@article {pmid41929129,
year = {2026},
author = {Hedouin, S and Hu, C and Biggins, S},
title = {An interdependent Cbf1-CCAN interaction stabilizes the budding yeast kinetochore.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41929129},
issn = {2692-8205},
support = {R35 GM149357/GM/NIGMS NIH HHS/United States ; },
abstract = {Chromosome segregation requires the proper assembly of kinetochores on centromeric DNA. The kinetochore is a complex multi-protein machine comprising more than 40 distinct proteins, but the functional roles of many components remain unclear. One such protein is the yeast transcription factor Cbf1, which directly binds to budding yeast centromeric DNA. Loss of Cbf1 significantly increases the rate of chromosome missegregation, however its precise molecular mechanism of action is unknown. It was recently found that Cbf1 inhibits transcription through the centromere by preventing the untimely pericentromeric transcriptional readthrough via a roadblock mechanism. Intriguingly, restoring the transcriptional roadblock in the absence of Cbf1 binding only partially rescued chromosome missegregation, indicating that Cbf1 performs additional centromeric activities. Here, we show that Cbf1 promotes inner kinetochore assembly both in vitro and in vivo. This assembly function depends on the direct interaction between Cbf1 and Okp1. Moreover, we found that Cbf1's stable association with the centromere requires its interaction with the inner kinetochore, revealing an interdependent interaction essential for the assembly and stability of the kinetochore. Thus, Cbf1 functions as a centromere-anchored hub that couples transcriptional roadblocking to CCAN assembly and kinetochore stability.},
}

@article {pmid41959409,
year = {2026},
author = {Habel, JR and Nguyen, THO and de Alwis, N and Allen, EK and Li, S and Skinner, MJ and Juno, JA and Kent, SJ and Bond, K and Williamson, DA and Lappas, M and Hannan, NJ and Walker, S and Schroeder, J and Crawford, JC and Thomas, PG and Kedzierska, K and Rowntree, LC},
title = {High-dimensional multiomics reveals perturbations to IL-6/IL-6R axis and RUNX3 in CD4[+] T cells during third trimester pregnancy.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41959409},
issn = {2692-8205},
abstract = {OBJECTIVES: CD4[+] T cells play key roles in regulating immune responses during pregnancy, therefore we aimed to understand the CD4[+] T cell surface proteome and transcriptome during pregnancy.

METHODS: CD4[+] T cells were analysed in blood and decidua from term-pregnancies (>37 weeks), and non-pregnant blood. >350 surface proteins were screened via flow cytometry, and transcriptomes were analysed using single-cell RNA sequencing with >130 CITE-seq barcoded antibodies.

RESULTS: Surface protein screening identified changes to ILT4/CD85d, CD9, IFN-γ receptor β-chain, CX3CR1 and CCR5 in the pregnant blood and decidual CD4[+] T cells. CX3CR1 and CCR5 had the highest expression on the effector-memory T cell (TEM) subset in the blood, with expression consistent across subsets in decidua. CD126/IL-6R was lower in pregnant blood and decidual CD4[+] T cells, while scRNAseq identified enrichment in the IL-6R signalling pathway in naive CD4[+] T cells in pregnant blood. Both sIL-6R and IL-6 concentrations were increased in plasma during pregnancy, suggesting perturbations to the IL-6/IL-6R signalling axis. Meanwhile, decidual CD4[+] T cells had increased expression of transcription factor RUNX3 in the CD69[+] tissue-resident-like subset.

CONCLUSIONS: Our findings demonstrate altered molecular expression in CD4[+] T cells during pregnancy. This provides important mechanistic insight of their adaptation and regulation during placental development, which may drive placental dysfunction or pregnancy complications including preeclampsia, fetal growth restriction and stillbirth. These new data may inform future studies that focus on determining the significance of differentially-expressed immune features in pregnancy to identify potential targets for immune modulation to treat pregnancy complications and infections.},
}

@article {pmid41960310,
year = {2026},
author = {Mtisi, TJ and Montano, MA and Chagomerana, MB and Bula, A and Dunda, W and Mugisha, NM and Niyonzima, N and Nassolo, C and Weza, S and Madya, F and Mapanga, W and Joffe, M and Ndlovu, N and Borok, M and Ignacio, RB and Mugo, C},
title = {Application of Process Mapping to catalyze integration of HIV services in cancer care.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {41960310},
issn = {2693-5015},
abstract = {INTRODUCTION: The World Health Organization advocates for integrated health services in low- and middle-income countries, with special focus on care for non-communicable diseases within HIV care. HIV diagnosis and management with antiretroviral therapy (ART) are crucial components of whole-person care; in addition to improving overall survival, ART provides basic immunotherapy during cancer treatment. However, most cancer centers in Africa are not currently equipped to provide integrated HIV care. We conducted process mapping at referral cancer centers in Malawi, South Africa, Uganda, and Zimbabwe to identify mechanisms of integrating HIV care interventions within established cancer treatment processes.

METHODS: Our research consortium identified multidisciplinary clinical and non-clinical staff important to care delivery in four referral cancer hospitals and proximal HIV clinics. Consortium-level researchers met separately in-person or virtually with each site team to conduct training. High-level and detailed levels process maps were developed in process mapping sessions with diverse staff at each site and flow diagrams created to identify sites of opportunity for care integration within cancer centers.

RESULTS: Forty-five diverse clinical and non-clinical staff participated in the process across the 4 cancer centers. Several points were identified in which care integration was already occurring, including requesting HIV diagnostic and monitoring laboratory tests and clinical consideration of HIV in care plan development. While HIV care was already available in a clinic within the same hospital campus in Soweto and referral and results pathways were more integrated than the other 3 sites, none of the centers provided ART, and all lacked the capacity to provide HIV-specific counseling and management of ART or non-cancer HIV complications.

DISCUSSION: We identified multiple points at which persons in HIV care were referred for cancer treatment and where people in cancer treatment not previously known to be living with HIV or not currently on ART could be referred for HIV treatment. Some services, while not integrated, had appropriate pathways in place; for others, we identified intervention points to improve care integration of HIV services into the cancer centers. While each cancer center has distinct features, we identified general service points that could be interrogated for HIV care integration opportunities.},
}

@article {pmid42037377,
year = {2026},
author = {Sircy, LM and Stevens-Ayers, TL and Krantz, EM and Joncas-Schronce, L and Ozbek, NSO and Blazevic, RL and Mose, L and Kimball, LE and Basom, R and Dasgupta, S and Heit, A and Schmitz, F and Heckerman, D and Bender Ignacio, RA and Hill, JA and Boonyaratanakornkit, J and Boeckh, M and Waghmare, A},
title = {Assessing VirScan serosurvey epitope profiling variability between in-clinic venous blood draw and capillary blood self-sampling device.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0245425},
doi = {10.1128/spectrum.02454-25},
pmid = {42037377},
issn = {2165-0497},
abstract = {Timely and ongoing in-clinic sample collections are a common logistical barrier to volunteer participation and retention in longitudinal clinical studies. To remove this barrier, clinical studies have recently begun to implement the use of at-home capillary blood self-sampling devices in place of in-clinic venous blood draws for participant blood sample collection. Thus, we assessed antibody responses to a broad library of over 300 viral, bacterial, and fungal pathogens using VirScan immunoassay testing on adult volunteer capillary (serum) and venous (plasma) blood samples collected by Tasso devices and in-clinic venipunctures on the same day to determine whether self-sampling devices are a more practical and convenient alternative for future clinical studies. Most VirScan measurements of antibodies specific for clinically relevant respiratory viruses and herpesviruses had strong concordance between participant-matched Tasso and venipuncture blood samples. While we did not identify a systematic bias in most pathogen-specific antibody measurements associated with blood collection method, we did observe intrinsic VirScan inter-assay variability across some clinically relevant viruses. Together, our data demonstrate that capillary blood self-sampling devices are a practical alternative to in-clinic venipunctures for VirScan clinical research studies. However, these blood collection methods should not be used interchangeably within longitudinal studies to minimize the introduction of technical variables.IMPORTANCEOur study assessed whether capillary blood self-sampling devices could reliably replace in-clinic venous blood collection methods for the VirScan immunoassay, which can detect antibodies specific to hundreds of pathogens. Longitudinal studies requiring multiple in-clinic visits for sample collection often experience low volunteer retention because of the inconvenience of traveling to research sites. Allowing volunteers to use at-home self-sampling devices reduces the burden of travel for participants and increases access to outreach for volunteers who would otherwise not participate in research. Importantly, VirScan only requires a small sample volume, so blood self-sampling devices would be appropriate to use despite their volume collection limitations. Overall, capillary blood self-sampling devices can be a reliable and efficient method for research studies to investigate antibody responses longitudinally using VirScan. However, to limit the introduction of technical variables, collection methods should not be used interchangeably within a longitudinal study.},
}

@article {pmid42038100,
year = {2025},
author = {Wang, R and Dai, R and Huang, Y and Neuhouser, ML and Lampe, JW and Raftery, D and Tabung, FK and Zheng, C},
title = {Variable Selection with FDR Control for Noisy Data - An Application to Screening Metabolites that Are Associated with Breast Cancer and Colorectal Cancer.},
journal = {Journal of data science : JDS},
volume = {23},
number = {3},
pages = {499-520},
pmid = {42038100},
issn = {1680-743X},
abstract = {The rapidly expanding field of metabolomics presents an invaluable resource for understanding the associations between metabolites and various diseases. However, the high dimensionality, presence of missing values, and measurement errors associated with metabolomics data can present challenges in developing reliable and reproducible approaches for disease association studies. Therefore, there is a compelling need for robust statistical analyses that can navigate these complexities to achieve reliable and reproducible disease association studies. In this paper, we construct algorithms to perform variable selection for noisy data and control the False Discovery Rate when selecting mutual metabolomic predictors for multiple disease outcomes. We illustrate the versatility and performance of this procedure in a variety of scenarios, dealing with missing data and measurement errors. As a specific application of this novel methodology, we target two of the most prevalent cancers among US women: breast cancer and colorectal cancer. By applying our method to the Women's Health Initiative data, we successfully identify metabolites that are associated with either or both of these cancers, demonstrating the practical utility and potential of our method in identifying consistent risk factors and understanding shared mechanisms between diseases.},
}

@article {pmid42038745,
year = {2026},
author = {Bock, AM and Hao, P and Xu, Y and Luttwak, E and Thiruvengadam, SK and Sekaran, K and Sano, D and Vaughn, J and Sharp, J and Major, A and Patel, V and Smilnak, G and Araujo, N and Mynam, R and Reef, D and Palmeri, M and Gerber, D and Abhyankar, A and Baek, G and Falade, A and Iqbal, M and Hu, B and Geethakumari, PR and Durani, U and Di, M and Niu, A and Cherng, HJ and Rhodes, JM and Grover, N and Pophali, P and Feldman, T and Shanmugasundaram, K and Svoboda, J and Voorhees, T and Diefenbach, C and Karimi, Y and Karmali, R and Herrera, AF and Torka, P and Epperla, N},
title = {Nivolumab in combination with AVD as frontline treatment for patients with classic Hodgkin lymphoma: A real-world analysis from 20 US centers.},
journal = {HemaSphere},
volume = {10},
number = {4},
pages = {e70346},
pmid = {42038745},
issn = {2572-9241},
}

@article {pmid42039685,
year = {2026},
author = {Cho, BC and Nishio, M and Ahn, MJ and García-Campelo, R and Ponce, S and Baik, C and Salgia, R and Kim, SW and Lee, JS and Yoshida, T and Yu, HA and Goldberg, SB and Johannes de Langen, A and Le, X and Piotrowska, Z and Riess, JW and Tanaka, K and Ambrose, H and Cosaert, J and Fraenkel, PG and Tang, KH and Lehman, JM and Smith, P and Goldman, JW},
title = {Durvalumab Plus Chemotherapy in Patients With EGFR-Mutated Advanced NSCLC Whose Disease Progressed on First-Line Osimertinib: ORCHARD.},
journal = {JTO clinical and research reports},
volume = {7},
number = {4},
pages = {100937},
pmid = {42039685},
issn = {2666-3643},
abstract = {INTRODUCTION: ORCHARD (NCT03944772) was a phase II, biomarker-directed platform study designed to characterize resistance mechanisms and evaluate novel therapy combinations after progressive disease (PD) on first-line osimertinib. We report results of the module assessing durvalumab plus chemotherapy.

METHODS: Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with PD on first-line osimertinib whose tumors did not harbor a prespecified alteration by next-generation sequencing of a post-osimertinib biopsy, or for whom a biomarker-matched treatment was not available, were eligible. Patients received 4 to 6 cycles of durvalumab 1500 mg plus carboplatin target area under the curve 5 and pemetrexed 500 mg/m[2]. After platinum-based chemotherapy, patients without PD could continue to receive durvalumab plus pemetrexed maintenance. Primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator assessment.

RESULTS: Overall, 25 patients received more than or equal to 1 dose of durvalumab plus chemotherapy; all had discontinued treatment at the primary analysis data cutoff. Confirmed ORR was 16% (80% confidence interval [CI]: 7-30); response was maintained for more than 6 months in the four patients with confirmed response. Furthermore, 22 patients (88%) had PD and median progression-free survival was 4.8 months (95% CI: 2.6-7.6). Ten patients (40%) had died, and median overall survival was 23.4 months (95% CI: 8.8-not calculable). Nine patients (36%) had grade 3 or higher adverse events, most often neutrophil count decreased (20%).

CONCLUSIONS: Durvalumab plus chemotherapy demonstrated limited clinical benefit for EGFR-mutated NSCLC after PD on first-line osimertinib. Although the combination was well tolerated, the overall risk-benefit profile did not warrant further evaluation.},
}

@article {pmid42043297,
year = {2026},
author = {Rosero, M and Bai, J},
title = {AFD thermosensory neurons mediate tactile-dependent locomotion modulation in C. elegans.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
doi = {10.7554/eLife.106496},
pmid = {42043297},
issn = {2050-084X},
support = {R01NS109476/NS/NINDS NIH HHS/United States ; R01NS115974/NS/NINDS NIH HHS/United States ; T32GM136534/GM/NIGMS NIH HHS/United States ; F31NS129545/NS/NINDS NIH HHS/United States ; },
mesh = {Animals ; *Caenorhabditis elegans/physiology ; *Sensory Receptor Cells/physiology ; *Locomotion ; Cyclic GMP/metabolism ; *Touch ; Caenorhabditis elegans Proteins/metabolism/genetics ; Signal Transduction ; Taxis Response ; *Thermosensing ; },
abstract = {Sensory neurons drive animal behaviors by detecting environmental stimuli and relaying information to downstream circuits. Beyond their primary roles in sensing, these neurons often form additional synaptic connections outside their main sensory modality, suggesting broader contributions to behavior modulation. Here, we uncover an unexpected role for the thermosensory neuron AFD in coupling tactile experience to locomotion modulation in Caenorhabditis elegans. We show that while AFD employs cyclic guanosine monophosphate (cGMP) signaling for both thermotaxis and tactile-dependent modulation, the specific molecular components of the cGMP pathway differ between these two processes. Interestingly, disrupting the dendritic sensory apparatus of AFD, which is essential for thermotaxis, does not impair tactile-based locomotion modulation, indicating that AFD can mediate tactile-dependent behavior independently of its thermosensory apparatus. In contrast, ablating the AFD neuron eliminates tactile-dependent modulation, pointing to an essential role for AFD itself, rather than its sensory dendritic endings. Further, we find tactile-dependent modulation requires the AIB interneuron, which connects AFD to touch circuits via electrical synapses. Removing innexins expressed in AFD and AIB abolishes this modulation, while re-establishing AFD-AIB connections with engineered electrical synapses restores it. Collectively, these findings uncover a previously unrecognized function of AFD beyond thermosensation, highlighting its influence on context-dependent neuroplasticity and behavioral modulation through broader circuit connectivity.},
}

Animals
*Caenorhabditis elegans/physiology
*Sensory Receptor Cells/physiology
*Locomotion
Cyclic GMP/metabolism
*Touch
Caenorhabditis elegans Proteins/metabolism/genetics
Signal Transduction
Taxis Response
*Thermosensing

@article {pmid42044061,
year = {2026},
author = {Landovitz, RJ and Fogel, JM and Gao, F and Hanscom, B and Piwowar-Manning, E and Moser, A and Marzinke, MA and Cyktor, J and Seisa, M and Halvas, EK and Kofron, R and Jennings, A and Clement, M and Viet Tran, H and Gaur, A and Fichtenbaum, CJ and Asmelash, A and Soto-Torres, L and Rooney, JF and Rinehart, AR and Cohen, MS and Grinsztejn, B and Eshleman, SH},
title = {Prospective HIV RNA screening with long-acting cabotegravir pre-exposure prophylaxis in HPTN 083.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciag285},
pmid = {42044061},
issn = {1537-6591},
abstract = {BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention. However, breakthrough infections can occur, even with optimal adherence. We evaluated the performance of prospective HIV RNA screening in cisgender men and transgender women who have sex with men using long-acting injectable cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) in HPTN 083.

METHODS: In the Open Label Extension of HPTN 083, sites performed HIV rapid, antigen/antibody (Ag/Ab) and RNA testing at each visit. Results from site testing and retrospective HIV testing were used to determine final HIV status and identify the first HIV positive visit.

RESULTS: HIV RNA screening was associated with fewer diagnostic delays (7% vs. 47% of cases, p=0.02) and earlier treatment initiation (median 15 vs. 62 days, p=0.02). Drug resistance was less frequent with RNA screening (15% vs. 31% of cases, p=0.22). Five cases were first detected with RNA testing only. Sensitivity and specificity of RNA testing were 93% (95% CI: 76, 99) and 99.92% (95% CI: 99.88, 99.95), respectively. However, positive predictive value (PPV) was low overall (55%; 95% CI: 40, 69) and was lower if CAB-LA was administered <6 months earlier (29%; 95% CI: 13, 49). Some false positive RNA test results led to delay or discontinuation of CAB-LA injections.

CONCLUSIONS: HIV RNA screening improved clinical outcomes in the setting of CAB-LA PrEP, but the PPV for RNA screening was low which could compromise patient care.},
}

@article {pmid42044462,
year = {2026},
author = {Milano, F and Dahlberg, A and Pedersen, J and Roberts, L and Azure, A and Martin, L and Mazziotta, F and Hadland, B and Chapuis, AG and Delaney, C},
title = {Safety and Clinical Outcomes of Pooled Donor, Nonengrafting Expanded Progenitor Cells in Single-Unit Cord Blood Transplantation.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2502510},
doi = {10.1200/JCO-25-02510},
pmid = {42044462},
issn = {1527-7755},
abstract = {PURPOSE: Cord blood transplantation (CBT) is limited by delayed hematopoietic recovery leading to frequent use of double-unit grafts. This phase II study evaluated the safety of adding dilanubicel, a cryopreserved, cord blood (CB)-derived, non-human leukocyte antigen-matched expanded progenitor cell product generated from pooled donors to single-unit CBT.

MATERIALS AND METHODS: Between March 2022 and July 2025, we enrolled 28 patients with hematologic malignancies in this single-center phase II trial. The infusion of a matched single CB unit was followed by a target dose of 800 × 10[6] CD34[+] cells of dilanubicel. All patients received a myeloablative conditioning regimen and graft-versus-host disease (GVHD) prophylaxis consisting of cyclosporine and mycophenolate mofetil.

RESULTS: The median age was 36 years (range, 10-63). Underlying diagnoses included acute leukemias (n = 25) and other hematologic malignancies (n = 3). All patients engrafted neutrophils (median, 18 days; range, 14-30) and platelets (median, 31 days; range, 26-43). Dilanubicel induced transient myelomonocytic recovery, peaking on day 7 and absent by day 14. An early lymphocyte expansion, derived exclusively from the CB graft, occurred by day 9 and peaked by day 11. No grade 3 to 4 acute or chronic GVHD was observed. At a median follow-up of 1.4 years, 27 patients remain alive and disease-free. When evaluated alongside a contemporaneous institutional cohort receiving standard single- or double-unit CBT, patients treated with dilanubicel demonstrated faster hematopoietic recovery and a markedly lower incidence of severe acute GVHD.

CONCLUSION: The addition of dilanubicel to single-unit CBT demonstrated a favorable safety profile, with no severe acute or chronic GVHD, and was associated with excellent clinical outcomes. These findings support further investigation of this strategy.},
}

@article {pmid42044466,
year = {2026},
author = {Stepan, L and Ansari, S and Abramson, JS and Okal, A and Dell'Aringa, J and Thompson, EG and Crotta, A and Chow, VA and Kamdar, M and Solomon, SR and Johnston, PB and Glass, B and Mutsaers, P and Arnason, J and Mielke, S and Shadman, M and Hernandez-Ilizaliturri, F and Izutsu, K and Bachanova, V and Ibrahimi, S and Chabon, JJ and Kurtz, DM and Alizadeh, AA and Peiser, L},
title = {Circulating Tumor DNA Assessment of Disease Response in Large B-Cell Lymphoma: Lisocabtagene Maraleucel Versus Autologous Stem Cell Transplantation Standard Therapy.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2503051},
doi = {10.1200/JCO-25-03051},
pmid = {42044466},
issn = {1527-7755},
abstract = {We report correlative circulating tumor DNA (ctDNA) analyses from TRANSFORM (ClinicalTrials.gov identifier: NCT03575351) evaluating lisocabtagene maraleucel (liso-cel) versus standard of care (salvage immunochemotherapy, high-dose chemotherapy, autologous stem cell transplantation [ASCT]) in second-line large B-cell lymphoma (LBCL). ctDNA association with efficacy was investigated at predefined time points (random assignment, day 43, day 64, and day 126 [3 months after liso-cel, approximately 2 months after ASCT]) for 136 patients using ultrasensitive PhasED-Seq. ctDNA clearance (measurable residual disease [MRD][neg]) predicted longer event-free survival (EFS) at all time points in both arms, with significantly more liso-cel-treated patients achieving MRD[neg]. Liso-cel demonstrated superior outcomes versus ASCT, including longer EFS, progression-free survival (PFS), and duration of response among patients in complete response (CR) and MRD[neg]. ctDNA re-emergence in patients with CR after ASCT confirmed its potential in predicting relapse. MRD[neg] remained significantly associated with EFS after adjusting for positron emission tomography (PET) response, while interaction testing revealed a significant interaction between PET status and treatment arm for EFS. Liso-cel achieved deeper, more durable molecular clearance by ctDNA, consistent with superior EFS and PFS versus ASCT for second-line LBCL treatment. ctDNA-MRD provided prognostic value beyond PET, supporting its role as a complementary biomarker for treatment response and relapse prediction.},
}

@article {pmid42044624,
year = {2026},
author = {Wendel, SO and Brooke, GM and Hu, C and Sandoval, AR and Haratipour, P and Gu, L and Young, M and Zangi, M and Rasche, BL and Banerjee, NS and Jossart, J and Garvin, K and Geisbrecht, BV and Cianciolo, R and Cawley, J and Perry, JJP and Hickey, RJ and Malkas, LH and Wallace, NA},
title = {Targeting Cancer-Associated PCNA with AOH1996 Induces Mitotic Catastrophe and Enhances Cisplatin Therapy in Cervical Cancer.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-25-0648},
pmid = {42044624},
issn = {2767-9764},
abstract = {Cervical cancers (CaCx) remain a significant health burden. Limitations on CaCx chemotherapeutic intervention caused by toxic side effects are a persistent barrier to care. Here, we show that the human papillomavirus oncogenes that cause most CaCx also increase the levels of a cancer-associated isoform of PCNA known as caPCNA. The abundance of caPCNA is specifically elevated in CaCx. Similar to observations in other cancers, we found that a small molecule inhibitor of caPCNA (AOH1996) selectively killed cell line, organoid, and xenograft models of CaCx. Our subsequent molecular analysis identified a novel ability of AOH1996 to induce cell death by disrupting the interaction between PCNA and gamma tubulin, resulting in mitotic arrest. We show AOH1996 selectively induces mitotic death in transformed cells, because these cells attempt to progress through mitosis, rather than decondensing their chromosomes and reforming their nuclear membranes like untransformed control cells. Further, we show that these differences allow AOH1996 to specifically sensitize CaCx cells to cisplatin, a frontline chemotherapeutic used to treat CaCx. We found that subtherapeutic doses of AOH1996 and cisplatin could reduce CaCx xenograft growth and improve survival, similarly to a therapeutic dose of cisplatin without the cisplatin-induced toxicity that restricts care. To our knowledge, this study provides the first evidence that AOH1996 can function as a cisplatin-sensitizing agent in cervical cancer models.},
}

@article {pmid42045564,
year = {2026},
author = {Prentice, RL and Aragaki, AK},
title = {The semi-competing risk problem revisited.},
journal = {Lifetime data analysis},
volume = {32},
number = {2},
pages = {},
pmid = {42045564},
issn = {1572-9249},
mesh = {Humans ; Proportional Hazards Models ; Female ; Disease-Free Survival ; Incidence ; Cohort Studies ; Hormone Replacement Therapy ; Risk Assessment/methods ; },
abstract = {Clinical trials and cohort studies often aim to assess treatment effects or exposure associations in relation to the risk of one or more diseases, with death of the study participant as a competing risk. If the diseases under study are major health concerns, it may not be appropriate to assume that death acts as an independent source of right-censoring. When this occurs, a summary of treatment or exposure influences should consider disease incidence and death jointly. Here we consider some modeling approaches to doing so, starting with type-specific (cause-specific) hazard functions. We also model marginal hazard rates for disease-free survival and death, along with their dual outcome hazard functions, with emphasis on Cox models for each hazard function. Furthermore, a simple hazard ratio summary statistic is proposed for covariate effects on disease incidence and death jointly. Analyses of data from the Women's Health Initiative hormone therapy trials provide illustration.},
}

Humans
Proportional Hazards Models
Female
Disease-Free Survival
Incidence
Cohort Studies
Hormone Replacement Therapy
Risk Assessment/methods

@article {pmid41929033,
year = {2026},
author = {Andrews, KR and Chang, J and Roemer, C and Hadfield, J and Lin, V and Brito, AF and Daodu, RO and Joia, IA and Kistler, K and Li, A and Moncla, LH and Paredes, MI and Kühnert, D and Torres, LM and Voitl, L and Aksamentov, I and Hodcroft, EB and Huddleston, J and McCrone, JT and Anderson, JSJ and Sibley, TR and Lee, J and Neher, RA and Bedford, T},
title = {Nextstrain automates real-time phylodynamic analysis of open data for endemic and emerging pathogens.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41929033},
issn = {2692-8205},
abstract = {MOTIVATION: Genome sequencing provides an exceptional window into the evolutionary and epidemiological dynamics of endemic and emerging pathogens, and thus allows for better, more targeted, public health interventions. Online genomic surveillance platforms can provide near real-time insight into these dynamics.

RESULTS: Nextstrain provides continually updated real-time genomic surveillance for 21 viruses and the bacterial pathogen Mycobacterium tuberculosis, with most analyses relying solely on open sequence data. Each pathogen includes steps to fetch and curate open data, classify sequences using established nomenclature systems, perform phylodynamic analyses, and share the results publicly. These analyses are automated, with most running daily to provide continually updated snapshots of pathogen evolution.

All source code is available at https://github.com/nextstrain. Phylodynamic results can be visualized and downloaded at https://nextstrain.org/pathogens, and open sequence data and curated metadata are available at https://nextstrain.org/pathogens/files.},
}

@article {pmid41929074,
year = {2026},
author = {Yang, Q and Padilla-Galvez, M and Uhl, S and Eggenberger, J and Kogut, S and Becker, S and Chen, S and Rosenberg, BR and Blanco-Melo, D},
title = {Pluripotency Factors Modulate Interferon Signaling in Embryonic Stem Cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41929074},
issn = {2692-8205},
abstract = {Despite lacking a robust interferon response, pluripotent stem cells remain highly resistant to viral infection, in part through the constitutive expression of immune genes traditionally classified as interferon-stimulated genes. While interferon signaling has been shown to be incompatible with the maintenance of pluripotency, the molecular mechanisms underlying this relationship remain poorly understood. Here, we investigate the transcriptional response of human embryonic stem cells (hESCs) to infection with a potent activator of the interferon response, an influenza A virus mutant lacking the viral NS1 protein. Single-cell RNA sequencing revealed that while most hESCs remain unresponsive to infection, a distinct subpopulation expresses type I and III interferons. Notably, only interferon-expressing cells mounted a robust antiviral response, characterized by strong induction of interferon-stimulated genes. In contrast to the bulk hESC population, interferon responding cells exhibited reduced expression of core pluripotency factors as well as negative regulators of interferon signaling, such as SOCS1 and SPRY4. Depletion of SOCS1 enabled hESCs to respond robustly to interferon stimulation, showing that this negative regulator is a key suppressor of interferon signaling in pluripotent stem cells. We further show that SOCS1 and additional negative regulators of IFN signaling are intrinsically expressed in hESCs and are transcriptionally controlled by pluripotency factors, such as NANOG, SOX2 and OCT4. Together, our findings support a model in which pluripotency factors regulate intrinsic immune gene expression, including negative regulators of interferon signaling, thereby suppressing canonical interferon signaling to preserve pluripotency while maintaining antiviral resistance.},
}

@article {pmid42028578,
year = {2026},
author = {Eaton, EJ and Wick, BJ and Chacón, JS and Wang, AJ and Kluesner, M and Barnes, JT and Kar, B and Wang, M and Johnson, MJ and Skeate, JG and Webber, BR and Moriarity, BS},
title = {Adenine base editor for knockout of proteins: A practical guide from design to analysis with updated MultiEditRbatch.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {2},
pages = {102908},
pmid = {42028578},
issn = {2162-2531},
abstract = {Adenine base editors (ABEs) are a promising yet underutilized tool for inducing protein knockout compared to Cas9 nuclease, owing in part to a lack of user-friendly platforms for reagent design and implementation. Here, we present a comprehensive workflow to achieve high-efficiency gene knockouts with ABE as an alternative to Cas9 nuclease-based approaches. This includes optimized guide RNA (gRNA) design using SpliceR, a web-based application, followed by genomic and functional validation of ABE-mediated knockouts for several target genes. We validated gRNAs for 14 immunologically relevant targets, using both NGG and NG PAM compatible ABE8e-variants in primary immune cells. To facilitate data analysis, we developed MultiEditRbatch, an updated version of MultiEditR as a user-friendly analysis tool with addition of batch mode for high-throughput analysis of Sanger sequencing data. MultiEditRbatch is available as a web-based application and an R package, enabling robust assessment of base editing outcomes.},
}

@article {pmid42030147,
year = {2026},
author = {Ukogu, OA and Montague, Z and Altan-Bonnet, G and Nourmohammad, A},
title = {Design principles of the cytotoxic CD8[+] T cell response.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {17},
pages = {e2528202123},
doi = {10.1073/pnas.2528202123},
pmid = {42030147},
issn = {1091-6490},
support = {2045054//National Science Foundation (NSF)/ ; R35 GM142795/GM/NIGMS NIH HHS/United States ; ZIA BC 012007//HHS | NIH | National Cancer Institute (NCI)/ ; },
mesh = {Animals ; Mice ; *T-Lymphocytes, Cytotoxic/immunology ; *CD8-Positive T-Lymphocytes/immunology ; Lymphocyte Activation/immunology ; *Models, Immunological ; Humans ; },
abstract = {Cytotoxic T lymphocytes eliminate infected or malignant cells, safeguarding surrounding tissues. Although experimental and systems-immunology studies have cataloged many molecular and cellular actors involved in an immune response, the design principles governing how the speed and magnitude of T cell responses emerge from cellular decision-making remain elusive. Here, we recast the T cell response as a feedback-controlled program, wherein the rates of activation, proliferation, differentiation, and death are regulated through antigenic, pro- and anti-inflammatory cues. By exploring a broad class of feedback-controller designs as potential immune programs, we demonstrate how the speed and magnitude of T cell responses emerge from optimizing signal-feedback to protect against diverse infection settings. We recover an inherent trade-off: infection clearance at the cost of immunopathology. We show how this trade-off is encoded into the logic of T cell responses by hierarchical sensitivity to different immune signals. Notably, we find the designs that balance harm from acute infections and autoimmunity produce immune responses consistent with the experimentally observed patterns of T cell effector expansion in mice. Extending our model to immune-based T cell therapies for cancer tumors, we quantify the trade-off between the affinity for tumor antigens ("quality") and the abundance ("quantity") of infused T cells necessary for effective treatment. Finally, we show how therapeutic efficacy can be improved by targeted genetic perturbations to T cells. Our findings offer a unified control-logic for cytotoxic T cell responses and point to specific regulatory programs that can be engineered for more robust T cell therapies.},
}

Animals
Mice
*T-Lymphocytes, Cytotoxic/immunology
*CD8-Positive T-Lymphocytes/immunology
Lymphocyte Activation/immunology
*Models, Immunological
Humans

@article {pmid42030410,
year = {2026},
author = {Omole, TE and Nguyen, HM and Marcinow, A and Jahan, N and Severini, G and Naicker, N and Thomas, K and Celum, C and Mugo, N and Mujugira, A and Kublin, J and Corey, L and Sivro, A and Lingappa, J and Gray, G and McKinnon, LR},
title = {Pre-Human Immunodeficiency Virus (HIV) infection Th17 CD4+ T cells as predictors of early HIV disease progression.},
journal = {PLoS pathogens},
volume = {22},
number = {4},
pages = {e1013852},
doi = {10.1371/journal.ppat.1013852},
pmid = {42030410},
issn = {1553-7374},
abstract = {Interleukin-17-producing T helper (Th17) CD4+ T cells are highly susceptible to HIV infection and are depleted early in people living with HIV. Here, we investigated whether systemic Th17 cell levels prior to HIV infection are associated with subsequent HIV disease progression. We analyzed archived cryopreserved peripheral blood mononuclear cells (PBMCs) collected within one year prior to HIV acquisition from participants enrolled in a South African cohort (HIV Vaccine Trials Network [HVTN] 503; n = 35) and an East African cohort (Partners Pre-exposure Prophylaxis/Couples' Observational Study [PP/COS]; n = 32). Th17 cell frequencies were quantified by flow cytometry. In HVTN 503, higher pre-HIV IL-17+ CD4+ T cell frequencies were inversely correlated with CD4/CD8 ratio measured both within 180 days (Spearman rank rs = -0.42, p = 0.012) and ≥180 days (rs = -0.55, p = 0.001) after HIV infection, and were associated with faster CD4+ T cells decline (adjusted hazard ratio [aHR] = 3.5, 95% CI: 1.2 - 9.9, p = 0.020). In contrast, no significant association with CD4 decline was observed in the PP/COS cohort (HR = 1.2, 95% CI: 0.4 - 3.4, p = 0.795). Sex-stratified analyses in HVTN 503 indicated a more pronounced association between pre-HIV IL-17+ CD4+ T cells and faster CD4 decline in males than females. In analyses combining all cohorts, higher pre-HIV IL-17+ CD4+ T cell frequencies remained associated with faster CD4 decline, particularly among younger participants (HR = 3.5; 95% CI: 1.35 - 9.22, p = 0.010). Pre-HIV IL-17+ CD4+ T cell frequencies were not associated with peak or set-point viral load in either cohort. Together, these findings suggest that pre-HIV Th17 cells abundance may influence subsequent HIV disease progression independently of early viral replication.},
}

@article {pmid42031341,
year = {2026},
author = {Chalitsios, CV and Chan, WC and Markozannes, G and Aglago, EK and Berndt, SI and Buchanan, DD and Campbell, PT and Cao, Y and Dimou, N and Drew, DA and French, AJ and Gallinger, S and Georgeson, P and Giannakis, M and Gruber, SB and Gunter, MJ and Harrison, TA and Brenner, H and Hoffmeister, M and Urruchúa-Rodríguez, MJ and Hsu, L and Huang, WY and Hullar, MAJ and Huyghe, JR and Jenkins, MA and Jayasekara, H and Moreno, V and Newton, CC and Nowak, JA and Obón-Santacana, M and Ogino, S and Pellatt, AJ and Peoples, A and Qu, C and Schmit, SL and Steinfelder, RS and Sun, W and Thomas, CE and Toland, AE and Trinh, QM and Ugai, T and Um, CY and Van Guelpen, B and Zaidi, SH and Peters, U and Phipps, AI and Tsilidis, KK},
title = {Alcohol consumption and molecular subtypes of colorectal cancer: Pooled observational and Mendelian randomisation analyses.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {101308},
doi = {10.1016/j.ajcnut.2026.101308},
pmid = {42031341},
issn = {1938-3207},
abstract = {BACKGROUND: Alcohol consumption is associated with colorectal cancer (CRC) risk, yet its association with distinct molecular subtypes remains unclear. Clarifying this could reveal insights into alcohol's carcinogenic mechanisms.

OBJECTIVE: We examined the association between alcohol consumption and the risk of CRC subtypes defined by individual tumour markers (and marker combinations), namely microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, BRAF and KRAS mutations.

METHODS: Pooled observational (ncases=11,826, ncontrols=10,888; nstudies=10) and genome-wide association data (ncases=8,178, ncontrols=10,472; nstudies=10) were utilised. Multivariable logistic regression models and Mendelian randomisation (MR) analyses were conducted to assess the association between alcohol consumption, modelled in MR as genetically predicted average drinks per week per one standard deviation increase (≈2.9 drinks/week), and risk of CRC subtypes defined by individual tumour markers (and marker combinations). Case-only analyses tested for differences between molecular subtypes. Bonferroni correction was applied for multiple tests.

RESULTS: Among drinkers, each additional 14 g/day of alcohol was associated with a 10% higher CRC risk (OR=1.10; 95%CI: 1.07, 1.13), but this association was primarily driven by heavy alcohol consumption (>28g/d). Including non-drinkers revealed a J-shaped association (Pnon-linearity=0.002). The associations with higher alcohol consumption were stronger in males compared to females. No significant heterogeneity was observed across MSI, CIMP, BRAF, or KRAS-defined subtypes. All associations were similar across smoking status, folate intake, tumour anatomical site, study design, early/late onset CRC, and across individual studies (Pheterogeneity>0.05). MR analyses supported that higher genetically predicted alcohol consumption was associated with CRC risk (ORIVW-per 1SD=1.25; 95%CI: 1.01, 1.57), but similarly to the observational analysis, without evidence of heterogeneity across molecular subtypes.

CONCLUSIONS: Heavy alcohol consumption may initiate colorectal carcinogenesis through mechanisms that operate across all examined molecular pathways for CRC. Although the largest available data were used, power is lower for subtype heterogeneity analyses, and modest interaction effects cannot be excluded.},
}

@article {pmid42031598,
year = {2026},
author = {Pluguez-Turull, CW and Koshy, J and McBee, MP and Oluyemi, E and Lam, DL and Desoky, SM and Desouches, SL and Siddiqui, S and Lodhi, T and Capiro, N and Agarwal, V and Kongara, T and Lampen-Sachar, K and Hui, LT and Choe, AI},
title = {Optimizing Timeliness of Healthcare Delivery in Diagnostic Radiology at U.S. Academic Centers.},
journal = {Academic radiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.acra.2026.03.057},
pmid = {42031598},
issn = {1878-4046},
abstract = {RATIONALE AND OBJECTIVES: Timely radiology access is essential for accurate diagnosis, treatment planning, and efficient care delivery. U.S. academic health centers face distinctive pressures, including workforce shortages, complex workflows, health inequities, and the need to balance trainee education with increasing clinical demand.

MATERIALS AND METHODS: This article summarizes consensus conclusions and literature review findings from the Radiology Research Alliance task force on optimizing healthcare delivery in U.S. academic centers. Task force members reviewed operational and systemic contributors to delayed imaging access and radiology report turnaround time (RTAT), with attention to disparities, workflow design, trainee involvement, and emerging artificial intelligence (AI) applications.

RESULTS: Delays in radiology care arise from social and insurance-related barriers, staffing shortages, workflow inefficiencies, and reporting delays. Underserved populations experience reduced access to preventive imaging, which may be improved through culturally tailored outreach, frontline staff engagement, and patient navigation. In academic settings, RTAT is influenced by image transmission, case complexity, reporting practices, and trainee participation. Evidence suggests that structured reporting, subspecialty or optimized workflow organization, critical results notification, and dual-reader trainee-attending models can improve efficiency while maintaining educational value. AI and machine learning (ML) show promise for clinical decision support (CDS), scheduling, no-show reduction, risk prediction, workflow optimization, and demand forecasting.

CONCLUSION: Improving radiology delivery in academic centers requires coordinated system-level strategies that address equity, staffing, workflow, and reporting efficiency. Thoughtful integration of AI, alongside operational redesign that preserves trainee development, can help academic radiology advance timely, high-quality, and equitable care.},
}

@article {pmid42031709,
year = {2026},
author = {Brcic, A and Lalic, H and Smoljo, T and Bardač, K and Dembitz, V and Penker, R and Rodriguez Blanco, G and Bedalov, A and Visnjic, D},
title = {Roles of RRM2 and RRM2B in pyrimidine stress responses and differentiation of acute myeloid leukemia cells.},
journal = {Cell death discovery},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41420-026-03105-y},
pmid = {42031709},
issn = {2058-7716},
support = {IP-2022-10-9146//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; DOK-2020-01-2873//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; DOK-NPOO-2023-10-9321//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; DOK-2025-02-6776//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; DOK-NPOO-2023-10-9321//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; HRZZ IP-2022-10-9146//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; HRZZ IP-2022-10-9146//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; DOK-2025-02-6776//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; EHA Innovation Award//European Hematology Association (EHA)/ ; RO1 GM117446//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {Differentiation therapy offers a promising approach in acute myeloid leukemia (AML) by overcoming the developmental block that maintains leukemic blasts. Increasing evidence indicates that DNA replication stress can promote differentiation rather than cytotoxicity; however, the metabolic mechanisms linking replication stress to differentiation remain poorly defined. Here, we investigated how perturbations in nucleotide metabolism regulate replication stress-driven differentiation. Using metabolomic and functional analyses in AML cell lines, we show that agents inducing differentiation through replication stress, including 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr), dihydroorotate dehydrogenase (DHODH) inhibition, and low-dose cytarabine, converge on disruption of nucleotide pool balance. Low-dose AICAr induced a pyrimidine-purine imbalance, S phase arrest, and enhanced differentiation, whereas high-dose reduced these effects. Although brequinar and cytarabine altered nucleotide metabolism through distinct mechanisms, differentiation induced by all agents was abolished by supplementation with high levels of ribo- and deoxyribonucleosides, confirming that nucleotide imbalance is a central driver. We further identify ribonucleotide reductase (RNR) as a critical modulator of this process. Replication stress induced context-dependent regulation of RNR subunits, with RRM2 upregulated in p53-mutant U937 cells and the p53-responsive RRM2B isoform predominating in p53-wild-type MOLM-13 cells. Consistent with these differences, RRM2 depletion enhanced differentiation in U937 cells without affecting viability but impaired differentiation and survival in MOLM-13 cells. These findings position nucleotide metabolism as a key regulator of AML differentiation and suggest that combining RNR-targeted and checkpoint-modulating strategies could optimize therapeutic responses.},
}

@article {pmid41959482,
year = {2026},
author = {Jurasin, AC and Frank, AR and Biggins, S},
title = {Proteomics reveals extensive phosphoregulation of outer kinetochore protein KNL1.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41959482},
issn = {2692-8205},
abstract = {Microtubules attach to kinetochores to facilitate chromosome movement to opposite spindle poles. Defective kinetochore-microtubule attachments lead to phosphorylation of the outer kinetochore protein KNL1 at conserved MELT motifs, which triggers spindle assembly checkpoint activation and recruitment of the fibrous corona. To identify additional phosphorylation sites that regulate kinetochores, we treated HEK 293T/17 cells with nocodazole, paclitaxel, or STLC to create defective kinetochore-microtubule attachment states. We then purified KNL1 and performed proteomics and identified 111 phosphorylation sites on KNL1, including several that may be attachment-state specific. These data demonstrate that KNL1 is extensively phosphoregulated in response to treatment with microtubule-disrupting compounds.},
}

@article {pmid42021259,
year = {2026},
author = {Yu, EY and Wesselius, A and Mehrkanoon, S and Goosens, M and Brinkman, M and van den Brandt, P and Grant, EJ and White, E and Weiderpass, E and Le Calvez-Kelm, F and Gunter, MJ and Huybrechts, I and Riboli, E and Tjonneland, A and Masala, G and Giles, GG and Milne, RL and Zeegers, MP},
title = {Correction: Vegetable intake and the risk of bladder cancer in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study.},
journal = {BMC medicine},
volume = {24},
number = {1},
pages = {},
pmid = {42021259},
issn = {1741-7015},
}

@article {pmid42021581,
year = {2026},
author = {Banerjee, R and Mohan, M and Shah, B and Prince, P and Gautam, N and Beebe, E and Pajerowski, W and Cantu, C and Meiseles, H and Hughes, D and Nador, G and Sandin, R and Hlavacek, P and Li, B and Meche, A and Hyun Kim, C and Perez Cruz, I and Sumaya, M and DiBonaventura, M},
title = {Real-world treatment patterns and outcomes of patients with multiple myeloma initiating elranatamab: results from the ALTITUDE-1 and ALTITUDE-2 retrospective cohort studies.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/14796694.2026.2662504},
pmid = {42021581},
issn = {1744-8301},
abstract = {BACKGROUND AND AIM: Elranatamab is a bispecific antibody currently approved in the United States (US) for the treatment of relapsed/refractory multiple myeloma (MM). Given its recent approval, real-world data are limited.

METHODS: Results from two real-world (RW) studies using administrative claims (ALTITUDE-1) and fee-for-service data (ALTITUDE-2) are collectively reported here. US patients with MM who initiated elranatamab after August 2023 were included and followed through September/October 2025. Patient characteristics, clinical history, treatment patterns, and effectiveness outcomes were reported.

RESULTS: One hundred and eighty-three and 391 patients were included from ALTITUDE-1 and -2, respectively. Median ages were 73 and 75, 43.2% and 33.0% were penta-drug exposed, and 17.5% and 21.0% were previously BCMA-exposed, respectively. RW treatment patterns showed less frequent dosing (27.9 and 27.1 elranatamab vials used per year) compared with expected on-label dosing (39 vials per year). Neither median time-to-next-treatment or death or median overall survival were reached; landmark analyses for each study estimated 70.0% (ALTITUDE-1) and 60.7% (ALTITUDE-2) of patients alive at 18 months.

CONCLUSION: US patients treated with elranatamab in the RW setting were heavily pre-treated. RW treatment patterns suggest less frequent administration of elranatamab compared with the label and effectiveness consistent with clinical trial results (MagnetisMM-3 trial [NCT04649359]).},
}

@article {pmid42023116,
year = {2026},
author = {Bender Ignacio, R and Rowan, K and Cook, D},
title = {Correction: How would Marie Kondo design a protocol? In favor of subtractive change in clinical trials.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1838161},
doi = {10.3389/fmed.2026.1838161},
pmid = {42023116},
issn = {2296-858X},
abstract = {[This corrects the article DOI: 10.3389/fmed.2026.1776929.].},
}

@article {pmid42023513,
year = {2026},
author = {Goel, U and Dragomirescu, C and Zanwar, S and Cassano, RC and Cicero, KI and Cowan, AJ and Banerjee, R and Anwer, F and Khouri, J and Dima, D},
title = {Functional high-risk phenotype predicts poor survival in multiple myeloma independent of front-line treatment: A secondary analysis of CIBMTR data.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70490},
pmid = {42023513},
issn = {1365-2141},
support = {//American Society of Hematology/ ; },
abstract = {Functional high-risk (FHR) multiple myeloma (FHRMM) is often defined as progression within 12-24 months of front-line autologous hematopoietic stem cell transplantation (AHSCT). For patients with early progression after suboptimal front-line therapies, it is challenging to assign the disease progression to a true FHR phenotype versus less effective front-line therapy. In this study, we combined data from three Center for International Blood and Marrow Transplant Research studies (MM18-02, MM19-01 and MM20-03). We included patients who received front-line AHSCT between 2008 and 2018 and had progression <12 (FHR12, n = 465), <18 (FHR18, n = 672) or <24 months (FHR24, n = 853) after AHSCT. We classified induction therapy as standard lenalidomide-containing triplets (bortezomib, lenalidomide, dexamethasone [VRD]/carfilzomib, lenalidomide, dexamethasone [KRD]) versus other (bortezomib, thalidomide, dexamethasone [VTD]/bortezomib, cyclophosphamide, dexamethasone [VCD]/bortezomib, dexamethasone [VD]/lenalidomide, dexamethasone [RD]) and studied the impact of front-line therapy on post-FHR overall survival (OS). In the FHR12 cohort (follow-up 48 months), the OS after VRD/KRD (n = 238) was 21 versus 17 months with other regimens (n = 227, hazard ratio [HR] = 1.2, 95% confidence interval [CI]: 0.6-1.06). In a multivariable model, the HR for OS was 0.94 (95% CI: 0.7-1.3, p = 0.69) for VRD/KRD versus other regimens. There was no significant interaction between type of first-line (1L) therapy and time from 1L AHSCT to first relapse in predicting OS. Similar results were seen for FHR18 and FHR24. FHRMM remains a negative prognostic factor irrespective of front-line therapy and warrants consideration of T-cell engagers' second-line therapy.},
}

@article {pmid42024416,
year = {2026},
author = {Unger, JM and Hershman, DL},
title = {Reassessing Treatment Outcomes Following Immune-Related Adverse Events-Reply.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2026.0785},
pmid = {42024416},
issn = {2374-2445},
}

@article {pmid42024654,
year = {2026},
author = {Korber, B and Seaman, MS and Mkhize, NN and Greene, K and Gao, H and Shen, X and Domin, E and Tang, H and Theiler, J and Wagh, K and Moore, PL and Williamson, C and Mullins, JI and Doria-Rose, NA and Montefiori, D and Giorgi, EE},
title = {Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.},
journal = {PLoS pathogens},
volume = {22},
number = {4},
pages = {e1013739},
doi = {10.1371/journal.ppat.1013739},
pmid = {42024654},
issn = {1553-7374},
mesh = {Humans ; *HIV-1/immunology ; *HIV Antibodies/immunology ; *HIV Infections/immunology/virology/prevention & control ; *env Gene Products, Human Immunodeficiency Virus/immunology ; *AIDS Vaccines/immunology ; *B-Lymphocytes/immunology ; *Antibodies, Neutralizing/immunology ; *Broadly Neutralizing Antibodies/immunology ; Cell Lineage/immunology ; },
abstract = {Although a protective HIV-1 vaccine has not yet been realized, significant progress has been made in vaccine designs that trigger B cell lineages with potential to produce broadly neutralizing antibodies (bnAbs). Advancing these strategies by optimizing vaccine boosting regimens requires early detection of maturing antibodies with neutralizing activity against native envelope glycoprotein (Env) trimers and streamlined strategies to identify antibodies as they begin to manifest desired levels of breadth and potency. Thus, we designed three types of pseudovirus screening panels based on Envs of contemporary HIV-1 isolates to facilitate detection of bnAb lineages that are on favorable trajectories during a vaccination course. The panels were selected from Tier 2 Transmitted Founder Lineage (TFL) HIV-1 Envs from placebo participants in the Antibody Mediated Prevention (AMP) efficacy trials. Using 15 bnAbs to evaluate the neutralization sensitivity of the viruses, we selected 8-member bnAb class-specific panels most sensitive to bnAbs representing their class: V2-apex, V3-glycan, CD4-receptor binding site (CD4bs), Membrane-Proximal External Region (MPER), or fusion peptide (FP). Next, we combined the most sensitive viruses among the class-specific panels to create a 12-virus panel to enable optimal detection of low-titer bnAb activity across epitope specificities. Finally, as HIV-1 continues to evolve greater levels of antigenic diversity and as current global pseudoviruses bnAb panels rely on viruses collected more than twenty years ago, we showed the importance of using contemporary viral panels to assess bnAb breadth and potency and designed a 12-virus panel representative of the spectrum neutralization profiles among AMP placebo viruses. We characterized pseudoviruses bearing each selected Env using standardized human sera to confirm their Tier 2 status and biological relevance. These updated panels enable sensitive screening of neutralization activity in vaccine studies and can also provide a realistic assessment of the expected breadth and potency of maturing responses against contemporary HIV-1 Envs.},
}

Humans
*HIV-1/immunology
*HIV Antibodies/immunology
*HIV Infections/immunology/virology/prevention & control
*env Gene Products, Human Immunodeficiency Virus/immunology
*AIDS Vaccines/immunology
*B-Lymphocytes/immunology
*Antibodies, Neutralizing/immunology
*Broadly Neutralizing Antibodies/immunology
Cell Lineage/immunology

@article {pmid42025961,
year = {2026},
author = {Hajibandeh, S and Tao, YA and Hsieh, MH and Liu, HG and Cheng, YF and Lee, KH and Hsieh, SY and Lu, CH},
title = {Semaglutide for obesity management: A narrative review of efficacy, safety, and future directions.},
journal = {Journal of the American Pharmacists Association : JAPhA},
volume = {},
number = {},
pages = {103117},
doi = {10.1016/j.japh.2026.103117},
pmid = {42025961},
issn = {1544-3450},
abstract = {BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide, have demonstrated substantial efficacy for glycemic control and weight management and are increasingly prescribed across diverse populations. Rapid expansion of indications, formulations, and real-world use has outpaced comprehensive evaluation of long-term safety, tolerability, and adherence, raising important concerns for clinical practice.

OBJECTIVES: This narrative review aims to synthesize current evidence on the efficacy and safety profile of semaglutide, with a focus on adverse events, treatment persistence, perioperative considerations, and use in special populations, to support clinical decision-making and pharmacist-led patient care.

METHODS: A review of clinical trials, observational studies, pharmacovigilance reports, regulatory communications, and professional guidelines was conducted. Evidence was drawn from randomized controlled trials, post-marketing safety reports, systematic reviews, and relevant clinical and regulatory documents.

RESULTS: From 1525 records, 34 studies and reports were included. Clinical trials consistently demonstrated meaningful weight reduction with semaglutide. Evidence regarding acute pancreatitis remains limited, although cases have been reported in clinical trials and postmarketing safety analyses. Evidence regarding suicidal ideation associated with semaglutide is mixed, with some analyses suggesting potential safety signals while others report no increased risk. Recent multi society clinical guidelines have addressed perioperative management of GLP-1 RAs, generally supporting individualized perioperative assessment. Emerging literature also examines semaglutide use in special populations, including patients with Alzheimer disease and individuals following bariatric surgery, although long-term neurologic and post-bariatric safety outcomes remain incompletely characterized.

CONCLUSIONS: Semaglutide represents an important therapeutic option for chronic weight management. As clinical use expands, continued evaluation of long-term safety, tolerability, and treatment persistence will be important. Pharmacists play a key role in counseling patients, monitoring adverse effects, supporting adherence, and contributing to multidisciplinary obesity care.},
}

@article {pmid42016169,
year = {2026},
author = {Schuster, DJ and Li, SS and Mielke, D and Seaton, KE and Brackett, C and Li, K and Shen, X and Wesley, MS and Eisel, N and Yates, NL and Zhang, L and Sawant, S and De Rosa, SC and Cohen, KW and Stanfield-Oakley, S and Sholukh, AM and Germain, RS and Li, X and Hu, J and Premkumar, L and Gallardo-Cartagena, JA and Randhawa, AK and Dennison, SM and Hural, JA and Corey, L and Karuna, S and McElrath, MJ and Ferrari, G and Hyrien, O and Tomaras, GD},
title = {Coordinated immune response distinguishes duration of SARS-CoV-2 viral particle shedding in humans.},
journal = {iScience},
volume = {29},
number = {4},
pages = {115277},
pmid = {42016169},
issn = {2589-0042},
abstract = {SARS-CoV-2 acquisition induces a spectrum of COVID-19 disease severity and duration among people. Prolonged viral antigen shedding (PVS) is defined as when a person tests positive by direct antigen tests performed a minimum of 21 days apart. It is unclear why some people exhibit delayed SARS-CoV-2 viral antigen clearance. In this cross-sectional observational study enrolling vaccine naive adults from the USA and Peru following recovery from SARS-CoV-2 acquisition, we examined a suite of blood-derived immune measures to understand differences between participants with PVS (n = 36) and without PVS (non-PVS, n = 223). While PVS participants demonstrated lower overall SARS-CoV-2-specific antibody magnitudes, over-representation analysis revealed that immune feature magnitude alone could not fully explain cohort differences. Hierarchical clustering and network analyses identified more highly coordinated antibody responses, T cell activation, and Fc-mediated function among non-PVS compared to PVS participants. These findings link control of viral antigen shedding to a coordinated immune response.},
}

@article {pmid42016725,
year = {2026},
author = {Gold, RS and Henrikson, NB and Issaka, RB and Gillespie, EF and Schuttner, L and Weiner, BJ and Marcotte, LM},
title = {How and Under What Conditions Do Patient Portals Improve Cancer Screening Completion: A Scoping Review.},
journal = {AJPM focus},
volume = {5},
number = {3},
pages = {100481},
pmid = {42016725},
issn = {2773-0654},
abstract = {INTRODUCTION: Studies have shown that patient portals facilitate cancer screening, but less is known about how. Causal pathway diagrams, which include influencing factors such as mechanisms and moderators, can be used to understand how portals improve screening. The authors conducted a scoping review of influencing factors to inform early causal pathway diagrams of the portal as a strategy to increase cancer screening.

METHODS: The authors searched PubMed for U.S. studies published from 2014 to 2024, including average-risk patients; portal interventions/evaluations; and primary outcomes of breast, cervical, colorectal, or lung cancer screening. Two authors completed manuscript screening and data extraction and synthesized findings to create causal pathway diagrams.

RESULTS: Thirty-two studies met inclusion criteria. Studies were often set in large academic health systems (n=13) or utilized survey data from nationally representative cohorts (n=11); 6 were RCTs. Most studies focused on breast (n=10) or colorectal (n=9) cancer screening. Of 21 studies comparing portal use with no use, 18 found that portals were associated with increased screening. Most proposed influencing factors were hypothetical, citing findings from prior literature rather than observed directly. Of the 10 studies that performed statistical analysis, significant moderators included provider recommendation for self-scheduling; significant mechanisms included cancer worry and patient activation for general portal use, cancer fatalism and patient activation for secure messaging with providers, and choice architecture for interventions delivered through secure messaging.

DISCUSSION: Few studies directly tested influencing factors, suggesting a significant research gap. More research is needed to further evaluate proposed mechanisms to understand how portals facilitate cancer screening and optimize implementation.

REGISTRATION: The protocol for this scoping review was registered through Open Science Framework.},
}

@article {pmid42017274,
year = {2026},
author = {Whalen, AM and Ma, W and Filigrana, P and Perreira, KM and Cai, J and Cordero, C and Daviglus, M and Kaplan, R and Lee, DJ and Llabre, MM and Penedo, FJ and Pichardo, MS and Pirzada, A and Suglia, SF and Gallo, LC and Isasi, CR},
title = {Intergenerational Socioeconomic Mobility and Adulthood All-Cause Mortality in the Hispanic Community Health Study/Study of Latinos.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwag086},
pmid = {42017274},
issn = {1476-6256},
abstract = {Socioeconomic mobility, the transition of an individual across different levels of socioeconomic position (SEP), may aid in understanding overall mortality trends in Hispanic/Latino adults by identifying subgroups with varying mortality experiences. We investigated whether intergenerational socioeconomic mobility was associated with all-cause mortality among US Hispanic/Latino adults aged 25-74 in the Hispanic Community Health Study/Study of Latinos (n = 12 095). Childhood SEP was measured as parental education, and adulthood SEP was measured using a 5-indicator index (income, homeownership, employment, occupation, education); both indicators were combined into a 4-group socioeconomic mobility measure: enduring adversity, downward mobility, upward mobility, and enduring advantage. Cox proportional hazards models were adjusted for potential confounders. Downward mobility (HR = 1.74; 95% CI: 1.19-2.55) and enduring adversity (HR = 1.44, 95% CI: 1.06-1.96) were significantly associated with an increased hazard of mortality compared to enduring advantage; the association was stronger among those born in the US. Adjustment for adulthood SEP confounders attenuated the association to non-significance. Socioeconomic mobility, particularly downward mobility, was associated with all-cause mortality in US Hispanic/Latino adults and may be partially explained by adulthood clinical and behavioral factors. Interventions should target structural barriers to socioeconomic advancement for Hispanic/Latino adults to improve health.},
}

@article {pmid42018610,
year = {2026},
author = {Petersdorf, EW and McKallor, C and Malkki, M and He, M and Spellman, SR and Gooley, TA and Stevenson, PA},
title = {Extended HLA Haplotypes and Transplant Survival.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025033031},
pmid = {42018610},
issn = {1528-0020},
abstract = {The benefit of extended HLA class I~class III~class II haplotypes in the reduction of mortality after hematopoietic-cell transplantation is unknown and requires information on functional class III variation. We identified a robust class III single-nucleotide-polymorphism (SNP), rs915654, informative for mortality and relapse in 1,436 patients and their haploidentical related donors through multivariable regression analysis of 26 candidate class III SNPs. Three-marker haplotypes as defined by one class I locus, one class II locus and rs915654 were determined in patients separately from donors. Inclusion of rs915654 into relapse and mortality models already containing patient HLA-E~DRB1 and donor HLA-B~DRB1 improved each model (likelihood ratio test P=0.06 and 0.004 respectively for relapse; P=0.10 and 0.01 respectively for mortality). The risks of mortality and relapse increased with decreasing numbers of favorable patient and donor markers. Re-testing in an independent cohort of 1,141 haploidentical transplants yielded similar results. The number of unfavorable markers additionally increased non-relapse mortality. HLA-A~C~B~DRB1~DQB1 haplotypes were defined according to their expected numbers of favorable markers, and the theoretical utility for selecting donors was explored. In summary, extended HLA class I~class III~class II haplotypes influence the success of transplantation and inform the biology of the MHC in health and disease. The selection of haploidentical donors for future patients may be optimized with knowledge of donor HLA haplotypes.},
}

@article {pmid41929148,
year = {2026},
author = {Keiser, DJ and Buddy, MS and Mojarad-Jabali, S and Li, Q and Kohler-Skinner, M and Parrish, AG and Gillespie, D and Nix, D and Holmen, S and Colman, H and Couldwell, W and Jensen, R and Szulzewsky, F},
title = {Comprehensive analysis of TEAD inhibition in meningioma identifies MEK and mTOR inhibition as effective combination therapies against resistant lines.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41929148},
issn = {2692-8205},
abstract = {Meningiomas are the most common primary central nervous system tumors in adults, posing a significant burden to society. Although a large percentage of lower-grade meningiomas are curable by surgery or radiation alone, high-grade and a subset of low-grade meningiomas demonstrate recurrences and complications from treatment. Systemic therapies for meningioma remain ineffective, and no targeted treatments are approved. Despite the central role of YAP1/TAZ-TEAD signaling in NF2-deficient/mutant tumors, no studies have systematically examined TEAD inhibition across molecularly defined meningioma subtypes or investigated mechanisms of resistance in this disease. We have recently shown that YAP1/TAZ signaling is an oncogenic driver of meningioma. Here, using established and patient-derived meningioma cell lines, we demonstrate that genetic ablation of YAP1/TAZ suppresses growth in both NF2 mutant and NF2 wild type cell lines, establishing YAP1/TAZ-TEAD signaling as a shared oncogenic dependency. Pharmacologic TEAD inhibition suppressed growth of benign NF2 mutant and a subset of higher-grade NF2 mutant meningiomas, whereas NF2 wild type meningiomas were generally more resistant. RNA-Seq and Western Blot analysis identified compensatory activation of MEK-ERK, mTOR-S6, and FAK signaling in resistant lines exhibit. Importantly, co-targeting these pathways was able to overcome resistance to TEADi and was superior to MEK/mTOR/FAK inhibition alone. These studies provide a compelling proof-of-concept that TEADi represents a novel therapeutic vulnerability in meningioma and reveal adaptive signaling responses that can be therapeutically exploited.},
}

@article {pmid41959788,
year = {2026},
author = {Walsh, SR and Hahn, WO and Williams, WB and Hyrien, O and Yu, PC and Parks, KR and Edwards, RJ and Parks, R and Barr, M and Polakowski, LL and Tindale, I and Jones, M and Yurdadon, C and Burnham, R and Yeh, CH and Heptinstall, J and Seaton, KE and Andriesen, JG and Sagawa, Z and Miner, MD and De Rosa, S and McElrath, MJ and Corey, L and Tomaras, GD and Montefiori, DC and Haynes, BF and Mayer, KH and Baden, LR and , },
title = {Safety and immunogenicity of an HIV envelope trimer immunogen that elicits CD4 binding site neutralizing antibody precursors (HVTN 300).},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41959788},
abstract = {BACKGROUND: Induction of HIV envelope (Env)-specific broadly neutralizing antibodies (bnAbs) is considered a key objective for HIV-1 vaccine development. One approach is to vaccinate with HIV Env immunogens that initially target the naïve B cell receptors of a bnAb type and boost with a series of HIV Env variants. We chose a priming immunogen, the CH505 transmitted/founder Env with high affinity for the naïve B cell receptor of the prototype CD4 binding site (bs) bnAb lineage, CH103, as a candidate priming immunogen to induce the initial critical step in CD4bs bnAb development.

METHODS: HVTN 300 is a first-in-human, open-label Phase 1 study evaluating the safety and immunogenicity of a CH505 TF chimeric (ch) Trimer adjuvanted with 3M-052-AF (a TLR7/8 agonist) + Alum. The immunogen is a recombinant, stabilized chimeric Env trimer protein with the N-terminal sequence of CH505 TF gp120 Env transplanted into the BG505 SOSIP sequence. Participants received the adjuvanted protein administered in both deltoid muscles at months 0, 2, 4, 8, and 12.

RESULTS: Adults (n=18) aged 18 to 55 were screened at a single site in Boston, USA, and 13 were enrolled. Local and systemic reactogenicity was typically mild to moderate. One participant had severe pain/tenderness, and five participants reported transient severe systemic symptoms at least once. Five participants chose to stop further vaccination due to reactogenicity. No vaccine-related SAEs occurred. Vaccine-specific B-cell response rates reached 100% two weeks post third and fifth vaccinations. Antibody blocking experiments with monoclonal antibodies demonstrated that most participants had antibodies directed to the CD4bs. Four out of 11 participants had serum neutralization signatures for CD4bs bnAb precursors.

CONCLUSIONS: No safety concerns were identified. The adjuvanted CH505 TF chTrimer elicited serum antibodies capable of CD4bs-mediated neutralization against strains designed to detect early precursors of the CD4bs B-cell lineages.

TRIAL REGISTRATION: NCT04915768.},
}

@article {pmid42008267,
year = {2026},
author = {Shankaran, V and Li, L and Khor, S and Yu, K and Kwendakwema, CN and Fedorenko, C and Kreizenbeck, K and Khan, HM and Kestner, S and Wright, W and Ramsey, S},
title = {Financial Hardship, End-of-Life Health Care Use, and Costs in Patients With Cancer.},
journal = {JAMA network open},
volume = {9},
number = {4},
pages = {e267923},
doi = {10.1001/jamanetworkopen.2026.7923},
pmid = {42008267},
issn = {2574-3805},
mesh = {Humans ; *Neoplasms/economics/therapy ; Male ; Female ; *Terminal Care/economics/statistics & numerical data ; Aged ; United States ; *Health Care Costs/statistics & numerical data ; *Financial Stress/economics/epidemiology ; Middle Aged ; *Patient Acceptance of Health Care/statistics & numerical data ; Emergency Service, Hospital/statistics & numerical data/economics ; Aged, 80 and over ; *Health Expenditures/statistics & numerical data ; Cohort Studies ; SEER Program ; Washington ; Hospitalization/economics/statistics & numerical data ; },
abstract = {IMPORTANCE: Patients with cancer are at higher risk of adverse financial events (AFEs) compared with individuals without cancer. However, little is known about how personal finances affect cancer care, particularly at the end of life (EOL).

OBJECTIVE: To investigate the association between AFEs and health care use and costs at EOL among patients with cancer.

In this cohort study, Western Washington Surveillance, Epidemiology, and End Results cancer registry cases were linked to claims from commercial payers and Medicare and to credit records from TransUnion. Patients with American Joint Committee on Cancer stage I to IV solid tumors who died between January 1, 2013, and December 31, 2019, were identified. Data analysis was performed from January 2023 and June 2025.

MAIN OUTCOMES AND MEASURES: Emergency department (ED) and inpatient visits in the last 3 months of life, place of death, and mean adjusted health care costs per patient were compared between patients with vs without new AFEs in the 2 years preceding EOL (charge-offs, third-party collections, tax liens, delinquent mortgage payments, foreclosures, or repossessions). A multivariate logistic regression analysis evaluated the association between AFEs and the outcomes of ED or inpatient visits and inpatient death. Health care costs in the last 3 and 6 months of life were analyzed using 2-part models to account for zero costs and right-skewed positive expenditures; adjusted average treatment effects were estimated.

RESULTS: A total of 10 826 patients (median [IQR] age, 75 [69-83] years; 5877 [54%] male; 932 [8.6%] with AFEs) were included. Patients with AFEs were more likely to have multiple ED or inpatient visits (odds ratio [OR], 1.41; 95% CI, 1.22-1.62; P < .001) and die in a hospital (OR, 1.50; 95% CI, 1.30-1.75; P < .001). Mean (SD) adjusted total health care costs were higher in patients with AFEs than those without in the last 3 months ($35 115 [$1415] vs $31 031 [$389]) and 6 months ($57 401 [$2181] vs $51 602 [$581]) of life, yielding a mean adjusted incremental costs in the AFE group of $4084 (95% CI, $1287-$7087; P = .006) and $5799 (95% CI, $1235-$9996; P = .01), respectively.

CONCLUSIONS AND RELEVANCE: In this cohort study, AFEs were associated with greater ED and inpatient use, higher risk of inpatient death, and higher care costs at EOL. These findings point to the need for future studies investigating whether interventions that mitigate financial hardship could improve the EOL experience and decrease health care costs for patients with cancer.},
}

Humans
*Neoplasms/economics/therapy
Male
Female
*Terminal Care/economics/statistics & numerical data
Aged
United States
*Health Care Costs/statistics & numerical data
*Financial Stress/economics/epidemiology
Middle Aged
*Patient Acceptance of Health Care/statistics & numerical data
Emergency Service, Hospital/statistics & numerical data/economics
Aged, 80 and over
*Health Expenditures/statistics & numerical data
Cohort Studies
SEER Program
Washington
Hospitalization/economics/statistics & numerical data

@article {pmid42008824,
year = {2026},
author = {Kanwal, F and Feng, Z and Hoshida, Y and Chhatwal, J and Wong, VW and Ioannou, GN and Nahon, P and Lotter, W and Ning, J and Taouli, B and Marquez, G and Fu, SW and Singal, AG},
title = {Development and validation of risk stratification models for hepatocellular cancer: A framework from the translational liver cancer consortium.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
pmid = {42008824},
issn = {1527-3350},
abstract = {Clinical practice guidelines recommend hepatocellular cancer (HCC) surveillance in patients with cirrhosis from any etiology and those with chronic hepatitis B virus (HBV) infection and additional risk factors. However, HCC incidence varies across groups. Several risk stratification models using clinical factors and/or biomarkers have been derived to facilitate tailored HCC surveillance. Although risk stratification models are used for patients with hepatitis B, few have been sufficiently validated in patients with cirrhosis. Indeed, many unanswered questions related to the development, validation, and impact evaluation of risk stratification models must be addressed before widespread implementation can be recommended. The National Cancer Institute's Translational Liver Cancer (TLC) Consortium was established to advance research focused on risk stratification and early detection of liver cancer. The TLC convened a multidisciplinary group, including clinicians, scientists, biostatisticians, and technology experts from the United States, Asia, and Europe, to provide a framework for the development, validation, and implementation of risk stratification models. The framework defines 4 phases of risk stratification model development and validation: phase 1-development and internal validation, phase 2-decision rule development, phase 3-external validation, and phase 4-impact evaluation. The group also defined a set of recommendations to improve the rigor of development and validation of HCC risk stratification strategies. This framework can inform best practices and highlight necessary steps for endorsement by practice guidelines and regulatory agencies, highlighting a path toward implementation in clinical practice.},
}

@article {pmid42009282,
year = {2026},
author = {Liu, Y and Goldrich, N and Redmond, KJ and Gabriel, J and Zhou, N and Swensen, S and Skalina, KA and Fekrmandi, F and Vellayappan, B and Guckenberger, M and Foote, M and Connell, PP and Hsu, CC and Vuong, W and Gillespie, EF and Tykodi, SS and Nguyen, TK and Mayerson, JL and Nguyen, QN and de Moraes, FY and Siva, S and Palmer, JD and Kim, M and Yang, JT and Sahgal, A and Lo, SS},
title = {Stereotactic Body Radiation Therapy for Non-Spine Bone Metastases: A Case-Based Radiosurgery Society Review.},
journal = {Practical radiation oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.prro.2026.04.004},
pmid = {42009282},
issn = {1879-8519},
abstract = {PURPOSE: Growing evidence supports stereotactic body radiation therapy (SBRT) over conventional radiation therapy for spine bone metastases, with an expanding role in non-spine bone metastases (NSBM). Our case-based review aims to inform radiation oncologists in the appropriate utilization of SBRT for representative cases of NSBM.

METHODS AND MATERIALS: Three cases were selected for discussion: (1) rib, (2) skull base, and (3) femur. Relevant literature was reviewed, and areas for future investigation were discussed.

RESULTS: SBRT can be effectively delivered in NSBM with appropriate patient selection, target volume delineation, prescription dose, organs at risk dose constraints, and treatment planning.

CONCLUSIONS: The Radiosurgery Society's case-based review offers guidance on the appropriate use of SBRT in NSBM with discussions and consensus recommendations from experts. SBRT can be considered for an oligometastatic patient with favorable prognosis in whom the goal is durable local control and/or symptom relief. It can be considered for radioresistant histologies and improved OAR sparing. Available MRI or PET/CT should be fused to improve target volume delineation. A CTV margin, generally of 5 mm, should be considered to cover microscopic disease. As bones are easily visualized on daily images acquired for accurate and precise set-up of patients, a PTV margin should be kept less than or equal to 3 mm. While SBRT can be delivered in 1 fraction, fractionated SBRT may be preferred to meet dose constraints when the CTV is adjacent to the OARs. NSBM of long bones that are weight bearing, lytic, or have a high MIRELS score should be evaluated by an orthopedic surgeon.},
}

@article {pmid42010121,
year = {2026},
author = {Saifudeen, M and Zhu, S and Liang, S and Eason, M and Goupil, A and Mische, DF and Loch, CM and Ma, H and Chan, M and Gujral, TS},
title = {Comprehensive profiling of clinically approved kinase inhibitors reveals mutation-specific inhibitors and opportunities for drug repurposing.},
journal = {Nature biotechnology},
volume = {},
number = {},
pages = {},
pmid = {42010121},
issn = {1546-1696},
abstract = {Protein kinases are central to cell signaling and key drug targets in cancer. To inform potential repurposing of kinase inhibitors, we profiled 86 of the ~100 approved kinase inhibitors against 758 kinases, including 409 wild-type and 349 oncogenic variants using a biochemical kinase assay. Our results increase the number of druggable kinases from 89 to 235, revealing that 94% of mutations and 97% of fusions represented in our samples are inhibited by at least one existing drug. The dataset revealed mutation-specific selectivity, especially in tyrosine kinases FGFR and MET, highlighting gaps and repurposing opportunities. We experimentally validated several actionable findings, including tepotinib to target the IRAK1/4-cholesterol pathway in glioblastoma, brigatinib to target the MARK2/3-Hippo pathway in pancreatic cancer and gilteritinib to overcome MET mutation-driven drug resistance and metastasis. To facilitate exploration of our data, we provide KIRHub, a web-based tool that allows identification of existing inhibitors of wild-type and mutated kinases to guide precision oncology.},
}

@article {pmid42011792,
year = {2026},
author = {de Abreu, M and Kowalski, LP and López, RM and Barul, C and Radoi, L and Bidoli, E and Polesel, J and Wunsch-Filho, V and Olshan, AF and Zevallos, J and Negri, E and Edefonti, V and Świątkowska, B and Mates, D and Fabianova, E and Lissowska, J and Shangina, O and Brennan, P and Pandics, T and Maso, LD and Morgenstern, H and Zhang, ZF and Kelsey, K and McClean, M and La Vecchia, C and Garavello, W and Chen, C and Schwartz, SM and Ramroth, H and Winkler, V and Cadoni, G and Boccia, S and Brenner, H and D'Souza, G and Gross, N and Muscat, J and Abedini, M and Sassano, M and Boffetta, P and Hashibe, M and Lee, YA and Curado, MP},
title = {Risk of Head and Neck Cancer in Former Smokers by Subsite: A Multicenter Analysis From the INHANCE Consortium.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.70497},
pmid = {42011792},
issn = {1097-0215},
support = {R03CA11315//National Cancer Institute grant/ ; //French National Research Agency (ANR)/ ; //French National Cancer Institute (INCA)/ ; //French Agency for Food, Environmental and Occupational Health and Safety (ANSES)/ ; //French Institute for Public Health Surveillance (InVS)/ ; //Fondation pour la Recherche Medicale (FRM)/ ; //Fondation de France/ ; //Fondation ARC pour la Recherche sur le Cancer/ ; //French Ministry of Labour (Direction Generale du Travail)/ ; //French Ministry of Health (Direction Generale de la Sante)/ ; GENCAPO 04/12054-9//Sao Paulo Research Foundation (FAPESP)/ ; 10/51168-0//Sao Paulo Research Foundation (FAPESP)/ ; NCI R01CA90731-01//North Carolina (2002-2006) study/ ; NIEHS P30ES010126//North Carolina (2002-2006) study/ ; //Italian Association for Research on Cancer (AIRC)/ ; //Italian League Against Cancer/ ; //World Cancer Research Fund/ ; IC15-CT98-0332//European Commission INCO-COPERNICUS Program/ ; P50CA090388/GF/NIH HHS/United States ; R01DA011386/GF/NIH HHS/United States ; R03CA077954/GF/NIH HHS/United States ; T32CA009142/GF/NIH HHS/United States ; U01CA096134/GF/NIH HHS/United States ; R21ES011667/GF/NIH HHS/United States ; R01CA078609/GF/NIH HHS/United States ; R01CA100679/GF/NIH HHS/United States ; R01CA048996/GF/NIH HHS/United States ; R01DE012609/GF/NIH HHS/United States ; R01CA051845/GF/NIH HHS/United States ; P01CA068384/GF/NIH HHS/United States ; K07CA104231/GF/NIH HHS/United States ; //Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center/ ; PRIN 2009 X8YCBN//Italian Ministry of Education/ ; 01GB9702/3//German Ministry of Education and Research/ ; //Ministry of Science/ ; //Research and Arts Baden-Wurttemberg/ ; //Johns Hopkins Richard Gelb Cancer Prevention Award/ ; 88887.929140/2023-00//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)/ ; },
abstract = {This study investigated risk factors associated with HNC by subsite including oral cavity cancer (OCC), oropharyngeal cancer (OPC), and laryngeal cancer (LC) among former smokers in the International Head and Neck Cancer Epidemiology Consortium (INHANCE). Case-control study including former smokers from the pooled INHANCE data, with information on sociodemographic, smoking, and alcohol history. Associations were assessed using logistic regression with 95% confidence intervals (CI). The study included 2143 cases with HNC and 5799 controls. Cancer cases were categorized by their respective subsites: 954 LC (44.5%), 685 OPC (32.0%), 504 OCC (23.5%). The risk of developing OCC was 2.8-fold higher [CI: 1.9-4.1], LC 2.6-fold higher [CI: 1.9-3.5], and OPC 2.1-fold higher [CI: 1.5-2.8] in individuals who smoked > 50 pack-years, compared to < 10 pack-years. The risk of OCC/OPC/LC increased with tobacco consumption in North-America, whereas in Western/Southern-Europe and South-America the association plateaued beyond 31-50 pack-years. Cessation after age 55 increased the risk of LC by 3.0-fold [CI: 2.2-4.2], and OCC by 2.2-fold [CI: 1.4-3.3] versus cessation age ≤ 45 years. Consuming ≥ 5 drinks/day was associated with 5-fold higher risk of OPC [CI: 3.7-6.6], 4.4-fold higher risk of OCC [CI: 3.2-6.1] and 3.1-fold higher risk of LC [CI: 2.4-3.9] compared to 0-0.9 drinks/day. The risk of HNC among former smokers is not homogeneous across regions and that there were distinct patterns for OCC, OPC, and LC. The amount of tobacco and alcohol consumption are key risk factors, with alcohol being more important for OCC/OPC, and tobacco being more strongly associated with LC risk.},
}

@article {pmid42013417,
year = {2026},
author = {Campbell, KM and Chen, DG and Bustami, ZE and Naser Al Deen, N and Medina, E and Gonzalez, CR and Maxey, J and Thompson, MA and Samorodnitsky, S and Kuklinski, LF and Perez Garcilazo, I and Baselga-Carretero, I and Vega-Crespo, A and Chen, JM and Elumalai, R and Visitacion, M and Schiemann, R and Padron, L and Chang, C and Zelin, AE and Chelluri, SS and Boffo, S and Kendra, KL and Chmielowski, B and Truong, TG and Khushalani, NI and Collichio, F and Ikeguchi, AP and Victor, AI and Margolin, KA and Johnson, DB and Chen, Y and Sosman, JA and Patel, SP and Hu-Lieskovan, S and Moon, J and Wells, DK and Spencer, CN and Bellasea, S and Vanderwalde, AM and Wu, MC and Scumpia, PO and Ribas, A},
title = {Cellular neighborhoods govern antitumor T-cell infiltration following anti-CTLA-4 in melanoma with primary resistance to anti-PD-1.},
journal = {Cancer discovery},
volume = {},
number = {},
pages = {},
doi = {10.1158/2159-8290.CD-25-1745},
pmid = {42013417},
issn = {2159-8290},
abstract = {In the phase 2 trial SWOG S1616 (NCT03033576), patients with advanced melanoma with primary resistance to anti-PD-1/L1 therapies had improved outcomes on the combination of the anti-CTLA-4 antibody ipilimumab with continued anti-PD-1 with nivolumab, over ipilimumab alone. Baseline biopsies from patients responsive to combination therapy had increased transcriptomic expression of complement by myeloid cells, interferon pathways by endothelial cells, and oxidative phosphorylation and lipid metabolism by melanoma cells. Using spatial proteomics, some on-therapy biopsies from patients responding to combination therapy had networks of activated CD8 T cells nearby melanoma cells, while others had T cells and myeloid cells, reflective of different timepoints in a dynamic antitumor response. Conversely, biopsies from patients progressing on combination immunotherapy displayed impaired T-cell infiltration adjacent to plasma cells. Our results define cellular neighborhoods and transcriptomes in melanoma biopsies when reversing resistance to anti-PD-1 with the addition of anti-CTLA4, and plasma cell sheets in non-responding biopsies.},
}

@article {pmid42013838,
year = {2026},
author = {Rathore, U and Dugan, E and Thornton, H and Kumar, VE and Dajani, R and Burdick, RC and Young, JM and Steinhart, Z and Lao, R and Delviks-Frankenberry, KA and Choi, W and Henriques, WS and Echeverria, I and Dann, E and Dureja, I and Pathak, N and Arce, MM and McKetney, J and Umhoefer, JM and Parulekar, S and Schmidt, R and Polacco, BJ and Neidleman, J and Montano, M and Nguyen, VQ and Sali, A and Levy, JA and Tenthorey, JL and Cheng, Y and Roan, NR and Swaney, DL and Kaake, RM and Dodgson, SE and Hiatt, J and Pathak, VK and Malik, HS and Krogan, NJ and Marson, A},
title = {Systematic discovery of pro- and anti-HIV host factors in primary human CD4+ T cells.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2026.03.046},
pmid = {42013838},
issn = {1097-4172},
abstract = {Host factors that promote or restrict human immunodeficiency virus (HIV) infection in human CD4+ T cells have not been comprehensively identified. We employed orthogonal genome-wide CRISPR activation (CRISPRa) and CRISPR knockout screens in primary CD4+ T cells to discover pro- and anti-HIV host factors systematically. Secondary pooled screens and individual perturbations validated high-confidence hits and revealed diverse mechanisms of action. CRISPRa uncovered multiple potent antiviral factors, including PI16, PPID, SHISA3, and ITM2A. PI16 interacts with host factors involved in HIV fusion and inhibits viral entry, whereas PPID (Cyp40), a paralog of the proviral cyclophilin CypA, binds capsid and reduces nuclear import of the HIV core. Structural modeling, evolutionary analyses, and targeted mutagenesis revealed domains and residues required for PPID-mediated HIV restriction, including non-human primate ortholog substitutions that enhance antiviral activity. Together, these data define the functional HIV-host interaction landscape in primary human T cells and uncover new mechanisms modulating infection.},
}

@article {pmid42014940,
year = {2026},
author = {Chari, A and Costello, C and Krishnan, A and Patel, K and Banerjee, R and Berdeja, JG and Biran, N and Callander, N and Costa, LJ and Dhakal, B and Gasparetto, C and Hansen, DK and Kumar, A and Nooka, AK and Pan, D and Richard, S},
title = {Integrating Recent Evidence and Expert Perspectives Into the Management of Multiple Myeloma: Consensus Recommendations From the 2025 Bridging the Gaps Conference.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70339},
pmid = {42014940},
issn = {1096-8652},
abstract = {The rapid expansion of therapeutic options for multiple myeloma (MM) has created uncertainty regarding optimal sequencing and clinical application. To address gaps in evidence, the 2025 Bridging the Gaps Consensus Conference convened 16 US MM experts who reviewed data, debated controversies, and voted on 51 questions that were developed using a modified Delphi approach. Eleven consensus recommendations were developed spanning smoldering MM, frontline therapy, transplant, maintenance, and relapsed/refractory disease. Key themes included integration of quadruplet induction, individualized maintenance, and early referral for CAR-T therapy. These expert-derived recommendations provide practical guidance while highlighting areas requiring further investigation.},
}

@article {pmid42001456,
year = {2026},
author = {McCulloch, DJ and Khawaja, F and Tverdek, FP and Ford, ES and Vora, SB and Waghmare, A and Vuong, N and Chemaly, RF and Hill, JA},
title = {First report on remdesivir use for the treatment of respiratory syncytial virus in five allogeneic hematopoietic cell transplant recipients.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag213},
pmid = {42001456},
issn = {1537-6613},
abstract = {Respiratory syncytial virus (RSV) infection causes substantial morbidity among hematopoietic cell transplant (HCT) patients and lacks approved therapies. Remdesivir demonstrates antiviral activity in vitro, but data in humans are lacking. We describe 5 HCT recipients with RSV lower respiratory tract infection who were treated with remdesivir with clinical improvement.},
}

@article {pmid42001506,
year = {2026},
author = {Brady, SW and Arnold, MA and Wang, M and Alsallaq, R and Dong, L and Khan, MA and Yang, W and Stratton, KL and Liu, W and Chen, Y and Plyler, E and Steele, JA and Powers, BB and Rosenfeld, D and Edmonson, MN and Feng, Y and Terekhanova, NV and Hagiwara, K and Arunachalam, S and Mulder, HL and Srivastava, DK and Rusch, M and Nolan, VG and McDonald, A and Sapkota, Y and Gramatges, MM and Turcotte, LM and Im, C and Howell, RM and Easton, J and Ma, X and Wang, Z and Leisenring, WM and Conces, M and Neglia, JP and Yasui, Y and Bhatia, S and Ellison, DW and Zhang, J and Armstrong, GT},
title = {Therapy-related mutational signatures in subsequent neoplasms among survivors of childhood cancer.},
journal = {Cancer discovery},
volume = {},
number = {},
pages = {},
doi = {10.1158/2159-8290.CD-25-0231},
pmid = {42001506},
issn = {2159-8290},
abstract = {Childhood cancer survivors have heightened risk of developing subsequent neoplasms (SNs) related to therapy. We analyzed whole-genome, exome and RNA sequencing of 200 breast, meningioma, and thyroid SNs, which developed a median of 26.4 years after childhood cancer, among 160 survivors. Meningioma and thyroid SNs were enriched for driver gene rearrangements compared to de novo tumors, including NF2-disrupting alterations and kinase fusions potentially induced by radiation. Radiation correlated with increased insertion-deletion signature ID5. Nitrogen mustard treatment correlated with elevated "flat" signature SBS5 in breast and meningioma SNs; in vitro, these agents caused an unresolved flat signature associated with multiple flat COSMIC signatures. In meningioma, platinum therapy correlated with NF2 splice-site variants. Analysis of 19 multi-sample survivors revealed intrapatient heterogeneity in meningioma, including clonally independent tumors. These results demonstrate the long-term impact of childhood cancer treatment on the genomes of SNs developing in adulthood, which may guide SN treatment and prevention.},
}

@article {pmid42001993,
year = {2026},
author = {Zhou, D and Nouet, J and Mesa, E and Yegneshwaran, V and Geukgeuzian, G and Adibemma, ID and Ramirez, E and Ali, NK and Hilfiker, S and Li, H and Liu, T and Yehia, G and Romanienko, PJ and Rodney, GG and Wehrens, XHT and Lampe, PD and Gourdie, RG and Xie, LH and Fraidenraich, D},
title = {Phospho-mimic βIII-tubulin rescues microtubule and cardiac defects in Duchenne muscular dystrophy mice.},
journal = {Journal of molecular and cellular cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.yjmcc.2026.04.004},
pmid = {42001993},
issn = {1095-8584},
abstract = {Duchenne muscular dystrophy (DMD) cardiomyopathy is caused by mutations in the dystrophin gene and characterized by profound cytoskeletal disorganization, particularly pathological remodeling of the cardiomyocyte microtubule network. While the role of dystrophin in maintaining sarcolemmal integrity is well-established, its specific association with microtubule dynamics through post-translational modifications (PTMs) remains underinvestigated. Here, we identified βIII-tubulin Ser172 phosphorylation as a specific regulatory residue in cardiac DMD microtubule pathology. Using CRISPR-generated mdx mice carrying a phospho-mimic S172E mutation in βIII-tubulin, we demonstrate rescue of microtubule organization defects, including normalization of orthogonal microtubule misalignment, and restoration of physiological density and polymerization kinetics. Microtubule stabilization further improved secondary phenotypes, including connexin-43 (Cx43) phosphorylation and retention to intercalated discs, critical for electrical coupling and signal transduction. Furthermore, S172E expression protected against isoproterenol-induced arrhythmias and cardiac fibrosis in the mdx mouse model. Lentiviral expression of S172E-mutant βIVb-tubulin confirmed conservation of these effects across cardiac β-tubulin isoforms. Our findings reveal a regulatory link between microtubule dynamics and Cx43, establish β-tubulin Ser172 phosphorylation as a key regulator of microtubule dynamics in dystrophic hearts, and will help develop novel therapeutic strategies targeting microtubule stabilization in DMD cardiomyopathy.},
}

@article {pmid42007251,
year = {2026},
author = {Davis, JA and McElwee, J and Gonzalez, R and Julian, K and Nachar, VR and Snyder, J and Mahmoudjafari, Z and Granger, K and Warrick, M and Smith, D and Baek, G and Huang, I and Portuguese, A and Dima, D and Banerjee, R and Atrash, S and Sborov, DW and Grajales-Cruz, A and Puglianini, OC and Dominick, A and Hansen, DK and Elsey, G and Moore, DC},
title = {Safety of MMR vaccination for patients with myeloma receiving daratumumab after autologous stem cell transplantation.},
journal = {Blood neoplasia},
volume = {3},
number = {2},
pages = {100220},
pmid = {42007251},
issn = {2950-3280},
}

@article {pmid41129124,
year = {2025},
author = {Su, CT and Ramsey, SD and Shankaran, V},
title = {Can We Use Credit Data to Assess Cancer Financial Hardship?.},
journal = {JAMA oncology},
volume = {11},
number = {12},
pages = {1420-1422},
doi = {10.1001/jamaoncol.2025.4371},
pmid = {41129124},
issn = {2374-2445},
}

@article {pmid41129142,
year = {2026},
author = {Jani, S and Bencomo, T and Shasha, C and Pulliam, T and Jojic, A and Church, CD and Gooley, TA and Koelle, DM and Newell, EW and Nghiem, P},
title = {Circulating Neoantigen- and Viral Oncoprotein-Specific CD8+ T Cells Share a Transcriptional Signature.},
journal = {Cancer immunology research},
volume = {14},
number = {1},
pages = {22-31},
pmid = {41129142},
issn = {2326-6074},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; R01 CA264646/CA/NCI NIH HHS/United States ; F30 CA254168/CA/NCI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; CA225517//National Cancer Institute (NCI)/ ; CA254168//National Cancer Institute (NCI)/ ; CA080416//National Cancer Institute (NCI)/ ; CA264646//National Cancer Institute (NCI)/ ; CA015704//National Cancer Institute (NCI)/ ; A187769//Odyssey Group Foundation/ ; //National Foundation for Cancer Research (NFCR)/ ; },
mesh = {Humans ; *CD8-Positive T-Lymphocytes/immunology/metabolism ; *Carcinoma, Merkel Cell/immunology/genetics/virology/blood ; *Antigens, Viral, Tumor/immunology ; *Antigens, Neoplasm/immunology ; Female ; Male ; *Transcriptome ; Aged ; *Skin Neoplasms/immunology/genetics ; Gene Expression Profiling ; Middle Aged ; },
abstract = {Tumor-specific CD8+ T cells in blood seem to be important for and predictive of response to anti-PD-1 therapies. However, as most tumor antigens are unique to a given patient, the identification of tumor-specific CD8+ T cells is not routinely feasible. In this study, we characterized polyomavirus-specific CD8+ T cells from the blood of 17 patients with virus-driven Merkel cell carcinoma. We identified a 98-gene signature [Signature of Peripheral Tumor-specific CD8+ T cells (SPoTT)] that discriminated circulating tumor-specific CD8+ T cells from other T cells in immunotherapy-naïve patients. We observed profound transcriptomic differences among tumor-specific CD8+ T cells from blood versus those from tumor. In validation cohorts of Merkel cell carcinoma, as well as neoantigen-driven cancers, the signature of peripheral tumor-specific CD8+ T cells was able to identify viral oncoprotein- and neoantigen-specific CD8+ T cells with both sensitivity and specificity above 75%. We also tested a previously described 151-gene signature (NeoTCRPBL) trained on neoantigen-specific CD8+ T cells and found it was able to recognize Merkel cell polyomavirus-specific T cells with a sensitivity of 66% and a specificity of 88%. These findings show that circulating tumor-specific CD8+ T cells share fundamental characteristics across diverse tumor antigen types. More broadly, insights into antitumor T cells gained from virus-driven cancers are also likely to be relevant in mutationally driven cancers.},
}

Humans
*CD8-Positive T-Lymphocytes/immunology/metabolism
*Carcinoma, Merkel Cell/immunology/genetics/virology/blood
*Antigens, Viral, Tumor/immunology
*Antigens, Neoplasm/immunology
Female
Male
*Transcriptome
Aged
*Skin Neoplasms/immunology/genetics
Gene Expression Profiling
Middle Aged

@article {pmid41129365,
year = {2026},
author = {Watling, CZ and Campbell, PT and Graubard, BI and Wang, Y and Gewirtz, AT and Zhang, X and Barnett, MJ and Buring, JE and Chen, Y and Eliassen, AH and Gaziano, JM and Hofmann, JN and Huang, WY and Kang, JH and Koshiol, J and Loftfield, E and Lee, IM and Moore, SC and Mucci, LA and Neuhouser, ML and Newton, CC and Purdue, MP and Sesso, HD and Shrubsole, M and Sinha, R and Tinker, L and Triplette, M and Um, CY and Visvanathan, K and Watts, EL and Wactawski-Wende, J and Willett, W and Wu, F and Zheng, W and Barupal, D and Petrick, JL and McGlynn, KA},
title = {Pre-diagnostic immunological markers of bacterial translocation and liver cancer risk: A nested case-control analysis of 12 prospective cohorts.},
journal = {International journal of cancer},
volume = {158},
number = {7},
pages = {1801-1812},
pmid = {41129365},
issn = {1097-0215},
support = {187861/CAPMC/CIHR/Canada ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; HL26490/NH/NIH HHS/United States ; U01 CA167462/CA/NCI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; 75N92021D00005/NH/NIH HHS/United States ; U01CA202979/NH/NIH HHS/United States ; 75N92021D00004/NH/NIH HHS/United States ; 75N92021D00001/NH/NIH HHS/United States ; NCI U01 167552/NH/NIH HHS/United States ; U24 ES035386/ES/NIEHS NIH HHS/United States ; UM1 CA182913/CA/NCI NIH HHS/United States ; R01 HL026490/HL/NHLBI NIH HHS/United States ; R01 CA034944/CA/NCI NIH HHS/United States ; U01CA164974/NH/NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; U01 CA063673/CA/NCI NIH HHS/United States ; CA097193/NH/NIH HHS/United States ; R01 HL043851/HL/NHLBI NIH HHS/United States ; HL080467/NH/NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; R01 HL034595/HL/NHLBI NIH HHS/United States ; U01CA63673/NH/NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; HL043851/NH/NIH HHS/United States ; HL09935/NH/NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; HL34595/NH/NIH HHS/United States ; R01 CA047988/CA/NCI NIH HHS/United States ; UM1CA186107/NH/NIH HHS/United States ; CA40360/NH/NIH HHS/United States ; R01 HL080467/HL/NHLBI NIH HHS/United States ; 75N92021D00003/NH/NIH HHS/United States ; U24ES035386/NH/NIH HHS/United States ; //National Institutes of Health Intramural/ ; 75N92021D00002/NH/NIH HHS/United States ; CA047988/NH/NIH HHS/United States ; R01 CA040360/CA/NCI NIH HHS/United States ; U01CA167462/NH/NIH HHS/United States ; U01 CA182913/CA/NCI NIH HHS/United States ; U01 CA202979/CA/NCI NIH HHS/United States ; UM1CA167462/NH/NIH HHS/United States ; CA182913/NH/NIH HHS/United States ; RC1 HL099355/HL/NHLBI NIH HHS/United States ; UM1 CA167462/CA/NCI NIH HHS/United States ; R01 CA097193/CA/NCI NIH HHS/United States ; //American Cancer Society/ ; CA34944/NH/NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; },
mesh = {Humans ; Male ; Case-Control Studies ; *Liver Neoplasms/immunology/microbiology/blood/epidemiology ; Female ; Middle Aged ; *Bacterial Translocation/immunology ; Prospective Studies ; Lipopolysaccharide Receptors/blood/immunology ; Aged ; Carrier Proteins/blood/immunology ; Membrane Glycoproteins/blood ; Risk Factors ; Flagellin/immunology ; Immunoglobulin G/blood ; Acute-Phase Proteins ; Lipopolysaccharides/immunology ; Adult ; Immunoglobulin A/blood ; Biomarkers, Tumor ; },
abstract = {The gut-liver axis may play an important role in hepatocarcinogenesis. However, limited prospective research has explored associations with liver cancer risk. We conducted a nested case-control study based in 12 prospective cohort studies from across the United States, which included 867 cases of liver cancer and 867 matched controls. We measured bacterial translocation markers, specifically immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide and flagellin; soluble CD14 (a co-receptor for lipopolysaccharide); and lipopolysaccharide-binding protein. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) between bacterial translocation marker concentrations per doubling in concentrations and liver cancer risk. Lipopolysaccharide-binding protein concentrations were most strongly associated with higher liver cancer risk (OR per doubling in concentrations: 1.48, 95% CI: 1.23-1.79). Concentrations of anti-flagellin IgA (1.13, 1.01-1.28) and IgG (1.13, 1.01-1.28), anti-lipopolysaccharide IgG (1.20, 1.01-1.42), and soluble CD14 (1.12, 1.01-1.24) were also associated with liver cancer risk. When analyses were separated into hepatocellular carcinoma (HCC, N = 436 cases) and intrahepatic cholangiocarcinoma (ICC, N = 110 cases), no evidence of heterogeneity was observed except for lipopolysaccharide-binding protein concentrations, which were positively associated with HCC (1.77, 1.34-2.33) but not ICC (0.67, 0.37-1.22; p-heterogeneity = .003). Associations did not differ by time to liver cancer diagnosis or other subgroups. These findings support the role of gut barrier dysfunction in hepatocarcinogenesis, necessitating further research to understand the complex interplay among the mechanisms and risk factors disrupting the gut barrier, microbiota, and liver cancer.},
}

Humans
Male
Case-Control Studies
*Liver Neoplasms/immunology/microbiology/blood/epidemiology
Female
Middle Aged
*Bacterial Translocation/immunology
Prospective Studies
Lipopolysaccharide Receptors/blood/immunology
Aged
Carrier Proteins/blood/immunology
Membrane Glycoproteins/blood
Risk Factors
Flagellin/immunology
Immunoglobulin G/blood
Acute-Phase Proteins
Lipopolysaccharides/immunology
Adult
Immunoglobulin A/blood
Biomarkers, Tumor

@article {pmid41129758,
year = {2025},
author = {Bagshaw, P and Potter, JD and Griffiths, N and Hornblow, A and Cox, B and Gower, K},
title = {Nurse endoscopists: a rational response to rising rates of young-onset colorectal cancer in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {138},
number = {1624},
pages = {76-86},
doi = {10.26635/6965.7100},
pmid = {41129758},
issn = {1175-8716},
mesh = {Humans ; New Zealand/epidemiology ; *Colorectal Neoplasms/epidemiology/diagnosis/nursing ; Middle Aged ; *Colonoscopy/nursing ; *Early Detection of Cancer ; Sigmoidoscopy/nursing ; Age of Onset ; Incidence ; *Mass Screening ; Aged ; Adult ; Female ; Male ; },
abstract = {Young-onset (<50 years) colorectal cancer (YOCRC) has been increasing in Aotearoa New Zealand since the birth cohort born around the mid-1950s. Possible responses include education and public health measures, none of which are likely to make a major impact in the foreseeable future. Many YOCRCs are presenting at late stages with predominantly distal cancers. Our current National Bowel Screening Programme (NBSP), screening people 60-75 years, was introduced with inadequate resources; as a result, some colonoscopy services have been moved from symptomatic cases to screening, resulting in diagnostic delays and poorer outcomes. Extending screening to 40 or 45 years will markedly increase the need for follow-up colonoscopies and stretch services beyond breaking point. Sigmoidoscopy is associated with a substantial and sustained reduction in risk of distal colorectal cancer incidence and mortality. As there are too few endoscopists for the existing workload, increasing the nurse endoscopist workforce is a rational step. Initial training would focus on flexible sigmoidoscopy (FS) and concentrate on symptomatic patients <50 years. Steadily increasing nurse endoscopist numbers will contribute to management of the rising incidence of YOCRC. Without disrupting the NBSP or putting much extra strain on need for follow-up colonoscopies, nurse-led FS clinical services can expand to anyone with relevant symptoms and, as a longer-term goal, eventually become part of an expanded screening programme that could include one-off FS at age 50. If we are agreed that this is essential, training and service must be adequately funded and accompanied by a public advocacy campaign to ensure sufficient resources.},
}

Humans
New Zealand/epidemiology
*Colorectal Neoplasms/epidemiology/diagnosis/nursing
Middle Aged
*Colonoscopy/nursing
*Early Detection of Cancer
Sigmoidoscopy/nursing
Age of Onset
Incidence
*Mass Screening
Aged
Adult
Female
Male

@article {pmid41129763,
year = {2025},
author = {Einstein, DJ and Abel, ML and Aragon-Ching, JB and Arlen, PM and Autio, KA and Bilusic, M and Carducci, MA and Choyke, PL and Citrin, DE and Figg, WD and Graff, JN and Gulley, JL and Halabi, S and Karzai, F and Lindenberg, L and Markowski, MC and Marshall, CH and McNeel, DG and Mena, E and Moon, H and Pachynski, RK and Paller, CJ and Patel, KR and Posadas, EM and Pienta, KJ and Regan, MM and Sena, LA and Walmsley, CS and Wei, XX and Yu, EY and Tran, PT and Madan, RA},
title = {National Cancer Institute's Working Group on Biochemically Recurrent Prostate Cancer: Clinical Trial Design Considerations.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {43},
number = {34},
pages = {3672-3683},
doi = {10.1200/JCO-25-01693},
pmid = {41129763},
issn = {1527-7755},
support = {U54 CA273956/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/therapy/pathology/diagnostic imaging/blood ; *Neoplasm Recurrence, Local/therapy/diagnostic imaging/blood ; United States ; National Cancer Institute (U.S.) ; *Research Design ; *Clinical Trials as Topic/methods ; Quality of Life ; Prostate-Specific Antigen/blood ; },
abstract = {PURPOSE: Biochemical recurrence (BCR) of prostate cancer (PCa) after definitive surgery and/or radiation (including salvage strategies) is a burgeoning area of clinical research inspired by ultrasensitive next-generation imaging. Most phase III trials in PCa have focused on metastatic disease, defined by conventional imaging. Despite the emergence of new imaging, clinical trial principles from metastatic studies will not optimize future BCR trials.

METHODS: A Working Group convened at the National Cancer Institute on November 13, 2024 (NCI BCR WG). Key areas of discussion included nomenclature, baseline criteria for data capture, imaging considerations, delineation of high-risk populations to be targeted for trial development, requirements of metastasis-directed therapy (MDT) or hormonal therapy, quality-of-life considerations, and potential study end points.

RESULTS: The NCI BCR WG defined the novel term "prostate-specific membrane antigen (PSMA)+BCR" to identify the emerging concept of recurrent PCa identifiable only on PSMA positron emission tomography (PET), overlapping with BCR and distinct from metastatic hormone-sensitive PCa as traditionally defined by conventional imaging. The WG suggested defining high-risk BCR with a prostate-specific antigen doubling time of ≤6 months, regardless of PET findings. The WG provided recommendations for baseline data capture and imaging requirements. Neither systemic therapy nor MDT were considered mandatory for control arms. The WG also discussed novel end points and quality-of-life metrics in this disease space.

CONCLUSION: These discussions should inform future clinical BCR trials in this distinct disease space relative to metastatic disease defined by conventional imaging. The NCI BCR WG strongly advocates that future trials explore deintensification of treatment to minimize toxicity in this relatively indolent disease state.},
}

Humans
Male
*Prostatic Neoplasms/therapy/pathology/diagnostic imaging/blood
*Neoplasm Recurrence, Local/therapy/diagnostic imaging/blood
United States
National Cancer Institute (U.S.)
*Research Design
*Clinical Trials as Topic/methods
Quality of Life
Prostate-Specific Antigen/blood

@article {pmid41130408,
year = {2026},
author = {Le, X and Baik, C and Cho, BC and Riess, JW and Piotrowska, Z and Johannes de Langen, A and Goldberg, SB and Goldman, JW and Reguart, N and Shiraishi, Y and Ambrose, H and Fraenkel, PG and Ruiz, BM and Smith, PE and Tang, KH and Yu, HA},
title = {Osimertinib Plus Savolitinib in Patients With EGFR-Mutated Advanced NSCLC With MET Alterations After First-Line Osimertinib: Clinical Outcomes, Safety, and Biomarker Analysis: A Brief Report.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {21},
number = {2},
pages = {318-327},
doi = {10.1016/j.jtho.2025.10.009},
pmid = {41130408},
issn = {1556-1380},
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology ; *Lung Neoplasms/drug therapy/pathology/genetics ; Female ; Male ; *Acrylamides/therapeutic use/pharmacology/administration & dosage ; *Aniline Compounds/therapeutic use/pharmacology ; Middle Aged ; Aged ; ErbB Receptors/genetics ; Mutation ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology ; *Proto-Oncogene Proteins c-met/genetics ; Biomarkers, Tumor/genetics ; Survival Rate ; Adult ; Prognosis ; Aged, 80 and over ; Indoles ; Pyrazines ; Pyrimidines ; Triazines ; },
abstract = {INTRODUCTION: The ORCHARD (NCT03944772) study was conducted to characterize resistance mechanisms and identify optimal treatments after progressive disease (PD) on first-line osimertinib. We report results from the osimertinib plus savolitinib module.

METHODS: Patients with EGFR-mutated NSCLC with PD on first-line osimertinib with MET gene amplification (≥4 copies of MET over tumor ploidy) per next-generation sequencing of a post-progression biopsy received osimertinib plus savolitinib. Primary end point was investigator-assessed objective response rate (ORR). Secondary end points included progression-free survival, duration of response, overall survival, and safety. Correlation of ORR with baseline molecular alterations was an exploratory analysis.

RESULTS: A total of 32 patients were enrolled; all had tumors with MET amplification. At primary analysis cutoff (January 2023), confirmed ORR was 47% (80% confidence interval [CI]: 34-60). Median duration of response was 14.5 months (95% CI: 5.6-18.7). Median progression-free survival was 7.6 months (95% CI: 3.2-15.9). There was a trend toward increased ORR in patients with high MET gene copy number (≥10 versus <10). Furthermore, 14 patients (44%) had grade 3 or higher treatment-emergent adverse events; most often pneumonia (n = 3; 9%). At final database lock (May 2024), 20 patients (63%) had died; median overall survival was 20.7 months (95% CI: 9.9-34.8).

CONCLUSIONS: Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with EGFR-mutated advanced NSCLC and MET amplification after PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs.},
}

Humans
*Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology
*Lung Neoplasms/drug therapy/pathology/genetics
Female
Male
*Acrylamides/therapeutic use/pharmacology/administration & dosage
*Aniline Compounds/therapeutic use/pharmacology
Middle Aged
Aged
ErbB Receptors/genetics
Mutation
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology
*Proto-Oncogene Proteins c-met/genetics
Biomarkers, Tumor/genetics
Survival Rate
Adult
Prognosis
Aged, 80 and over
Indoles
Pyrazines
Pyrimidines
Triazines

@article {pmid41134118,
year = {2025},
author = {Chua, KJ and Quilang, RC and Sallinger, K and Aktipis, CA and Arck, P and Bianchi, DW and Chang, HD and Cleaves, HJ and Eikmans, M and Fjeldstad, HES and Haig, D and Harrington, WE and Horsnell, W and Jacobsen, DP and Kamper-Jørgensen, M and Kanaan, SB and Khosrotehrani, K and Lambert, NC and Nelson, JL and Olsen, MB and Pan, TD and Prins, JR and Schildberg, FA and Staff, AC and Ståhlberg, A and Stelzer, IA and Urbschat, C and Way, SS and Wilson, MA and Ye, J and Kroneis, T and Boddy, AM},
title = {Identifying Key Questions and Challenges in Microchimerism Biology.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {48},
pages = {e14969},
pmid = {41134118},
issn = {2198-3844},
support = {62214//John Templeton Foundation/ ; //Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health/ ; },
mesh = {Animals ; Female ; Humans ; *Chimerism ; Male ; },
abstract = {Microchimerism research has recently gained renewed attention despite known existence of these rare cells for decades. Fetal and maternal microchimeric-derived cells may have functional capabilities, and are increasingly associated with both beneficial and adverse health outcomes. Yet, establishing the role of microchimerism in health has been largely constrained methodologically and theoretically. The Microchimerism, Human Health, and Evolution Project address these challenges by calling on 29 leading microchimerism experts to put forth key research questions that can substantially advance the field. Seven major categories are identified: function and mechanism; microchimerism in interventions, treatment, and transplant; mapping "generational microchimerism"; evolution; microchimerism detection; appropriate experimental model systems; and definition of microchimerism. Identifying these questions - and continuing to find answers - will be crucial for advancing the knowledge of microchimerism in health and disease.},
}

Animals
Female
Humans
*Chimerism
Male

@article {pmid41135058,
year = {2026},
author = {Adesina, OO and Voutsinas, J and Wu, QV and Teos, LY and Rokni, M and Nalbant, H and Nardo, L and Wun, T and Zemel, B},
title = {Low bone mineral density and pain impact in adults with sickle cell disease.},
journal = {Blood advances},
volume = {10},
number = {3},
pages = {748-758},
pmid = {41135058},
issn = {2473-9537},
support = {K23 HL148310/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Anemia, Sickle Cell/complications ; Female ; Male ; Adult ; *Bone Density ; *Pain/etiology ; Middle Aged ; Absorptiometry, Photon ; Quality of Life ; },
abstract = {Low bone mineral density (BMD) is a prevalent skeletal finding in sickle cell disease (SCD), but its clinical consequences are poorly understood. We hypothesized that low BMD, independent of osteonecrosis (ON), would associate with pain in adults with SCD. In the SCD Bone Pain study, 53 ambulatory adults (64% females; mean age, 38 ± 11 years; 66% hemoglobin [Hb] SS/Sβ0 thalassemia) underwent dual-energy X-ray absorptiometry scans of their lumbar spine, hip, forearm, and whole body. They also completed the Adult Sickle Cell Quality of Life Measurement Information System pain impact questionnaire. Twenty-three participants (43%) had low BMD, defined as lumbar spine, total hip, or femoral neck BMD z scores of -2 or less. In multivariate linear regression, lumbar spine BMD z scores significantly changed by +0.31, -0.29, -0.14, and -1.3 for every unit increase in Hb, indirect bilirubin, and white blood cell count, and with crizanlizumab use, respectively. Pain impact T-scores significantly decreased (worsened) by 6.0 and 6.5 with reduced estimated glomerular filtration rate and chronic opioid therapy but increased (improved) by 3.8 for every unit increase in serum phosphate. The median [interquartile range] pain impact T-scores were significantly lower in participants with low BMD and ON (38.3 [37.4, 40.1]) than those with either low BMD (49.5 [43.6, 54.4]; P = 3 × 10-5) or ON (52.7 [45.3, 57]; P = 2 × 10-4) alone. Whether sickle cell-related low BMD results from impaired bone formation and/or accelerated bone loss remains unclear. Understanding how low bone density, with or without ON, mediates SCD pain warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT05283148.},
}

Humans
*Anemia, Sickle Cell/complications
Female
Male
Adult
*Bone Density
*Pain/etiology
Middle Aged
Absorptiometry, Photon
Quality of Life

@article {pmid41135920,
year = {2026},
author = {Medlin, AR and Abrams, HR and Kent, EE and Ogunjesa, BA and Park, S and Tan, KR},
title = {Variations in Mental Distress Among Caregivers of Individuals With Chronic Illnesses and Comorbid Cognitive Impairment.},
journal = {American journal of preventive medicine},
volume = {70},
number = {4},
pages = {108165},
doi = {10.1016/j.amepre.2025.108165},
pmid = {41135920},
issn = {1873-2607},
mesh = {Humans ; *Caregivers/psychology/statistics & numerical data ; Male ; Female ; *Cognitive Dysfunction/epidemiology/psychology ; Middle Aged ; Chronic Disease/psychology ; Aged ; Adult ; Behavioral Risk Factor Surveillance System ; *Mental Disorders/epidemiology ; Comorbidity ; Alzheimer Disease ; *Stress, Psychological/epidemiology ; *Psychological Distress ; },
abstract = {INTRODUCTION: This study was aimed to examine the rates of mentally unhealthy days and frequent mentally unhealthy days among caregivers of patients with cancer, heart disease, mental illness, and Alzheimer's disease and related dementias on the basis of caregiving intensity and how cognitive impairment in non-Alzheimer's disease and related dementias caregiving moderates these relationships.

METHODS: Data from 22,550 caregivers in the 2019-2023 Behavioral Risk Factor Surveillance System were used to explore the relationship between caregiving intensity, mentally unhealthy days, and the presence of cognitive impairment. Zero-inflated negative binomial regressions assessed the associations of caregiving intensity on mentally unhealthy days, and logistic regressions examined the patterns in frequent mentally unhealthy days, controlling for demographics and survey weighting.

RESULTS: Caregivers of individuals with mental illness reported the highest frequent mentally unhealthy days (27.53%), followed by caregivers of those with cancer (20.3%), heart disease (18.57%), and Alzheimer's disease and related dementias (17.82%). Increased caregiving intensity correlated with higher mentally unhealthy day rates, particularly among caregivers of patients with cancer, heart disease, and Alzheimer's disease and related dementias. Caregivers of those with cancer showed increased mentally unhealthy days when moderating for cognitive impairment. Higher caregiving intensity was linked to increased frequent mentally unhealthy days in the caregivers of patients with cancer and Alzheimer's disease and related dementias, with cancer caregivers showing more frequent mentally unhealthy days when moderating for cognitive impairment.

CONCLUSIONS: Caregiving intensity affects mental health outcomes differently across illnesses. Tailored support is needed for caregivers, especially those providing care for individuals with comorbid cognitive impairment.},
}

Humans
*Caregivers/psychology/statistics & numerical data
Male
Female
*Cognitive Dysfunction/epidemiology/psychology
Middle Aged
Chronic Disease/psychology
Aged
Adult
Behavioral Risk Factor Surveillance System
*Mental Disorders/epidemiology
Comorbidity
Alzheimer Disease
*Stress, Psychological/epidemiology
*Psychological Distress

@article {pmid41136348,
year = {2025},
author = {Duran, MC and Shah, PD and Bell-Brown, AM and Rojina, J and Glascock, M and Ramirez, M and Ibarra, G and Garza, L and Linde, S and Bishop, S and Garrison, MM and Pascoe, KM and Drain, PK and Zhou, C and Ko, LK},
title = {Back to school: a qualitative study evaluating a community-informed COVID-19 risk communication intervention for rural elementary school children and their families.},
journal = {Translational behavioral medicine},
volume = {15},
number = {1},
pages = {},
pmid = {41136348},
issn = {1613-9860},
support = {UL1 TR002319/TR/NCATS NIH HHS/United States ; OT2 HD107544/GF/NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/prevention & control ; Child ; Qualitative Research ; Female ; Male ; Rural Population ; Focus Groups ; Schools ; Parents/psychology ; SARS-CoV-2 ; *Students/psychology ; *Return to School ; Communication ; School Health Services ; Health Knowledge, Attitudes, Practice ; Adult ; },
abstract = {BACKGROUND: ReOpening Schools Safely and Educating Youth (ROSSEY) was a cluster randomized controlled trial of a risk communication intervention for COVID-19 prevention to promote safe return to school among students in a rural, agricultural community.

PURPOSE: This qualitative study evaluated the implementation of a risk communication intervention and a school district's COVID-19 testing program through parent focus groups and interviews with school staff and students.

METHODS: Parents (n = 37), students (n = 19), and school staff (n = 14) from seven schools that received the intervention shared their experience via focus groups and interviews informed by the RE-AIM framework. Deductive and inductive coding was conducted by four data analysts. Themes were validated with community members.

RESULTS: Parent focus groups, student and staff interviews provided insight into the ROSSEY study implementation. We identified five main themes: (i) social and financial drivers of participation; (ii) personal beliefs and unique challenges to research participation; (iii) intervention reinforced knowledge and shifted behavior; (iv) the appeal of comic books and videos supported adoption; and (v) multimodal communication and partnerships enhanced implementation.

CONCLUSIONS: The risk communication intervention was deemed culturally appropriate, reinforced previous knowledge, and encouraged adoption of preventive behaviors. The partnership with the school district and collaboration with the district's COVID-19 testing program ensured success of recruitment, study implementation, and adoption of preventive behaviors.},
}

Humans
*COVID-19/prevention & control
Child
Qualitative Research
Female
Male
Rural Population
Focus Groups
Schools
Parents/psychology
SARS-CoV-2
*Students/psychology
*Return to School
Communication
School Health Services
Health Knowledge, Attitudes, Practice
Adult

@article {pmid41136629,
year = {2025},
author = {Corey, L and Ratevosian, J and Beyrer, C and Currier, J and Eron, J and Cohen, MS and Deeks, SG},
title = {How HIV research drives health innovation in multiple diseases.},
journal = {Nature medicine},
volume = {31},
number = {12},
pages = {3965-3967},
pmid = {41136629},
issn = {1546-170X},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1AI068636//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1AI068619//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1 AI068614/AI/NIAID NIH HHS/United States ; },
}

@article {pmid41137757,
year = {2025},
author = {Fong, Y and Huang, Y and Huang, Y and Woo, W and McGarry, A and Áñez, G and Dunkle, LM and Cho, I and Houchens, CR and Martins, K and Jayashankar, L and Castellino, F and Petropoulos, CJ and Leith, A and Haugaard, D and Webb, W and Lu, Y and Yu, C and Carpp, LN and Randhawa, AK and Andrasik, MP and Kublin, JG and Hutter, J and Keshtkar-Jahromi, M and Beresnev, TH and Rodriguez, CA and Tapia, M and Turley, CB and Zorrilla, CD and Cohen, SH and Kline, SE and Barranco, E and Corey, L and Neuzil, KM and Follmann, D and Ake, JA and Gay, CL and Kotloff, KL and Jones, T and Koup, RA and Donis, RO and Gilbert, PB},
title = {Analysis of antibody markers as immune correlates of risk of severe COVID-19 in the PREVENT-19 efficacy trial of the NVX-CoV2373 recombinant protein vaccine.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
pmid = {41137757},
issn = {1537-6591},
support = {S10 OD028685/OD/NIH HHS/United States ; C0000008/CL/CLC NIH HHS/United States ; UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; R37 AI054165/AI/NIAID NIH HHS/United States ; UM1 AI148684/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; UM1 AI068619/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: We previously showed that ancestral-specific anti-Spike binding IgG concentration and 50% inhibitory dilution neutralizing antibody titer (nAb-ID50) measured at 2 weeks post-dose 2 (∼peak) were inverse correlates of risk (CoRs) of COVID-19 over 2 months post ∼peak in the PREVENT-19 trial of the NVX-CoV2373 vaccine; there were not sufficient data to assess CoRs of severe COVID-19.

METHODS: Here we assessed, in the same vaccinated cohort, Delta- and ancestral-specific Spike IgG and nAb-ID50 at ∼peak and over time as CoRs of severe COVID-19 and of Delta COVID-19 over 3.5-10 months post ∼peak (287 breakthrough Delta cases, including 8 severe; 446 non-cases).

RESULTS: ∼Peak antibody levels were much higher for non-cases vs. severe cases (all inferred Delta), with nAb-ID50 Delta geometric mean 209.5 arbitrary units (AU)/mL (95% CI: 176.1, 249.1) vs. 9.6 AU/mL (95% CI: 2.4, 38.6), respectively. Frequency of detectable nAb-ID50 titer was 98.3% (97.2, 99.0) for non-cases vs. 62.5% (22.3, 93.9) for severe cases. All markers were inverse CoRs of severe COVID-19, with a ∼peak hazard ratio (HR) of 0.13 (95% CI: 0.03, 0.57) per 10-fold nAb-ID50 Delta increase. Severe COVID-19 risk through 305 days post-Day 35 was 0.0338 (0.0043, 0.206) at the nAb-ID50 Delta 2.5th percentile (8.4 AU/ml), and 0.002 (0.0000, 0.0108) and 0.0002 (0.0000, 0.0035) at the 50th and 95th percentiles (210, 2522 AU/ml).

CONCLUSIONS: Post-vaccination NVX-CoV2373 antibody levels are stronger predictors of severe COVID-19 than any-severity Delta COVID-19. Low antibody responses indicate vulnerability to severe COVID-19.},
}

@article {pmid41138741,
year = {2025},
author = {Anderson, BO and Duggan, C},
title = {Lessons from CONCORD and VENUSCANCER: closing global gaps in cancer care for women.},
journal = {Lancet (London, England)},
volume = {406},
number = {10517},
pages = {2298-2300},
doi = {10.1016/S0140-6736(25)01580-6},
pmid = {41138741},
issn = {1474-547X},
}

@article {pmid41138816,
year = {2026},
author = {Shadman, M and Ahmed, S and Byrne, MT and Chavez, JC and Kamdar, M and Sorror, ML and Perales, MA and Hill, JA and Moslehi, J and Miklos, DB},
title = {Who Is Eligible for Chimeric Antigen Receptor T Cell Therapy? Expert Perspectives on Overcoming Referral Barriers.},
journal = {Transplantation and cellular therapy},
volume = {32},
number = {3},
pages = {277-287},
doi = {10.1016/j.jtct.2025.10.025},
pmid = {41138816},
issn = {2666-6367},
mesh = {Humans ; *Immunotherapy, Adoptive/methods ; *Referral and Consultation ; *Receptors, Chimeric Antigen/immunology ; *Hematologic Neoplasms/therapy/immunology ; },
abstract = {CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies, including lisocabtagene maraleucel, axicabtagene ciloleucel, and tisagenlecleucel, have revolutionized the treatment landscape for patients with hematologic malignancies. However, identification and referral of patients who could benefit from treatment remains a significant challenge, Here, we report expert recommendations for CAR-T therapy referral gathered from 10 experts in oncology, hematology, cardiology, and infectious diseases from a roundtable meeting and/or subsequent reviews between November 13, 2024, and June 9, 2025. We considered the following potential factors: age, performance status, disease status, cardiovascular function, pulmonary function, renal function, hepatic function, infections, and psychological health. Based on existing evidence, we agreed that none of the factors discussed should preclude patients from receiving referrals/further evaluation for CAR-T therapy, particularly with current advances in supportive care and integration of services from other specialties. Timely referral should be made by the patient's primary oncologist to specialists as early as the disease is deemed relapsed or refractory, preferably before the starting the subsequent line of therapy to allow better access to care and improve treatment outcomes. Before CAR-T therapy, holding therapy (before leukapheresis) and/or bridging therapy (after leukapheresis) may be given to patients with high-volume disease, in consultation with CAR-T therapy specialists. Based on the safety profile of CAR-T therapies, experts recommended flexible monitoring and transfer of care back to primary/community oncology physicians, starting from 2 weeks after infusion to improve access to this potentially curative therapy. Adaptations to clinical practice based on the most recent regulations, policy requirements, and institutional guidelines should be made as needed. In summary, a panel of 10 experts provided recommendations for timely patient referral for CAR-T therapy on the occurrence of relapsed or refractory disease and before the initiation of subsequent lines of therapy to improve care access and treatment outcomes. Experts noted that with close collaboration between CAR-T therapy specialists and other medical disciplines, CAR-T therapy remains a feasible option for most patients despite their comorbidities. © 2025 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.},
}

Humans
*Immunotherapy, Adoptive/methods
*Referral and Consultation
*Receptors, Chimeric Antigen/immunology
*Hematologic Neoplasms/therapy/immunology

@article {pmid41138914,
year = {2026},
author = {Zhang, Y and Alver, S and Shan, Z and Mossavar-Rahmani, Y and Hu, J and Zhang, J and St-Onge, MP and Kaplan, R and Xue, X and Qi, Q},
title = {The timing of macronutrient and major food group intake and associations with mortality among United States adults, 1999‒March 2020: a serial cross-sectional study.},
journal = {The American journal of clinical nutrition},
volume = {123},
number = {1},
pages = {101097},
pmid = {41138914},
issn = {1938-3207},
support = {R35 HL155670/HL/NHLBI NIH HHS/United States ; R01 DK128154/DK/NIDDK NIH HHS/United States ; R01 DK126698/DK/NIDDK NIH HHS/United States ; R01 DK119268/DK/NIDDK NIH HHS/United States ; R01 HL170904/HL/NHLBI NIH HHS/United States ; R01 HL142648/HL/NHLBI NIH HHS/United States ; T32 CA094880/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; United States/epidemiology ; Adult ; Middle Aged ; Nutrition Surveys ; *Nutrients/administration & dosage ; *Diet ; Energy Intake ; Aged ; Time Factors ; *Feeding Behavior ; *Mortality ; Young Adult ; *Eating ; },
abstract = {BACKGROUND: Eating timing has been increasingly linked to health, yet national trends in macronutrient/food group timing and their health implications remain unclear.

OBJECTIVES: To characterize trends in the timing of energy, macronutrient, and food group intake among United States adults and examine their associations with mortality.

METHODS: In this serial cross-sectional study of adults aged ≥20 y with ≥1 valid 24-h dietary recall (National Health and Nutrition Examination Survey, 1999‒March 2020), we examined secular trends in timing of energy, macronutrients, and major food group intake. Associations with mortality (through December 2019) were examined using Cox models.

RESULTS: Among 50,264 adults, evening (18:00-22:00) accounted for the highest daily energy intake (weighted mean proportions across years, 31.9%‒33.3%), followed by noon (10:00-14:00, 24.7%‒26.8%), afternoon (14:00-18:00, 19.9%‒21.8%), morning (06:00-10:00, 13.5%‒14.9%), and overnight (22:00-06:00, 5.6%‒6.5%); midnight (22:00-02:00) eating occurred in 23.4%‒28.0% of the population. Macronutrient and food groups followed similar patterns, except whole grain (peaked in the morning) and fruit, egg, and dairy intake (more evenly distributed). Over the years, noon and midnight energy intake proportions declined, whereas the afternoon proportion increased; secular trends varied by macronutrients/food groups. Fasting started at 20:34-20:51 and ended at 08:41-08:51; intake midpoint was 14:37-14:48; intake duration was 11.9‒12.2 h. Male, non-Hispanic Black, and socioeconomically disadvantaged groups had greater midnight intake proportions and later intake midpoints. Reallocating 5% of daily energy to midnight was associated with higher cardiovascular mortality (hazard ratio: 1.09; 95% confidence interval: 1.02,1.17), driven by carbohydrates; reallocating 5% to predawn (02:00-06:00) was associated with higher cancer mortality (hazard ratio: 1.22; 95% confidence interval: 1.05, 1.41), driven by proteins. Each 1-h delay in fasting and intake midpoint was associated with an 8%‒9% higher cardiovascular mortality.

CONCLUSIONS: Overnight intake and delayed eating timing are prevalent among United States adults, especially between socioeconomically disadvantaged groups, and were associated with higher mortality, particularly for specific macronutrients/foods, supporting eating timing recommendations integrating food composition.},
}

Humans
Cross-Sectional Studies
Male
Female
United States/epidemiology
Adult
Middle Aged
Nutrition Surveys
*Nutrients/administration & dosage
*Diet
Energy Intake
Aged
Time Factors
*Feeding Behavior
*Mortality
Young Adult
*Eating

@article {pmid41141367,
year = {2025},
author = {Wick, BJ and Kluesner, MG and Slipek, NJ and Skeate, JG and Niemeyer, EM and Webber, BR and Moriarity, BS},
title = {Installation of dominant-negative mutations in FAS and TGFβR2 via base editing in primary T cells.},
journal = {Molecular therapy. Oncology},
volume = {33},
number = {4},
pages = {201063},
pmid = {41141367},
issn = {2950-3299},
support = {R01 AI161017/AI/NIAID NIH HHS/United States ; P30 CA077598/CA/NCI NIH HHS/United States ; F30 CA305905/CA/NCI NIH HHS/United States ; R61 AG090358/AG/NIA NIH HHS/United States ; U54 CA232561/CA/NCI NIH HHS/United States ; R21 AI163731/AI/NIAID NIH HHS/United States ; T32 HL007062/HL/NHLBI NIH HHS/United States ; U24 OD026641/OD/NIH HHS/United States ; R21 CA237789/CA/NCI NIH HHS/United States ; R37 CA276345/CA/NCI NIH HHS/United States ; P01 CA254849/CA/NCI NIH HHS/United States ; R01 AI146009/AI/NIAID NIH HHS/United States ; U54 CA268069/CA/NCI NIH HHS/United States ; P50 CA136393/CA/NCI NIH HHS/United States ; },
abstract = {Adoptive cell transfer (ACT) of engineered T cells is effective against B cell malignancies but has faltered against solid tumors due to the immunosuppressive tumor microenvironment (TME). FAS ligand (FASL) and transforming growth factor β (TGF-β) are key mediators of T cell dysfunction in the TME and overexpressing dominant negative (dn) forms of their receptors in T cells increases anti-tumor efficacy in solid tumor models. However, an approach that directly targets the endogenous genes would be more amenable to multiplex editing and reduce competition with WT alleles. Here, we employ base editing (BE) in primary human T cells to install naturally occurring dominant negative FAS and TGFβR2 mutations. In vitro survival and proliferation assays demonstrate that BE T cells are resistant to pro-apoptotic and anti-proliferative effects of FAS and TGF-β signaling. Chimeric antigen receptor (CAR)-T cells with BE-installed dn TGFβR2 or dn FAS exhibit improvements in cytotoxicity, while dn TGFβR2 CAR T demonstrate increased persistence and reduced expression of phenotypic markers of exhaustion compared to controls. Moreover, BE-engineered dn CAR T outperform lentiviral-engineered cDNA over expression counterparts in several functional assays. Considering the efficiency of BE and its amenability for multiplex editing, our approach lends itself to engineering strategies necessary to overcome T cell dysfunction in solid tumors.},
}

@article {pmid41141393,
year = {2026},
author = {Choudhury, SR and Kaushal, A and Biswas, P and Padilla, C and Sarthy, JF and Chavan, A and Gonzalez, GA and Meshinchi, S and Farrar, JE},
title = {Transcriptional rewiring by enhancer methylation in CBFA2T3-GLIS2-driven pediatric acute megakaryoblastic leukemia.},
journal = {Genes & diseases},
volume = {13},
number = {1},
pages = {101843},
pmid = {41141393},
issn = {2352-3042},
abstract = {Resistance to chemotherapy and subsequent relapse remain the primary challenge in pediatric acute myeloid leukemia (pAML), particularly in CBFA2T3-GLIS2 (C/G) fusion-positive acute megakaryoblastic leukemia. Here we demonstrate that the C/G fusion drives extensive DNA methylation changes and oncogenic enhancer activation at cis-regulatory elements (CREs), reshaping gene expression. This multi-omics analysis reveals a distinct hypermethylation pattern at promoters of up-regulated genes in C/G[+] pAML across patient samples (n = 24) and representative cell lines, notably enriched in adhesion-related, TGFβ, or Wnt signaling pathways. Hypermethylated regions adjacent to transcription start sites (TSS) maintain open chromatin with H3K27ac enrichment, supporting a mechanism of de novo chromatin looping and active transcription in a non-canonical manner. Additionally, C/G fusion binding near the DNA methyltransferase 3B (DNMT3B) promoter correlates with elevated DNMT3B expression, implicating its role in aberrant DNA methylation changes at CREs. This study elucidates the epigenetic mechanisms driving C/G[+] pAML, showing how the fusion reshapes chromatin and DNA methylation landscapes by impacting the expression (and likely activity) of epigenetic modifiers like DNMT3B. Functionally, DNMT3B inhibition enhances apoptotic sensitivity to BCL2 blockade, indicating that targeting DNMT3B may overcome apoptotic resistance in C/G[+] leukemic cells and offer a therapeutic strategy for this high-risk subtype.},
}

@article {pmid41141451,
year = {2025},
author = {Reed, JC and Hall, L and McKhann, A and Kwak, G and Goecker, EA and Coombs, RW and Chen, H and Roa, J and Vecchio, A and Daar, ES and Hunt, PW and Marra, CM and Campbell, TB and Ma, Q and Swaminathan, S and Macatangay, BJC and Morse, GD and Miller, T and Rusin, D and Ha, B and Alston-Smith, B and Paul, R and Letendre, SL and Spudich, SS and Greninger, AL},
title = {Antiretroviral Therapy Intensification With Dolutegravir and/or Maraviroc Did Not Affect HIV-1 Cell-Associated DNA, RNA, and 2--LTR Circles Over 12 Weeks.},
journal = {Open forum infectious diseases},
volume = {12},
number = {10},
pages = {ofaf594},
pmid = {41141451},
issn = {2328-8957},
support = {P30 AI027757/AI/NIAID NIH HHS/United States ; U01 AI068634/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Neurocognitive impairment (NCI) among people living with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) may result from residual viral replication. The A5324 trial found that ART intensification with dolutegravir (DTG) with or without maraviroc (MVC) did not affect NCI in PWH. We evaluated the impact of ART intensification on peripheral virological measures during the first 12 weeks of intensification.

METHODS: The A5324 study was a randomized, double-blind, placebo (PBO)-controlled, 96-week trial of ART intensification with either dual PBO, DTG + PBO, or DTG + MVC in PWH with NCI on ART who were naive to integrase strand transfer inhibitors and MVC. At baseline and weeks 2, 4, and 12, HIV-1 RNA was measured in plasma with a low-copy assay, while HIV-1 cell-associated DNA (caDNA), cell-associated unspliced RNA (caRNA), and cell-associated 2-long terminal repeat circles (ca2LTR) were quantified from peripheral blood mononuclear cells using droplet digital polymerase chain reaction.

RESULTS: Of the 171 participants, 59 were randomized to dual PBO, 57 to DTG + PBO, and 55 to DTG + MVC. Changes in caDNA and caRNA and detection of plasma RNA did not differ between treatment arms over 12 weeks (P > 0.05). Detection of ca2LTR was less frequent at weeks 2-4 in the DTG + MVC arm (40.4%) than in the dual-PBO (70.7%; P =0 .02) and DTG + PBO (68.4%; P = 0.03) arms. However, this difference diminished by week 12, and baseline ca2LTR detection in the DTG + MVC arm was lower than in the other groups.

CONCLUSIONS: DTG intensification had no effect on peripheral markers of HIV-1 persistence. DTG + MVC intensification reduced ca2LTR detection at weeks 2-4, though this effect did not persist through week 12. These findings indicate the minimal impact of intensification on the HIV-1 peripheral reservoir, consistent with prior studies.},
}

@article {pmid41143136,
year = {2025},
author = {Tanaka, K and Chikowore, TJB and Deeks, SG and Estes, JD and Ho, YC and Jiang, S and Lee, MJ and Li, C and Machinda, A and Martins, M and Mdletshe, P and Ndhlovu, ZM and Neogi, U and Ott, MM and Rasmussen, TA and Reddy, K and Rutishauser, RL and Farrell-Sherman, A and Tiemessen, CT and Voss, JE and Kityo, C and Lewin, SR and Ndung'u, T and McCune, JM},
title = {Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025.},
journal = {Pathogens & immunity},
volume = {10},
number = {2},
pages = {196-229},
pmid = {41143136},
issn = {2469-2964},
abstract = {Antiretroviral therapy (ART) can effectively control human immunodeficiency virus (HIV) replication; however, lifelong treatment is required due to viral reservoirs, which fuel viral rebound. This necessitates curative interventions that can achieve either eradication of the reservoir or durable remission off ART. Advances in technology have fostered development of multi-omic techniques encompassing molecular tools, proteomic analyses, imaging, and artificial intelligence (AI)-driven data analysis to understand HIV reservoir biology and persistence. These have informed the investigation of therapeutic interventions such as broadly neutralizing antibodies, latency reversal, immune cell augmentation, antivirals, and gene therapy. From April 7-10, 2025, experts in the field convened at the Keystone Symposia conference, HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, to discuss novel strategies for eradication and/or durable ART-free control of HIV.},
}

@article {pmid41143601,
year = {2026},
author = {Cliff, ERS and Pelaez, GD and Wan, F and Iyengar, V and Zhou, J and Chung, K and Abdel-Razeq, N and Allen, J and Major, A and Sharp, J and Epperla, N and Gould, P and Cherng, HJ and Houshyar, S and Wallace, DS and Lynch, RC and Kallam, A and Mei, MG and Merryman, RW and Fleyshman, M and Rhodes, JM and Kidwell, A and Fenske, TS and Malakhov, N and Mulvey, E and Watkins, MP and Alhaj Moustafa, M and Hilal, T and Nowakowski, GS and Wang, Y and Torka, P and Russler-Germain, DA},
title = {Cell-of-Origin Subtype Predicts Response to Polatuzumab Vedotin in Large B-cell Lymphoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {32},
number = {1},
pages = {159-168},
pmid = {41143601},
issn = {1557-3265},
support = {T32CA247815//National Cancer Institute (NCI)/ ; K12 CA167540/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K12CA167540//National Cancer Institute (NCI)/ ; //Lymphoma Research Foundation (LRF)/ ; T32 CA247815/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality ; Male ; Female ; Middle Aged ; Aged ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage ; *Immunoconjugates/administration & dosage/therapeutic use ; Aged, 80 and over ; Prognosis ; Treatment Outcome ; Antibodies, Monoclonal ; },
abstract = {PURPOSE: Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used.

EXPERIMENTAL DESIGN: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL.

RESULTS: Of 740 patients, 305 received polatuzumab in the first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77-3.84; P < 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66-4.02; P < 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5-0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP.

CONCLUSIONS: Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.},
}

Humans
*Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality
Male
Female
Middle Aged
Aged
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Adult
*Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage
*Immunoconjugates/administration & dosage/therapeutic use
Aged, 80 and over
Prognosis
Treatment Outcome
Antibodies, Monoclonal

@article {pmid41145253,
year = {2025},
author = {Kataria, I and Selmouni, F and Duggan, C and Sullivan, R and Purushotham, A and Sankaranarayanan, R and Taghavi, K and Basu, P},
title = {Application of implementation science methods and theories for cancer control planning in low-income and middle-income countries: a scoping review.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e108755},
pmid = {41145253},
issn = {2044-6055},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Humans ; *Neoplasms/prevention & control/therapy ; *Developing Countries ; *Implementation Science ; Health Policy ; Delivery of Health Care/organization & administration ; *Health Planning ; },
abstract = {INTRODUCTION: Implementation science (IS) is increasingly recognised as vital in cancer control planning and integrating evidence-based interventions across the cancer care continuum. Contextual differences often cause variability in delivering optimised healthcare, which IS approaches could mitigate. While IS improves planning effectiveness, many programme and policy planners remain unaware of its benefits. To address this, we examined IS theories applied to national cancer control plans (NCCPs)/strategies across five domains: stakeholder engagement, situational analysis, capacity assessment, economic evaluation and impact assessment.

METHODS: We conducted a scoping review using the Arksey and O'Malley framework to analyse NCCPs and strategies from 16 and 17 countries belonging to low and medium categories of Human Development Index (HDI), focusing on resource-constrained settings. We identified plans through the International Cancer Control Partnership portal, categorised them by WHO region and included only those available in English or French. We extracted data into a Microsoft Excel database and performed thematic analysis across five IS domains. Multiple IS experts, selected purposively based on their familiarity with resource-constrained settings, validated the findings, assessed policy relevance and helped develop a pathway for integrating IS into national cancer control planning. They reviewed structured questions in advance and provided feedback on analyses, practical utility, dissemination and simplifying IS application, which was used to refine the pathway and reach consensus.

RESULTS: While many NCCPs incorporated key IS elements such as stakeholder engagement, situational analysis and impact measurement, these often needed to be more explicit and consistently applied. None of the plans assessed health system capacity to determine readiness for implementing new interventions. Although most plans described stakeholder engagement, it was typically unstructured and incomplete. Four low HDI and nine medium HDI countries included costed plans, generally using an activity-based approach. All plans included impact measures (eg, key performance indicators), but five lacked mechanisms for engaging stakeholders or responsible entities to achieve the targets. These findings informed a proposed pathway to integrate IS principles into cancer control planning.

CONCLUSION: Integrating IS into national cancer control planning offers a structured framework for achieving equitable and feasible cancer control policies, particularly in resource-constrained settings, by enabling realistic goal setting and benchmarking against regional and global standards.},
}

Humans
*Neoplasms/prevention & control/therapy
*Developing Countries
*Implementation Science
Health Policy
Delivery of Health Care/organization & administration
*Health Planning

@article {pmid41146877,
year = {2025},
author = {Kuhlmann, AS and Madkhali, N and Moskovitz, E and Parrott, JE and Raman, SS and Riker, AO and Martinez-Reyes, J and Gupta, M and Jang, RA and Nelson, V and Gray, MD and Taylor, JJ and Peterson, CW and Kiem, HP},
title = {Heavy-chain immunoglobulin locus editing in rhesus macaque B cells to confer antibody production.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {4},
pages = {101598},
pmid = {41146877},
issn = {2329-0501},
support = {P51 OD011092/OD/NIH HHS/United States ; R01 AI167004/AI/NIAID NIH HHS/United States ; },
abstract = {Antibody-based immunotherapies are promising; however, their application remains limited to acute diseases due to rapid clearance of antibodies in vivo. Some chronic conditions could benefit from sustained therapeutic antibody expression. One such instance is human immunodeficiency virus type 1 (HIV-1), where the efficiency of broadly neutralizing antibodies by passive immunization has been limited in clinical trials. B cell editing to enable sustained production of an antibody of interest in vivo could address this issue. However, the long-term potential of this approach and feasibility to perform editing in B cells from people living with HIV remain to be determined. We investigated editing of rhesus macaque B cells from healthy or simian/human immunodeficiency virus (SHIV)-infected animals to model this approach. An antibody-encoding cassette was inserted in the immunoglobulin locus by CRIPSR-Cas9-mediated ex vivo B cell editing. Similar indel efficiencies were achieved in B cells from both uninfected and infected animals, and expression of the antibody of interest was detected in up to 10% of uninfected B cells. This study paves the way for future in vivo work to assess the long-term potential of this approach and its impact on B cell development and function in an immunocompetent in vivo nonhuman primate model of HIV persistence and cure.},
}

@article {pmid41147516,
year = {2025},
author = {Thomas, AB and Matthews, AL and Brooks, O and Winquist, A and Nelson, LA and Arias-Fontenot, R and Buchwald, D and Casaletto, KB and Weintraub, S and Heaton, RK and French, BF and Suchy-Dicey, A and Barbosa-Leiker, C},
title = {Psychometric properties of the NIH Toolbox Cognition Battery composites in older adults at risk for Alzheimer's disease and related dementias: A systematic review.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70673},
pmid = {41147516},
issn = {1552-5279},
support = {P30 AG066509/AG/NIA NIH HHS/United States ; R01 AG071677/AG/NIA NIH HHS/United States ; 1RF1AG071677-01//National Institute of Health/National Institute on Aging/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnosis/psychology ; *Psychometrics ; United States ; National Institutes of Health (U.S.) ; *Neuropsychological Tests ; *Dementia/diagnosis/psychology ; Aged ; *Cognition ; },
abstract = {This systematic review evaluated the psychometric performance of the National Institutes of Health's Toolbox Cognition Battery (NIHTB-CB) composite scores in older adults with and without Alzheimer's disease and related dementias (ADRD). A systematic literature search was conducted using MEDLINE, Embase, PsycINFO, and CINHAL databases. The evidence quality of NIHTB-CB measurement properties was assessed using integrated Consensus-based Standards for the Selection of Health Measurement Instrument (COSMIN) methodology and the Interpretation/Use Argument framework. Fourteen studies met inclusion criteria for this review of the NIHTB-CB. Evidence supporting the scoring, generalization, and extrapolation inferences of the Total, Crystallized, and Fluid composite scores in older adults ranged from developing through exemplary ratings. Findings indicate additional research is warranted on the NIHTB-CB in older adult and ADRD populations. The present study highlights the importance of continued use and research of the NIHTB-CB in diverse, older populations who are at risk for ADRD. HIGHLIGHTS: Limited research focuses on the National Institutes of Health's Toolbox Cognition Battery (NIHTB-CB) composites in older adults. The general psychometric robustness of the NIHTB-CB has been es. The Crystallized composite shows proficient psychometric evidence. The psychometric evidence of Fluid composite is developing due to limited data.},
}

Humans
*Alzheimer Disease/diagnosis/psychology
*Psychometrics
United States
National Institutes of Health (U.S.)
*Neuropsychological Tests
*Dementia/diagnosis/psychology
Aged
*Cognition

@article {pmid41149505,
year = {2025},
author = {Rios-Doria, E and Reichel, JB and Radke, MR and Manhardt, E and Rubin-Saika, M and Lockwood, C and Swisher, EM and Banda, K},
title = {Dynamic Monitoring of Recurrent Ovarian Cancer Using Serial ctDNA: A Real-World Case Series.},
journal = {Current oncology (Toronto, Ont.)},
volume = {32},
number = {10},
pages = {},
pmid = {41149505},
issn = {1718-7729},
support = {T32 CA009515/CA/NCI NIH HHS/United States ; 0000//Brotman Baty Institute/ ; },
mesh = {Humans ; Female ; *Ovarian Neoplasms/genetics/blood/pathology ; *Circulating Tumor DNA/blood/genetics ; *Neoplasm Recurrence, Local/blood/genetics ; Middle Aged ; Aged ; *Biomarkers, Tumor/blood/genetics ; Adult ; CA-125 Antigen/blood ; },
abstract = {Recurrent ovarian cancer (OC) is challenging to detect early using current methods like CA-125 and imaging. Circulating tumor DNA (ctDNA) may improve disease monitoring. Here, we assess the real-world clinical utility of serial ctDNA analyses in patients with recurrent OC. We analyzed serial plasma samples (N = 23) from six patients with recurrent OC using a tumor-informed next-generation sequencing assay targeting 68 cancer-related genes developed at the University of Washington. ctDNA variant allele frequencies (VAFs) were correlated with CA-125 levels, radiographic findings, and clinical outcomes. ctDNA levels generally reflected clinical status, accurately mirroring disease progression and therapeutic response. In one patient, rising ctDNA preceded clinical recurrence by four months, despite normal CA-125 and imaging, highlighting its potential advantage. Conversely, some patients exhibited clinical progression with undetectable ctDNA, indicating limitations in assay sensitivity, biological factors, or metastatic sites (e.g., brain metastases). ctDNA and CA-125 showed complementary value in most cases, suggesting potential combined use in clinical monitoring. Our findings demonstrate that ctDNA is a promising biomarker to complement existing monitoring approaches for recurrent OC. In some cases, capable of predicting relapse and treatment response ahead of current clinical indicators. However, identified discordances underscore technical and biological challenges that warrant further investigation. Larger prospective studies are necessary to refine ctDNA's clinical utility and integration into personalized OC care.},
}

Humans
Female
*Ovarian Neoplasms/genetics/blood/pathology
*Circulating Tumor DNA/blood/genetics
*Neoplasm Recurrence, Local/blood/genetics
Middle Aged
Aged
*Biomarkers, Tumor/blood/genetics
Adult
CA-125 Antigen/blood

@article {pmid41152111,
year = {2026},
author = {Jindal, T and Jiang, CY and Alhalabi, O and Davidsohn, M and Freeman, D and Epstein, IY and Bakaloudi, DR and Talukder, R and Nizam, A and Nguyen, CB and Oh, E and Tsung, I and Glover, MJ and Khaki, AR and Taylor, AK and Jaime-Casas, S and Jang, A and Lemke, E and Pywell, C and Evans, ST and Shin, D and Bilen, MA and Basu, A and Kilari, D and Tripathi, A and Brown, J and Emamekhoo, H and Davis, NB and Shah, S and Gupta, S and Grivas, P and Bellmunt, J and Alva, A and Campbell, MT and Koshkin, VS},
title = {Efficacy of sacituzumab govitecan after enfortumab vedotin in advanced urothelial carcinoma: Analysis of the UNITE study.},
journal = {Urologic oncology},
volume = {44},
number = {1},
pages = {65.e1-65.e11},
doi = {10.1016/j.urolonc.2025.09.025},
pmid = {41152111},
issn = {1873-2496},
mesh = {Humans ; Male ; Female ; Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology ; Retrospective Studies ; Middle Aged ; *Immunoconjugates/therapeutic use ; *Carcinoma, Transitional Cell/drug therapy/pathology/mortality ; *Camptothecin/analogs & derivatives/therapeutic use ; Treatment Outcome ; *Urologic Neoplasms/drug therapy/pathology ; *Urinary Bladder Neoplasms/drug therapy/pathology/mortality ; Aged, 80 and over ; Antibodies, Monoclonal/therapeutic use ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate used for advanced urothelial carcinoma (aUC) refractory to platinum-based chemotherapy and immune checkpoint inhibitors (ICI). Real-world data are needed to better define SG outcomes, particularly following treatment with enfortumab vedotin (EV). In this analysis, we aim to evaluate efficacy of SG after EV and assess putative biomarkers associated with outcomes.

METHODS: In the UNITE retrospective study, we identified patients who received ≥1 SG cycle after therapy with EV. Observed response rate (ORR) was assessed in evaluable patients and correlated with baseline clinical characteristics and biomarkers. ORRs were compared using logistic regression, while progression free survival (PFS) and overall survival (OS) from SG start were estimated via Kaplan-Meier and Cox proportional hazard (PH) model. Biomarkers of response were evaluated in multivariate Cox PH models after accounting for relevant clinical variables.

RESULTS: Among 107 patients treated with SG after EV, 97 (91%) had NGS data. Median age was 69 years, 73% were male, 33% had ≥4 prior lines of therapy, and 42% received G-CSF. ORR was 18% (95% CI: 10%-26%), median PFS 3.2 months, and median OS 6.0 months. In patients with disease control on EV, ORR was 22% compared to 8% in primary progressors on EV. No significant associations were found between molecular biomarkers and SG outcomes in the multivariate analysis.

CONCLUSION: SG showed modest activity after EV in heavily pretreated patients with aUC. ORR with SG after EV was lower than reported in phase 2 and phase 3 clinical trials for SG in the postplatinum/ICI setting.},
}

Humans
Male
Female
Aged
*Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology
Retrospective Studies
Middle Aged
*Immunoconjugates/therapeutic use
*Carcinoma, Transitional Cell/drug therapy/pathology/mortality
*Camptothecin/analogs & derivatives/therapeutic use
Treatment Outcome
*Urologic Neoplasms/drug therapy/pathology
*Urinary Bladder Neoplasms/drug therapy/pathology/mortality
Aged, 80 and over
Antibodies, Monoclonal/therapeutic use
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use

@article {pmid41152450,
year = {2025},
author = {Ding, F and Liu, S and Sun, W},
title = {Exploration of the roles of HLAs when predicting infection status by T cell receptors.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {37638},
pmid = {41152450},
issn = {2045-2322},
support = {R01 GM105785/GM/NIGMS NIH HHS/United States ; R56 AI169192/AI/NIAID NIH HHS/United States ; GM105785/GM/NIGMS NIH HHS/United States ; R56AI169192//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Receptors, Antigen, T-Cell/genetics/immunology ; *HLA Antigens/genetics/immunology ; Alleles ; T-Lymphocytes/immunology ; *Virus Diseases/immunology/genetics ; },
abstract = {T cells are critical components of the human immune system. When a cell is infected by a virus, it presents viral peptides on its surface using human leukocyte antigen (HLA) proteins. These peptide-HLA complexes are recognized by T cells through interactions with T cell receptors (TCRs). A human blood sample can contain millions of unique TCRs, which is a sample from the individual's TCR repertoire. TCR repertoire-wide association studies (TReWAS) aim to evaluate the associations between individual TCRs and disease or exposure status. Previous studies have shown that TCRs associated with viral infections can be identified using TReWAS, and these TCRs can be used to predict current or past infection with high accuracy. Many TCRs are strongly associated with specific HLA alleles, suggesting that the incorporation of HLA information could improve the precision of TReWAS analyses and predictions based on TCRs. In this study, we evaluated TCR-based predictions while conditioning on individual HLA alleles or their k-nearest neighbors. We observed improved prediction accuracy for some HLA alleles. Furthermore, these HLA-specific predictions provide insight into the role of specific HLAs in coordinating immune response to immunogenic antigens, demonstrating the benefit of HLA-aware analysis of TCR data.},
}

Humans
*Receptors, Antigen, T-Cell/genetics/immunology
*HLA Antigens/genetics/immunology
Alleles
T-Lymphocytes/immunology
*Virus Diseases/immunology/genetics

@article {pmid41155216,
year = {2025},
author = {Qin, R and Hua, M and Wang, Y and Zhang, Q and Cao, Y and Dai, Y and Ma, C and Zheng, X and Ge, K and Zhang, H and Li, S and Liu, Y and Cao, L and Wang, L},
title = {Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment: CCL5 as a Prognostic and Therapeutic Target.},
journal = {International journal of molecular sciences},
volume = {26},
number = {20},
pages = {},
pmid = {41155216},
issn = {1422-0067},
support = {82304250//National Natural Science Foundation of China/ ; 82273734//National Natural Science Foundation of China/ ; 82173629//National Natural Science Foundation of China/ ; },
mesh = {*Glioblastoma/immunology/genetics/drug therapy/pathology/metabolism ; Humans ; *Tumor Microenvironment/immunology/genetics ; *Chemokine CCL5/genetics/metabolism ; Prognosis ; *T-Lymphocytes/immunology/metabolism ; Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; *Brain Neoplasms/immunology/genetics/drug therapy/pathology ; Multiomics ; },
abstract = {Glioblastoma multiforme (GBM) is a common malignancy with poor prognosis, and exhausted T (TEX) cells, a subset of T cells characterized by progressive loss of effector functions, play a critical role in its progression. This study aimed to investigate the impact of TEX-related genes on immune function, prognosis, and drug sensitivity in GBM through multiomics analysis. Initially, we identified a novel set of TEX-related genes specific to GBM and screened hub genes (CCL5, IL18, CXCR6, FCER1G, TNFSF13B) using conventional statistical methods combined with machine learning. A prognostic risk model was subsequently constructed based on TCGA data and validated in the CGGA cohort. Single-cell and pharmacogenomic analyses revealed significant differences in tumor microenvironment composition and drug sensitivity between risk groups. Notably, Palbociclib emerged as a potential therapeutic agent targeting the novel discovered biomarker CCL5. RT-qPCR results showed that T cells with low CCL5 expression exhibited reduced expression of immune checkpoint-related genes (PD1, TIM3, LAG3) and increased expression of CD28, suggesting enhanced immune function. In conclusion, our findings highlight five hub genes as prognostic markers that could stratify GBM patients with different immune landscapes and levels of drug sensitivity. Furthermore, experimental results suggest that low CCL5 expression could alleviate T cell exhaustion and represent a promising therapeutic target, offering new strategies for improving GBM prognosis.},
}

*Glioblastoma/immunology/genetics/drug therapy/pathology/metabolism
Humans
*Tumor Microenvironment/immunology/genetics
*Chemokine CCL5/genetics/metabolism
Prognosis
*T-Lymphocytes/immunology/metabolism
Biomarkers, Tumor/genetics
Gene Expression Regulation, Neoplastic
*Brain Neoplasms/immunology/genetics/drug therapy/pathology
Multiomics

@article {pmid41158962,
year = {2025},
author = {Cummings, CL and Stephan, SB and Fitzgerald, K and Stephan, MT},
title = {Bedside manufacturing of engineered stem cells using gene therapy foam.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {4},
pages = {101612},
pmid = {41158962},
issn = {2329-0501},
abstract = {Hematopoietic stem cell (HSC) gene therapies hold immense potential for treating a growing list of genetic disorders, but the field has reached an inflection point where novel technologies are needed to overcome significant challenges, including high costs, unequal access, and prolonged disruption of daily life. Here, we describe a bedside cell manufacturing strategy in which HSCs are genetically targeted within gene therapy foam that is mixed with freshly isolated bone marrow aspirate concentrate and then directly injected back into the marrow. We demonstrate that highly efficient genetic reprogramming of CD34+ HSCs can be accomplished within methylcellulose-based foam, using low vector doses that are inefficient with conventional liquid-based approaches. In an ex vivo model of perfused bone marrow, we show that foam retains vector at the injection site and locally boosts gene transfer into embedded CD34+ progenitor cells while minimizing off-target events. We also establish that this foam technology is compatible with freshly harvested human bone marrow aspirate. Once implemented in the clinic, this new method, which can be performed in an outpatient setting of any regional hospital, could improve the effectiveness of stem cell-based gene therapies, while concomitantly lowering costs to make these treatments accessible to all who need them.},
}

@article {pmid41159270,
year = {2025},
author = {Farooq, MS and Amini, N and Sun, V and Deutsch, GB and Deneve, JL and Grant, M and Arnold, KB and Secord, AA and Anderson, G and Krouse, RS},
title = {Optimizing Palliative Cancer Surgery Trial Completion: Lessons Learned From Qualitative Content Analysis of S1316 - Comparative Effectiveness Trial for Malignant Bowel Obstruction.},
journal = {The American journal of hospice & palliative care},
volume = {},
number = {},
pages = {10499091251391420},
doi = {10.1177/10499091251391420},
pmid = {41159270},
issn = {1938-2715},
abstract = {BackgroundMalignant bowel obstruction (MBO) is a complex clinical entity and there remains a relative lack of high-quality comparative trials on surgical management, in part due to a heterogeneous patient population and different treatment modalities which contribute to challenges in trial design and completion. SWOG S1316 is the only prospective randomized trial evaluating surgical vs non-surgical management of MBO and involved a trial framework in which patients were recruited for a randomization pathway as well as a patient choice pathway. Importantly, successful completion of S1316 required numerous amendment modifications to the trial during its course. We aimed to highlight aspects of S1316 trial design, execution, and modification that potentially contributed to trial completion.MethodsIterative qualitative content analysis of trial modification amendments through the course of the trial from 2015 to 2020.Results133 unique amendments were made to S1316 from 2015 to 2020. We found four dominant domains for the amendments: Accrual Barriers, Study Design Changes, Data Collection Issues, and Clarifications. Accrual amendments were essential to completing the trial and included increasing participating sites from six to 30 (including international sites) and the inclusion of Spanish-speaking participants (11% of final study population).ConclusionsContent analysis of S1316 trial amendments highlighted that Accrual amendments were important in trial completion. Future investigators may benefit from better anticipating trial modifications as they design their studies. It is likely that rapid initiation of trial amendments can lead to improved accrual and study completion.},
}

@article {pmid41159377,
year = {2026},
author = {Smith, KS and Dhanda, SK and Billups, CA and Sioson, E and Lu, C and Peraza, AZ and Gangwani, K and Li, Y and Li, Q and Lin, T and Michalski, JM and Packer, RJ and Olson, JM and Leary, SES and Fouladi, M and Gajjar, A and Zhou, X and Onar-Thomas, A and Northcott, PA and Robinson, GW},
title = {An integrated analysis of three medulloblastoma clinical trials refines risk-stratification approaches for reducing toxicity and improving survival.},
journal = {Neuro-oncology},
volume = {28},
number = {1},
pages = {268-281},
pmid = {41159377},
issn = {1523-5866},
support = {//St. Baldrick's Foundation/ ; P01CA096832//CCSG 5P30CA021765-43 Developmental Funds/ ; //American Lebanese Syrian Associated Charities/ ; R50 CA275857/CA/NCI NIH HHS/United States ; P30CA021765//the National Cancer Institute/ ; 1R01CA270785-01A1//CCSG 5P30CA021765-43 Developmental Funds/ ; },
mesh = {Humans ; *Medulloblastoma/therapy/mortality/genetics/pathology ; *Cerebellar Neoplasms/mortality/therapy/genetics/pathology ; Female ; Male ; Child ; Child, Preschool ; Adolescent ; Survival Rate ; Prognosis ; Craniospinal Irradiation/mortality ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Risk Assessment ; Follow-Up Studies ; Young Adult ; DNA Methylation ; *Chemoradiotherapy/mortality ; Clinical Trials as Topic ; Adult ; Mutation ; },
abstract = {BACKGROUND: The identification of clinical and molecular heterogeneity in medulloblastoma has produced risk-stratified therapy, but establishing the most effective yet least toxic regimens has remained elusive owing to numerous treatment options. To improve risk-stratification, we performed an integrated analysis from three clinical trials.

METHODS: Medulloblastoma patients from ACNS0331/NCT00085735, ACNS0332/NCT00392327, and SJMB03/NCT00085202 were included if they had methylation profiling. Molecular groups [WNT, SHH, Group 3 (G3), and Group 4 (G4)], subgroups, and copy number variations were procured from methylation profiles and mutations from next-generation sequencing. Data was assembled into an interactive portal to capture patient characteristics. Cross-trial comparisons, univariable, and multivariable analyses were conducted and used to derive a risk-stratification schema.

RESULTS: Eight hundred ninety-eight patients (WNT = 131, SHH = 151, G3 = 220, G4 = 396) were included. Progression-free-survival (PFS) distributions among analogous cross-trial cohorts were not different, demonstrating no survival advantage of any one therapy over another. The addition of carboplatin to high-dose craniospinal irradiation (HDCSI) containing regimen was selectively superior in PFS in G3/G4 subgroup 3 (P = 0.048) and G3/G4 subgroup 2 (P = 0.035) to HDCSI regimens without carboplatin. Nine actionable risk-stratified groups were identified consisting of 2 WNT groups (low, high-risk), 3 SHH groups (low-, average-, very-high-risk), and 4 G3/G4 groups (low-, average-, high-, and very-high-risk).

CONCLUSIONS: Our integrated cross-trial analysis suggests toxicity can be reduced by eliminating disproportionate differences in therapy in favor of a more uniform treatment backbone. Moreover, we propose and model a risk-classification system that identifies the most appropriate cohorts on which to trial significant dose reductions in craniospinal irradiation or select treatment intensifications.},
}

Humans
*Medulloblastoma/therapy/mortality/genetics/pathology
*Cerebellar Neoplasms/mortality/therapy/genetics/pathology
Female
Male
Child
Child, Preschool
Adolescent
Survival Rate
Prognosis
Craniospinal Irradiation/mortality
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Risk Assessment
Follow-Up Studies
Young Adult
DNA Methylation
*Chemoradiotherapy/mortality
Clinical Trials as Topic
Adult
Mutation

@article {pmid41159380,
year = {2026},
author = {Arora, S and Nuechterlein, N and Jensen, M and Glatzer, G and Sievers, P and Varadharajan, S and Korshunov, A and Sahm, F and Mack, SC and Taylor, MD and Gujral, TS and Holland, EC},
title = {Integrated transcriptomic landscape of medulloblastoma and ependymoma reveals novel tumor subtype-specific biology.},
journal = {Neuro-oncology},
volume = {28},
number = {2},
pages = {505-519},
pmid = {41159380},
issn = {1523-5866},
support = {1R35 CA253119-01A1/NH/NIH HHS/United States ; U54 CA243125/NH/NIH HHS/United States ; C11orf95/NH/NIH HHS/United States ; //RELA fusion-driven ependymoma/ ; 1R35 CA253119-01A1//Fred Hutch Cancer Center/ ; },
mesh = {Humans ; *Medulloblastoma/genetics/classification/pathology ; *Ependymoma/genetics/classification/pathology ; *Transcriptome ; *Cerebellar Neoplasms/genetics/classification/pathology ; *Biomarkers, Tumor/genetics ; Child ; Gene Expression Profiling ; DNA Copy Number Variations ; Female ; Male ; Child, Preschool ; Prognosis ; Gene Expression Regulation, Neoplastic ; Adolescent ; },
abstract = {BACKGROUND: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

METHODS: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

RESULTS: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with specific RNA fusions and molecular signatures. In medulloblastoma, we observed precise stratification of Group 3/4 tumors by subtype and in Sonic Hedgehog (SHH) tumors by patient age. We also identified subtype-specific pathways and gene fusions, enriched in each group.

CONCLUSIONS: This transcriptomic landscape serves as a resource for biomarker discovery, diagnostic refinement, and prediction of tumor biology and outcome. By enabling projection of new patients' bulk RNA-seq data onto the reference map using nearest neighbor analysis, the framework supports accurate subtype classification. The landscape is publicly available via Oncoscape, an interactive platform for global exploration and application.},
}

Humans
*Medulloblastoma/genetics/classification/pathology
*Ependymoma/genetics/classification/pathology
*Transcriptome
*Cerebellar Neoplasms/genetics/classification/pathology
*Biomarkers, Tumor/genetics
Child
Gene Expression Profiling
DNA Copy Number Variations
Female
Male
Child, Preschool
Prognosis
Gene Expression Regulation, Neoplastic
Adolescent

@article {pmid41160408,
year = {2026},
author = {Nyquist, MD and Nelson, PS},
title = {Targeting the Androgen Receptor Pathway in Prostate Cancer: A PROTrACted Struggle.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {32},
number = {1},
pages = {13-15},
pmid = {41160408},
issn = {1557-3265},
support = {P50 CA097186/CA/NCI NIH HHS/United States ; R01 CA266452/CA/NCI NIH HHS/United States ; P50CA097186//National Cancer Institute (NCI)/ ; R01CA266452//National Cancer Institute (NCI)/ ; },
mesh = {Humans ; Male ; *Receptors, Androgen/metabolism/genetics ; *Signal Transduction/drug effects ; *Prostatic Neoplasms/drug therapy/metabolism/pathology ; *Androgen Receptor Antagonists/therapeutic use/pharmacology ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/drug effects ; Animals ; },
abstract = {The androgen receptor (AR) is the most important therapeutic target for metastatic prostate cancer. Though clinical responses to AR inhibition are nearly universal, so is progression, usually accompanied by reactivation of AR signaling. A new small-molecule dual AR degrader/inhibitor shows promise in overcoming resistance and improving clinical outcomes. See related article by Nayak et al., p. 224.},
}

Humans
Male
*Receptors, Androgen/metabolism/genetics
*Signal Transduction/drug effects
*Prostatic Neoplasms/drug therapy/metabolism/pathology
*Androgen Receptor Antagonists/therapeutic use/pharmacology
Molecular Targeted Therapy
Drug Resistance, Neoplasm/drug effects
Animals

@article {pmid41160804,
year = {2026},
author = {Rashidi, A and Gao, F},
title = {Antibiotic risk score for acute graft-versus-host disease.},
journal = {Blood advances},
volume = {10},
number = {3},
pages = {555-561},
pmid = {41160804},
issn = {2473-9537},
support = {P01 CA018029/CA/NCI NIH HHS/United States ; P01 CA078902/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Graft vs Host Disease/etiology/diagnosis/epidemiology ; Middle Aged ; Male ; Female ; Adult ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; Aged ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Risk Factors ; Young Adult ; Acute Disease ; Risk Assessment ; Transplantation, Homologous/adverse effects ; },
abstract = {Certain antibiotic exposures have been associated with increased rates of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplant (alloHCT). Using data from 2023 alloHCTs performed at our center (2010-2021), we recently developed an antibiotic risk score based on antibacterial antibiotic exposure between days -7 and +30 of alloHCT. The objective was to estimate the added risk for aGVHD due to exposures to antibiotics in the early peritransplant period. Here, we validated the score in an independent, more recent cohort. Data from 297 recipients of alloHCT (2022-2023) including 8382 antibiotic use records (9 antibiotic classes) were analyzed. Median (range) age was 61 (19-78) years, and 175 (59%) patients were male. Higher scores predicted a greater added antibiotic-related risk for grade 3 to 4 (severe) aGVHD, with the upper 25% score quantile identifying a distinctly high-risk subset of patients (hazard ratio for the upper 25% risk quantile was 2.37 compared with the lower 75%; 95% confidence interval, 1.21-4.63; P = .01). A similar, though less strong, pattern was observed for grade 2 to 4 aGVHD. A free online antibiotic risk calculator was developed, identifying antibiotic exposures associated with higher added risk for severe aGVHD. In addition to its potential future use to identify patients who were at higher risk for aGVHD due to antibiotic exposures, the antibiotic-based risk score provided here can be included as a single continuous covariate in multivariable analysis of future GVHD prophylaxis trials.},
}

Humans
*Graft vs Host Disease/etiology/diagnosis/epidemiology
Middle Aged
Male
Female
Adult
*Anti-Bacterial Agents/adverse effects/therapeutic use
Aged
*Hematopoietic Stem Cell Transplantation/adverse effects
Risk Factors
Young Adult
Acute Disease
Risk Assessment
Transplantation, Homologous/adverse effects

@article {pmid41161981,
year = {2025},
author = {Vishnu, P and Aboulafia, DM},
title = {Hemostatic Disorders Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection, COVID-19 Vaccination, and Long-COVID Syndrome: Current Evidence and Controversies in Clinical Practice.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {643-655},
doi = {10.1016/j.cll.2025.07.008},
pmid = {41161981},
issn = {1557-9832},
mesh = {Humans ; *COVID-19/complications/prevention & control ; *COVID-19 Vaccines/adverse effects ; *Hemostatic Disorders/etiology ; SARS-CoV-2 ; *Vaccination/adverse effects ; },
abstract = {The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented profound global health challenges. Beyond acute illness, a substantial proportion of individuals experience persistent symptoms including fatigue, brain fog, and post-exertional malaise, collectively known as Long-COVID. Among the complications associated with SARS-CoV-2 infection and vaccination, hemostatic disorders ranging from mild platelet dysfunction to severe thromboembolic events, and rare but serious coagulation-related adverse effects, such as vaccine-induced immune thrombotic thrombocytopenia, have emerged as a significant concern. Herein we provide an overview of current information and controversies surrounding hemostatic complications in SARS-CoV-2 infection and COVID-19 vaccination.},
}

Humans
*COVID-19/complications/prevention & control
*COVID-19 Vaccines/adverse effects
*Hemostatic Disorders/etiology
SARS-CoV-2
*Vaccination/adverse effects

@article {pmid41161982,
year = {2025},
author = {Vishnu, P and Aboulafia, DM},
title = {Recent Advances in Extended Half-Life Products, Nonfactor Replacement Therapies, and Gene Therpy for the Treatment of Hemophilia.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {657-673},
doi = {10.1016/j.cll.2025.07.010},
pmid = {41161982},
issn = {1557-9832},
mesh = {*Hemophilia A/therapy/genetics ; Humans ; *Genetic Therapy/methods ; Half-Life ; *Blood Coagulation Factors/therapeutic use/pharmacokinetics ; Factor VIII/therapeutic use/pharmacokinetics ; },
abstract = {Hemophilia, a rare X-linked hereditary bleeding disorder, is characterized by deficiency of coagulation factors. Symptoms range from spontaneous joint and muscle bleeds to life-threatening hemorrhage, for which patients require frequent infusion of coagulation factors, profoundly impacting their quality of life. Novel therapeutics and advances in gene therapy now offer patients long-term disease control and improved quality of life. Here, we focus on important developments in the use of extended half-life factor products, non-factor replacement therapies, and gene therapy. We also highlight the mechanism of action, clinical efficacy, and safety of these newer approaches.},
}

*Hemophilia A/therapy/genetics
Humans
*Genetic Therapy/methods
Half-Life
*Blood Coagulation Factors/therapeutic use/pharmacokinetics
Factor VIII/therapeutic use/pharmacokinetics

@article {pmid41161984,
year = {2025},
author = {Zhang, C and Lam, BD and Lucas, F and Foy, BH},
title = {Machine Learning and Artificial Intelligence-Based Clinical Decision Support for Modern Hematology.},
journal = {Clinics in laboratory medicine},
volume = {45},
number = {4},
pages = {691-705},
doi = {10.1016/j.cll.2025.07.011},
pmid = {41161984},
issn = {1557-9832},
mesh = {*Machine Learning ; Humans ; *Hematology/methods ; *Decision Support Systems, Clinical ; *Artificial Intelligence ; *Hematologic Diseases/diagnosis ; },
abstract = {Hematology is one of the most data-rich areas of medicine and has consistently been at the forefront of technological innovation. With the increasing integration of machine learning (ML) into the diagnostic process, it is vital that both patient-facing and laboratory-facing members of the care team understand how these tools may interact with existing workflows and affect their work. We review the current landscape of ML research and clinical applications. We cover a wide variety of subdomains (eg, hematopathology, hemoglobinopathies, and coagulopathy) and explore both the success and limitations of corresponding research and deployments.},
}

*Machine Learning
Humans
*Hematology/methods
*Decision Support Systems, Clinical
*Artificial Intelligence
*Hematologic Diseases/diagnosis

@article {pmid41162424,
year = {2025},
author = {Fergus, KB and Newberg, J and Greenstein, R and Fejerman, L and Carvajal-Carmona, L and Collisson, E and Dixit, N and Frampton, G and Huang, FW and Neuhausen, SL and Ziv, E},
title = {Association between ancestry and tumor somatic mutations in a large national cohort of women with breast cancer.},
journal = {NPJ breast cancer},
volume = {11},
number = {1},
pages = {117},
pmid = {41162424},
issn = {2374-4677},
support = {2023YIA-9977333099//American Society of Clinical Oncology/ ; R01CA223978, U54CA283766 and U54CA280811/CA/NCI NIH HHS/United States ; OPR18111//California Initiative to Advance Precision Medicine/ ; OPR18111//California Initiative to Advance Precision Medicine/ ; },
abstract = {Somatic mutations and copy number alterations in breast tumors are important to determine prognosis, predict treatment response, and identify targets for therapy. We utilized somatic sequencing data of breast tumors from Foundation Medicine Inc. to evaluate the association between genetic ancestry and somatic mutations. We used germline variants to infer genetic ancestry with both principal components analysis and ADMIXTURE. Overall, we identified 91 ancestry-specific somatic differences across 58 unique genes, which included potentially targetable genes such as PIK3CA found in higher frequency in European ancestry, and EGFR found in higher frequency in East Asian ancestry. Pan-cancer analysis of East Asian ancestry and EGFR also found higher frequency in prostate, thyroid, and kidney cancers. African ancestry was associated with increased frequency of copy number alterations overall and decreased frequency of multiple genes on the PI3K-AKT pathway. Future research is warranted to elicit the genetic and environmental conditions that underly these findings.},
}

@article {pmid41162557,
year = {2025},
author = {Damera, S and Lee, JR and Hong, YR and Nyame, YA and Hammarlund, N},
title = {Negative perceptions of the health system and racial inequities in PSA screening.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {41162557},
issn = {1476-5608},
abstract = {BACKGROUND: Black individuals in the U.S. experience significantly higher prostate cancer mortality and are more likely to be diagnosed at younger ages with aggressive disease. This disparity may be influenced by negative healthcare perceptions and racial discordance between patients and providers, impacting lower rates of prostate-specific antigen (PSA) screening. We hypothesized that these factors would be associated with reduced PSA screening uptake, particularly among Black men.

OBJECTIVES: This study aimed to examine the association between negative healthcare perceptions and PSA screening, assess whether this relationship differs by race, and evaluate the role of racial discordance in influencing screening behavior.

METHODS: We analyzed data from the 2018-2022 Medical Expenditure Panel Survey. The sample included 2373 men aged 45-70 who self-identified as non-Hispanic White or Black and had complete data on PSA screening, healthcare perceptions, and demographics. Negative healthcare perceptions were measured using a Health Perceptions Index (HePI), constructed from MEPS items (higher scores reflect more negative perceptions).

RESULTS: Higher HePI scores were significantly associated with lower PSA screening rates (p < 0.01). Interaction models indicated that Black men with higher HePI scores were disproportionately less likely to undergo screening. Racial discordance with providers was independently associated with reduced screening likelihood (~10.2 percentage points; p < 0.01). Models including interaction terms (age, race, and discordance) showed that older Black men with high HePI scores and discordant providers were least likely to be screened.

CONCLUSIONS: PSA screening disparities are shaped by negative healthcare perceptions and racial discordance, particularly among older Black men. Addressing these barriers through culturally tailored education, improved workforce diversity, and strengthened provider-patient relationships may help close screening gaps. These findings highlight the relevance of healthcare system perceptions in understanding screening disparities and may inform future strategies to identify at-risk individuals.},
}

@article {pmid41165693,
year = {2025},
author = {Shadman, M and Gopal, AK},
title = {Bispecific antibodies in action: the reality of engagement.},
journal = {Blood},
volume = {146},
number = {18},
pages = {2148-2150},
doi = {10.1182/blood.2025030376},
pmid = {41165693},
issn = {1528-0020},
}

@article {pmid41165705,
year = {2025},
author = {MacKay, EJ and Talham, CJ and Szeto, WY and Brown, CR and Augoustides, JG and Desai, ND and Groeneveld, PW and Zhang, B},
title = {Surgical Volume and Outcomes of Intraoperative Transesophageal Echocardiography in Coronary Artery Bypass Graft.},
journal = {JAMA network open},
volume = {8},
number = {10},
pages = {e2540559},
pmid = {41165705},
issn = {2574-3805},
mesh = {Humans ; *Coronary Artery Bypass/mortality/statistics & numerical data/methods ; Male ; Female ; *Echocardiography, Transesophageal/statistics & numerical data/methods ; Retrospective Studies ; Aged ; Middle Aged ; Treatment Outcome ; *Intraoperative Care/methods ; },
abstract = {IMPORTANCE: The routine use of intraoperative transesophageal echocardiography (TEE) during coronary artery bypass graft (CABG) surgery remains controversial. Its benefit across different patient populations is unclear.

OBJECTIVES: To identify patient subgroups with the greatest or least likelihood to benefit from intraoperative TEE during CABG, stratified by hospital surgical volume.

This 2-stage, matched retrospective cohort study applied target trial emulation methodologies to the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) to quantify the conditional treatment effect of intraoperative TEE among subpopulations undergoing isolated CABG at low, medium, and high surgical volume hospitals. The study cohort consisted of patients aged 18 years or older who underwent isolated CABG surgery between July 1, 2014, and June 30, 2022. Data analysis was conducted from August 8, 2023, to December 15, 2024.

EXPOSURE: Receipt of an intraoperative TEE during CABG surgery.

MAIN OUTCOMES AND MEASURES: The primary outcome was mortality within 30 days of surgery. Statistical analyses included multivariable logistic regression and multiple TEE vs without TEE matched comparisons stratified by surgical volume and patient subpopulations.

RESULTS: Of 1 266 055 patients who underwent isolated CABG, 963 976 (76.1%) were male, and the mean (SD) age was 65.7 (10.0) years. Among these patients, 61.8% received TEE and 39.0% did not receive TEE. Intraoperative TEE use (vs without TEE) was associated with a significant survival benefit among patients treated at hospitals with low surgical volume (2.47% vs 2.94%; odds ratio [OR], 0.83 [95% CI, 0.78-0.89], P < .001) and medium surgical volume (2.09% vs 2.34%; OR, 0.89 [95% CI, 0.85-0.93], P < .001) but not high surgical volume (1.72% vs 1.77%; OR, 0.97 [95% CI, 0.91-1.03], P = .48). Among patients who underwent isolated CABG at low and medium surgical volume hospitals, TEE provided the greatest survival benefit to subpopulations with greater than 50% (vs ≤50%) left-main coronary stenosis, 3 or more (vs <3) diseased coronaries, and (3) a preoperative inotropic requirement.

CONCLUSIONS AND RELEVANCE: In isolated CABG, intraoperative TEE was associated with survival benefit at low- and medium-volume hospitals, particularly in patients with complex coronary disease or hemodynamic instability, but not at high-volume hospitals. These results highlight persistent equipoise and the need for randomized evaluation.},
}

Humans
*Coronary Artery Bypass/mortality/statistics & numerical data/methods
Male
Female
*Echocardiography, Transesophageal/statistics & numerical data/methods
Retrospective Studies
Aged
Middle Aged
Treatment Outcome
*Intraoperative Care/methods

@article {pmid41168411,
year = {2025},
author = {Jiang, SJ and Thomas, M and Rosenthal, EA and Phipps, AI and Sakoda, LC and van Duijnhoven, FJB and Pellatt, AJ and Avery, CL and Berndt, SI and Bishop, DT and Castellví-Bel, S and Chan, AT and Grant, RC and Gignoux, C and Gsur, A and Gunter, MJ and Haiman, CA and Hoffmeister, M and Jarvik, GP and Jenkins, MA and Keku, TO and Küry, S and Lee, JK and Marchand, LL and Moreno, V and Newcomb, PA and Newton, CC and Ogino, S and Palmer, JR and Pearlman, R and Qu, C and Schoen, RE and Um, CY and Van Guelpen, B and Visvanathan, K and Vymetalkova, V and White, E and Woods, MO and Platz, EA and Brenner, H and Corley, DA and Vogelaar, IL and Hsu, L and Peters, U},
title = {Multiple polygenic score approach in colorectal cancer risk prediction.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {38006},
pmid = {41168411},
issn = {2045-2322},
support = {001/WHO_/World Health Organization/International ; U01 CA164973, R01 CA126895, R01 CA060987, R01 CA072520, U24 CA074806/CA/NCI NIH HHS/United States ; U01HG008657/HG/NHGRI NIH HHS/United States ; U01 CA137088/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Colorectal Neoplasms/genetics/epidemiology ; *Multifactorial Inheritance/genetics ; *Genetic Predisposition to Disease ; Female ; Male ; Machine Learning ; Aged ; Middle Aged ; Risk Factors ; Risk Assessment ; Genome-Wide Association Study ; ROC Curve ; Polymorphism, Single Nucleotide ; Case-Control Studies ; },
abstract = {Recent studies have demonstrated that for various diseases, incorporating polygenic risk scores (PRSs) for other traits and diseases into the PRS-based risk prediction model may improve predictive performance - known as Multiple Polygenic Score (MPS) approach. We aimed to examine whether the MPS approach improves colorectal cancer (CRC) risk prediction. We included 2,187 non-CRC PRSs from the polygenic Score (PGS) Catalog and used machine learning (ML) models to select the most predictive non-CRC PRSs, utilizing individual-level data from 31,257 CRC cases and 33,408 controls. An independent dataset from the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort (4,852 cases and 67,939 controls) was randomly split into subsets for model estimation and validation. The model combined MPS with two existing CRC-PRSs based on known loci and genome-wide genotyping. We then assessed model performance by calculating the area under the receiver operating curve (AUC) in the validation set and performed 1,000 bootstrapped iterations to evaluate AUC improvements. The ML model selected 337 non-CRC PRSs predictive of CRC risk. Adding MPS to the CRC-PRSs significantly improved AUC by 0.017 (95% CI: 0.011-0.022, p < 0.0001) when combined with known-loci CRC-PRS, 0.005 (95% CI: 0.002-0.007, p = 0.0005) with genome-wide CRC-PRS, and 0.004 (95% CI: 0.002-0.006, p = 0.0005) with both the known loci and genome-wide CRC-PRSs. These findings demonstrate MPS's potential to refine CRC risk prediction models and highlight opportunities for further advancements in risk prediction.},
}

Humans
*Colorectal Neoplasms/genetics/epidemiology
*Multifactorial Inheritance/genetics
*Genetic Predisposition to Disease
Female
Male
Machine Learning
Aged
Middle Aged
Risk Factors
Risk Assessment
Genome-Wide Association Study
ROC Curve
Polymorphism, Single Nucleotide
Case-Control Studies

@article {pmid41168431,
year = {2025},
author = {Jabbar, KS and Priya, S and Xu, J and Das Adhikari, U and Pishchany, G and Mohamed, ATM and Johansen, J and Thurimella, K and McCabe, C and Vlamakis, H and Okello, S and Delorey, TM and Lankowski, A and Mosepele, M and Siedner, MJ and Plichta, DR and Kwon, DS and Xavier, RJ},
title = {Human immunodeficiency virus and antiretroviral therapies exert distinct influences across diverse gut microbiomes.},
journal = {Nature microbiology},
volume = {10},
number = {11},
pages = {2720-2735},
pmid = {41168431},
issn = {2058-5276},
support = {R01 DK101354/DK/NIDDK NIH HHS/United States ; DK120485//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 HL141053/HL/NHLBI NIH HHS/United States ; R01 HL138646/HL/NHLBI NIH HHS/United States ; R01 DK120485/DK/NIDDK NIH HHS/United States ; K24 HL166024/HL/NHLBI NIH HHS/United States ; R21 HL124712/HL/NHLBI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; },
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *HIV Infections/drug therapy/microbiology ; Uganda ; Alkynes ; Metagenomics ; Benzoxazines/therapeutic use/adverse effects ; Male ; Female ; Feces/microbiology ; Cyclopropanes ; Adult ; Botswana ; *Anti-Retroviral Agents/therapeutic use ; Middle Aged ; United States ; Reverse Transcriptase Inhibitors/therapeutic use ; *Anti-HIV Agents/therapeutic use ; Bacteria/classification/genetics/drug effects/isolation & purification ; },
abstract = {Human immunodeficiency virus (HIV) infection alters gut microbiota composition and function, but the impact of geography and antiretroviral therapy remains unclear. Here we determined gut microbiome alterations linked to HIV infection and antiretroviral treatment in 327 individuals with HIV and 260 control participants in cohorts from Uganda, Botswana and the USA via faecal metagenomics. We found that while HIV-associated taxonomic differences were mostly site specific, changes in microbial functional pathways were broadly consistent across the cohorts and exacerbated in individuals with acquired immunodeficiency syndrome. Microbiome perturbations associated with antiretroviral medications were also geography dependent. In Botswana and Uganda, use of the non-nucleoside reverse transcriptase inhibitor efavirenz was linked to depletion of Prevotella, disruption of interspecies metabolic networks, exacerbation of systemic inflammation and atherosclerosis. Efavirenz-associated Prevotella depletion may occur through cross-inhibition of prokaryotic reverse transcriptases involved in antiphage defences, as shown by computational and in vitro experiments. These observations could inform future geography-specific and microbiome-guided therapy.},
}

Humans
*Gastrointestinal Microbiome/drug effects
*HIV Infections/drug therapy/microbiology
Uganda
Alkynes
Metagenomics
Benzoxazines/therapeutic use/adverse effects
Male
Female
Feces/microbiology
Cyclopropanes
Adult
Botswana
*Anti-Retroviral Agents/therapeutic use
Middle Aged
United States
Reverse Transcriptase Inhibitors/therapeutic use
*Anti-HIV Agents/therapeutic use
Bacteria/classification/genetics/drug effects/isolation & purification

@article {pmid41169120,
year = {2025},
author = {Marzinke, MA and Hanscom, B and Haines, D and Scarsi, KK and Agyei, Y and Piwowar-Manning, E and Hendrix, CW and Gollings, R and Rose, S and Mathew, C and Panchia, R and Spooner, E and Singh, N and Bock, P and Rinehart, AR and Ford, SL and Rooney, JF and Soto-Torres, L and Cohen, MS and Hosseinipour, MC and Delany-Moretlwe, S and , },
title = {Evaluation of pharmacokinetic interactions between long-acting cabotegravir or emtricitabine/tenofovir disoproxil fumarate and hormonal contraceptive agents: a tertiary analysis of South African participants in HPTN 084.},
journal = {Journal of the International AIDS Society},
volume = {28},
number = {11},
pages = {e70056},
pmid = {41169120},
issn = {1758-2652},
support = {P30 AI094189/AI/NIAID NIH HHS/United States ; UM1AI068617/NH/NIH HHS/United States ; OPP1154174//Bill and Melinda Gates Foundation/ ; UM1AI068619/NH/NIH HHS/United States ; UM1AI068613/NH/NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Young Adult ; *Anti-HIV Agents/pharmacokinetics ; *Contraceptive Agents, Hormonal/pharmacokinetics/administration & dosage ; Desogestrel/pharmacokinetics/blood ; Drug Interactions ; *Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination/pharmacokinetics/administration & dosage ; *HIV Infections/prevention & control ; Medroxyprogesterone Acetate/pharmacokinetics/blood ; Norethindrone/analogs & derivatives/pharmacokinetics/blood ; Pre-Exposure Prophylaxis ; *Pyridones/pharmacokinetics/administration & dosage ; South Africa ; Diketopiperazines ; },
abstract = {INTRODUCTION: HPTN 084 found that long-acting cabotegravir (CAB-LA) was well-tolerated and significantly reduced the risk of HIV acquisition in women compared to tenofovir disoproxil fumarate/emtricitabine (F/TDF). During the blinded phase of the trial, participants were required to use an effective method of contraception, including an injectable or implantable hormonal contraceptive (HC) agent. A contraceptive sub-study assessed the pharmacokinetic interactions between pre-exposure prophylaxis agents (CAB-LA or F/TDF) and etonogestrel (ENG), medroxyprogesterone acetate (MPA) or norethindrone enanthate (NET-EN).

METHODS: Participants were enrolled in a nested sub-study between 24 February 2020 and 26 October 2020. Via a convenience sampling strategy, plasma concentrations of ENG, MPA and NET-EN were evaluated at enrolment and weeks 25, 49 and 73; plasma tenofovir (TFV) and CAB concentrations were determined at contemporaneous visits. Participants were allowed to switch contraceptives, and HC assessments were adjusted accordingly. Geometric mean concentrations were calculated and compared using t-tests or Fisher's exact tests.

RESULTS: One hundred and seventy participants were included in this analysis. Hormone concentrations at all study visits were comparable between the CAB-LA and F/TDF study arms. Among participants randomized to the CAB-LA arm, geometric mean concentrations declined from enrolment to the follow-up period for ENG (335 to 202 pg/ml), MPA (1520 to 1138 pg/ml) and NET-EN (3715 to 1888 pg/ml); similar findings were observed among participants randomized to the F/TDF arm. Observed HC declines are likely attributed to the timing of contraceptive administration relative to sampling; the percentage of participants with hormone concentrations above thresholds associated with ovulation suppression was high (73-100%) and did not differ between arms. CAB concentrations were comparable across contraceptive types, with 97.8-98.1% of participants yielding trough CAB concentrations above the protocol-specified target threshold. TFV concentrations were unquantifiable for most participants, irrespective of contraceptive agent, rendering comparisons largely uninformative.

CONCLUSIONS: Given the comparable hormone concentrations between arms and the likely influence of the timing of sample collection on observed measurements, clinically significant interactions between CAB-LA and HC are not expected. Associations between F/TDF and hormone concentrations could not be effectively evaluated due to low adherence to F/TDF.

CLINICAL TRIAL REGISTRATION: NCT0316456.},
}

Adolescent
Adult
Female
Humans
Young Adult
*Anti-HIV Agents/pharmacokinetics
*Contraceptive Agents, Hormonal/pharmacokinetics/administration & dosage
Desogestrel/pharmacokinetics/blood
Drug Interactions
*Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination/pharmacokinetics/administration & dosage
*HIV Infections/prevention & control
Medroxyprogesterone Acetate/pharmacokinetics/blood
Norethindrone/analogs & derivatives/pharmacokinetics/blood
Pre-Exposure Prophylaxis
*Pyridones/pharmacokinetics/administration & dosage
South Africa
Diketopiperazines

@article {pmid41171480,
year = {2025},
author = {Mahdi, J and Gust, JA and Vitanza, NA and Scott, B and Monje, M and Ronsley, R},
title = {Neurotoxicity in central nervous system tumors treated with CAR T cell therapy: a review.},
journal = {Journal of neuro-oncology},
volume = {176},
number = {1},
pages = {60},
pmid = {41171480},
issn = {1573-7373},
}

@article {pmid41172559,
year = {2025},
author = {Ebadi, M and Fan, X and Schoch, G and Gooley, T and Rashidi, A and Smith, SD and Shadman, M and Holmberg, L and Ujjani, C and Poh, C and Raghunathan, V and Ali, N and Vo, PT and Manjappa, S and Menon, M and Di, M and Lynch, R and Ho, C and Till, BG and Ermoian, R and Gopal, AK and Tseng, YD},
title = {Total Body Irradiation Versus Chemotherapy-Only Conditioning in Autologous Haematopoietic Stem Cell Transplantation for Relapsed/Refractory Large B-cell Lymphoma.},
journal = {Clinical oncology (Royal College of Radiologists (Great Britain))},
volume = {48},
number = {},
pages = {103959},
doi = {10.1016/j.clon.2025.103959},
pmid = {41172559},
issn = {1433-2981},
mesh = {Humans ; Male ; Female ; Middle Aged ; *Transplantation Conditioning/methods ; *Lymphoma, Large B-Cell, Diffuse/therapy/pathology/mortality ; *Hematopoietic Stem Cell Transplantation/methods ; Retrospective Studies ; *Whole-Body Irradiation/methods ; Transplantation, Autologous ; Aged ; Adult ; *Neoplasm Recurrence, Local/therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {AIMS: In the era of chimeric antigen receptor T-cell (CAR-T) therapy, there remains a role for autologous stem cell transplant (ASCT) for patients with large B-cell lymphoma (LBCL) without access to CAR T-cell therapy or who have late, chemosensitive relapse (>12 months). Typically, the ASCT conditioning regimen is chemotherapy only. Given the radioresponsiveness of LBCL, we retrospectively evaluated whether ASCT outcomes are improved with total body irradiation (TBI)-based conditioning compared to chemo-only conditioning.

MATERIALS AND METHODS: We included patients with relapsed/refractory (r/r) LBCL who underwent ASCT at our centre (2012-2021). As TBI is generally offered only to younger patients, we excluded patients in the chemo-only group who were older than the oldest patient in the TBI group, leaving 56 patients in the final dataset (TBI: 19; chemo: 37).

RESULTS: The TBI cohort had more adverse features including male sex (89.5% vs 62.2%), relapse ≤12 months (52.6% vs 32.4%), and shorter time between diagnosis and ASCT (median: 11.7 vs 21.8 months). Two-year progression-free survival (PFS) was 58% (95% confidence interval [CI]: 39%-85%) and 67% (53%-84%) in TBI and chemotherapy cohorts, respectively. Two-year overall survival (OS) was 79% (63%-100%) and 80% (68%-95%) in TBI and chemotherapy cohorts, respectively. Multivariable hazard ratio (HR) of PFS failure (TBI vs chemo) was 1.35 (95% CI: 0.59-3.12). The HR of death was 1.33 (95% CI: 0.49-3.58). While conditioning regimen was not associated with PFS, positron emission tomography (PET) positivity at time of ASCT (HR: 6.97, 95% CI: 2.98-16.27, P < 0.001) was associated with PFS failure.

CONCLUSION: Despite the presence of more adverse features among patients treated with TBI, there was no difference in PFS or OS among patients that underwent chemo-only vs TBI-based conditioning. Though hypothesis generating, this suggests that TBI may be able to partially compensate for adverse fatures.},
}

Humans
Male
Female
Middle Aged
*Transplantation Conditioning/methods
*Lymphoma, Large B-Cell, Diffuse/therapy/pathology/mortality
*Hematopoietic Stem Cell Transplantation/methods
Retrospective Studies
*Whole-Body Irradiation/methods
Transplantation, Autologous
Aged
Adult
*Neoplasm Recurrence, Local/therapy
Antineoplastic Combined Chemotherapy Protocols/therapeutic use

@article {pmid41173578,
year = {2025},
author = {Fairlie, L and Szydlo, DW and Mayo, A and Bunge, K and Mhlanga, F and Piper, J and Dadabhai, S and Gatsi, VM and Horne, E and Ssemambo, PK and Mandiwa, V and Mgodi, NM and Owor, M and Anderson, PL and Marzinke, MA and Nakabiito, C and Scheckter, R and Chappell, C and Hillier, SL and , },
title = {Safety outcomes among infants whose mothers used the dapivirine vaginal ring or oral PrEP during pregnancy (MTN-042/DELIVER): a randomised phase 3b study.},
journal = {The lancet. HIV},
volume = {12},
number = {11},
pages = {e763-e773},
doi = {10.1016/S2352-3018(25)00261-9},
pmid = {41173578},
issn = {2352-3018},
support = {UM1 AI069518/AI/NIAID NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; Young Adult ; Administration, Oral ; *Anti-HIV Agents/administration & dosage/adverse effects ; *Contraceptive Devices, Female ; Emtricitabine/administration & dosage ; *HIV Infections/prevention & control ; *Infectious Disease Transmission, Vertical/prevention & control ; *Pre-Exposure Prophylaxis/methods ; *Pregnancy Complications, Infectious/prevention & control/drug therapy ; *Pyrimidines/administration & dosage/adverse effects ; South Africa ; Tenofovir/administration & dosage ; Uganda ; },
abstract = {BACKGROUND: HIV acquisition risk during pregnancy remains high and additional data supporting pre-exposure prophylaxis (PrEP) in pregnancy are needed. The aim of the MTN-042/DELIVER study was to evaluate the dapivirine vaginal ring (DVR) and daily oral tenofovir disoproxil fumarate plus emtricitabine use as PrEP during pregnancy. We report infant outcomes following confirmed in-utero exposure.

METHODS: This randomised, controlled, open-label, phase 3b study was conducted in four clinical research sites in Malawi, South Africa, Uganda, and Zimbabwe. Pregnant, HIV-negative, healthy women aged 18-40 years were enrolled at 36-37 weeks' (cohort 1), 30-35 weeks' (cohort 2), and 12-29 weeks' (cohort 3) gestation and randomly assigned 2:1 (cohorts 1 and 2) and 4:1 (cohort 3) to receive the DVR (dapivirine 25 mg) or oral PrEP (tenofovir disoproxil fumarate 300 mg plus emtricitabine 200 mg). All infants born to maternal participants were enrolled and included in the primary infant analysis to evaluate infant safety with in-utero exposure to study product. Infant visits were conducted at less than 2 weeks, 6 weeks, 6 months, and 12 months of age. The primary infant composite safety outcome included serious adverse events and grade 3 or higher adverse events. Birth outcomes (livebirth or stillbirth, prematurity), adverse events (including frequency between each study visit), and growth up to 12 months were evaluated and collected. This study is registered with ClinicalTrials.gov (NCT03965923). The trial is completed and the database closed.

FINDINGS: The study was conducted between Feb 7, 2020, and May 13, 2024. In total, 545 infants were included: 147 in cohort 1, 154 in cohort 2, and 244 in cohort 3. Mean intrauterine exposure was 23·3, 59·7, and 113·8 days, respectively. Overall, 545 (99%) of 550 pregnancy outcomes were livebirths. Serious adverse events occurred in 66 (17%) of 398 infants in the DVR group and 15 (10%) of 147 in the oral PrEP group. Grade 3 or higher adverse events occurred in 95 (24%) of 398 and 29 (20%) of 147 infants, respectively, none related to product exposure. 41 (51%) of 81 new-onset serious adverse events occurred by age 6 weeks, and ten (91%) of 11 congenital anomalies were diagnosed by age 6 months. There were no maternal or infant HIV acquisitions.

INTERPRETATION: Over 12 months of follow-up of infants, the DVR and oral PrEP were generally safe, with no composite adverse events related to study product. Together with available maternal safety data, this supports use of the DVR and oral PrEP by pregnant women to prevent HIV.

FUNDING: US National Institutes of Health.},
}

Adolescent
Adult
Female
Humans
Infant
Infant, Newborn
Male
Pregnancy
Young Adult
Administration, Oral
*Anti-HIV Agents/administration & dosage/adverse effects
*Contraceptive Devices, Female
Emtricitabine/administration & dosage
*HIV Infections/prevention & control
*Infectious Disease Transmission, Vertical/prevention & control
*Pre-Exposure Prophylaxis/methods
*Pregnancy Complications, Infectious/prevention & control/drug therapy
*Pyrimidines/administration & dosage/adverse effects
South Africa
Tenofovir/administration & dosage
Uganda

@article {pmid41175446,
year = {2025},
author = {Levine, KM and Uy, NF and Gooley, TA and Voutsinas, J and Tratt, M and Eaton, KD and Santana-Davila, R and Berger, AH and Baik, CS},
title = {Osimertinib retreatment for patients with advanced EGFR-mutated non-small cell lung cancer.},
journal = {Cancer treatment and research communications},
volume = {45},
number = {},
pages = {101026},
pmid = {41175446},
issn = {2468-2942},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; T32 CA009515/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Aniline Compounds/therapeutic use/pharmacology ; *Acrylamides/therapeutic use/pharmacology ; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology/mortality ; Male ; *Lung Neoplasms/drug therapy/genetics/pathology/mortality ; Female ; Middle Aged ; Aged ; ErbB Receptors/genetics ; Retrospective Studies ; Mutation ; Retreatment ; *Protein Kinase Inhibitors/therapeutic use ; Adult ; Aged, 80 and over ; Indoles ; Pyrimidines ; },
abstract = {Resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a key challenge in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Although retreatment with earlier-generation EGFR tyrosine kinase inhibitors has been studied, data on osimertinib rechallenge are limited. We conducted a single institution retrospective analysis of patients with EGFR-mutated NSCLC who were rechallenged with osimertinib following progression on prior osimertinib and interim systemic therapy, including chemotherapy. Seventeen patients met inclusion criteria, all with adenocarcinoma histology and either EGFR exon 19 deletions or L858R mutations. Median interval between osimertinib treatments was 10.5 months. Osimertinib retreatment resulted in a partial response in 18 % (3/17) and stable disease in 35 % of patients (6/17), for a disease control rate of 53 % (9/17). Median retreatment duration was 4.3 months, and median overall survival following retreatment initiation was 8.9 months. Among patients with central nervous system involvement, several experienced intracranial stability without additional radiation. Duration of initial osimertinib therapy did not strongly predict retreatment benefit. These findings suggest that osimertinib rechallenge may provide clinically meaningful disease control in a subset of patients, especially given its tolerability and oral formulation. Further research is needed to identify biomarkers of sensitivity and to optimize patient selection for osimertinib retreatment following interval chemotherapy.},
}

Humans
*Aniline Compounds/therapeutic use/pharmacology
*Acrylamides/therapeutic use/pharmacology
*Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology/mortality
Male
*Lung Neoplasms/drug therapy/genetics/pathology/mortality
Female
Middle Aged
Aged
ErbB Receptors/genetics
Retrospective Studies
Mutation
Retreatment
*Protein Kinase Inhibitors/therapeutic use
Adult
Aged, 80 and over
Indoles
Pyrimidines

@article {pmid41176371,
year = {2025},
author = {Carpenter, PA and Warkentin, PI},
title = {Improving Outcomes in Hematopoietic Cell Transplantation and Cellular Therapy: Evolution of ASTCT Practice Guidelines and FACT Inspections.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {11},
pages = {843-848},
doi = {10.1016/j.jtct.2025.10.008},
pmid = {41176371},
issn = {2666-6367},
}

@article {pmid41176373,
year = {2025},
author = {Biernacki, MA},
title = {Capturing the Big Picture of HY Antigens and Transplantation Outcomes.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {11},
pages = {851-853},
doi = {10.1016/j.jtct.2025.10.009},
pmid = {41176373},
issn = {2666-6367},
}

@article {pmid41176520,
year = {2025},
author = {Yu, EY and Suzuki, H and Pieczonka, CM and Gotto, G and Briganti, A and Luz, M and Murphy, D and Malone, R and Hamilton, J and Chan, JE and Sieber, P and Given, RW and Hellmis, E and Kretz, T and Spiegelhalder, P and Gómez-Caamaño, A and Amela, YM and Artignan, X and Uemura, H and Fujita, N and Adorjan, P and Ghadessi, M and Verholen, F and Armstrong, AJ},
title = {DARolutamide ObservationaL (DAROL) study in patients with nonmetastatic castration-resistant prostate cancer: prespecified third interim analysis.},
journal = {Prostate cancer and prostatic diseases},
volume = {},
number = {},
pages = {},
pmid = {41176520},
issn = {1476-5608},
abstract = {BACKGROUND: DAROL is an ongoing study of real-world safety and effectiveness of darolutamide in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).

SUBJECTS/METHODS: This prespecified interim analysis included 550 patients with nmCRPC who completed ≥6 months of treatment with darolutamide 600 mg twice daily.

RESULTS: Darolutamide showed consistent safety and effectiveness in DAROL vs ARAMIS. Most treatment-emergent adverse events were grade 1/2. Two-year overall survival and metastasis-free survival rates and prostate-specific antigen responses were similar to ARAMIS.

CONCLUSIONS: These findings indicate that darolutamide offers effectiveness and a favorable safety profile in the broad range of patients seen in clinical practice.},
}

@article {pmid41177463,
year = {2025},
author = {Jons, CK and Kasse, CM and Mayer, BT and Hyrien, O and Sen, S and Meany, EL and d'Aquino, AI and Ganesh, P and Eckman, N and Dong, C and Yan, J and Nguyen, LT and Doulames, VM and Song, YE and Saouaf, OM and Williams, CM and Williams, SC and Paredes, J and Raghavan, R and Palomares, M and Alpert, M and Yates, NL and Tomaras, GD and Seaman, MS and Farzan, M and Appel, EA},
title = {Hydrogel formulations for sustained-release of broadly neutralizing antibodies.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {388},
number = {Pt 2},
pages = {114349},
pmid = {41177463},
issn = {1873-4995},
support = {INV-036842/GATES/Gates Foundation/United States ; R01 AI154989/AI/NIAID NIH HHS/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; T32 GM008412/GM/NIGMS NIH HHS/United States ; K01 EB033870/EB/NIBIB NIH HHS/United States ; INV-027411/GATES/Gates Foundation/United States ; S10 OD026831/OD/NIH HHS/United States ; },
mesh = {Animals ; Delayed-Action Preparations/pharmacokinetics/administration & dosage/chemistry ; *Hydrogels/chemistry/administration & dosage ; *Antibodies, Neutralizing/administration & dosage ; Mice ; Humans ; *Broadly Neutralizing Antibodies/administration & dosage ; Female ; Rats ; Nanoparticles/chemistry/administration & dosage ; Male ; Drug Liberation ; Rats, Sprague-Dawley ; },
abstract = {Sustained serum levels of broadly neutralizing antibodies (bnAbs) are crucial for effective passive immunization against infectious diseases as protection persists only while these bnAbs remain at adequate concentrations within the body. Current obstacles, such as poor pharmacokinetics (PK) and burdensome administration, must be overcome to make bnAbs a viable option for pre- and post-exposure prophylaxis. In this work, we explore how a polymer-nanoparticle (PNP) hydrogel depot technology can be engineered to prolong protein delivery and enable drug exposure on the order of weeks to months. In-vivo studies in mice and rats demonstrate extended protein release compared to bolus administration, and modeling efforts predict the impact of both the elimination half-life of the active pharmaceutical ingredient and hydrogel depot volume on overall pharmacokinetics. Moreover, flow cytometry characterization reveals that immune cell infiltration into the hydrogel depot can result in faster-than-expected release of antibody cargo on account of active transport via cellular uptake. We then demonstrate that co-formulation of antibodies with an anti-inflammatory agent reduces cellular infiltration and resulting active transport, further extending delivery and pharmacokinetics. Finally, multicompartmental modeling predicts the human PK profiles of clinically relevant HIV bnAbs delivered via subcutaneous hydrogel injection. These findings aid in the development of next generation hydrogel materials that stabilize and slowly release bnAbs for long-term pre-exposure immunoprophylaxis.},
}

Animals
Delayed-Action Preparations/pharmacokinetics/administration & dosage/chemistry
*Hydrogels/chemistry/administration & dosage
*Antibodies, Neutralizing/administration & dosage
Mice
Humans
*Broadly Neutralizing Antibodies/administration & dosage
Female
Rats
Nanoparticles/chemistry/administration & dosage
Male
Drug Liberation
Rats, Sprague-Dawley

@article {pmid41178332,
year = {2025},
author = {Newell, EW},
title = {Seeing First: Introducing the Resource Report at Cancer Immunology Research.},
journal = {Cancer immunology research},
volume = {13},
number = {11},
pages = {1696-1697},
doi = {10.1158/2326-6066.CIR-25-1175},
pmid = {41178332},
issn = {2326-6074},
support = {R01 CA264646/CA/NCI NIH HHS/United States ; },
}

@article {pmid41178673,
year = {2026},
author = {Gong, IY and Rafinejad-Farahani, B and Majeed, H and Soto, MJ and Oza, A and Ehrlich, T and Fernandez Lynch, H and Guerra, CE and Lofters, A and Unger, JM and Conti, RM and Rosenthal, M and Rodin, D},
title = {Reporting and enrollment disparities in hematologic malignancy trials between 2000-2023.},
journal = {Leukemia & lymphoma},
volume = {67},
number = {1},
pages = {176-189},
doi = {10.1080/10428194.2025.2579735},
pmid = {41178673},
issn = {1029-2403},
mesh = {Humans ; *Hematologic Neoplasms/therapy/epidemiology ; *Healthcare Disparities/statistics & numerical data ; *Patient Selection ; *Clinical Trials as Topic/statistics & numerical data ; United States/epidemiology ; SEER Program ; Ethnicity/statistics & numerical data ; Male ; Female ; },
abstract = {Despite initiatives to enhance diversity in clinical trials (CTs), disparities persist in hematologic malignancy (HM) studies. We reviewed 1,230 US-based phase II-III HM CTs (2000-2023) including 149,434 participants and compared enrollment to SEER benchmarks. Race was reported in 59% of trials and ethnicity in 40%, with significant improvement over time. Trials initiated in 2016 or later were more likely to report race (OR 36.3) and ethnicity (OR 8.0) than those before 2008. Compared with NIH-sponsored studies, institutional (OR 0.34) and industry trials (OR 0.52) had lower odds of reporting demographics. Black and Hispanic individuals were consistently underrepresented, most notably in multiple myeloma (7.0% vs. 20.0% expected) and acute lymphoblastic leukemia (21.5% vs. 36.9% expected). NIH-funded trials enrolled more Black participants than other sponsor types. These findings emphasize the need for enforceable mandates on race and ethnicity reporting, as well as representation targets, to ensure equitable access and generalizability.},
}

Humans
*Hematologic Neoplasms/therapy/epidemiology
*Healthcare Disparities/statistics & numerical data
*Patient Selection
*Clinical Trials as Topic/statistics & numerical data
United States/epidemiology
SEER Program
Ethnicity/statistics & numerical data
Male
Female