancer (CRC) survival. However, body composition measurements have traditionally relied on single-slice, axial imaging. Fully automated volumetric body composition analysis is widely available, but associations with CRC survival have yet to be examined in detail.

METHODS: Among a nested case-control sample of CRC patients with existing CT scans, volumetric and single-slice body composition analysis was performed, including total area and proportional skeletal muscle (SM), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT). Body composition was measured from the T12 vertebra to the sacrum, with the mid-L3 level used for single-slice analysis. We used multivariable Cox regression models to estimate associations between height-indexed volumetric and single-slice body composition metrics with all-cause mortality.

RESULTS: The mean age of the 121 enrolled patients was 61, and 38 (31 %) died over a mean follow-up of 7.7 years. The T12-sacrum, T12-L3, and L3-sacrum volumetric measurements were correlated with each other and their corresponding mid-L3 metric (all ρ > 0.8). In adjusted models, the T12-sacrum VAT index proportion yielded the strongest association with CRC survival (per 1-SD increase, HR: 2.07, 95 % CI: 1.13, 3.80, P = 0.02). Mid-L3 and volumetric composition metrics showed similar associations with CRC survival.

CONCLUSIONS: Volumetric body composition metrics are associated with CRC survival but did not outperform single-slice metrics in predicting CRC survival. Proportional metrics, which account for total abdominal muscle and adipose tissue area, may be a novel computational technique for assessing body composition.},
}

@article {pmid40532178,
year = {2025},
author = {Uppaluri, R and Haddad, RI and Tao, Y and Le Tourneau, C and Lee, NY and Westra, W and Chernock, R and Tahara, M and Harrington, KJ and Klochikhin, AL and Braña, I and Vasconcelos Alves, G and Hughes, BGM and Oliva, M and Pinto Figueiredo Lima, I and Ueda, T and Rutkowski, T and Schroeder, U and Mauz, PS and Fuereder, T and Laban, S and Oridate, N and Popovtzer, A and Mach, N and Korobko, Y and Costa, DA and Hooda-Nehra, A and Rodriguez, CP and Bell, RB and Manschot, C and Benjamin, K and Gumuscu, B and Adkins, D and , },
title = {Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer.},
journal = {The New England journal of medicine},
volume = {},
number = {},
pages = {},
doi = {10.1056/NEJMoa2415434},
pmid = {40532178},
issn = {1533-4406},
abstract = {BACKGROUND: The benefit of the addition of perioperative pembrolizumab to standard care with surgery and adjuvant therapy for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) is unclear.

METHODS: In this phase 3, open-label trial, we randomly assigned participants with locally advanced HNSCC in a 1:1 ratio to receive 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both at a dose of 200 mg every 3 weeks) in addition to standard care (pembrolizumab group) or standard care alone (control group). Standard care was surgery and adjuvant radiotherapy with or without concomitant cisplatin. The primary end point was event-free survival, sequentially assessed in participants whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of 10 or more (CPS-10 population), participants whose tumors expressed PD-L1 with a CPS of 1 or more (CPS-1 population), and all the participants. A higher CPS indicates a higher proportion of cells that express PD-L1.

RESULTS: A total of 363 participants (234 with a CPS of ≥10 and 347 with a CPS of ≥1) were assigned to the pembrolizumab group and 351 (231 with a CPS of ≥10 and 335 with a CPS of ≥1) to the control group. Surgery was completed in approximately 88% of the participants in each group. At the first interim analysis, the median follow-up was 38.3 months. Event-free survival at 36 months was 59.8% in the pembrolizumab group and 45.9% in the control group (hazard ratio for progression, recurrence, or death, 0.66; 95% confidence interval [CI], 0.49 to 0.88; two-sided P = 0.004) in the CPS-10 population; 58.2% and 44.9%, respectively (hazard ratio, 0.70; 95% CI, 0.55 to 0.89; two-sided P = 0.003), in the CPS-1 population; and 57.6% and 46.4%, respectively (hazard ratio, 0.73; 95% CI, 0.58 to 0.92; two-sided P = 0.008), in the total population. Grade 3 or higher treatment-related adverse events occurred in 44.6% of the participants in the pembrolizumab group and in 42.9% of those in the control group, including death in 1.1% and 0.3%, respectively. Potentially immune-mediated adverse events of grade 3 or higher occurred in 10.0% of the participants in the pembrolizumab group.

CONCLUSIONS: The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced HNSCC. Neoadjuvant pembrolizumab did not affect the likelihood of surgical completion. No new safety signals were identified. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-689 ClinicalTrials.gov number, NCT03765918.).},
}

@article {pmid40532127,
year = {2025},
author = {Fay, M and Liao, RS and Lone, ZM and Reddy, CA and Muhammad, H and Xie, C and Jain, P and Huang, W and Basu, HS and Nair, SS and Chakravarty, D and Williamson, SR and Gupta, S and Weight, C and Roy, R and Wilding, G and Tewari, AK and Klein, EA and Mian, OY},
title = {Artificial Intelligence-Based Digital Histologic Classifier for Prostate Cancer Risk Stratification: Independent Blinded Validation in Patients Treated With Radical Prostatectomy.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2400292},
doi = {10.1200/CCI-24-00292},
pmid = {40532127},
issn = {2473-4276},
mesh = {Humans ; Male ; *Prostatic Neoplasms/surgery/pathology/diagnosis/mortality ; *Prostatectomy/methods ; *Artificial Intelligence ; Middle Aged ; Aged ; Retrospective Studies ; Prognosis ; Risk Assessment/methods ; Neoplasm Grading ; Follow-Up Studies ; },
abstract = {PURPOSE: Artificial intelligence (AI) tools that identify pathologic features from digitized whole-slide images (WSIs) of prostate cancer (CaP) generate data to predict outcomes. The objective of this study was to evaluate the clinical validity of an AI-enabled prognostic test, PATHOMIQ_PRAD, using a clinical cohort from the Cleveland Clinic.

METHODS: We conducted a retrospective analysis of PATHOMIQ_PRAD using CaP WSIs from patients who underwent radical prostatectomy (RP) between 2009 and 2022 and did not receive adjuvant therapy. Patients also had Decipher genomic testing available. WSIs were deidentified, anonymized, and outcomes were blinded. Patients were stratified into high-risk and low-risk categories on the basis of predetermined thresholds for PATHOMIQ_PRAD scores (0.45 for biochemical recurrence [BCR] and 0.55 for distant metastasis [DM]).

RESULTS: The study included 344 patients who underwent RP with a median follow-up of 4.3 years. Both PathomIQ and Decipher scores were associated with rates of biochemical recurrence-free survival (BCRFS; PathomIQ score >0.45 v ≤0.45, P <.001; Decipher score >0.6 v ≤0.6, P = .002). There were 16 patients who had DM, and 15 were in the high-risk PathomIQ group (Mets Score >0.55). Both PathomIQ and Decipher scores were associated with rates of metastasis-free survival (PathomIQ score >0.55 v ≤0.55, P <.001; Decipher score >0.6 v ≤0.6, P = .0052). Despite the low event rates for metastasis, multivariable regression demonstrated that high PathomIQ score was significantly associated with DM (>0.55 v ≤0.55, hazard ratio, 10.10 [95% CI, 1.28 to 76.92], P = .0284).

CONCLUSION: These findings independently validate PATHOMIQ_PRAD as a reliable predictor of clinical risk in the postprostatectomy setting. PATHOMIQ_PRAD therefore merits prospective evaluation as a risk stratification tool to select patients for adjuvant or early salvage interventions.},
}

Humans
Male
*Prostatic Neoplasms/surgery/pathology/diagnosis/mortality
*Prostatectomy/methods
*Artificial Intelligence
Middle Aged
Aged
Retrospective Studies
Prognosis
Risk Assessment/methods
Neoplasm Grading
Follow-Up Studies

@article {pmid40288368,
year = {2025},
author = {Lespine, LF and Rueda-Delgado, LM and Vahey, N and Ruddy, KL and Kiiski, H and Enz, N and Boyle, R and Rai, L and Pragulbickaite, G and Bricker, JB and McHugh, L and Whelan, R},
title = {Changes in Inhibition-Related Brain Function and Psychological Flexibility during Smoking Abstinence: A Machine-Learning Prediction of Time to Relapse.},
journal = {European addiction research},
volume = {},
number = {},
pages = {1-14},
pmid = {40288368},
issn = {1421-9891},
abstract = {INTRODUCTION: Despite substantial health benefits, smoking cessation attempts have high relapse rates. Neuroimaging measures can sometimes predict individual differences in substance use phenotypes - including relapse - better than behavioral metrics alone. No study to date has compared the relative prediction ability of changes in psychological processes across prolonged abstinence with corresponding changes in brain activity.

METHODS: Here, in a longitudinal design, measurements were made 1 day prior to smoking cessation, and at 1 and 4 weeks post-cessation (total n = 120). Next, we tested the relative role of changes in psychosocial variables versus task-based functional brain measures predicting time to nicotine relapse up to 12 months. Abstinence was bio-verified 4-5 times during the first month. Data were analyzed with a novel machine-learning approach to predict relapse.

RESULTS: Results showed that increased electrophysiological brain activity during inhibitory control predicted longer time to relapse (c-index = 0.56). However, reward-related brain activity was not predictive (c-index = 0.45). Psychological variables, notably an increase during abstinence in psychological flexibility when experiencing negative smoking-related sensations, predicted longer time to relapse (c-index = 0.63). A model combining psychosocial and brain data was predictive (c-index = 0.68). Using a best-practice approach, we demonstrated generalizability of the combined model on a previously unseen holdout validation dataset (c-index = 0.59 vs. 0.42 for a null model).

CONCLUSION: These results show that changes during abstinence - increased smoking-specific psychological flexibility and increased inhibitory control brain function - are important in predicting time to relapse from smoking cessation. In the future, monitoring and augmenting changes in these variables could help improve the chances of successful nicotine smoking abstinence.},
}

@article {pmid40531856,
year = {2025},
author = {McTiernan, A},
title = {In Motion: Experimental Evidence on Exercise and Breast Cancer in Women and Mice.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-1313},
pmid = {40531856},
issn = {1557-3265},
abstract = {Strong evidence from observational studies show that high levels of physical activity are associated with a reduced risk of breast cancer, with a dose-response effect. Human trials and animal models have identified mechanisms explaining these associations, which aid in designing prescriptions and guidelines for exercise in breast cancer prevention.},
}

@article {pmid40528125,
year = {2025},
author = {Bilen, MA and Burbage, S and Rossi, C and Khilfeh, I and Diaz, L and Wang, Y and Pilon, D and Brown, G and Shore, N and Lowentritt, B and Lin, DW},
title = {Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative Metastatic Castration-Sensitive Prostate Cancer.},
journal = {Advances in therapy},
volume = {},
number = {},
pages = {},
pmid = {40528125},
issn = {1865-8652},
abstract = {INTRODUCTION: This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with BRCA1/2-positive (BRCA+) and homologous recombination repair-negative (HRR-) metastatic castration-sensitive prostate cancer (mCSPC).

METHODS: Patients who received a genetic test and initiated treatment for mCSPC (index date) after 1/1/2018 were selected from the Flatiron Health-Foundation Medicine, Inc. Metastatic PC Clinico-Genomic Database (1/1/2017-12/31/2022). Outcomes were compared between patients with ≥ 1 positive BRCA test (BRCA+) and those without detected HRR mutations (HRR-) using weighted Kaplan-Meier analyses and Cox proportional hazards models after baseline characteristics (12 months pre-index) were balanced using inverse-probability of treatment weighting.

RESULTS: In total, 149 patients with BRCA+ and 1066 with HRR- mCSPC were included. Baseline characteristics were well-balanced after weighting. By 24 months after treatment initiation, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to next treatment [69.7% vs. 56.8%; hazard ratio (HR) = 1.45 (95% confidence interval (CI) 1.10, 1.92), p = 0.009]; median TTNT was shorter in the BRCA+ than the HRR- cohort (10.9 vs. 18.7 months). By 24 months, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to castration resistance [72.2% vs. 61.4%; HR = 1.46 (95% CI 1.16, 1.84), p = 0.001]; median TTCR was shorter in the BRCA+ than HRR- cohort (12.9 vs. 16.9 months). Numerically fewer patients in the BRCA+ than the HRR- cohort survived 24 months after PC diagnosis [80.6% vs. 85.4%; HR = 1.46 (95% CI 0.99, 2.14), p = 0.054].

CONCLUSION: Findings demonstrate worse outcomes for patients with BRCA+ mCSPC treated with available advanced therapies, supporting the need for effective genetically targeted therapies in this population.},
}

@article {pmid40527319,
year = {2025},
author = {Purice, MD and Quitevis, EJA and Manning, RS and Severs, LJ and Tran, NT and Sorrentino, V and Finkbeiner, C and Wu, F and Zager, M and Setty, M and Singhvi, A},
title = {Molecular profiling of adult C. elegans glia across sexes by single-nuclear RNA-seq.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2025.05.013},
pmid = {40527319},
issn = {1878-1551},
abstract = {A comprehensive understanding of nervous system function requires molecular insight into the diversity and sex dimorphism of both its component cell types, glia and neurons. Here, we present a single-nuclear RNA sequencing (RNA-seq) census of all neuroectoderm-derived glia in the adult C. elegans nervous system, across sexes. By iteratively coupling computational modeling and custom analytics with in vivo validations, we uncovered molecular markers for all glia, as well as class-specific and pan-glial molecular signatures. These identified that each glia is functionally heterogeneous across the nervous system and variably sex dimorphic between sexes. Thus, this glial transcriptome (wormglia.org) offers deep mechanistic insights into glial biology brain wide. Complementing the existing C. elegans neuronal transcriptome and mapped connectome, it also enables single-cell and molecular resolution insight into the entire nervous system of an adult metazoan.},
}

@article {pmid40526835,
year = {2025},
author = {Poh, C and Voutsinas, JM and Shadman, M and Lynch, RC and Warren, EH and Crimp, CA and Till, BG and Ujjani, CS and Di, M and Raghunathan, V and Smith, SD and Wu, QV and Shinohara, MM and Gopal, AK},
title = {Pralatrexate Is Effective in Cytotoxic Cutaneous T-cell Lymphomas.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016680},
pmid = {40526835},
issn = {2473-9537},
abstract = {Cytotoxic cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of T-cell lymphomas with variable prognoses and no standard of care. We identified patients with primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL), primary cutaneous gamma-delta T-cell lymphoma (PCGDTL) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) who were treated with at least one dose of pralatrexate between 2015 and 2024 at the University of Washington/Fred Hutchinson Cancer Center. Eighteen patients met criteria, 3 with CD8+ PCAETL, 6 with PCGDTL, and 9 with SPTCL. The median number of prior systemic therapies was 1 (range 0-4), and the median pralatrexate treatment duration was 14 weeks (range 8-43). The overall response rate was 100%, with 12 (67%) achieving complete response. Median progression-free and overall survival was 5.6 months and not reached, respectively. Among CR patients, the median response duration was 22 months. At a median follow-up of 45 months, 6 (33%) patients remain in sustained remission. This retrospective analysis is the first to evaluate pralatrexate's efficacy in this aggressive disease population, demonstrating its effectiveness and association with durable responses in cytotoxic CTCL.},
}

@article {pmid40523534,
year = {2025},
author = {Dominitz, JA and Ladabaum, U and Holub, JL and Issaka, RB and Ko, CW and Robertson, DJ},
title = {Association Between Adenoma Detection Rate and Prevalent Colorectal Cancer Detection Rate in a National Colonoscopy Registry Subtitle: Association Between Adenoma and Colorectal Cancer Detection.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2025.06.009},
pmid = {40523534},
issn = {1528-0012},
abstract = {BACKGROUND: While the adenoma detection rate (ADR) is associated with post-colonoscopy colorectal cancer (PCCRC) risk, it is unknown to what extent this reflects missed colorectal cancer (CRC) versus missed pre-cancerous lesions. We evaluated the association between physician ADR and prevalent CRC detection during colonoscopy.

METHODS: We used cross-sectional 2019-2022 GI Quality Improvement Consortium (GIQuIC) data for >1.73 million colonoscopies performed by 3567 endoscopists for screening or abnormal fecal test (AFT) follow-up from 683 US endoscopy units. Endoscopist ADR and sessile serrated lesion detection rate (SSLDR) were determined based on screening exams.

RESULTS: CRC was detected in 0.3% of screening and 1.5% of follow-up colonoscopies. From lowest to highest endoscopist ADR quintile, CRC detection increased from 26.6 (95% confidence interval (CI) 24.4-27.9) to 33.1 (95%CI 29.7-33.7), and from 107.8 (95%CI 96.2-129.4) to 164.7 (95% CI 140.8-188.6) per 10,000 screening and AFT follow-up colonoscopies, respectively. In multivariable models with lowest ADR quintile as reference, the odds ratios (ORs) of CRC detection in the highest ADR quintile were 1.27 (95% CI 1.14-1.41) for screening and 1.50 (95% CI 1.16-1.93) for AFT follow-up colonoscopies. Compared to high-ADR/high-SSLDR endoscopists, the ORs of CRC detection were lower for low-ADR endoscopists irrespective of SSLDR (high-SSLDR, 0.87, 95% CI 0.80-0.96; low-SSLDR 0.92, 95% CI 0.85-0.98), but similar for high-ADR/low-SSLDR endoscopists.

CONCLUSIONS: ADR reflects prevalent CRC detection as well as detection and removal of CRC precursors. Our findings suggest that PCCRC is not uncommonly due to missed CRC, especially among endoscopists with low ADR.},
}

@article {pmid40523203,
year = {2025},
author = {Rutherford, SC and Li, H and Herrera, AF and LeBlanc, M and Ahmed, S and Davison, K and Parsons, SK and Unger, JM and Perry, AM and Casulo, C and Bartlett, NL and Tuscano, JM and Hess, BT and Torka, P and Kumar, P and Jacobs, R and Song, JY and Castellino, SM and Kahl, B and Leonard, JP and Smith, SM and Friedberg, JW and Evens, AM},
title = {Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Older Patients With Advanced-Stage Classic Hodgkin Lymphoma Enrolled on S1826.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500204},
doi = {10.1200/JCO-25-00204},
pmid = {40523203},
issn = {1527-7755},
abstract = {Older patients with classic Hodgkin lymphoma (cHL) have inferior survival compared with younger patients. We report a subset analysis of older patients (60 years and older) enrolled in the phase three S1826 trial conducted by SWOG that randomly assigned patients with newly diagnosed advanced-stage (III-IV) cHL to six cycles of nivolumab (N)-AVD or brentuximab vedotin (BV)-AVD. Of 103 enrolled patients 60 years and older, 99 were eligible. At a median follow-up of 2.1 years, the 2-year progression-free survival was 89% after N-AVD (n = 50) and 64% after BV-AVD (n = 49, HR 0.24, 95%CI 0.09-0.63, 1-sided stratified log-rank P = .001). The 2-year OS was 96% with N-AVD versus 85% with BV-AVD (HR 0.16, 95%CI 0.03-0.75 stratified 1-sided log-rank P = .005). Six cycles were delivered without dose reduction in 69% on N-AVD and 26% on BV-AVD; 55% discontinued BV, and 14% discontinued nivolumab. The nonrelapse mortality was 16% with BV-AVD and 6% with N-AVD. Despite more neutropenia with N-AVD, febrile neutropenia, sepsis, and infections were higher with BV-AVD, as was peripheral neuropathy. Patient-reported outcomes of key adverse events confirmed the improved toxicity profile of N-AVD over BV-AVD. N-AVD was better tolerated and more effective than BV-AVD and is therefore a new standard of care for older patients with advanced-stage cHL fit for anthracycline-based combination therapy.},
}

@article {pmid40522834,
year = {2025},
author = {Kulsuptrakul, J and Emerman, M and Mitchell, PS},
title = {CARD8 inflammasome activation during HIV-1 cell-to-cell transmission.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {40522834},
issn = {2050-084X},
support = {DP1 DA051110/DA/NIDA NIH HHS/United States ; DP2 AI154432/AI/NIAID NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; DP1 DA051110/NH/NIH HHS/United States ; T32 GM007270/NH/NIH HHS/United States ; DP2 AI 154432-01/NH/NIH HHS/United States ; },
mesh = {Humans ; *HIV-1/physiology ; *CARD Signaling Adaptor Proteins/metabolism/genetics ; *Inflammasomes/metabolism ; *HIV Infections/virology/transmission/immunology ; Macrophages/virology/immunology ; HIV Protease/metabolism/genetics ; T-Lymphocytes/virology ; Neoplasm Proteins ; },
abstract = {Our previous work demonstrated that CARD8 detects HIV-1 infection by sensing the enzymatic activity of the HIV protease, resulting in CARD8-dependent inflammasome activation (Kulsuptrakul et al., 2023). CARD8 harbors a motif in its N-terminus that functions as a HIV protease substrate mimic, permitting innate immune recognition of HIV-1 protease activity, which when cleaved by HIV protease triggers CARD8 inflammasome activation. Here, we sought to understand CARD8 responses in the context of HIV-1 cell-to-cell transmission via a viral synapse. We observed that cell-to-cell transmission of HIV-1 between infected T cells and primary human monocyte-derived macrophages induces CARD8 inflammasome activation in a manner that is dependent on viral protease activity and largely independent of the NLRP3 inflammasome. Additionally, to further evaluate the viral determinants of CARD8 sensing, we tested a panel of HIV protease inhibitor-resistant clones to establish how variation in HIV protease affects CARD8 activation. We identified mutant HIV-1 proteases that differentially cleave and activate CARD8 compared to wildtype HIV-1, thus indicating that natural variation in HIV protease affects not only the cleavage of the viral Gag-Pol polyprotein but also likely impacts innate sensing and inflammation.},
}

Humans
*HIV-1/physiology
*CARD Signaling Adaptor Proteins/metabolism/genetics
*Inflammasomes/metabolism
*HIV Infections/virology/transmission/immunology
Macrophages/virology/immunology
HIV Protease/metabolism/genetics
T-Lymphocytes/virology
Neoplasm Proteins

@article {pmid40522215,
year = {2025},
author = {Lin, N and Vitonis, AF and Mongiovi, JM and Farland, LV and Huang, T and Terry, KL and Eliassen, AH and Townsend, MK and Zhang, C and Hu, FB and Sasamoto, N},
title = {History of breastfeeding in relation to circulating inflammatory and metabolic biomarkers.},
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-25-0034},
pmid = {40522215},
issn = {1538-7755},
abstract = {BACKGROUND: Breastfeeding history has been associated with reduced risk of chronic diseases, although the underlying biological link is unclear.

METHODS: The study included 16,165 parous women in the Nurses' Health Studies who reported lactation history and biomarkers measured using plasma samples collected at mid-life. We calculated multivariable-adjusted geometric means of ten inflammatory biomarkers [high sensitivity C-reactive protein(hsCRP), interleukin-6 (IL6), IL8, IL10, insulin-like growth factor-1 (IGF1), soluble tumor necrosis factor α receptor 2 (sTNFR2), B-cell activating factor, C-X-C motif chemokine ligand 13 (CXCL13), sIL2-receptor-α (Rα), sIL6Rα] and eight metabolic biomarkers[triglyceride, total cholesterol, high- and low-density lipoprotein (HDL and LDL), leptin, soluble leptin receptor, adiponectin, retinol-binding protein 4] by self-reported history of breastfeeding prior to blood collection. False discovery rate (FDR) was used for multiple testing corrections.

RESULTS: Average age at blood collection was 52.6 years. Ever breastfeeding was associated with higher IGF1 (149.22 vs. 143.76 ng/mL, p-value=0.0002/FDR=0.004) compared with never breastfeeding. Longer breastfeeding duration was associated with lower IL10 (p-trend=0.001/FDR=0.01) and higher IGF1 (p-trend=0.0005/FDR=0.01). No significant associations were observed for other biomarkers. Longer breastfeeding duration was associated with higher IGF1 among premenopausal women but not among postmenopausal women (p-interaction=0.02). Longer breastfeeding duration was associated with lower soluble leptin receptor levels among those with BMI≥25kg/m2 (p-trend=0.01/FDR=0.09) but not among those with BMI<25 kg/m2 (p-interaction=0.0002).

CONCLUSION: Ever breastfeeding and longer breastfeeding duration was associated with higher IGF1 levels measured in mid-life.

IMPACT: Our results support the potential long-term systemic impact of breastfeeding on circulating IGF1 levels, which may influence future chronic disease risk.},
}

@article {pmid40521388,
year = {2024},
author = {Puleo, J and Buchanan, A and Katenka, N and Halloran, ME and Friedman, SR and Nikolopoulos, G},
title = {Assessing Spillover Effects of Medications for Opioid Use Disorder on HIV Risk Behaviors among a Network of People Who Inject Drugs.},
journal = {Stats},
volume = {7},
number = {2},
pages = {549-575},
pmid = {40521388},
issn = {2571-905X},
support = {DP1 DA034989/DA/NIDA NIH HHS/United States ; DP2 DA046856/DA/NIDA NIH HHS/United States ; P30 DA011041/DA/NIDA NIH HHS/United States ; R01 AI085073/AI/NIAID NIH HHS/United States ; },
abstract = {People who inject drugs (PWID) have an increased risk of HIV infection partly due to injection behaviors often related to opioid use. Medications for opioid use disorder (MOUD) have been shown to reduce HIV infection risk, possibly by reducing injection risk behaviors. MOUD may benefit individuals who do not receive it themselves but are connected through social, sexual, or drug use networks with individuals who are treated. This is known as spillover. Valid estimation of spillover in network studies requires considering the network's community structure. Communities are groups of densely connected individuals with sparse connections to other groups. We analyzed a network of 277 PWID and their contacts from the Transmission Reduction Intervention Project. We assessed the effect of MOUD on reductions in injection risk behaviors and the possible benefit for network contacts of participants treated with MOUD. We identified communities using modularity-based methods and employed inverse probability weighting with community-level propensity scores to adjust for measured confounding. We found that MOUD may have beneficial spillover effects on reducing injection risk behaviors. The magnitudes of estimated effects were sensitive to the community detection method. Careful consideration should be paid to the significance of community structure in network studies evaluating spillover.},
}

@article {pmid40519326,
year = {2025},
author = {Mittal, A and Jones, T and Karkar, R and Suh, J and Williams, S and Zheng, Y and Andris, LM and Bates, N and Bauer, AM and Lostutter, TW and Fann, JR and Fogarty, J and Hsieh, G},
title = {SCOPE: Examining Technology-Enhanced Collaborative Care Management of Depression in the Cancer Setting.},
journal = {Proceedings of the ACM on human-computer interaction},
volume = {9},
number = {2},
pages = {},
pmid = {40519326},
issn = {2573-0142},
support = {P50 MH115837/MH/NIMH NIH HHS/United States ; R01 CA244171/CA/NCI NIH HHS/United States ; R01 LM012810/LM/NLM NIH HHS/United States ; TL1 TR002318/TR/NCATS NIH HHS/United States ; },
abstract = {Collaborative care management is an evidence-based approach to integrated psychosocial care for patients with comorbid cancer and depression. Prior work highlights challenges in patient-provider collaboration in navigating parallel cancer care and psychosocial care journeys of these patients. We design and deploy SCOPE, a platform for technology-enhanced collaborative care combining a patient-facing mobile app with a provider-facing registry. We examine SCOPE through a total of 45 interviews with patients and providers conducted in SCOPE's 15 months of design and development and 24 months of SCOPE's deployment for actual care in 6 cancer clinics. We find that: (1) SCOPE supported patient engagement in its underlying collaborative care and behavioral activation interventions, (2) patient-generated data in SCOPE improved patient-provider collaboration between and within in-person sessions, (3) SCOPE supported providers in delivering care and improved care team collaboration, (4) experience with SCOPE created evolving expectations for collaboration around data, and (5) SCOPE's deployment in actual care surfaced important implementation barriers. We discuss the implications of our findings in terms of designing for engagement with behavioral health interventions, negotiating patient data sharing and provider responsiveness, supporting personalized self-tracking goals in evidence-based interventions, exploring the role of digital health navigators in technology-enhanced care, and the need for flexibility in aligning technology-supported interventions to patient needs.},
}

@article {pmid40518799,
year = {2025},
author = {Grzelak, CA and Ghajar, CM},
title = {Incorporating Centrally Tolerized Mice as a Design Principle to Circumvent Reporter Immunogenicity in Cancer Research Models.},
journal = {Cancer research},
volume = {85},
number = {12},
pages = {2143-2145},
doi = {10.1158/0008-5472.CAN-25-1055},
pmid = {40518799},
issn = {1538-7445},
mesh = {Animals ; Mice ; *Disease Models, Animal ; Mice, Transgenic ; *Neoplasms/immunology/pathology ; *Immune Tolerance ; Humans ; Genes, Reporter/immunology ; Luminescent Proteins/immunology/genetics ; },
abstract = {The study of tumor progression and metastasis in a physiologic setting commonly involves implantation of tumor cells into immunocompetent mice. For this purpose, tumor cells are labeled routinely with bioluminescent and/or fluorescent proteins prior to transplantation, despite the fact that these foreign proteins generate adaptive immune responses. We have described previously how incorporating centrally tolerized mouse strains into tumor and metastasis modeling can be used as a study design principle to properly control for artifactual immune responses against such reporters. In this issue of Cancer Research, Khan and colleagues applied a tolerized mouse strain-the Tol mouse-to overcome limitations associated with the use of xenoantigenic fluorescent and bioluminescent reporters in immunocompetent settings. The authors showed how antigenic responses against such proteins can confound interpretation of study results when measuring the efficacy of immunotherapy regimens. This study readily demonstrates the utility of employing centrally tolerized transgenic models to improve preclinical investigations of cancer metastasis and therapeutic resistance. See related article by Khan et al., p. 2165.},
}

Animals
Mice
*Disease Models, Animal
Mice, Transgenic
*Neoplasms/immunology/pathology
*Immune Tolerance
Humans
Genes, Reporter/immunology
Luminescent Proteins/immunology/genetics

@article {pmid40516922,
year = {2025},
author = {Batista, MV and Chaer, FE and Englund, JA and Boeckh, M and Carpenter, PA and Dadwal, SS and Waghmare, A and Navarro, D and Hirsch, HH and Piñana, JL and Papanicolaou, GA and Chemaly, RF},
title = {American Society for Transplantation and Cellular Therapy Series #10: Management of Parainfluenza and Human Metapneumovirus Infections in Hematopoietic Cell Transplantation and Cellular Therapy Recipients.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.06.016},
pmid = {40516922},
issn = {2666-6367},
abstract = {In 2019, The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Diseases Special Interest Group to update the 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). The new format is now structured around frequently asked questions (FAQs), concise tables, and figures to better support clinical providers. Here, a panel of experts in HCT and infectious diseases identified relevant FAQs, which they graded based on the strength of clinical practice recommendations and the level of supporting evidence, as described herein. In the ninth set of guidelines in the series, the focus is on parainfluenza virus and human metapneumovirus, with FAQs addressing epidemiology, incidence, clinical manifestations, risk factors, diagnosis, prevention (including vaccines), and therapeutic management in recipients of HCT and chimeric antigen receptor T cells (cellular therapy). Special considerations for pediatric patients, unmet needs, and future research directions are conveyed in the guidelines.},
}

@article {pmid40516446,
year = {2025},
author = {Dasari, AKR and Bhatt, N and Haque, MA and Irving, R and Kayed, R and Lim, KH},
title = {Cryo-EM structural analyses reveal diverse porous structures in brain-derived tau oligomers.},
journal = {Biochemical and biophysical research communications},
volume = {776},
number = {},
pages = {152189},
doi = {10.1016/j.bbrc.2025.152189},
pmid = {40516446},
issn = {1090-2104},
abstract = {Misfolding and aggregation of tau into oligomers and neurofibrillary tangles are associated with Alzheimer's disease and related dementia (ADRD). Misfolded oligomeric species are widely believed to play a critical role in both disrupting cellular functions and propagating protein misfolding between cells. Characterization of the misfolded oligomers is crucial for understanding the mechanisms underlying protein aggregation and its role in disease pathogenesis. However, structural characterization of these misfolded oligomers has proven challenging due to their transient and heterogeneous nature. Here we report structural features of brain-derived tau oligomers extracted from Alzheimer's brains. Initial screening using negative staining transmission electron microscopy (TEM) and atomic force microscopy (AFM) reveal that tau (2N4R) forms a diverse array of pore-like oligomers with a diameter of 5-20 nm and a height of ∼2-8 nm. Higher-resolution structural analyses using cryo-EM on oligomers with diameters of 10-20 nm revealed the presence of two distinct layers within the pore-like structures, resolved at 2.5-4 Å. Our structural studies support the hypothesis that misfolded proteins may function as pore-forming toxins, potentially disrupting cellular membranes.},
}

@article {pmid40516378,
year = {2025},
author = {Huang, Y and Zhang, L and Gelderblom, H and Seaton, KE and Yates, NL and Paez, CA and Karuna, ST and Andrew, P and Gamble, T and Robinson, ST and Ledgerwood, JE and Hyrien, O and Walsh, SR and Gay, CL and Gwira, JA and Spiegel, HML and Sobieszczyk, ME and Mannheimer, SB and Edupuganti, S and Hurt, CB and Stephenson, KE and Yu, C and Kelley, CF and Mahomed, S and Siegel, M and Yacovone, M and Pensiero, MN and Donnell, D and Cohen, MS and Corey, L and Gilbert, PB and Koup, RA and Tomaras, GD and , },
title = {Fixed dosing versus weight-based dosing of HIV-1 prophylactic monoclonal antibodies in adults: a post-hoc, cross-protocol pharmacokinetics modelling study.},
journal = {EBioMedicine},
volume = {117},
number = {},
pages = {105804},
doi = {10.1016/j.ebiom.2025.105804},
pmid = {40516378},
issn = {2352-3964},
abstract = {BACKGROUND: Pharmacokinetic (PK) modelling and simulations have been used to support label changes of dosing levels or strategies for multiple marketed therapeutic monoclonal antibodies (mAbs). Using data from early-phase clinical trials in adults without HIV-1, we compared fixed and weight-based dosing strategies for three HIV-1 broadly neutralising mAbs planned for prevention efficacy evaluation: PGDM1400LS, PGT121.414.LS, and VRC07-523LS.

METHODS: We used a two-compartment population PK model to describe overall trends and inter-individual variability in post-administration serum concentrations over time from individuals administered PGDM1400LS (n = 95), PGT121.414.LS (n = 113), or VRC07-523LS (n = 251) subcutaneously or intravenously. We evaluated the effect of body weight on various PK parameters, including clearance rate, and simulated mAb concentrations after fixed and weight-based dosing administrations using sex-specific weights observed in participants from two recent HIV-1 mAb efficacy trials. We compared magnitudes and inter-individual variabilities of concentrations at specific post-administration timepoints, areas under the time-concentration curves (AUC), and predicted neutralisation titres against representative HIV-1 virus strains.

FINDINGS: For all three mAbs, we observed a modest effect of body weight on clearance rate and volumes of the central and peripheral compartments. The population-level magnitude and variability in time-specific concentrations, AUC, and predicted neutralisation titres were comparable between the two dosing strategies for both sexes. The relationship between body weight and concentrations differed between the two dosing strategies with a positive correlation for weight-based dosing and a negative correlation for fixed dosing. For individuals with body weight below the 15th or above the 85th percentiles, fixed dosing resulted in <3% difference in median AUC compared to the overall population. For lower weight individuals, fixed dosing improved AUC, potentially correcting the underdosing seen in the previous weight-based mAb efficacy trials. For higher weight individuals (e.g., >100 kg), body weight-based dosing or a higher fixed dose may be preferred.

INTERPRETATION: For HIV-1 prophylactic mAbs, a fixed-dose approach, possibly banded by weight categories may be advantageous over weight-based dosing, as it offers increased operational efficiency while maintaining comparable pharmacokinetics and inter-individual consistency.

FUNDING: NIAID.},
}

@article {pmid40514012,
year = {2025},
author = {Schoettler, ML and Gavriilaki, E and Carreras, E and Cho, BK and Dandoy, CE and Ho, VT and Jodele, S and Moiseev, I and Sánchez-Ortega, I and Srivastava, A and Atsuta, Y and Carpenter, PA and Koreth, J and Kröger, N and Ljungman, P and Page, K and Popat, U and Shaw, BE and Sureda, AM and Soiffer, R and Vasu, S},
title = {An ASTCT, CIBMTR, EBMT, and APBMT Consensus Statement Defining Response Criteria for Hematopoietic Cell Transplantation Associated Thrombotic Microangiopathy (TA-TMA) Directed Therapy: Consensus Response Criteria for TA-TMA.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.05.028},
pmid = {40514012},
issn = {2666-6367},
abstract = {BACKGROUND: Transplant associated thrombotic microangiopathy (TA-TMA) confers significant morbidity and mortality in hematopoietic cell transplant recipients. The safety and efficacy of multiple TA-TMA directed therapeutic agents are being tested in ongoing clinical trials. In the absence of approved drugs, several treatments are used off-label. Response definitions to TA-TMA directed therapy from retrospective studies and ongoing interventional clinical trials vary widely, limiting cross study comparisons. An expert panel from multiple international blood and marrow transplant societies (ASTCT, CIBMTR, EBMT, APBMT) who initially convened to harmonize diagnostic and risk stratification criteria for TA-TMA extended its mandate to review response criteria.

OBJECTIVE: Our objective was to propose clinically meaningful response criteria for TA-TMA directed therapy to enhance consistent evaluation of therapeutic agents in clinical practice, interventional trials, and registry studies.

METHODS: After a relevant literature review, the Delphi method was used to achieve consensus on proposed response criteria.

RESULTS: The panel focused on the three key concepts. First, due to ongoing concurrent co-morbidities and severity of illness, the complete resolution of TA-TMA manifestations may be difficult to achieve immediately after initiating treatment, making the definition of clinically meaningful partial responses essential to assess early efficacy of TA-TMA-directed therapies. Second, because hematologic manifestations may resolve faster than organ damage, we suggest assessing hematologic/biochemical and organ manifestations independently, in addition to having an overall response assessment. Finally, using the previously established diagnostic criteria as a framework, we propose objective response definitions for each TA-TMA criterion and organ manifestation. While consensus was achieved on response definitions, due to the lack of evidence, there was no agreement on standardized time points for assessing response or when to consider alternative therapies for patients unresponsive to initial treatments. Hematologic and biochemical response assessments include anemia and thrombocytopenia, with criteria accounting for transfusion dependence or independence at the time of treatment, schistocytes, lactate dehydrogenase, and soluble C5b-9. Patients with other established etiologies of cytopenias (i.e. poor graft function or relapsed hematologic malignancy) should be considered unevaluable for hematologic response. Responses for involved organ manifestations were also proposed. In an overall assessment, the best overall response is limited by the lowest hematologic/biochemical or organ response. NR of either hematologic/biochemical or organ is considered an overall NR.

CONCLUSION: The consensus response criteria proposed by this expert panel are a step towards standardizing the assessment of treatment responses of TA-TMA directed agents for future studies and interventional clinical trials. Adoption of these criteria will enhance consistency of response assessment and facilitate the comparison of TA-TMA treatments. Since achieving an early overall CR may be challenging/protracted in patients with organ injury; establishment of criteria for clinically meaningful PR is important and may be a more useful early endpoint in studies. Given the complexity of these patients and assessment of response, these definitions may need be revised in the future after application in large cohorts diverse in age, HCT approaches, and interventional agents.},
}

@article {pmid40475658,
year = {2025},
author = {Yu, TC and Kikawa, C and Dadonaite, B and Loes, AN and Englund, JA and Bloom, JD},
title = {Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40475658},
issn = {2692-8205},
abstract = {The evolution of human influenza virus hemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability. Epistasis shapes this evolution, as an antigenic mutation that is deleterious in one genetic background may become tolerated in another. However, the extent to which epistasis can alleviate pleiotropic conflicts between immune escape and protein function/stability is unclear. Here, we measure how all amino acid mutations in the HA of a recent human H3N2 influenza strain affect its cell entry function, acid stability, and neutralization by human serum antibodies. We find that epistasis has enabled emergence of antigenic mutations that were detrimental to HA's cell entry function in earlier strains. However, epistasis appears insufficient to overcome the pleiotropic costs of antigenic mutations that impair HA's stability, explaining why some mutations that strongly escape human antibodies never fix in nature. Our results refine our understanding of the mutational constraints that shape influenza evolution: epistasis can enable antigenic change, but pleiotropic effects can restrict its trajectory.},
}

@article {pmid40514010,
year = {2025},
author = {Kharfan-Dabaja, MA and Kumar, A and Pinilla-Ibarz, J and Brown, JR and Shadman, M and Awan, FT and Kenderian, SS and Siddiqi, T and Abramson, JS and Al-Juhaishi, T and Brander, DM and Coombs, CC and Furman, RR and Jain, N and Khan, N and Saba, NS and Collins, JM and Beitinjaneh, A and Stephens, DM and Woyach, J and Hamadani, M},
title = {Clinical practice recommendations on the role of allogeneic hematopoietic cell transplantation and chimeric antigen receptor T-cell therapy in patients with chronic lymphocytic leukemia on behalf of the American Society for Transplantation and Cellular Therapy.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.06.002},
pmid = {40514010},
issn = {2666-6367},
abstract = {Chimeric antigen receptor T-cell therapy (CAR T-cell) is a new treatment option for relapsed and/or refractory (R/R) chronic lymphocytic leukemia (CLL). Novel therapies including Bruton's tyrosine kinase inhibitors (BTK), covalent or non-covalent, and an inhibitor of the B-cell leukemia/lymphoma 2 protein (BCL-2), venetoclax, have replaced chemoimmunotherapy (CIT) regimens in the front-line and the R/R setting, and have relegated allogeneic hematopoietic cell transplantation (allo-HCT) to later treatment stages. Updating the 2016 clinical practice recommendations on allo-HCT in CLL is necessary to help guide contemporary clinical practice. A panel of 18 physicians with diverse expertise across different CLL treatment modalities and one methodologist participated in this effort. Any recommendation receiving ≥ 70% votes was considered a consensus. CAR T-cell therapy is recommended for patients not responding or relapsing after at least 2 lines of therapy consisting of a covalent BTK inhibitor and a BCL-2 inhibitor. In addition, CAR T-cell therapy is recommended for patients who subsequently received a non-covalent BTK inhibitor in the third-line or later setting, regardless of response. CAR T-cell therapy is also recommended in CLL relapsing after an allo-HCT, assuming that patients are fit for the procedure. In those CLL patients who are candidates, allo-HCT is recommended if disease is R/R to CAR T-cell therapy provided that an objective response is demonstrated prior to the allograft. Allo-HCT is also recommended in patients with clonally-related Richter transformation (RT) after demonstrating an objective response to front-line CIT or other treatments. CAR T-cell therapy is recommended in R/R RT. We emphasize the importance of enrolling patients in clinical trials whenever available to continue to advance the field and improve prognosis of R/R CLL. We acknowledge that there are unique clinical scenarios not covered herein which may require a case-by-case approach.},
}

@article {pmid40513563,
year = {2025},
author = {Khan, AT and Adebamowo, C and Fullerton, SM and Hirbo, J and Konigsberg, IR and Kraft, P and Martin, I and Nelson, SC and Ramsay, M and Wojcik, GL and Adebamowo, SN and Conomos, MP and Darst, BF and Hysong, MR and Li, Y and Martin, AR and Mathias, RA and Rich, SS and Sakoda, LC and Schrider, DR and Sharma, J and Smith, JL and Sun, Q and Zhang, Y and , and Gogarten, SM},
title = {A data model for population descriptors in genomic research.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2025.05.011},
pmid = {40513563},
issn = {1537-6605},
abstract = {Population descriptors used in genetic studies have broad social and translational implications. There are no globally agreed-upon definitions or usages of common population descriptors (e.g., race, ethnicity, nationality, and tribe), many of which are applied ad hoc and/or derived from political or bureaucratic conventions. Recent recommendations have encouraged the retention of as much granularity in population descriptors as possible during data preparation, analysis, and interpretation of research results. However, genomic research infrastructures (i.e., current practices, resources, and workflows in genomic research) often lack systematic and flexible organization, structure, and harmonization of multifaceted and detailed population descriptor data. This can lead to loss of information, barriers to international collaboration, and potential issues in clinical translation. Here, we describe a data model, developed by the NIH-funded Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium, that organizes and retains detailed population descriptor data for future research use. The model supports a versatile, traceable, and reproducible harmonization system that offers multiple benefits over existing data structures. This data model affords researchers the flexibility to thoughtfully choose and scientifically justify their choice of population descriptors. It avoids the conflation of social identities with biological categories and guards against harmful typological inferences. Genomic research tools of this kind will be crucial for producing scientifically robust findings that minimize potential harms of descriptor misuse while maximizing benefits for diverse communities.},
}