@article {pmid42467592,
year = {2026},
author = {Friedman, D and Kramer, G and Alice, AF and Baird, J and Ramin, S and Medler, T and Young, KH and Kaiser, MG and Grassberger, C and Crittenden, MR and Gough, MJ},
title = {Fluorescence tracking CD8 T cells from tumor-draining lymph nodes to irradiated tumors and their activation in the tumor environment.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {215},
number = {7},
pages = {},
pmid = {42467592},
issn = {1550-6606},
support = {R01CA182311/BC/NCI NIH HHS/United States ; R01CA244142/BC/NCI NIH HHS/United States ; R01CA208644/BC/NCI NIH HHS/United States ; R01CA293806/BC/NCI NIH HHS/United States ; //Providence Foundation/ ; },
mesh = {Animals ; *CD8-Positive T-Lymphocytes/immunology/radiation effects ; *Lymph Nodes/immunology/radiation effects/pathology ; Mice ; *Lymphocyte Activation/immunology/radiation effects ; *Tumor Microenvironment/immunology/radiation effects ; Mice, Inbred C57BL ; Antigens, CD/metabolism ; Female ; Cell Tracking/methods ; *Lymphocytes, Tumor-Infiltrating/immunology/radiation effects ; Lectins, C-Type/metabolism ; Antigens, Differentiation, T-Lymphocyte/metabolism ; Cell Line, Tumor ; },
abstract = {Radiation is an effective site-specific cytotoxic therapy for cancer cells. In preclinical models, CD8 T cells are essential for optimum tumor control by radiation therapy, yet CD8 T cells are radiosensitive and depleted within the treatment field. Irradiated tumors can be refilled with T cells that were outside the field at the time of treatment. Using the Kaede photoconvertible mouse model we tracked CD8 T cells that originated in the tumor-draining lymph node and entered the tumor following radiation therapy. We show that radiation induces CD69 expression in newly infiltrating CD8 T cells within the tumor; however, this activation is not antigen-specific activation, but rather ois mediated by type I interferon released following radiation therapy. This effect is radiation dose dependent and requires cGAS expression in the cancer cells. Mathematical modeling demonstrates that radiation results in increased retention of surviving CD8 T cells in the tumor environment following treatment. By tracking the movement of tumor antigen-specific CD8 T cells from the tumor-draining lymph node to the tumor, we can observe that these cells rapidly express exhaustion markers in the tumor environment. These events occur in advance of radiation-mediated antigen-specific T cell expansion in the tumor-draining lymph node. These data formally demonstrate movement of CD8 T cells from the tumor-draining lymph node to the irradiated tumor and identify a mechanism of innate inflammation-mediated T cell activation that may impact T cell retention and accelerates refilling of the irradiated tumor.},
}

Animals
*CD8-Positive T-Lymphocytes/immunology/radiation effects
*Lymph Nodes/immunology/radiation effects/pathology
Mice
*Lymphocyte Activation/immunology/radiation effects
*Tumor Microenvironment/immunology/radiation effects
Mice, Inbred C57BL
Antigens, CD/metabolism
Female
Cell Tracking/methods
*Lymphocytes, Tumor-Infiltrating/immunology/radiation effects
Lectins, C-Type/metabolism
Antigens, Differentiation, T-Lymphocyte/metabolism
Cell Line, Tumor

@article {pmid42469190,
year = {2026},
author = {Hoffman, KL and Marshall, G and Frivold, C and Acker, Z and Arnould, IS and Babu, TM and Barnes, SR and Briggs-Hagen, M and Casto, A and Clark, E and Cox, SN and Drummond, M and Ehmen, B and Englund, JA and Gamboa, L and Greninger, AL and Grindstaff, S and Grioni, H and Han, P and Hatchie, T and Hollcroft, M and Kuntz, JL and Lo, NK and Lockwood, CM and McAllister, KD and McCormick, CJ and MacMillan, MP and Midgley, CM and Nguyen, D and Plumb, ID and Reed, JC and Reich, S and Roychoudhury, P and Schmidt, M and Starita, LM and Stone, J and Varga, A and Weil, AA and Wolock, CJ and Yetz, N and Gilbert, PB and Naleway, AL and Chu, HY and Carone, M},
title = {Immune correlates of risk for SARS-CoV-2 infection in children: a prospective, community-based cohort study.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-74684-8},
pmid = {42469190},
issn = {2041-1723},
support = {75D30120C09322 AM002//U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC)/ ; },
abstract = {Few studies have characterized immune correlates of SARS-CoV-2 infection risk in children, particularly those with hybrid immunity from vaccination and prior infection. We conduct a prospective community-based cohort study of 1509 U.S. children (2022-2024), performing weekly SARS-CoV-2 PCR testing and measuring baseline binding and neutralizing antibody titers against multiple variants. Higher antibody levels, notably nucleocapsid-binding and Omicron-specific neutralizing antibodies, are significantly associated with reduced risk of SARS-CoV-2 infection after adjusting for age, recent infection, exposure settings, and temporal trends (adjusted hazard ratios ranging from 0.60 to 0.87 per positive unit difference in log10-fold antibody level (AU/mL)). Secondary analyses suggest these findings are robust to multiple stratifications of SARS-CoV-2 immune status, are relevant across different pediatric age groups, and appear to apply to both overall and symptomatic infection risk. Together, the results suggest that specific antibodies can predict relative infection risk in pediatric populations with diverse immune histories. Understanding these immune correlates may inform tailored vaccination strategies and risk assessments as SARS-CoV-2 continues to evolve.},
}

@article {pmid42462191,
year = {2026},
author = {Nahleh, Z and Alfano, CM and Somerfield, MR and Lee, JM and Hieken, TJ and Magnuson, A and Rao, RD and Chew, HK and Chia, SKL and Harvey, BE and Landsberger, E and Lim, B and Mwanzi, SA and Parsons, HA and Patt, D and Sukumar, JS and Sung, H and Werutsky, G and Lustberg, M},
title = {Breast Cancer Follow-Up and Surveillance After Primary Treatment: ASCO Guideline Update.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {101200JCO2601700},
doi = {10.1200/JCO-26-01700},
pmid = {42462191},
issn = {1527-7755},
abstract = {PURPOSE: To offer clinicians recommendations concerning breast cancer follow-up and surveillance after primary treatment.

METHODS: ASCO convened an Expert Panel to develop recommendations based on a systematic review and a formal consensus process.

RESULTS: One randomized controlled trial (RCT) was identified and formed the evidentiary basis for the surveillance mammography guideline recommendation. No RCTs were identified that evaluated different follow-up approaches by risk of relapse in patients treated for early-stage breast cancer. Given the dearth of evidence identified in the systematic review of the literature, formal modified Delphi consensus-based recommendations were generated.

RECOMMENDATIONS: The guideline offers recommendations on the role of a risk-based approach to the frequency and intensity of follow-up among patients with breast cancer in the adjuvant setting. Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Either virtual or in-person visits can be offered. Certain patients at high risk of cancer recurrence warrant closer surveillance, such as those patients with locally advanced disease or residual disease following neoadjuvant chemotherapy. Recommendations on the use of blood-based biomarkers and supplemental imaging are provided. Guideline recommendations will be updated once additional evidence-based tools become available to better individualize surveillance.Additional information is available at www.ascopubs.org/topics/asco-guidelines/breast-cancer.},
}

@article {pmid42462716,
year = {2026},
author = {Hong, A and Liu, M and Truta, A and Talaie, A and Smith, GR and Bondy-Denomy, J},
title = {Gabija restricts phage circularization and DNA replication.},
journal = {Cell host & microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chom.2026.06.016},
pmid = {42462716},
issn = {1934-6069},
abstract = {Anti-bacteriophage systems such as restriction-modification and CRISPR-Cas have DNA substrate specificity mechanisms that enable the identification of invaders. How Gabija, a highly prevalent nuclease-helicase antiphage system, limits phage replication while executing self- vs. non-self-discrimination remains unknown. Here, we show that phage-encoded DNA end-binding proteins that antagonize host RecBCD sensitize phages to Gabija. When targeting a temperate lambda-like phage in Pseudomonas aeruginosa, Gabija prevents phage genome circularization and subsequent replication. DNA end-binding complexes, including a phage exonuclease and a single-stranded DNA (ssDNA)-annealing protein or GamMu dimers that prevent loading of the host repair complex RecBCD, are necessary and sufficient to license phage and plasmid sensitivity to Gabija. Mutant escape phages lacking these DNA end-binding proteins become protected from Gabija by RecBCD translocation activities. RecBCD activity on the bacterial genome, presumably whenever it is linearized, also prevents Gabija from targeting self-DNA. Therefore, we propose that Gabija antagonizes the circularization and replication of linear DNA devoid of RecBCD as a mechanism to identify and antagonize foreign invaders.},
}

@article {pmid42463988,
year = {2026},
author = {Wells-Di Gregorio, S and McAlister, B and Kayser, K and Siston, A and Flowers, S and Donnell, C and Fitchett, G and Gray, TF and Fann, JR and Vanderlan, J and Snyder, D and Bates, N and Deshields, T and Baltimore, S and Voinovich, M and Smit, T and Marks, DR},
title = {The American Psychosocial Oncology Society's Psychosocial Oncology Virtual Academy: Enhancing Access to Specialized Psychosocial Oncology Care.},
journal = {Psycho-oncology},
volume = {35},
number = {7},
pages = {e70520},
pmid = {42463988},
issn = {1099-1611},
support = {//American Psychosocial Oncology Society/ ; //Parthenon Management Company/ ; },
mesh = {Humans ; *Psycho-Oncology/education ; *Health Services Accessibility ; Societies, Medical ; Curriculum ; United States ; Female ; Medical Oncology/education ; },
abstract = {OBJECTIVE: By 2040, there will be 26 million cancer survivors in the United States, with approximately 40% experiencing cancer-related challenges warranting psychosocial care. Simultaneously, the US has a psychosocial workforce shortage. The American Psychosocial Oncology Society (APOS) created the Psychosocial Oncology (PSO) Virtual Academy in 2022 to expand the PSO workforce. This study provides a formative evaluation of this curriculum.

METHODS: The PSO Virtual Academy is a 15-session training program provided via the Trusted Provider Network (TPN), a continuing education platform. The majority of registrants come from West Virginia (n = 28) and California (n = 21), states in which APOS has partnered to increase access to evidence-based PSO care. After finishing each session, course participants completed a brief mixed methods survey. In this study, we examine feasibility (educational, technical, and operational), acceptability, learning effectiveness, strengths, and areas for improvement.

RESULTS: Since 2022, 262 behavioral health specialists have registered, and 147 (56%) have completed the certificate course. Eighty-four percent reported satisfaction with their overall experience with the program. Technology use was satisfactory for 76% of participants. Ninety-six percent reported learning an average amount to a great deal. Areas of strength included engaging faculty and inclusion of clinical discussions. Areas for improvement included providing slide handouts, greater focus on clinical interventions, and assessment tools.

CONCLUSIONS: The PSO Virtual Academy 1.0 has provided satisfactory and useful training to over 147 behavioral health professionals, helping APOS to expand the PSO workforce in several mental health shortage areas. Work is underway to complete a summative evaluation and develop version 2.0, which will incorporate a briefer, standardized format for didactic content, in-person skills-based training components, and a case-based community of practice.},
}

Humans
*Psycho-Oncology/education
*Health Services Accessibility
Societies, Medical
Curriculum
United States
Female
Medical Oncology/education

@article {pmid42466974,
year = {2026},
author = {Wu, X and Shadman, M and Voutsinas, JM and Hippe, DS and Randolph, T and Ujjani, CS and Crider, C and Keshmiri, S and Smith, SD and Lynch, RC and Di, M and Huang, JJ and Martin, PS and Till, BG and Gopal, AK},
title = {Incidence and clinical impact of absolute lymphocyte count-only progression in chronic lymphocytic leukemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026020680},
pmid = {42466974},
issn = {2473-9537},
abstract = {An increase in the absolute lymphocyte count (ALC) is a component of progressive disease (PD) in chronic lymphocytic leukemia (CLL) and contributes to progression free survival (PFS) in phase 3 trials. Prior studies with chemoimmunotherapy demonstrated that PD by ALC alone (ALC PD) conferred better outcomes than other modalities of PD (other PD). To evaluate the incidence and impact of ALC PD with modern treatments, we retrospectively examined 339 consecutive CLL/SLL patients treated between 2016 - 2025 at the University of Washington/Fred Hutchinson Cancer Center. Patients received frontline therapy with continuous Bruton tyrosine kinase inhibitors (BTKi, n=179), bendamustine-rituximab (BR, n=66), and time-limited BCL2 inhibitors (BCL2i, n=94). The cumulative incidence of ALC PD was higher with BR than BTKi and BCL2i (p=0.021). Across treatment groups, overall survival (OS) from progression was longer for ALC PD than other PD (median 116 vs 71 months, p=0.0012, HR 3.15, 95% CI 1.52-6.53) with 5-year OS rates of 83% and 56%. Time to next treatment or death (TTNT-D) was longer for ALC PD (median 14 vs 2.2 months, p<0.0001, HR 3.36, 95% CI 2.27-4.95). OS from treatment initiation was longest for non-progressors, intermediate for ALC PD (HR 3.62, 95% CI 1.48-8.85, p=0.005), and worst for other PD (HR 11.7, 95% CI 5.99-22.9, p<0.001). These findings suggest that ALC PD may vary based on treatment modality and is associated with longer survival and TTNT-D. If confirmed in larger phase 3 datasets, future response criteria may consider reporting ALC PD separately from other PD.},
}

@article {pmid42458791,
year = {2026},
author = {Abdou, Y and Hoag, J and Barlow, WE and Albain, KS and Gralow, JR and Meric-Bernstam, F and Hayes, DF and Lin, NU and Perez, EA and Goldstein, LJ and Chia, SKL and Dhesy-Thind, S and Rastogi, P and Schott, AF and Racz, J and Baehner, FL and Tripathy, D and Hortobagyi, GN and Pusztai, L and Sharma, P and Kalinsky, K},
title = {Recurrence Score® gene group components and outcomes in the RxPONDER trial (SWOG S1007).},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag221},
pmid = {42458791},
issn = {1460-2105},
abstract = {BACKGROUND: The RxPONDER trial has guided adjuvant chemotherapy use in node-positive HR+/HER2- breast cancer; however, prior analyses showed poorer outcomes among non-Hispanic Black (NHB) women compared with non-Hispanic White (NHW) women despite similar 21-gene Recurrence Score® (RS) results. This suggests contributors to disparities may not be captured by the composite RS. We evaluated RS gene group components-proliferation, estrogen receptor (ER), HER2 (GRB7), and invasion-by ethnicity, body mass index, and menopausal status, and assessed associations with outcomes.

METHODS: RxPONDER enrolled 5,083 women with HR+/HER2- breast cancer, 1-3 positive nodes, and RS ≤ 25, randomized to endocrine therapy ± chemotherapy. 3,102 participants with ethnicity and gene expression data were included. RS components were compared across subgroups, and associations with invasive disease-free survival (IDFS) and distant recurrence-free interval were evaluated using multivariable Cox models adjusted for clinicopathologic factors and treatment.

RESULTS: Among 3,102 women (70.2% NHW, 15.5% Hispanic, 9.5% Asian, 4.7% NHB), RS distributions were similar across groups and prognostic overall. Tumors from NHB (p = 0.003) and Hispanic (p = 0.02) had higher proliferation scores versus NHW women, while Asian women had higher HER2 (p = 0.006) and ER scores (p = 0.028). IDFS differences were not statistically significant for NHB vs. NHW women (HR 1.41; 95% CI 0.98-2.03), whereas Asian women had improved IDFS (HR 0.63; 95% CI 0.43-0.91).

CONCLUSIONS: Despite similar overall RS distributions, component pathways vary by ethnicity and may contribute to outcome differences. These findings support evaluating gene-specific biology beyond composite scores to better understand disparities and refine risk stratification.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT01272037.},
}

@article {pmid42460617,
year = {2026},
author = {de Marinis, F and Kim, TM and Bonanno, L and Cheng, S and Kim, SW and Tiseo, M and Chu, Q and Proto, C and Sacher, A and Luo, YH and Novello, S and Hao, D and Baik, C and Bazhenova, L and Lee, JS and Cho, BC and Cadranel, J and Diep, TB and Metro, G and Narayanan, P and Yoneshima, Y and de Castro Carpeño, J and Baldotto, C and Yang, JC and Sequist, LV and Levy, B and Hartmaier, R and Igwegbe, I and Poole, L and Xu, W and Ahn, MJ},
title = {A plain language summary of the SAVANNAH study: savolitinib plus osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification whose cancer had grown or spread on osimertinib.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/14796694.2026.2692029},
pmid = {42460617},
issn = {1744-8301},
}

@article {pmid42461076,
year = {2026},
author = {Rooks, E and Lee, M and Bhowmik, O and Hernandez-Lopez, V and Stacey, AW and Mustafi, D},
title = {Integrative Genomic Mapping and Visualization From Curated Public Datasets Reveals Germline RB1 Variant Diversity in Retinoblastoma.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {8},
pages = {40},
doi = {10.1167/iovs.67.8.40},
pmid = {42461076},
issn = {1552-5783},
mesh = {Humans ; *Retinoblastoma/genetics ; *Retinal Neoplasms/genetics ; *Germ-Line Mutation ; *Retinoblastoma Binding Proteins/genetics ; *Ubiquitin-Protein Ligases/genetics ; Databases, Genetic ; *Genetic Variation ; *Chromosome Mapping/methods ; Genomics/methods ; },
abstract = {PURPOSE: To consolidate and refine RB1 disease-causing variants in retinoblastoma (RB) and to develop a visual, integrative tool for variant exploration at the gene and protein level.

METHODS: RB1 variants associated with RB were compiled from the Leiden Open Variation Database, 13 published cohort studies between 2014 and 2025, and the Catalogue of Somatic Mutations in Cancer. Case information was recovered where available, and variants were reannotated using Human Genome Variation Society (HGVS) nomenclature on transcript NM_000321.3 and mapped to Genome Reference Consortium Human Build 38 (GRCh38). PANORAMA was built in Python using Dash and Plotly.

RESULTS: After filtering for variants with unique identifiers and interpretable descriptions, 3004 variants (1943 germline, 797 somatic, and 264 variants of unknown origin) underwent HGVS standardization, GRCh38 mapping, and statistical analysis. Truncating germline variants accounted for more than 80% of variants, whereas missense variants comprised 9.2%. Germline variant density was highest in exons 4 and 15 and lowest in exons 25 to 27. Nonsense variants predominated in the N-terminal, Pocket A, and C-terminal regions, whereas missense variants were concentrated in Pocket B. Among 1539 germline variants with known tumor laterality, 81.2% were bilateral. Only 39.4% of germline variants were reported in ClinVar. PANORAMA allowed interactive visualization and filtering of aggregated and user-uploaded RB1 variants.

CONCLUSIONS: This work consolidates dispersed RB1 variant data into an unified resource and reveals domain-specific patterns of genetic disruption in RB. Integration with PANORAMA supports exploratory analysis, variant interpretation, and comparison of external cohorts to the global RB1 landscape.},
}

Humans
*Retinoblastoma/genetics
*Retinal Neoplasms/genetics
*Germ-Line Mutation
*Retinoblastoma Binding Proteins/genetics
*Ubiquitin-Protein Ligases/genetics
Databases, Genetic
*Genetic Variation
*Chromosome Mapping/methods
Genomics/methods

@article {pmid42461244,
year = {2026},
author = {Mallett, DR and Jiang, M and Minnuto, GM and Biggins, S},
title = {Kinetochore clustering is mediated by Mps1 phosphorylation of conserved MELT motifs in Stu1.},
journal = {The Journal of cell biology},
volume = {225},
number = {9},
pages = {},
doi = {10.1083/jcb.202601143},
pmid = {42461244},
issn = {1540-8140},
support = {P30 CA015704/NH/NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {Phosphorylation ; *Kinetochores/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism/chemistry/genetics ; *Protein Serine-Threonine Kinases/metabolism/genetics ; *Cell Cycle Proteins/metabolism/genetics/chemistry ; *Saccharomyces cerevisiae/metabolism/genetics ; *Protein-Tyrosine Kinases/metabolism/genetics ; Amino Acid Motifs ; Microtubules/metabolism ; Mitosis ; },
abstract = {Unattached kinetochores promote microtubule capture while preventing cell cycle progression during mitosis. The Mps1 kinase controls these events by mediating kinetochore assembly of the fibrous corona in animal cells and by triggering the spindle checkpoint. In budding yeast, which does not assemble a fibrous corona, the Stu1 and Slk19 spindle proteins promote microtubule capture by clustering unattached kinetochores, but the underlying mechanism is unclear. Here, we show that Mps1 controls this pathway by phosphorylating two conserved MELT motifs in Stu1 to recruit Slk19 and mediate kinetochore clustering. Structural analysis of the Stu1:Slk19 complex reveals long, string-like filaments and offers mechanistic insight into how kinetochores might cluster. Our findings suggest the regulation of kinetochore capture is a conserved Mps1 function across eukaryotes.},
}

Phosphorylation
*Kinetochores/metabolism
*Saccharomyces cerevisiae Proteins/metabolism/chemistry/genetics
*Protein Serine-Threonine Kinases/metabolism/genetics
*Cell Cycle Proteins/metabolism/genetics/chemistry
*Saccharomyces cerevisiae/metabolism/genetics
*Protein-Tyrosine Kinases/metabolism/genetics
Amino Acid Motifs
Microtubules/metabolism
Mitosis

@article {pmid42462027,
year = {2026},
author = {Orchard, P and Blackwell, TW and Kachuri, L and Castaldi, PJ and Cho, MH and Christenson, SA and Durda, P and Gabriel, S and Hersh, CP and Huntsman, S and Hwang, S and Joehanes, R and Johnson, M and Li, X and Lin, H and Liu, CT and Liu, Y and Mak, ACY and Manichaikul, AW and Paik, DT and Saferali, A and Smith, JD and Taylor, KD and Tracy, RP and Wang, J and Wang, M and Weinstock, JS and Weiss, J and Wheeler, HE and Zhou, Y and Zöllner, S and Wu, JC and Mestroni, L and Graw, S and Taylor, MRG and Ortega, VE and Johnson, WC and Gan, W and Abecasis, G and Nickerson, DA and Gupta, N and Ardlie, K and Woodruff, PG and Bowler, RP and Meyers, DA and Reiner, A and Kooperberg, C and Ziv, E and Vasan, RS and Larson, MG and Cupples, LA and Silverman, EK and Rich, SS and Heard-Costa, N and Tang, H and Rotter, JI and Smith, AV and Levy, D and , and , and Aguet, F and Scott, LJ and Raffield, LM and Parker, SCJ and Abe, N and Almasy, L and Ament, S and Anugu, P and Auer, P and Avramopoulos, D and Balasubramanian, A and Barr, RG and Barwick, L and Beaty, T and Becker, D and Becker, L and Beitelshees, A and Benos, T and Bezerra, M and Bis, J and Brody, J and Broeckel, U and Broome, J and Bunting, K and Buth, E and Carey, V and Carty, C and Casaburi, R and Chaffin, M and Chang, C and Chang, YC and Chavan, S and Chen, BJ and Chen, WM and Choi, SH and Chuang, LM and Chung, RH and Conomos, M and Cornell, E and Crandall, C and Crapo, J and Curtis, J and Damcott, C and David, S and de Las Fuentes, L and de Vries, P and Deka, R and DeMeo, D and Devine, S and Dinh, H and Doddapaneni, H and Duan, Q and Duggirala, R and Eaton, C and Ekunwe, L and El Boueiz, A and Emery, L and Farber, C and Farek, J and Franceschini, N and Frazar, C and Fu, M and Fullerton, SM and Fulton, L and Gao, S and Gao, Y and Gass, M and Geiger, H and Ghosh, A and Gignoux, C and Glahn, D and Gogarten, S and Gong, DW and Goring, H and Grine, D and Gu, CC and Guan, Y and Hall, M and Han, Y and Harris, D and Heavner, B and Herrington, D and Hobbs, B and Hong, E and Hoth, K and Hsiung, CA and Hu, J and Hung, YJ and Huston, H and Hwu, CM and Jackson, R and Jain, D and Johnsen, J and Johnston, R and Jones, K and Kessler, M and Khan, A and Khan, Z and Kim, W and Kimoff, J and Kinney, G and Kramer, H and Lange, C and Lange, E and Laurie, C and Laurie, C and LeBoff, M and Lee, S and Lee, WJ and Levine, D and Lewis, J and Li, Y and Lin, X and Liu, S and Liu, Y and Make, B and Manning, A and Manson, J and Martin, L and Marton, M and Mathai, S and May, S and McArdle, P and McDonald, ML and McFarland, S and McGoldrick, D and McHugh, C and Mei, H and Meigs, J and Menon, V and Min, N and Moll, M and Momin, Z and Montasser, M and Mychaleckyj, JC and Naik, R and Naseri, T and Natarajan, P and Nelson, SC and Neltner, B and Nessner, C and Nkechinyere, O and O'Connell, J and O'Connor, T and Ochs-Balcom, H and Okwuonu, G and Pankow, J and Parker, C and Peloso, G and Peralta, JM and Perez, M and Perry, J and Peters, U and Phillips, LS and Pollin, T and Becker, JP and Boorgula, MP and Psaty, B and Qiao, D and Rafaels, N and Rajendran, M and Rasmussen-Torvik, L and Ratan, A and Reed, R and Regan, E and Reupena, MS and Robillard, R and Roselli, C and Ruczinski, I and Runnels, A and Russell, P and Ryan, K and Sabino, EC and Salimi, S and Salvi, S and Salzberg, S and Sandow, K and Santibanez, J and Schwander, K and Sciurba, F and Sériès, F and Shetty, A and Shetty, A and Silver, B and Skomro, R and Smith, T and Smoller, S and Snively, B and Stilp, AM and Storm, G and Streeten, E and Su, JL and Sung, YJ and Sylvia, J and Szpiro, A and Taub, M and Taylor, S and Thornton, TA and Threlkeld, M and Tinker, L and Tirschwell, D and Tiwari, H and Tong, C and Tsai, M and Vaidya, D and Walker, T and Wallace, R and Walts, A and Wang, FF and Wang, H and Watson, K and Watt, J and Weng, LC and Wessel, J and Williams, K and Wilson, C and Wilson, J and Winterkorn, L and Wong, Q and Wu, B and Xu, H and Yanek, L and Yang, I and Zekavat, SM and Zhao, SX and Zhao, W and Zhu, X},
title = {Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed.},
journal = {Science (New York, N.Y.)},
volume = {393},
number = {6808},
pages = {eadx2989},
doi = {10.1126/science.adx2989},
pmid = {42462027},
issn = {1095-9203},
mesh = {Humans ; Cohort Studies ; *Gene Expression Regulation ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; *RNA Splicing/genetics ; Sequence Analysis, RNA ; UK Biobank ; *Precision Medicine ; *Gene Expression Profiling ; Organ Specificity ; },
abstract = {Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood (n = 6454) and lung (n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank-derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.},
}

Humans
Cohort Studies
*Gene Expression Regulation
Genome-Wide Association Study
Polymorphism, Single Nucleotide
*Quantitative Trait Loci
*RNA Splicing/genetics
Sequence Analysis, RNA
UK Biobank
*Precision Medicine
*Gene Expression Profiling
Organ Specificity

@article {pmid42448319,
year = {2026},
author = {Auletta, JJ and Stanek, J and Bo-Subait, S and Al Malki, MM and Cook, RJ and Gooptu, M and Shaffer, BC and Jimenez Jimenez, AM and Modi, D and Hill, JA and Huppler, AR and Kou, J and Cusatis, RN and Broglie, L and Shaw, BE and Stefanski, HE and Spellman, SR and Devine, SM},
title = {Infection Burden in Mismatched Unrelated Donor Hematopoietic Cell Transplantation: Results from the ACCESS Trial.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026020882},
pmid = {42448319},
issn = {2473-9537},
abstract = {Human leukocyte antigen (HLA)-mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) has emerged as an effective therapy for adult patients with hematologic malignancies. The MMUD ACCESS Trial (NCT04904588), which incorporated post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis, demonstrated combined overall survival of 81% in enrolled patients, 59% who were ethnically diverse. Given PTCy is also associated with significant bacterial and viral infections, we defined infection burden in the full adult cohort (N=268) using infections graded according to an international standard (CTCAE, Common Terminology Criteria for Adverse Events, version 5.0). Infection density (number of infections per 100 days at risk), cumulative incidence of infection, and frequency of pathogen types were categorized by post-HCT time, conditioning intensity, level of donor HLA mismatch, and presence of acute GvHD. Of 465 recorded CTCAE grade 2-5 infections recorded in 183 (68%) adults, 176 (38%) infections were significant or life-threatening and most infections (296, 64%) occurred within the first 100 days. Infection density at Days 0-30 was significantly higher than at other times and was similar by conditioning and level of HLA mismatch as were pathogen types and isolates. Multivariable analysis showed that acute GvHD is significantly associated with infection. Lastly, 21 (7.8%) patients died from infection. Results show significant infection burden using standard dose PTCy in the MMUD HCT setting, irrespective of conditioning and level of donor HLA mismatch, and will serve as a benchmark for trials investigating reducing infection burden following MMUD HCT.},
}

@article {pmid42448573,
year = {2026},
author = {McCornack, D and Ivory, CF and Zhang, Z and Dong, WJ},
title = {Avidin-Functionalized Gold Nanoparticles Enable Cationic Isotachophoresis for Enhanced Lateral Flow Assays.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.6c00357},
pmid = {42448573},
issn = {1520-6882},
abstract = {Lateral flow assays (LFAs) are widely used for rapid, point-of-care diagnostics but struggle with sensitivity in part due to passive migration and interference from high-abundance serum proteins. Here, we introduce the lateral isotachophoresis-guided migration analysis (LIGMA) assay, a novel diagnostic platform that leverages cationic isotachophoresis (+ITP) to enhance biomolecular separation and detection in LFAs. Using avidin-functionalized gold nanoparticles (AV-S-GNPs) as positively charged nanocarriers, this system enables the direct electrophoretic migration of negatively charged analytes, overcoming a major limitation of conventional cationic electrokinetic focusing methods. The functionalized nanoparticles exhibited superior stability across physiological pH ranges and maintained consistent electrophoretic mobility under + ITP conditions. LIGMA achieved a limit of detection of 1.97 nM and a limit of quantification of 4.12 nM for human immunoglobulin G (IgG), requiring only 1 μL of sample volume and under 2 min of assay time. Compared to standard LFAs, ITP-enhanced migration produced sharper capture line resolution, improved analyte focusing, and minimized background interference from abundant serum proteins. This work establishes the LIGMA assay as a viable electrokinetic strategy for improving paper-based biosensors, providing a foundation for expanded applications in clinical diagnostics, multiplexed detection, and portable field-deployable biosensing platforms.},
}

@article {pmid42449719,
year = {2026},
author = {Potter, JD and Macrae, FA and Sampson, JR and Haupt, S and Seppälä, TT and Cameron-Mackintosh, S and Ahadova, A and Kloor, M and Møller, P and Plsd Collaborators, },
title = {Incidence Rates of Melanoma and Lung Cancer Are Generally Low in the Lynch Syndromes and Vary Across path_MMR Variants: A Prospective Lynch Syndrome Database Report.},
journal = {Cancers},
volume = {18},
number = {13},
pages = {},
doi = {10.3390/cancers18132177},
pmid = {42449719},
issn = {2072-6694},
abstract = {Background/Objectives It is not established whether melanoma and lung cancer are part of the tumor spectrum of the Lynch syndromes (LS). Our first hypothesis was that, if melanoma is associated with LS, most prospectively observed cases would be carriers of pathogenic MSH2 variants (path_MSH2), as for other LS non-endodermal tumors. Our second hypothesis, which was derived from findings of the first study, was that the pattern of differences in the incidence of lung cancer in path_MMR carriers would mirror that for melanoma. Methods We used the Prospective Lynch Syndrome Database (PLSD) data and methods. Results Firstly, consistent with hypothesis, ten of 3154 path_MSH2 carriers followed for 26,309 years developed melanoma, compared with 6 of 5288 path_MLH1/MSH6/PMS2 carriers followed for 45,081 years (p = 0.04). Secondly, although the incidence of melanoma in carriers of path_MSH2 was 0.00041-similar to the populations in which the carriers resided-the average incidence rates for path_MLH1/MSH6/PMS2 carriers was 0.00012, lower than the corresponding population rates. Thirdly, the average lung cancer incidence rates in PLSD were 0.00112 in path_MSH2 carriers and 0.00032 in path_MLH1/MSH6/PMS2 carriers (p = 0.02), both lower than the population rates. Conclusions Melanomas and lung cancers-both of which are immunogenic through mechanisms independent of mismatch repair deficiency-may become even more immunogenic when they also exhibit microsatellite instability. This may lead to an increased likelihood that both tumors are eliminated by the immune system and, thus, show variable and lower incidence. These insights may help inform strategies for cancer prevention or treatment that are aimed at simultaneously interrupting multiple carcinogenic pathways.},
}

@article {pmid42453141,
year = {2025},
author = {Li, F and Liu, S and Sun, W},
title = {Improved Deep Learning Prediction of TCR-HLA Associations.},
journal = {Statistics in biosciences},
volume = {},
number = {},
pages = {},
pmid = {42453141},
issn = {1867-1764},
abstract = {Understanding the relationship between T cell receptors (TCRs) and human leukocyte antigens (HLAs) is essential for elucidating immune response specificity, uncovering mechanisms of autoimmunity, and advancing targeted immunotherapies. We have previously developed a deep learning method, DePTH (Deep Learning Prediction of TCR-HLA associations), to predict the association between a TCR and an HLA based on their amino acid sequences. In this work, we evaluated the performance of DePTH in two additional datasets, and investigated the influence of two potential confounding factors: TCR generation probability and the sequence length of CDR3 (Complementarity-Determining Region 3), which is a key region in the antigen-binding site of TCRs. Building on these insights, we combined training data from two datasets to train a new version of DePTH: DePTH 2.0.},
}

@article {pmid42453565,
year = {2026},
author = {Chen, K and Cheng, J and Halloran, ME and Small, DS},
title = {Using case description information to reduce sensitivity to bias for the attributable fraction among the exposed.},
journal = {Journal of the Royal Statistical Society. Series A, (Statistics in Society)},
volume = {189},
number = {3},
pages = {1340-1356},
pmid = {42453565},
issn = {0964-1998},
abstract = {The attributable fraction among the exposed (A F e) is the proportion of disease cases among the exposed that could be avoided by eliminating the exposure. In this article, we propose a new approach to reduce sensitivity to hidden bias for conducting statistical inference on the A F e by leveraging case description information such as subtype of cancer. The proposed method is examined through an asymptotic tool, design sensitivity, simulation studies, and case studies of alcohol consumption and the risk of postmenopausal invasive breast cancer utilizing information on the subtype of cancer using data from the Women's Health Initiative Observational Study allowing the possibility that leveraging case definition information may introduce selection bias through an additional sensitivity parameter.},
}

@article {pmid42456914,
year = {2026},
author = {Singal, AG and Lopez, C and Feng, Z and Hoshida, Y and Marrero, J and Parikh, ND},
title = {Longitudinal assessment of clinical risk scores for HCC in patients with cirrhosis.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cgh.2026.06.035},
pmid = {42456914},
issn = {1542-7714},
}

@article {pmid42456977,
year = {2026},
author = {Li, C and Venkatesh, H and Trieu, L and Fong, L},
title = {Strategic engineering B cell immunity for cancer immunotherapy.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115182},
doi = {10.1016/j.jconrel.2026.115182},
pmid = {42456977},
issn = {1873-4995},
abstract = {Clinical datasets across versatile types of cancer indicate a strong association between B-cell tumor presence and cancer patients' responses and survival following immune checkpoint blockade. Indeed, many clinical observations have identified mature tumor associated tertiary lymphoid structure (TLS) with distinct B cell and T cell zones as a key determinant of patients' responses to immunotherapy. However, differences in clinical associations and B cells functions across tumor contextures necessitate in-depth investigations on context-dependent anti- and pro-tumorigenic roles of B-cell immunity-antibody secretion, antigen presentation, and cytokine production-and its importance for tumor control. Therapeutic strategies that promote B cell infiltration, TLS formation and maturation show promise in re-programing the tumor microenvironment, enhancing anti-tumor immunity, and promoting tumor clearance.},
}

@article {pmid42457959,
year = {2026},
author = {Gschwind, AR and Mualim, KS and Karbalayghareh, A and Sheth, MU and Dey, KK and Jagoda, E and Nurtdinov, RN and Xi, W and Tan, AS and Galante, J and Jones, H and Ma, XR and Yao, D and Amgalan, D and Ray, J and Munger, CJ and Nasser, J and Avsec, Ž and James, BT and Shamim, MS and Durand, NC and Rao, SSP and Mahajan, R and Doughty, BR and Andreeva, K and Ulirsch, JC and Fan, K and Perez, EM and Nguyen, TC and Kelley, DR and Finucane, HK and Moore, JE and Weng, Z and Kellis, M and Bassik, MC and Ustun, B and Price, AL and Beer, MA and Guigó, R and Stamatoyannopoulos, JA and Lieberman Aiden, E and Greenleaf, WJ and Leslie, CS and Steinmetz, LM and Kundaje, A and Engreitz, JM},
title = {An encyclopedia of human enhancer-gene regulatory interactions.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {42457959},
issn = {1476-4687},
abstract = {Identifying transcriptional enhancers and their target genes is essential for understanding gene regulation and the effect of human genetic variation on disease[1-6]. Here we create and evaluate a resource of more than 92 million enhancer-gene regulatory interactions across 1,458 biosamples covering 369 cell types and tissues, by integrating predictive models, chromatin states, three-dimensional contacts and large-scale genetic perturbations generated by the ENCODE Consortium[7]. We first create a systematic benchmarking pipeline to compare predictive models, assembling a dataset of 10,356 element-gene pairs measured in CRISPR perturbation experiments, more than 30,000 fine-mapped expression quantitative trait loci and 569 fine-mapped genome-wide association study (GWAS) variants linked to a probable causal gene. Using this framework, we develop ENCODE-rE2G, a predictive model achieving state-of-the-art performance across several prediction tasks, demonstrating that iterative perturbations and supervised machine learning can build increasingly accurate predictive models of enhancer regulation. Using ENCODE-rE2G, we build an encyclopedia of enhancer-gene regulatory interactions in the human genome, revealing global properties of enhancer networks, identifying differences in regulatory complexity across genes and improving analyses linking noncoding variants to target genes and cell types for common complex diseases. By interpreting the model, we find that beyond enhancer activity and three-dimensional enhancer-promoter contacts, additional features that guide enhancer-promoter communication include promoter class and enhancer-enhancer synergy. These genome-wide maps of enhancer-gene regulatory interactions, benchmarking software, predictive models and insights about enhancer function provide a valuable resource for future studies of gene regulation and human genetics.},
}

@article {pmid42085640,
year = {2026},
author = {Orgel, E and Maese, LD and Devidas, M and Militano, O and Rau, RE and Angiolillo, AL and McNeer, JL and Schore, RJ and Borowitz, MJ and Wood, B and Raetz, EA and Silverman, LB and Winick, NJ and Larsen, EC and Carroll, WL and Winter, SS and Dunsmore, KP and Hunger, SP and Loh, ML},
title = {Toxicity from asparaginase during acute lymphoblastic leukemia induction: a report from the Children's Oncology Group.},
journal = {Blood advances},
volume = {10},
number = {14},
pages = {4923-4930},
doi = {10.1182/bloodadvances.2026019870},
pmid = {42085640},
issn = {2473-9537},
mesh = {Humans ; *Asparaginase/adverse effects/therapeutic use/administration & dosage ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/complications ; Child ; Child, Preschool ; Female ; Adolescent ; Infant ; Male ; Adult ; Young Adult ; *Antineoplastic Agents/adverse effects/therapeutic use ; Risk Factors ; Hyperbilirubinemia ; Body Mass Index ; Thrombosis ; Induction Chemotherapy ; },
abstract = {Asparaginase-associated toxicities (AAT) often compromise therapy for acute lymphoblastic leukemia (ALL), affecting relapse risk and survival. There are conflicting data on the contributions of older age, obesity by body mass index (BMI), and/or large body surface area (BSA) to AAT. We examined the association of these risk factors with AAT and the impact of AAT on disease response. Induction data were examined from 4925 patients aged between 1 and 30 years enrolled in the Children's Oncology Group ALL trials AALL0232 and AALL0434, which included a single dose of pegaspargase (2500 IU/m2) without a maximum dose. The associations of age, BMI, and BSA with hyperbilirubinemia, elevated alanine aminotransferase (ALT), thrombosis, and pancreatitis were evaluated. The impact of AAT on minimal residual disease (MRD) positivity (≥0.01%) at the end of induction (EOI) was assessed. Increased risk of developing at least 1 AAT was observed in patients aged ≥10 years (P = .002) and in those with obesity and high BSA (P< .0001) but not with high BSA alone. Risks for hyperbilirubinemia, ALT elevations, and thrombosis were all increased in patients with obesity and high BSA (odds ratio [OR], 3.5; 95% confidence interval [CI], 2.2-5.7; OR, 3.3; 95% CI, 1.7-6.6; and OR, 3.1; 95% CI, 1.5-6.5, respectively). AAT were not associated with EOI MRD positivity. To our knowledge, we report the largest data set of AAT in children, adolescents, and young adults. Preventive strategies are indicated for older patients and for those with obesity and high BSA, but not with high BSA alone. These trials were registered at www.clinicaltrials.gov as NCT00075725 and NCT00408005.},
}

Humans
*Asparaginase/adverse effects/therapeutic use/administration & dosage
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/complications
Child
Child, Preschool
Female
Adolescent
Infant
Male
Adult
Young Adult
*Antineoplastic Agents/adverse effects/therapeutic use
Risk Factors
Hyperbilirubinemia
Body Mass Index
Thrombosis
Induction Chemotherapy

@article {pmid42442344,
year = {2026},
author = {Kim, O and Jung, J and Sathe, S and Yu, G and Sergi, Z and Li, Q and Lu, P and Zhang, M and Hsia, RC and Kruhlak, MJ and Chari, R and Wang, H and Tran, B and Holewinski, RJ and Chan, M and Andresson, T and Liu, ZG and Graves, LM and Gujral, TS and Iwanowicz, EJ and Wu, J},
title = {Targeting mitochondrial protease in diffuse gliomas.},
journal = {Molecular cancer therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1158/1535-7163.MCT-26-0156},
pmid = {42442344},
issn = {1538-8514},
abstract = {Caseinolytic protease proteolytic subunit (ClpP) is part of the mitochondrial ClpXP protease responsible for degrading damaged proteins in the matrix, thus maintaining metabolic homeostasis. Small molecule activators of ClpP (ClpP agonists) have recently shown great promise against metabolically active cancers. TR107, a novel ClpP activator, demonstrates potent and selective cytotoxicity against glioma cells at nanomolar concentrations. Compared to the FDA-approved ClpP agonist ONC201 (Dordaviprone), TR107 shows greater efficacy across patient-derived and isogenic glioma models. TR107 effects are ClpP-dependent and result in widespread mitochondrial dysfunction evident by extensive protein degradation, impaired OxPhos, reduced mtDNA copy number, and ATP depletion. These disruptions are more severe in IDH-mutant than IDH-wildtype glioma cells, leading to enhanced cell cycle arrest, apoptosis, and inhibition of mTOR/AKT/4EBP1 signaling pathway. In this study, we show that ClpP agonism demonstrates preferential anti-tumor activity against IDH-mutant glioma in in vitro, ex vivo, and in vivo models. These findings support TR107 as a promising new targeted therapeutic for IDH-mutant gliomas.},
}

@article {pmid42442707,
year = {2026},
author = {Hall, C and Wellman, R and Cruz, M and Shortreed, SM and Simon, GE and Williamson, BD and Yeargans, R and Ahmedani, BK and Boggs, JM and Coleman, KJ and Daida, YG and Lynch, F and Rossom, R and Sterling, S and Coley, RY},
title = {Validation of a self-harm prediction model in black youth seeking outpatient mental health care.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwag162},
pmid = {42442707},
issn = {1476-6256},
}

@article {pmid42443407,
year = {2026},
author = {Halpern, AB and Othus, M and Percival, MM and Ghiuzeli, C and Appelbaum, JS and Hendrie, PC and Cassaday, RD and Smith, M and Russell, K and Scott, BL and Cooper, JP and Veatch, JR and Keel, SB and Oehler, VG and Kimble, EL and Mawad, R and Walter, RB},
title = {Randomized phase 2 trial of CPX-351 vs. CLAG-M (cladribine, cytarabine, G-CSF, and mitoxantrone) for medically unfit adults with acute myeloid leukemia or other high-grade myeloid neoplasms.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {42443407},
issn = {1476-5551},
abstract = {Even with new drugs available, how best to treat unfit adults with acute myeloid leukemia (AML) remains uncertain. In a previous trial in such patients, we found high-dose cytarabine-based therapy with CLAG-M yielded higher response rates but no more toxicity than lower-intensity therapy with dose-attenuated CLAG-M. Here, we conducted a single-institution phase 2 trial (NCT04195945) randomizing 60 adults with untreated AML and medical unfitness with Treatment-Related Mortality (TRM) score of ≥13.1 (68% with ECOG performance status 3-4) 1:1 to standard-dose CPX-351 or CLAG-M. Primary endpoint was 3-month overall survival (OS); key secondary endpoints included overall response rate, rate of measurable residual disease (MRD) negativity, toxicity/mortality rates, and survival estimates. Only CLAG-M met the primary endpoint of ≥63% 3-month OS (70% vs. 60%; P = 0.41), and CLAG-M therapy was associated with a non-significantly higher complete remission (CR) plus CR with incomplete hematologic recovery rate (73% vs. 47%, P = 0.064). Nonetheless, there was no statistically significant difference in relapse-free survival following CLAG-M vs. CPX-351 (median 37.6 vs. 19.9 months; P = 0.80) or OS (median 10.5 vs. 5.8 months; P = 0.76). In patients with proliferative disease, however, OS following CLAG-M was longer (median 18.5 vs. 3.9 months; P = 0.02) suggesting a role for intensive therapy in this patient subset.},
}

@article {pmid42446944,
year = {2026},
author = {Jin, S and Zaiken, MC and McDonald-Hyman, C and Hartigan, CR and Bolivar-Wagers, S and Larson, JH and Peng, Y and Hani, S and Riddle, M and Saha, A and Panoskaltsis-Mortari, A and Ko, E and Zhao, Y and Amaro Marquez, R and Marri Baskar, PS and Eide, CR and Murphy, WJ and Hippen, KL and Hill, GR and Tolar, J and Sage, PT and Pennell, CA and Kean, LS and Blazar, BR},
title = {CAR19 Tregs treat murine chronic Graft-Versus-Host Disease through immune suppression in absence of measurable B-cell cytolysis.},
journal = {JCI insight},
volume = {},
number = {},
pages = {},
doi = {10.1172/jci.insight.196197},
pmid = {42446944},
issn = {2379-3708},
abstract = {Chronic Graft-Versus-Host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic transplantation. CGVHD pathophysiology involves cooperation between Tfollicular helper cells (TFH) and germinal center B-cells (GCB), allo- and auto-antibody depositions in cGVHD tissues, and fibrosis. We evaluated human CD19-directed chimeric antigen receptor (CAR19) T-cell therapy in a clinically relevant murine cGVHD model with bronchiolitis obliterans syndrome (BOS). Although CD8 CAR19 T-cells effectively reduced peripheral B-cell and GCB frequencies, pulmonary function was unimproved. In contrast, a single CAR19 CD4 regulatory T-cells (Treg) infusion mitigated ongoing pulmonary disease and modulated germinal centers (GC) associated with reduced TFH frequencies compared to control Tregs but without measurable B-cell depletion. Compared to EGFR Treg infusion, mice receiving CAR19 Tregs exhibited enhanced suppression of B-cell activation, preserved splenic architecture, and provided greater opportunities for interaction with CD19+ B-cells at the B-cell follicle boundary zones. Taken together with the absence of detectable B-cell cytolysis, these findings are most consistent with GC suppression rather than B-cell depletion as the dominant mechanism. Overall, our findings suggest that CAR19 Tregs represent a promising and safe cGVHD/BOS therapeutic strategy, offering immunosuppressive benefits and improved disease outcomes that may be more limited with CD8 CAR19 T-cell treatment.},
}

@article {pmid42441933,
year = {2026},
author = {Al-Samkari, H and Shatzel, JJ and Panch, SR and Keating, JH and Walsh, EP and Weekes, CD and Kardosh, A and Cohen, SA and Cohen, JJ and Hodges, PG and Dhaver, SE and Strojny, N and Donovan, C and Belibasakis, C and Soff, GA},
title = {Avatrombopag Versus Placebo for Persistent Chemotherapy-Induced Thrombocytopenia in GI Cancers: The Phase II ACT-GI Trial.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2600568},
doi = {10.1200/JCO-26-00568},
pmid = {42441933},
issn = {1527-7755},
abstract = {PURPOSE: Chemotherapy-induced thrombocytopenia (CIT) is a challenging and common complication of cytotoxic chemotherapy in patients with GI cancers. There is no widely available approved treatment. Avatrombopag is a potent, second-generation oral thrombopoietin receptor agonist promising for CIT management.

METHODS: We conducted a multicenter, randomized, double-blind, investigator-initiated US trial of avatrombopag or placebo (1:1) in GI cancer patients with persistent CIT (platelets ≤85 × 10[9]/L on day 1 of a chemotherapy cycle despite adequate time to recover from the prior cycle). The primary end point was successful correction of CIT and prevention of recurrence (defined as recovery of platelets to ≥100 × 10[9]/L, no chemotherapy dose modification/delay, and prevention of CIT recurrence [platelets ≥100 × 109/L] at end of the on-study cycle).

RESULTS: The trial was closed to enrollment by the data and safety monitoring board at the planned interim analysis after meeting prespecified stopping criteria for efficacy. Sixteen of 23 patients (70% [95% CI, 47 to 87]) receiving avatrombopag achieved the primary end point versus 4/24 patients (17% [95% CI, 5 to 37]) receiving placebo (Z = 3.67, P < .001). The median (IQR) platelet count at the end of the on-cycle treatment period was 157 (136-202) × 10[9]/L with avatrombopag versus 72 (68-134) × 10[9]/L with placebo. Adverse events (AEs) and serious AEs occurred in 78% and 17% of patients receiving avatrombopag and 46% and 0% of patients receiving placebo, respectively. No serious AEs were study drug-related. There were no treatment-related AEs leading to death or discontinuation of study drug.

CONCLUSION: In this randomized, placebo-controlled trial, avatrombopag was efficacious in the management of persistent CIT in patients with GI cancers. These findings are promising for a common, challenging oncologic complication that prevents delivery of full-dose, on-time, cancer-directed therapy.},
}

@article {pmid42441937,
year = {2026},
author = {Lipsyc-Sharf, M and Hurvitz, SA},
title = {Current Management of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in a Changing Landscape.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2600672},
doi = {10.1200/JCO-26-00672},
pmid = {42441937},
issn = {1527-7755},
abstract = {Over the past three decades, the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has undergone a remarkable transformation. Once associated with poor outcomes and a median survival of <2 years in the metastatic setting, HER2-positive metastatic breast cancer is at present increasingly managed for years, with long-term survival beyond 5 years becoming common. Parallel advances in early-stage therapy have substantially reduced recurrence rates and altered the clinical landscape of metastatic disease, with a growing proportion of patients currently presenting with de novo metastatic disease rather than relapse after prior HER2-directed treatment. These improvements have been driven by successive generations of HER2-targeted therapies, including monoclonal antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates. Most recently, trastuzumab deruxtecan (T-DXd) has demonstrated unprecedented efficacy and is rapidly moving earlier in treatment algorithms across both metastatic and curative-intent settings. This shift raises important questions regarding optimal sequencing, toxicity management-particularly for interstitial lung disease-and the downstream implications for other HER2-directed therapies. In this review, we summarize the evolution of HER2-targeted therapy and discuss strategies for managing HER2-positive breast cancer across disease stages in the era of earlier treatment with T-DXd.},
}

@article {pmid42367850,
year = {2026},
author = {Rodriguez, LR and Hall, J and Cardozo-Ojeda, EF and Lynch, RM and Perelson, AS and Schiffer, JT and Reeves, DB},
title = {Modeling quantifies in vivo neutralization, Fc-mediated killing, and resistance in human clinical trials of five anti-HIV broadly neutralizing antibodies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42367850},
issn = {2692-8205},
abstract = {Broadly neutralizing antibodies (bnAbs) are a promising intervention for HIV prevention, therapy, and cure. bnAb optimization requires precise quantification of in vivo functions, many of which cannot be directly measured in humans. We therefore performed a mathematical modeling meta-analysis which integrated four clinical trials and reproduced serial bnAb concentrations, viral loads, and bnAb sensitivities (IC50) in 43 viremic trial participants who received an infusion of VRC01, VRC01LS, VRC07-523LS, 3BNC117 or 10-1074. We compared >300 mathematical models for their ability to recapitulate multi-strain HIV dynamics following bnAb infusion. For each bnAb, our best model identified a scaling factor of 36-462 to project in vivo activity from in vitro IC50, quantified Fc-mediated infected cell killing in humans over time, and projected the timing of bnAb-resistant strain emergence. Using this holistic profile, VRC07-523-LS was generally optimal.},
}

@article {pmid42431148,
year = {2026},
author = {Modi, S and Murthy, RK and Chien, AJ and Lin, NU and McAndrew, NP and Specht, JM and Zelnak, AB and Ramos, J and Xie, D and Ho, J and Inoue, JK and Carey, LA and Hamilton, EP},
title = {Tucatinib in Combination With Trastuzumab Deruxtecan in Patients With Previously Treated HER2+ Unresectable Locally Advanced or Metastatic Breast Cancer: An Open-Label Phase 2 Study.},
journal = {Clinical breast cancer},
volume = {26},
number = {8},
pages = {21-30},
doi = {10.1016/j.clbc.2026.05.010},
pmid = {42431148},
issn = {1938-0666},
abstract = {INTRODUCTION: Recent advances in HER2-directed therapies have improved outcomes for patients with HER2+ advanced/metastatic breast cancer (a/mBC), but disease progression ultimately occurs in most cases. Dual targeting of HER2 with tyrosine kinase inhibitors and antibody-drug conjugates has the potential for non-cross-resistant treatments that improve disease control.

METHODS: HER2CLIMB-04, a single-arm, open-label, phase 2 study, evaluated tucatinib plus trastuzumab deruxtecan (T-DXd) in patients with HER2+ a/mBC who experienced disease progression on or were intolerant of previous HER2-directed therapy and a taxane. Patients with stable or progressing brain metastases (BMs) were permitted. The primary endpoint was confirmed objective response rate (cORR) by the investigator. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: A total of 70 patients (median age 57 years, median 2 prior lines for a/mBC) received tucatinib 300 mg orally BID and T-DXd on day 1 of each 21-day cycle. The cORR was 51.4% with a median DOR of 11.9 months (95% CI, 6.0-not estimable); median PFS was 11.5 months, and OS was 28.4 months. The most common treatment-emergent adverse events were diarrhea (80.0%), nausea (77.1%), and fatigue (72.9%). Antidiarrheal prophylaxis, introduced for 44 patients, was associated with reduced any grade diarrhea. Survival outcomes in patients with or without BMs are described.

CONCLUSION: Although the addition of tucatinib to T-DXd did not demonstrate a clear benefit compared with previously demonstrated T-DXd monotherapy efficacy, when given with antidiarrheal prophylaxis, the combination was tolerable and showed clinical activity in patients with HER2+ a/mBC.

CLINICAL TRIAL NUMBER: NCT04539938.},
}

@article {pmid42431728,
year = {2026},
author = {Coupland, SE and Rao, A and Jonigk, D and Bülow, R and Chetty, R and Rane, SU and Dave, S and Naresh, KN},
title = {Promise and pragmatism of AI in global-scale digital pathology: pan-cancer approaches for clinical practice.},
journal = {Journal of clinical pathology},
volume = {},
number = {},
pages = {},
doi = {10.1136/jcp-2026-210720},
pmid = {42431728},
issn = {1472-4146},
abstract = {Artificial intelligence (AI) tools for digital pathology have crossed the threshold from pilot project to clinical deployment, with regulatory approvals, commercial products and prospective trials now accumulating across multiple tumour types. However, global-scale implementation demands careful evaluation of both opportunities and challenges. Traditional histopathology faces mounting pressures including interobserver variability and escalating workloads. At the same time, molecular diagnostics have become increasingly complex, while core workflows have remained fundamentally unchanged for decades. Digital pathology infrastructure and AI algorithms promise solutions through enhanced diagnostic accuracy, improved efficiency, democratised access to expertise and unprecedented research capabilities. AI has already demonstrated clinical value across multiple subspecialties, including prostate, breast and colorectal cancer, with applications spanning automated biomarker quantification, molecular subtype prediction and prognostic modelling. Systematic reviews also identify important limitations that temper enthusiasm for AI adoption. These include heterogeneity in study design, publication bias favouring positive results, limited generalisability across diverse populations and practice settings, concentration of research in narrow subspecialties and insufficient external validation. Critical implementation barriers include substantial infrastructure requirements, concerns around data privacy and security, gaps in regulatory oversight and the risk that algorithmic bias may exacerbate health disparities. Professional bodies advocate for responsible deployment guided by evidence-based standards. Key priorities include rigorous validation, workforce training, workflow integration and continuous performance monitoring. Making transformation equitable, safe and effective requires balancing innovation with accountability. AI should augment rather than replace pathologist expertise and be supported by robust governance frameworks that prioritise patient safety and diagnostic quality over commercial consideration.},
}

@article {pmid42434521,
year = {2026},
author = {Jeon, JJ and Kim, YH and Son, H and Heo, YW and Seo, JH and Ha, MC and Jung, SW and Lee, JY and Lee, H and Koh, SB and Song, H and Kong, JH and Choi, E and Kim, H and Hwang, S and Hyun, CS and Hippe, DS and Park, SY and Shin, JI and Lee, S and Choi, EH},
title = {Risk of selected immune-mediated inflammatory diseases after solid organ transplantation in a Korean nationwide cohort.},
journal = {JAAD international},
volume = {27},
number = {},
pages = {119-121},
pmid = {42434521},
issn = {2666-3287},
}

@article {pmid42436075,
year = {2026},
author = {de Ligt, KM and Psutka, SP and Mertens, LS},
title = {Re: Martino Pedrani, Alberto De Giorgi, Andrea Gallina, et al. When Patients Refuse Radical Cystectomy: Integrating Trimodality Therapy in the Perioperative ICI/ADC Era. Eur Urol Oncol. In press. http://dx.doi.org/10.1016/j.euo.2026.04.008.},
journal = {European urology oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euo.2026.06.016},
pmid = {42436075},
issn = {2588-9311},
}

@article {pmid42437510,
year = {2026},
author = {Goodsell, KE and Carter, JA and Abrams, HR and Mogal, H and Loggers, ET and Sharib, J},
title = {Current Evidence for Circulating Tumor DNA in Sarcoma: Challenges and Opportunities for Clinical Application.},
journal = {Journal of surgical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jso.70326},
pmid = {42437510},
issn = {1096-9098},
abstract = {Sarcomas represent a diverse group of mesenchymal tumors with high rates of recurrence after resection. While recent technical advances have enabled the detection of rare circulating tumor DNA (ctDNA) in other malignancies, the complexity and heterogeneity of sarcoma genomics have historically limited ctDNA in these cancers. This narrative review highlights the rapidly evolving evidence supporting potential clinical applications of ctDNA in common sarcoma subtypes including gastrointestinal stromal tumor, leiomyosarcoma, rhabdomyosarcoma, osteosarcoma, and Ewing sarcoma.},
}

@article {pmid42439327,
year = {2026},
author = {Lv, H and Feng, Z and Teo, QW and Chen, C and Gopal, AB and Choi, D and Tan, TJC and Tang, YS and Siu, L and Nourmohammad, A and Bruzzone, R and Wilson, IA and Yuan, M and Wu, NC and Mok, CKP},
title = {Somatic Evolution of a Germline Antibody Expands its Breadth to Neutralize Early SARS-CoV-2 Omicron Variants.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76522},
doi = {10.1002/advs.76522},
pmid = {42439327},
issn = {2198-3844},
support = {//Calmette and Yersin scholarship from the Pasteur International Network Association/ ; //Carl R. Woese Institute for Genomic Biology (IGB) postdoctoral fellowship/ ; 14115125//Research Grants Council of the Hong Kong Special Administrative Region, China/ ; C4002-24Y//Research Grants Council of the Hong Kong Special Administrative Region, China/ ; 22210332//Health and Medical Research Fund/ ; //Vallee Scholars Program/ ; //Searle Scholars Program/ ; //Howard Hughes Medical Institute Emerging Pathogens Initiative/ ; },
abstract = {Rapid antigenic drift of the SARS-CoV-2 receptor-binding domain (RBD) underlies immune escape and continues to challenge the durability of antibody-mediated protection. Among the major classes of RBD-directed antibodies, germline-encoded IGHV3-53 responses are highly potent against early SARS-CoV-2 variants but are generally compromised by Omicron-associated mutations. Here, we identify an intrinsically cross-reactive IGHV3-53 germline antibody that recognizes multiple pre-Omicron variants, including SARS-CoV-2 wild-type, Alpha, and Delta. Notably, we demonstrate that targeted somatic evolution can further expand this breadth to overcome the immune escape of different Omicron variants. Guided by integrated structural and sequence analyses, we introduce four somatic mutations (G26E, T28I, S53P, and Y58F) into the germline antibody, resulting in markedly enhanced binding and neutralization of Omicron BA.1, and BA.4/5. High-resolution crystal structures reveal that these mutations re-establish interactions disrupted by substitutions in the Omicron RBD and improve binding at a remodeled epitope interface. Collectively, our findings define the structural basis by which specific mutations enhance cross-variant recognition of SARS-CoV-2. This work highlights the underappreciated breadth encoded within the naïve B-cell repertoire and provides a conceptual framework for engineering and eliciting antibody responses resilient to future antigenic drift.},
}

@article {pmid42440026,
year = {2026},
author = {Childers, CP and Takahashi, H and Koch, KL and Bath, NM and Selfridge, J and Selby, LV},
title = {A National Survey of Contracts, Compensation, and Workplace Culture Among Junior Surgical Oncologists.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
pmid = {42440026},
issn = {1534-4681},
abstract = {BACKGROUND: The transition from surgical training to independent practice is challenging, and little quantitative data exist to guide junior surgeons on contracts and compensation. Qualitative evidence suggests compensation model type may influence workplace dynamics and attrition, but this has not been formally examined.

PATIENTS AND METHODS: A cross-sectional survey of Society of Surgical Oncology members in their first 8 years of practice was conducted in October-November 2025 (n = 221; response rate = 20.2%). Outcomes included contract and compensation characteristics, attrition risk, and workplace collegiality.

RESULTS: Respondents were 53% female, 68% non-Hispanic white, and 65% academic; 40% were within their first 2 years of practice. Most (69%) attempted contract negotiation and 79% succeeded in at least one domain. Nearly all (79%) had a guaranteed salary period (median 3 years), after which most transitioned to work relative value unit (wRVU)-based compensation. One in four respondents (25%) were considering leaving within the year; this rose to nearly 80% among those who strongly disagreed their compensation was fair (p < 0.01). Greater productivity emphasis was inversely associated with workplace collegiality (odds ratio 1.8 per standard deviation [SD] increase, 95% confidence interval [CI] 1.1-3.0; p = 0.02).

CONCLUSIONS: This national survey provides contract and compensation data for junior surgical oncologists and demonstrates associations between perceived compensation fairness and attrition risk, and between productivity-based compensation emphasis and workplace hostility. These findings suggest that how surgeons perceive their compensation-not merely its structure-may be a target for institutional efforts to improve retention and culture.},
}

@article {pmid42441929,
year = {2026},
author = {Sallman, DA and Garcia-Manero, G and Daver, N and Abboud, CN and Stein, E and Larkin, K and Halpern, AB and McCurdy, SR and Al Malki, MM and Subramanian Guru Murthy, G and Silverman, LR and Larson, RA and Greenberg, P and Gojo, I and Wrobel, T and Platzbecker, U and Forsyth, C and Vachhani, P and Dong, M and Shao, J and Johnson, LDS and Tan, A and Lee, C and Doshi, P and Vyas, P and Wei, AH},
title = {Magrolimab Plus Azacitidine Versus Placebo Plus Azacitidine in Patients With Untreated Higher-Risk Myelodysplastic Syndromes: The Phase III ENHANCE Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500617},
doi = {10.1200/JCO-25-00617},
pmid = {42441929},
issn = {1527-7755},
abstract = {PURPOSE: To evaluate the efficacy and safety of the cluster of differentiation 47-targeted antibody magrolimab plus azacitidine (Magro/Aza) versus azacitidine alone in treatment-naïve patients with higher-risk myelodysplastic syndromes (MDS) in the phase III ENHANCE study (ClinicalTrials.gov identifier: NCT04313881).

METHODS: Based on the Revised International Prognostic Scoring System, patients with intermediate- to very-high-risk MDS were randomly assigned to receive Magro (1 mg/kg on days [D]1 and 4; 15 mg/kg on D8; 30 mg/kg on D11 and D15, and then once per week for five doses, followed by 30 mg/kg maintenance doses once every 2 weeks)/Aza (75 mg/m[2] daily on D1-7 or on D1-5 and 8-9 in 28-day cycles) or matched placebo plus azacitidine (Placebo/Aza). Dual primary end points were complete remission (CR) rate (per 2006 International Working Group criteria) and overall survival (OS).

RESULTS: At final analysis, 539 patients were randomly assigned to Magro/Aza (n = 268) or Placebo/Aza (n = 271) arms. Baseline characteristics were generally well balanced between treatment arms. In the Magro/Aza versus Placebo/Aza arms, the CR rate was 21.3% versus 23.6% (odds ratio, 0.876 [95% CI, 0.585 to 1.312]; P = .5218), and median OS was 15.9 versus 18.6 months (hazard ratio, 1.203 [95% CI, 0.947 to 1.528]; P = .1299). Magro/Aza had a higher incidence of grade ≥3 adverse events (AEs; 92.8% v 79.2%), AE-associated study drug discontinuations (24.0% v 12.1%), serious AEs (71.9% v 51.5%), and fatal AEs (15.2% v 9.8%) versus Placebo/Aza.

CONCLUSION: ENHANCE did not meet the primary end points of CR rate and OS, and showed more frequent severe AEs in patients treated in the Magro/Aza arm.},
}

@article {pmid42367880,
year = {2026},
author = {Tran-Kiem, C and Kistler, K and Hisner, R and Bedford, T},
title = {SARS-CoV-2 saltational events are recurrent and trace to persistent human infections.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42367880},
issn = {2692-8205},
abstract = {SARS-CoV-2 evolution is characterized by gradual mutation accumulation but has been punctuated by rare yet impactful highly mutated variants. Whether such saltational jumps are a broad feature of SARS-CoV-2 evolution or rare anomalies remains unclear. We systematically investigate SARS-CoV-2 saltational evolution by developing a scalable framework to detect saltational events from 4.4 million high-quality viral genomes. Saltational events occurred at low but detectable rates during the pandemic and post-pandemic periods and across geographies. Their mutational signature closely matches that seen in persistent human infections but is inconsistent with the signatures of mink or deer infections. This points to persistent infection, rather than reverse zoonosis, as their primary source. While most saltational events lack evidence of onward transmission, those that do tend to carry mutations found in successful clades. Our work demonstrates that the emergence of highly mutated SARS-CoV-2 variants reflects a recurrent evolutionary process, with implications for preparedness.},
}

@article {pmid42367976,
year = {2026},
author = {Alvarado, C and Lapointe, CP and Wang, J and Sokabe, M and Grosely, R and Dhepe, AA and Stackhouse, CI and Palo, MZ and Mamot, A and Jemielity, J and Fraser, CS and Puglisi, JD},
title = {Remodeling of mRNA by eIF4F in human translation initiation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42367976},
issn = {2692-8205},
abstract = {For the ribosome to load onto an mRNA during the early steps of translation initiation, the mRNA must be activated by the eIF4F complex. The mechanism of this activation step has remained elusive. Here we employ multi-perspective real-time single-molecule assays to observe directly mRNA-eIF4F binding near the 5' end, mRNA conformational remodeling, and 40S ribosomal subunit loading. eIFs 4E, 4G, and 4B play distinct roles in promoting eIF4F association and stabilizing eIF4A binding. Binding of eIF4F is the rate-limiting step in mRNA activation: once bound, mRNA conformation is rapidly extended in an ATP-dependent manner. The mRNA extended state is the necessary substrate for 43S PIC loading and perturbations to extension delay loading. Features of the mRNA, such as the 7-methylguanosine cap at the 5' end and secondary structures, modulate these steps and regulate ribosome loading. Our results establish a kinetic and mechanistic framework for the early steps in translation initiation.},
}

@article {pmid42429571,
year = {2026},
author = {Watling, CZ and Watts, EL and Loftfield, E and Graubard, BI and Hong, HG and Zhang, X and Barnett, MJ and Buring, JE and Barnard, ME and Chen, Y and Eliassen, AH and Gaziano, JM and Hofmann, JN and Huang, WY and Kang, JH and Koshiol, J 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 Wactawski-Wende, J and Willett, WC and Wu, F and Zheng, W and Campbell, PT and Barupal, D and Petrick, JL and Mcglynn, KA},
title = {Circulating pre-diagnostic metabolites and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: a population-based study of 12 cohorts.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag227},
pmid = {42429571},
issn = {1460-2105},
abstract = {BACKGROUND: Underlying metabolic perturbations may offer insight into etiological factors related to liver cancer development. The objective of this study was to explore associations between pre-diagnostic metabolites and risk of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

METHODS: We conducted a nested case-control study within 12 prospective U.S. cohort studies, including 727 HCC cases and 126 ICC cases with matched controls. Metabolomic profiling was performed on pre-diagnostic blood samples using the Metabolon platform. Multivariable conditional logistic regression estimated adjusted odds ratios and 95% confidence intervals for associations between metabolites (per doubling in levels) and liver cancer risk. Elastic net regression selected metabolites predictive of HCC and ICC, with predictive performance assessed by area under the curve (AUC).

RESULTS: Median time from blood collection to diagnosis was 11.6 years. Of 1,485 pre-diagnostic metabolites, 600 were associated with HCC risk after false discovery rate correction (366 positively, 234 negatively); no metabolites were significantly associated with ICC. Enriched pathways among HCC cases included methylhistidine metabolism, amino acid metabolism, and bile acid biosynthesis; ICC showed enrichment in valine, leucine, and isoleucine pathways. Elastic net models for HCC selected 38 metabolites with strong predictive performance (AUC = 0.87; 95% CI: 0.83 to 0.91), while eight metabolites were selected for ICC with modest discrimination (AUC = 0.64; 95% CI: 0.49 to 0.80).

CONCLUSIONS: Numerous pre-diagnostic metabolites were associated with HCC risk, potentially reflecting underlying liver dysfunction. Enrichment patterns suggest distinct metabolic perturbations between HCC and ICC. Larger studies are needed to characterize metabolic risk factors for ICC and evaluate metabolites as predictors of HCC risk.},
}

@article {pmid42369512,
year = {2026},
author = {Williamson, BD and Cronkite, DJ and Yu, O and Ramaprasan, A and Fuller, S and Covey, J and Kiniry, E and Park, D and Winter, R and Whitaker, J and McLemore, MF and Wittayanukorn, S and Stojanovic, D and Zhao, Y and Dutcher, S and Carrell, DS and Jackson, LA and Nelson, JC and Smith, JC},
title = {Identifying anaphylaxis using weakly-supervised prediction models and natural language processing.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {42369512},
abstract = {OBJECTIVES: Scalable computable phenotyping algorithms are critical for conducting high-throughput disease-outcome research in large, distributed-data electronic health record (EHR) and claims data settings. We developed and evaluated a claims- and EHR-based computable phenotyping algorithm for anaphylaxis, a rare acute condition that is challenging to accurately identify using claims data alone.

MATERIALS AND METHODS: Potential anaphylaxis events came from two healthcare systems (Kaiser Permanente Washington [KPWA] and Vanderbilt University Medical Center [VUMC]). We engineered features from clinical text using automated natural language processing (NLP) methods. We then developed a phenotyping algorithm using four NLP- and diagnosis code-based silver labels (proxies for the gold-standard labels). Gold-standard abstracted outcomes were used to evaluate algorithm performance.

RESULTS: The largest area under the receiver operating characteristic curve (AUC) was 0.931 for an NLP-based silver-label model at KPWA. Depending on the model and healthcare system site, positive predictive value (PPV) and sensitivity at the threshold of predicted probability that maximized F1 score ranged from 0.52 to 0.77 (PPV) and 0.78 to 1 (sensitivity).

DISCUSSION: NLP-based silver-label models had large AUC at KPWA but not at VUMC. This may be because clinical text at KPWA is only available for outpatient encounters and secure messaging. High sensitivity for identifying anaphylaxis can be obtained using our best-performing models.

CONCLUSION: The best-performing models had better PPV and sensitivity tradeoffs than prior bespoke anaphylaxis models with costly, manually curated features. The simplicity of the approach compared to traditional phenotyping methods allows it to be deployed easily at multiple health care systems.},
}

@article {pmid42396494,
year = {2026},
author = {Tasnim, H and Forrest, S and Hofmeyr, S and Friedman, AM and Etemadpour, R and Mehdikhani, H and Andrews, A and Cannon, JL and Moses, ME},
title = {Spatial Immune Model of Alveolar Lung Infection (SIMALI) Identifies Structural Determinants of Lung Inflammation.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42396494},
issn = {2693-5015},
abstract = {Inflammation and lung damage in response to respiratory viral infection is a major cause of morbidity and mortality. How specialized lung alveolar structures contribute to variation in inflammatory lung damage observed in patients is a gap in current knowledge. Filling this gap is important for understanding how respiratory infections can lead to persistent and chronic sequelae after acute viral infection, including post-acute sequelae of COVID-19, or "long COVID". Few computational models have incorporated the spatial complexity of alveolar sacs, key sites where infection and inflammation damage lung function. We propose a novel computational model, SIMALI, which represents a sample of the lung's alveolar space as a structured 3D lattice of alveoli composed of air and epithelial cells surrounded by structural lung tissue through which virus and inflammation diffuse. SIMALI extends a previous agent-based model by adding key structural components of the lung, including physiological percentages of infectable cells and differential diffusion of virus through air and lung tissue. SIMALI's simulation predictions are validated against the spatial-temporal growth of lung lesions from Computed Tomography (CT) scans of patients with SARS-CoV-2 infection. By combining parameters validated in a prior study with alveolar structure, the model accurately predicts the typical growth of lung inflammation observed in patient CT scans. SIMALI demonstrates how the spatial architecture of alveolar sacs and the distribution of infectable cell types in the lung constrain the spread of virus and inflammation. Furthermore, SIMALI simulations show how the initial deposition of foci of viral infection distributed across alveolar sacs is an important mechanistic cause of variation in lung damage due to inflammation. The spatial SIMALI model demonstrates a key role for the structure of the alveolar space in driving inflammatory responses. Lung alveolar structure, combined with variation in immune response and the amount and location of initial viral deposition in the lung, all contribute to the highly variable damage to lung recapitulating variation observed across patients with SARS-CoV-2 infection.},
}

@article {pmid42423252,
year = {2026},
author = {Figgins, MD and Bedford, T},
title = {Inferring variant-specific effective reproduction numbers from combined case and sequencing data.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {42423252},
issn = {2050-084X},
support = {DGE- 1762114//National Science Foundation Graduate Research Fellowship Program/ ; },
mesh = {Humans ; United States/epidemiology ; *SARS-CoV-2/genetics ; *COVID-19/epidemiology/transmission/virology ; *Basic Reproduction Number/statistics & numerical data ; Bayes Theorem ; },
abstract = {Accurately estimating relative transmission rates of SARS-CoV-2 variants remains a scientific and public health priority. Recent studies have used the sample proportions of different variants from genetic sequence data to describe variant frequency dynamics and relative transmission rates, but frequencies alone cannot capture the rich epidemiological behavior of SARS-CoV-2. Here, we extend methods for inferring the effective reproduction number of an epidemic using confirmed case data to jointly estimate variant-specific effective reproduction numbers and frequencies of co-circulating variants using cases and sequences across states in the United States from January 2021 to March 2022. Our method can be used to infer structured relationships between effective reproduction numbers across time series, allowing us to estimate fixed variant-specific growth advantages. We use this model to estimate the effective reproduction number of SARS-CoV-2 variants of concern and variants of interest in the United States, and to estimate consistent growth advantages of particular variants across different locations.},
}

Humans
United States/epidemiology
*SARS-CoV-2/genetics
*COVID-19/epidemiology/transmission/virology
*Basic Reproduction Number/statistics & numerical data
Bayes Theorem

@article {pmid42424632,
year = {2026},
author = {Tsai, CS and Szewczyk, W and Lee, H and Drerup, M and Blakeney, EA and Greenlee, H and Heffner, JL and Vasbinder, A and Reding, KW},
title = {Exploring Breast Cancer Survivors' Preferences for Text Messaging-Based Mobile Health Interventions Targeting Sleep and Physical Activity: Qualitative Study.},
journal = {JMIR formative research},
volume = {10},
number = {},
pages = {e85386},
pmid = {42424632},
issn = {2561-326X},
mesh = {Humans ; Female ; *Breast Neoplasms/psychology/complications ; *Text Messaging/statistics & numerical data/standards ; *Cancer Survivors/psychology/statistics & numerical data ; Middle Aged ; *Exercise/psychology ; Focus Groups ; Qualitative Research ; Aged ; *Patient Preference/psychology/statistics & numerical data ; *Sleep Wake Disorders/therapy/psychology ; Sleep ; Telemedicine ; },
abstract = {BACKGROUND: Sleep disturbances and low physical activity are common among breast cancer (BC) survivors and are associated with increased morbidity and mortality. Given the increased access to technological devices and the growing popularity of SMS text messaging-based mobile health interventions, these tools have the potential to both address sleep disturbances and promote physical activity in a scalable and cost-effective way. To understand and make effective use of these tools, it is important to consider the preferences of BC survivors with sleep disturbances, including how SMS text messaging-based mobile health interventions could deliver interventions involving physical activity and sleep hygiene.

OBJECTIVE: The objective of this study was to explore the perspectives and preferences of BC survivors regarding text messaging-based mobile interventions targeting sleep and physical activity.

METHODS: Three focus groups (n=13 participants) and 3 individual interviews (n=3) were conducted from May 2020 to March 2021 with 16 BC survivors (mean age=59.3, SD 8.9 y) currently experiencing sleep disturbances. The interview questions focused on their experiences with poor sleep and preferences for text messaging-based mobile health interventions. Thematic analysis was applied to the deidentified transcriptions of audio recordings.

RESULTS: Three themes were identified: (1) attitudes toward health interventions delivered through text messaging, (2) specific user needs, and (3) technology usage habits and preferences. Most participants reported a positive attitude toward the possibility of using technology to help improve their sleep and increase their physical activity. Most expressed a high level of acceptance toward some technologies, such as text messaging and mobile apps, but not others, such as voice interactions. In terms of desired features, reminders and accountability features, such as meeting physical activity goals, were mentioned most frequently. In addition, incorporating bedtime and relaxation exercise reminders was thought to be helpful. Regarding time and frequency, a daily reminder scheduled for 1 hour before bedtime was found to be acceptable.

CONCLUSIONS: The insights have been used to guide the development of a messaging-based mobile health intervention for improving sleep and physical activity in BC survivors. Future research will focus on delivering an intervention addressing these health behaviors and assessing its acceptability and effectiveness.},
}

Humans
Female
*Breast Neoplasms/psychology/complications
*Text Messaging/statistics & numerical data/standards
*Cancer Survivors/psychology/statistics & numerical data
Middle Aged
*Exercise/psychology
Focus Groups
Qualitative Research
Aged
*Patient Preference/psychology/statistics & numerical data
*Sleep Wake Disorders/therapy/psychology
Sleep
Telemedicine

@article {pmid42428793,
year = {2026},
author = {Wyss, AB and Hrytsenko, Y and Hu, L and Broce, IJ and Kaplan, RC and Tarraf, W and Yu, B and Boerwinkle, E and Qi, Q and Fornage, M and DeCarli, C and González, HM and Sofer, T},
title = {An integrated lifestyle-, genetic- and metabolomics-based prediction model for mild cognitive aging in the HCHS/SOL.},
journal = {NPJ dementia},
volume = {2},
number = {1},
pages = {58},
pmid = {42428793},
issn = {3005-1940},
abstract = {Prediction models for cognitive aging measures have largely evaluated demographic variables and APOE carrier status in populations of European ancestry. To comprehensively assess prediction models among Hispanic/Latinos, we considered 12 models (6 predictor sets and 2 methods) for global cognitive score change (GCSC) and mild cognitive impairment (MCI) in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) (N = 5856). Based on the average mean squared error (MSE) for GCSC or average area under the curve (AUC) for MCI across 100 randomly split testing and training sets, performance was similar across models, but slightly better for the following models: the chronic conditions model and genetic model (mean MSEs = 0.2464) using gradient-boosted trees for GCSC prediction and the chronic conditions model (mean AUC = 62%) and metabolite model (mean AUC = 60%) using logistic regression for MCI prediction. Using the Shapley Additive Explanations (SHAP) method, age at baseline, time between exams, and sex were the most important predictors for GCSC, followed by diabetes and global ancestral proportions. Diabetes and the metabolite ribitol had the highest influence on prediction of MCI. Although prediction performance was not especially high and did not vary greatly across models, incorporating information on diabetes, ancestry and metabolites may help improve prediction of GCSC and MCI.},
}

@article {pmid42429230,
year = {2026},
author = {Schaefer, MA and Black, AR and Hyde, RK and Kuppers, DA and Hewitt, KJ},
title = {Applications of the Human Bone Marrow Organoid System to Study Hematopoiesis and Anemia Stress.},
journal = {Tissue engineering. Part C, Methods},
volume = {},
number = {},
pages = {19373384261463760},
doi = {10.1177/19373384261463760},
pmid = {42429230},
issn = {1937-3392},
abstract = {Hematopoietic stem and progenitor cells (HSPCs) are precisely organized within specialized bone marrow niches containing hematopoietic and nonhematopoietic cell types. Physiologically accurate human models of this niche environment that include functional HSPCs have been lacking until recently. Using induced pluripotent stem cells (iPSCs) grown in mixed-matrix hydrogels, vascularized three-dimensional human bone marrow organoids (hBMOs) can now be generated that contain mesenchymal, endothelial, and hematopoietic cells, all vital components of the bone marrow niche. While hBMOs have been shown to support engraftment of normal and malignant cells, there are numerous opportunities to use hBMOs for developing a wider experimental toolkit to test gene functions and stress responses. Here, we establish two new applications for the hBMO platform. First, we demonstrate successful engraftment of gene-edited CD34[+] cells from healthy donors, enabling direct investigation of gene-specific effects on human hematopoiesis in a defined microenvironment. Gene-edited engrafted HSPCs are maintained in hBMOs for 7 days and undergo multilineage differentiation. Second, we adapted a method to induce stress erythropoiesis-a response to acute anemia in mice and humans-in hBMOs, resulting in robust expansion of immunophenotypically defined hematopoietic progenitors and erythroid populations. These two advances expand the laboratory uses for hBMOs and establish this system as a versatile platform for studying human hematopoiesis and erythropoiesis, stress responses, and gene functions within a physiologically relevant bone marrow microenvironment.},
}

@article {pmid42370247,
year = {2026},
author = {Boelens, JJ and Lakkaraja, M and Mauguen, A and Hosszu, K and McAvoy, D and Greco-Stewart, V and Schmidt, G and Levine, J and Angel Perales, M and Giralt, SA and Baker, KS},
title = {ATG Exposure in T Replete Transplant for Hematological Malignancies: Real World Analysis from BMT CTN 1202.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42370247},
issn = {2693-5015},
abstract = {Traditional weight-based dosing results in variable rabbit anti-thymocyte globulin (rATG) clearance, delaying CD4 + Tcell-immune-reconstitution (CD4 + IR) and impacting outcomes. In a retrospective pharmacokinetic/pharmacodynamic analysis of patients undergoing first T-replete hematopoietic cell transplantation (HCT), enrolled on BMT CTN 1202, we estimated post-HCT rATG-exposures as area under the curve (arbitrary unit per day/milliliter [AUxd/mL]) using a validated pharmacokinetic-model. Results were compared to patients who did not receive rATG. Previously defined post-HCT rATG-exposure groups: A:<30, B:30-55 and C:≥55 AUxd/mL were correlated with outcomes of interest using cox-proportional-hazard and cause-specific-hazards models. 325 patients (median age 51 years) were included: 228 received rATG. Median post-HCT rATG-exposure was 44.1 (Range 6.2-125.0). Among patients who received rATG, higher exposure correlated with worse five-year overall survival (OS) (no-ATG:51%; group A:67%; B:49%; C:34%, p = 0.01), higher five-year relapse incidence (no-ATG:31%; A:27%; B: 42%; C: 58%, p < 0.001) and lower CD4 + IR (no-ATG:64%; A:73%; B:51%; C:19%, p = 0.001). Grade 2-4 acute graft versus host disease (GVHD) rates were: no-ATG:40%; A:26%, B:39%, C:35%, (p = 0.44). Any rATG-exposure was associated with lower moderate/severe chronic GVHD (HR:0.63, p = 0.025). Low post-HCT rATG-exposure (< 30AUxd/mL) but not absent correlated with higher OS, lower relapse, and lower GVHD related deaths. Model-based-dosing could be used to target optimal post-HCT rATG-exposure and improve HCT outcomes.},
}

@article {pmid42418713,
year = {2026},
author = {Rey-Suarez, I and Pathni, A and Fazekas, F and Connell, M and Upadhyaya, A},
title = {Nuclear morphology and chromatin compaction modulate T cell cytoskeletal remodeling and immune synapse formation.},
journal = {Molecular biology of the cell},
volume = {},
number = {},
pages = {mbcE25100487},
doi = {10.1091/mbc.E25-10-0487},
pmid = {42418713},
issn = {1939-4586},
abstract = {T cell activation induces a rapid reorganization of the actin cytoskeleton, facilitating cell spreading on antigen-presenting cells (APCs). As the nucleus, the cell's largest organelle, constrains cell shape changes, its mechanical properties, governed by chromatin compaction and heterochromatin density, are likely to play a critical role in T cell spreading and activation. However, the contribution of nuclear mechanics to T cell activation remains elusive. Here, we demonstrate that T cell spreading is accompanied by nuclear deformation and increased chromatin compaction. Reducing chromatin compaction, which is known to soften the nucleus, enhances cell spread area and nuclear deformation but decreases F-actin accumulation and peripheral enrichment at the immune synapse. Conversely, enhancing chromatin compaction restricts spreading and deformation but promotes peripheral F-actin organization. This reveals a reciprocal relationship between chromatin compaction and cytoskeletal organization. We identify SUN proteins and myosin as key mediators through which chromatin compaction modulates actin morphology and cell shape, enabling T cells to adapt to antigen presenting surfaces of varying stiffness. These findings underscore the pivotal role of chromatin compaction in T cell activation, highlighting the mechanical interplay between the nucleus and cytoskeleton, and suggest novel insights into T cell mechano-responsiveness. [Media: see text] [Media: see text].},
}

@article {pmid42421622,
year = {2026},
author = {Oehler, VG and Leyte-Vidal, A and Huang, IJ},
title = {Olverembatinib: real progress in BCR::ABL1 leukemia?.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2026.300834},
pmid = {42421622},
issn = {1592-8721},
abstract = {Olverembatinib (HQP1351) is a potent third-generation (3G) tyrosine kinase inhibitor (TKI) that binds to both the active and inactive conformations of native ABL1 and mutant BCR::ABL1. It was developed as a potent inhibitor with activity against wild-type and mutated BCR::ABL1 for chronic myeloid leukemia (CML) patients. It is effective against the T315I mutation, which confers resistance to first and second generation TKIs. The results of clinical trials in China have led to olverembatinib approval by China's regulatory authority, National Medical Products Administration (NMPA), for adult patients with TKIresistant chronic phase (CP) or accelerated phase (AP) CML harboring the T315I mutation and for adult CP CML patients with resistance or intolerance to imatinib or 2G TKIs. Olverembatinib has also received breakthrough therapy designation by the NMPA in combination with low intensity chemotherapy for the first-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Global studies of olverembatinib are underway in CML and Ph +ALL, with the results of the US phase 1b study published in 2025. This review will summarize the safety, tolerability, and efficacy of olverembatinib in CML and Ph+ ALL in China and globally and discuss the role of olverembatinib among existing therapeutics and its future development.},
}

@article {pmid42421955,
year = {2026},
author = {Cashman, HP and Turtle, CJ},
title = {The impact of the large B-cell lymphoma tumor microenvironment on efficacy of CD19-directed CAR-T immunotherapy.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1819591},
pmid = {42421955},
issn = {1664-3224},
mesh = {Humans ; *Tumor Microenvironment/immunology ; *Immunotherapy, Adoptive/methods/adverse effects ; *Antigens, CD19/immunology ; *Lymphoma, Large B-Cell, Diffuse/therapy/immunology/pathology ; Animals ; *Receptors, Chimeric Antigen/immunology ; Treatment Outcome ; },
abstract = {Large B-cell lymphoma is an aggressive lymphoma subtype with poor outcomes in the relapsed and refractory setting. Despite considerable improvements in long-term survival with CD19 CAR-T immunotherapy, over half of patients do not achieve durable remissions. A deeper understanding of the mechanisms within the tumor microenvironment that drive treatment resistance is critical to informing the development of improved CAR-T therapies that can overcome immunosuppressive elements. In this review, we synthesize current knowledge on how histological, cellular, molecular and spatial features of the large B-cell lymphoma microenvironment influence clinical responses following CD19 CAR-T therapy and highlight key knowledge gaps in the field. We discuss data from clinical trials of emerging novel CAR-T engineering strategies aimed at reprogramming the immunosuppressive tumor microenvironment and underscore the growing need for advanced analytical approaches capable of integrating multimodal, high-dimensional datasets to comprehensively characterize this complex tumor ecosystem.},
}

Humans
*Tumor Microenvironment/immunology
*Immunotherapy, Adoptive/methods/adverse effects
*Antigens, CD19/immunology
*Lymphoma, Large B-Cell, Diffuse/therapy/immunology/pathology
Animals
*Receptors, Chimeric Antigen/immunology
Treatment Outcome

@article {pmid42368023,
year = {2026},
author = {Sankaranarayanan, A and Zhao, C and Hernandez, MG and Clemens, EA and Smythe, KS and Kazerouni, AS and Carr, LL and Li, CI and Partridge, SC and Vinayak, S and Mittal, S},
title = {PhenoBIC: operator-free single-cell spatial phenotyping in multiplex imaging data using deep learning of cell staining patterns.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42368023},
issn = {2692-8205},
abstract = {Multiplex imaging is a valuable tool for spatially examining tissue microenvironments at the single-cell level to uncover biological and clinical insights. However, most multiplex image analysis workflows currently require manual intervention for cell phenotyping, which slows progress, demands human effort, and yields operator-dependent outputs. Here, we developed PhenoBIC, a pre-trained deep learning model for image classification of the multiplexed biomarker signals in a cell (Biomarker Imprint of a Cell) to classify cell phenotypes. We show that PhenoBIC (F1-score ~0.88) outperforms manual gating (widely used) and other machine learning-based computational approaches for cell marker expression classification. We validated this across multiple biomarkers, tissue sampling strategies (whole biopsies and tissue microarrays), multiplex panels, imaging platforms, and tissue types. We have released our in-house training and validation datasets of ~1.4 million manually curated cell expression ground truth labels. We have also open-sourced PhenoBIC and enabled its community-wide deployment via the QuPath interface.},
}

@article {pmid42416786,
year = {2026},
author = {Winestone, LE and Logan, BR and Liu, X and Williams, O and Dunn, EA and Thakar, MS and Kidd, SA and Mousallem, T and Dorsey, MJ and O'Reilly, RJ and Kapoor, N and Forbes Satter, L and Kapadia, M and Jyonouchi, SC and Chandra, S and Ebens, CL and Chellapandian, D and Chaudhury, S and Chen, K and Dávila Saldaña, BJ and Rayes, A and Quigg, TC and Chandrakasan, S and Bednarski, JJ and DeSantes, KB and Teira, P and Gillio, AP and Eissa, H and Knutsen, AP and Aquino, VM and Shereck, EB and Moore, TB and Caywood, EH and Vander Lugt, MT and Rozmus, J and Broglie, L and Yu, LC and Shah, AJ and Joshi, AY and Buckley, RH and Dara, J and Oved, JH and Abdel Azim, H and Martinez, CA and Prockop, S and Sullivan, KE and Bleesing, JJ and Keller, MD and Madden, LM and Parikh, S and Shenoy, S and Seroogy, CM and Rubin, T and Licata, J and Andolina, JR and Kohn, DB and Burroughs, L and Leiding, JW and Marsh, RA and Notarangelo, LD and Pai, SY and Torgerson, TR and Pulsipher, MA and Heimall, J and Cuvelier, GDE and Griffith, LM and Puck, JM and Dvorak, CC and Cowan, MJ and Haddad, E},
title = {Newborn screening reduces survival disparities in SCID after stem cell transplant: A PIDTC report.},
journal = {Journal of human immunity},
volume = {2},
number = {5},
pages = {e20250231},
pmid = {42416786},
issn = {3065-8993},
abstract = {Black race and Hispanic ethnicity are associated with higher mortality in severe combined immunodeficiency (SCID) following hematopoietic cell transplantation (HCT), though mechanisms remain unclear. We evaluated 796 children with SCID who received nonsibling HCT between 1982 and 2020 using data from the Primary Immune Deficiency Treatment Consortium. Overall survival for Black (aHR 2.47, 95%CI 1.64, 3.71) and Asian/Pacific Islander patients (aHR 1.82, 95%CI 1.00, 3.30) was significantly lower compared with non-Hispanic White patients, while Hispanic patients had lower event-free survival (aHR 1.83, 95%CI 1.27, 2.63) compared with non-Hispanic White patients. Even after adjusting for age and infection, Black patients with SCID had more than twofold hazard of death compared with non-Hispanic White patients. NBS was associated with earlier diagnosis, reduced infection at HCT, and elimination of survival disparities between Black and non-Hispanic White patients. These findings suggest that universal, system-level interventions such as NBS can mitigate disparities in outcomes for children with SCID.},
}

@article {pmid42417054,
year = {2026},
author = {Petersen, E and Sheldon, J and Torgerson, H and Kirschenbaum, M and Paratore, J and Iida, K and Psutka, S},
title = {The impact of cachexia and sarcopenia in bladder cancer.},
journal = {Current opinion in supportive and palliative care},
volume = {},
number = {},
pages = {},
doi = {10.1097/SPC.0000000000000811},
pmid = {42417054},
issn = {1751-4266},
abstract = {PURPOSE OF REVIEW: Bladder cancer disproportionately affects older adults and is characterized by recurrent disease and cumulative treatment exposure, resulting in a population with limited physiologic reserve and increased susceptibility to muscle and metabolic decline. Understanding the role of sarcopenia and cachexia in shaping treatment tolerance, functional recovery, and outcomes is, therefore, increasingly important.

RECENT FINDINGS: Sarcopenia and cancer cachexia are prevalent across the bladder cancer continuum and are consistently associated with treatment toxicity, impaired recovery, and decreased survival. These syndromes evolve with both disease progression and cumulative treatment exposures, including surgery and contemporary systemic therapies. Advances in CT-based body composition analysis, circulating biomarkers of neuromuscular integrity and inflammation, and integration with geriatric assessment frameworks have improved the ability to characterize patient vulnerability. Emerging evidence supports multimodal strategies, including exercise-based prehabilitation, nutritional optimization, and targeted metabolic therapies, to mitigate muscle and metabolic decline.

SUMMARY: Sarcopenia and cachexia are clinically meaningful and potentially modifiable drivers of adverse outcomes in bladder cancer. Incorporating a structured assessment of muscle and metabolic health into routine care may improve risk stratification, inform treatment planning, and support more individualized, function-preserving management.},
}

@article {pmid42418167,
year = {2026},
author = {Thakuria, M and Akaike, T and Silk, AW and Hippe, DS and Ch'en, PY and Alam, R and Chan, JE and Park, SY and Khaddour, K and Biese, KB and Jabbour, AJ and Fu, A and Gilmour, MW and Finberg, A and Chiu, MW and Kim, H and Urman, NM and Hall, ET and Bhatia, S and Nghiem, P and Zaba, LC},
title = {ctDNA or Merkel Virus Antibodies for Surveillance of Merkel Cell Carcinoma Recurrence.},
journal = {JAMA dermatology},
volume = {},
number = {},
pages = {},
pmid = {42418167},
issn = {2168-6084},
abstract = {IMPORTANCE: Merkel cell carcinoma (MCC) is associated with a high recurrence rate of 40%. It is important to know which of 2 blood-based tumor biomarkers available for use in clinical practice is more accurate in detecting MCC recurrence.

OBJECTIVE: To compare the performance of circulating tumor DNA (ctDNA) and the MCC polyomavirus (MCPyV) oncoprotein antibody test for detecting MCC recurrence.

In this multicenter cohort study across 3 US academic centers (Stanford, Dana-Farber Brigham, and University of Washington), patients with stage I-IV MCC underwent serial paired ctDNA and antibody testing for disease surveillance between April 2020 and March 2024. ctDNA was considered positive if mean tumor molecules per milliliter of plasma values were greater than 0.00, while a rising antibody test result was defined as a 30% or greater increase in titer. Inclusion criteria were clinically disease-free at baseline, detectable MCPyV antibodies at diagnosis, and both ctDNA and antibody tests performed within 45 days of each other in at least 1 time point per patient. Predictive performance for recurrence was assessed and compared between tests.

MAIN OUTCOMES AND MEASURES: The primary outcome was clinical recurrence. Predictive performance measures for each test included positive (PPV), negative predictive value (NPV), and hazard ratios (HRs).

RESULTS: In this study among 169 patients with 703 paired tests (median testing interval, 96 days; 109 males [64%]; 60 females [36%]), there were 36 clinical recurrences from 32 patients over a median follow-up of 483 days (IQR, 274-714 days). Compared with antibody testing, ctDNA had a significantly higher PPV at 365 days (73% [95% CI, 58%-85%] vs 52% [95% CI, 32%-71%]; P = .02), higher NPV at 90 days (99% [95% CI, 98.8%-100%] vs 97% [95% CI, 95%-98%]; P = .001), and a greater HR (HR, 47.9 [95% CI, 16.5-139.0] vs 7.3 [95% CI, 3.8-13.9]; HR ratio, 6.6 [95% CI, 2.5-41.0]; P < .001). Use of both ctDNA and antibody tests together identified only 1 additional recurrence compared with the use of ctDNA testing alone.

CONCLUSIONS AND RELEVANCE: This study found that ctDNA was more accurate than MCPyV antibody testing in detecting recurrence of MCC. ctDNA appears to be a more reliable guide than the MCPyV antibody for surveillance practices and ongoing risk stratification in most patients with MCC.},
}

@article {pmid42418682,
year = {2026},
author = {Hosoya, H and Velayati, A and Dima, D and Jensen, A and Portuguese, AJ and Hovanky, V and Mikkilineni, L and Peres, LC and Grajales-Cruz, AF and Homsy, S and Rana, MS and Cancilla, J and Patil, S and Sahaf, B and Latchford, T and Freeman, CL and Scott, BJ and Song, KW and Castaneda-Puglianini, OA and Khan, H and Dahiya, S and Locke, FL and Mackall, CL and Miklos, DB and Banerjee, R and Hansen, DK and Alsina, M and Sidana, S},
title = {Rapid Peak Cilta-cel Expansion is Associated with Delayed Neurotoxicity in Multiple Myeloma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025032844},
pmid = {42418682},
issn = {1528-0020},
abstract = {The impact of chimeric antigen receptor (CAR)-T cell expansion and persistence on clinical outcomes and treatment-related morbidity in patients with relapsed/refractory multiple myeloma (RRMM) remains incompletely defined, in part due to limited availability of standardized CAR-T cell quantification assays. We evaluated CAR-T cell kinetics and their association with efficacy and toxicity in RRMM patients treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). Using a uniform flow cytometry-based platform (N=90; cilta-cel, n=54; ide-cel, n=36), we observed significantly greater CAR-T cell expansion with cilta-cel than with ide-cel (median 106 vs 49 cells/uL). Peak CAR-T cell expansion was associated with clinical response in the ide-cel cohort but not with cilta-cel, where rapid and excessive expansion was instead associated with an increased risk of delayed neurotoxicities (DNTs), a complication with potential long-term functional consequences (median peak 1,009 vs 96 cells/uL). To identify clinically accessible biomarkers of CAR-T cell expansion, we analyzed absolute lymphocyte count (ALC) as a surrogate biomarker in a larger multicenter cohort (N=532; cilta-cel, n=256; ide-cel, n=276). Higher peak ALC was significantly associated with the development of DNTs, particularly Parkinsonism after cilta-cel. A peak ALC [3]3000/uL - or [3]2500/uL following a daily twofold increase - predicted elevated DNT risk (sensitivity 81%, specificity 59%). Together, these findings delineate distinct expansion-toxicity relationships in cilta-cel and ide-cel therapy, establish ALC as a practical, uniformly available surrogate for CAR-T cell expansion, and define quantitative thresholds that may enable early recognition of patients at risk for DNT, informing preemptive strategies to mitigate morbidity following cilta-cel.},
}

@article {pmid42282035,
year = {2026},
author = {Foss, EJ and Nodelman, IM and Usenko, A and Furutani, H and Goel, A and Lofts, B and Miles, S and Zhang, Z and Bowman, GD and Tsukiyama, T and Bedalov, A},
title = {Chromatin architecture sets origin licensing capacity.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42282035},
issn = {2693-5015},
abstract = {Replication origin licensing enables complete and faithful genome duplication, yet how chromatin regulates this process in vivo remains unclear. Using MCM-ChEC-seq to track helicase loading from metaphase through G1 in budding yeast, we find that licensing occurs in a rapid, synchronous burst at mitotic exit and then reaches an early plateau despite continued permissive cell-cycle conditions and persistent ORC binding at origins. Here we show that this plateau is imposed by chromatin architecture at replication origins, which limits the extent of origin licensing. Histone H3K56 acetylation marks newly replicated chromatin and is removed at S-phase exit by the deacetylases Hst3 and Hst4. Persistent H3K56ac severely impairs MCM loading without affecting ORC occupancy, indicating that chromatin limits licensing at the helicase-loading step. Strikingly, deletion or catalytic inactivation of the chromatin remodeler Isw2 increases licensing by approximately 40% in wild-type cells and fully suppresses the licensing defect in hst3Δ hst4Δ mutants, identifying Isw2 as a physiological inhibitor of origin licensing. Isw2-dependent nucleosome repositioning narrows the origin nucleosome-depleted region and restricts helicase loading. Together, these findings show that chromatin architecture at replication origins sets licensing capacity. Newly replicated chromatin transiently adopts an Isw2-dependent inhibitory configuration that is relieved, but not completely eliminated, by post-replicative chromatin maturation. Genome-wide licensing thus reflects integration of chromatin-imposed licensing capacity with cell cycle-dependent control of licensing timing.},
}

@article {pmid42409317,
year = {2026},
author = {Namoglu, EC and Flanagan, MR and Teles, MS and Javid, SH and Kim, JN and Kang, KH and Li, BC and Nair, V and Lam, DL and Meisner, A and Gillespie, EF},
title = {Omission of sentinel lymph node biopsy among women age 50-70 with early-stage breast cancer: applying an updated ASCO Guideline to a real-world population.},
journal = {Practical radiation oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.prro.2026.06.005},
pmid = {42409317},
issn = {1879-8519},
abstract = {BACKGROUND: Recent practice-changing guidelines from the American Society of Clinical Oncology (ASCO) recommend the omission of sentinel lymph node biopsy (SLNB) in patients over the age of 50 with early-stage breast cancer. We aimed to evaluate the association of clinicopathologic factors with SLN-positivity (SLN+) and the association of SLN+ with adjuvant therapy recommendation in this population.

METHODS: A single-institution retrospective cohort study of patients 50-70 years old with early-stage invasive breast cancer (cT1N0, grade 1-2, ER+, HER2-) between 2022-2024 who underwent SLNB. Pre-operative axillary ultrasound was not required. The univariate relationship between covariates and SLN+ was assessed using Fischer's exact test or logistic regression, followed by multivariable logistic regression. Fisher's exact test was also used to evaluate the relationship between SLN+ and receipt of adjuvant therapy. Two-year disease-free survival (DFS) was estimated using the Kaplan-Meier method.

RESULTS: Among 268 patients meeting the new ASCO Guideline criteria, the average age was 62 years (standard deviation 5.1). The majority were ductal histology (81.0%), pathologic T1 (94.8%) and grade 1 (51.5%). Adjuvant therapy included endocrine therapy (86.9%), whole breast radiation (WBRT) (73.1%), partial breast radiation (19.4%), chemotherapy (5.6%), and CDK4/6 inhibitor (0.7%). SLN was positive in 15 (5.6%) patients (8 pN1mi, 7 pN1a). Factors statistically significantly associated with SLN+ included pathologic tumor category (p=0.006) and 21-gene recurrence score (p<0.001). A SLN+ result potentially impacted adjuvant recommendations for 11 patients (4.1%): 1 with low 21-gene recurrence score received chemotherapy, 1 received CDK4/6 inhibitor, and 9 eligible for partial breast radiation received WBRT. With median follow up of 24.0 months, 2-year DFS was 98% (95%CI 96.1-99.9%).

CONCLUSION: In patients age 50-70 meeting the 2025 ASCO Guideline for SLNB omission, SLN+ was infrequent. Adjuvant treatment recommendations were unchanged in >95% of patients, due in part to information from other factors such as recurrence score.},
}

@article {pmid42411467,
year = {2026},
author = {Shih, RM and Arimura, Y and Konishi, HA and Funabiki, H},
title = {Impacts of DNA methylation on H2A.Z deposition and nucleosome stability.},
journal = {eLife},
volume = {15},
number = {},
pages = {},
pmid = {42411467},
issn = {2050-084X},
support = {R35GM132111/NH/NIH HHS/United States ; Osamu Hayaishi Memorial Scholarship for Study Abroad//The Japanese Biochemical Society/ ; },
mesh = {*DNA Methylation ; *Histones/metabolism ; Animals ; *Nucleosomes/metabolism ; Xenopus laevis ; Cryoelectron Microscopy ; Xenopus ; DNA/metabolism ; },
abstract = {The histone variant H2A.Z and DNA methylation are enriched at mutually exclusive genomic segments, though its mechanistic bases remain unclear. Here, we examine DNA methylation's influence on the intrinsic stability of the H2A.Z nucleosome and chaperone-mediated H2A.Z deposition. Cryo-EM and endonuclease analyses suggest that DNA methylation subtly increases the openness and accessibility of the H2A.Z nucleosome on satellite II-derived DNA sequences. In transcriptionally silent Xenopus egg extracts, H2A.Z preferentially associates with unmethylated DNA though a substantial proportion of H2A.Z is recruited to methylated DNA. Preferential H2A.Z deposition to unmethylated DNA depends on the SRCAP complex, whose DNA binding is suppressed by methylation, while an SRCAP-independent and DNA methylation-insensitive mechanism for H2A.Z deposition also exists. Altogether, we propose that SRCAP drives the biased association of H2A.Z to unmethylated DNA, while additional mechanisms, potentially taking advantage of the subtle DNA methylation-induced physical effects, further assist the exclusion of H2A.Z from methylated DNA.},
}

*DNA Methylation
*Histones/metabolism
Animals
*Nucleosomes/metabolism
Xenopus laevis
Cryoelectron Microscopy
Xenopus
DNA/metabolism

@article {pmid42413982,
year = {2026},
author = {Awan, FT and Gamse, JT and Overdijk, MB and Breij, ECW and Jure-Kunkel, M and Sanghavi, K and Brady, LK and Guan, M and Verbrugge, I and Chen, J and Gong, N and Gillespie, M and Tees, M and Gallogly, M and Hutchings, M and Christensen, JH and Sureda, A and Cordoba, R and Ahmed, S and Woei-A-Jin, FJSH and Abrisqueta, P and Giné, E and Roost Clausen, M and Bhat, SA and Gopal, AK and Chamuleau, MED},
title = {Pharmacologic activity, safety, and preliminary efficacy of GEN3009, a CD37-targeting DuoHexaBody, in relapsed or refractory B-cell non-Hodgkin's lymphoma.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {7},
pages = {},
doi = {10.1136/jitc-2025-014311},
pmid = {42413982},
issn = {2051-1426},
mesh = {Humans ; Animals ; *Tetraspanins/antagonists & inhibitors/immunology ; Female ; Male ; *Lymphoma, B-Cell/drug therapy/pathology ; Middle Aged ; Macaca fascicularis ; Aged ; Adult ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology/adverse effects ; *Antigens, Neoplasm/immunology ; *Antineoplastic Agents, Immunological/therapeutic use/pharmacology/adverse effects ; },
abstract = {BACKGROUND: Tetraspanin CD37, highly expressed in mature B-cells, represents an opportunity for therapeutic targeting in B-cell malignancies. GEN3009 (DuoHexaBody-CD37), a humanized biparatopic IgG1 antibody with an E430G hexamerization-enhancing mutation targeting two non-overlapping CD37 epitopes, was shown to induce potent tumor cell killing through enhanced complement-dependent cytotoxicity (CDC) and other fragment crystallizable-mediated effector functions, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), in vitro and in vivo. GEN3009 was assessed in non-clinical studies and a phase 1 dose-escalation study of B-cell non-Hodgkin's lymphoma (B-NHL).

METHODS: After a non-clinical toxicity study was conducted in cynomolgus monkeys, a phase 1, first-in-human, open-label, multicenter dose-escalation trial of GEN3009 monotherapy enrolled adults with relapsed/refractory (R/R) B-NHL (NCT04358458). A modified Bayesian optimal interval design informed dose escalation and de-escalation with dose levels ranging from 6 mg to 2000 mg. Primary endpoints were the rate of dose-limiting toxicities (DLTs) to determine the recommended phase 2 dose (RP2D) and safety and tolerability.

RESULTS: In the toxicity study, 10 mg/kg GEN3009 weekly was identified as the highest non-severely toxic dose. In the phase 1 study, from March 13, 2020, to July 28, 2023, 46 patients with R/R B-NHL received intravenous GEN3009 infusions. Median duration of treatment was 1.2 months (range, 0.0-14.5). No DLTs were observed up to 1600 mg. The most common treatment-emergent adverse events were neutropenia (n=41 (89.1%)), infusion-related reactions (n=39 (84.8%)), and thrombocytopenia (n=18 (39.1%)). Plasma GEN3009 concentrations increased over time with increasing GEN3009 doses, with no apparent accumulation of GEN3009 observed over the course of treatment. Antitumor activity was observed at dose levels of ≥180 mg in both aggressive and indolent NHL. GEN3009 treatment reduced total hemolytic complement activity (CH50) levels in serum, and peak changes in CH50 levels were significantly correlated with clinical response (p=0.008 by Wilcoxon rank-sum test).

CONCLUSIONS: Based on safety, efficacy, and pharmacokinetics, the RP2D of GEN3009 was determined to be 1200 mg. Preliminary data suggest that GEN3009 monotherapy demonstrated an acceptable safety profile at the RP2D of 1200 mg, with modest clinical activity. These findings provide the first clinical proof-of-concept for hexamerization-potentiated molecules that induce antitumor activity through enhanced CDC.},
}

Humans
Animals
*Tetraspanins/antagonists & inhibitors/immunology
Female
Male
*Lymphoma, B-Cell/drug therapy/pathology
Middle Aged
Macaca fascicularis
Aged
Adult
*Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology/adverse effects
*Antigens, Neoplasm/immunology
*Antineoplastic Agents, Immunological/therapeutic use/pharmacology/adverse effects

@article {pmid42414273,
year = {2026},
author = {Best, S and Hippe, DS and Grunblatt, E and Fatherree, J and Chanana, P and Wu, F and Ivey, R and Kennedy, JJ and Sokolov, D and Ibrahim, A and Xu, H and Monnat, RJ and Sullivan, LB and Paddison, P and Paulovich, AG and MacPherson, D},
title = {Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-75117-2},
pmid = {42414273},
issn = {2041-1723},
support = {1R01CA281133//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P50CA228944//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30CA015704//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Small cell lung cancer (SCLC) responds exceptionally well to cytotoxic chemotherapy. However, relapse with the emergence of chemoresistant disease is rapid and accompanied by poor treatment outcomes. To understand the genetic basis of chemoresistance in SCLC, we apply in vivo CRISPR deletion screening to patient-derived xenograft (PDX) models. Top screen hits include genes encoding components of the transcriptional co-activator SAGA (Spt-Ada-Gcn5 acetyltransferase) complex. We demonstrate that deletion of the SAGA deubiquitylase USP22 confers cisplatin-etoposide resistance in two chemosensitive PDX models, and that restoring expression in a PDX model harboring homozygous truncating mutation of USP22 re-sensitizes tumors to chemotherapy. USP22 loss increases gene body histone H2AK119 monoubiquitylation at key regulators of neuronal differentiation and suppresses neural and neuroendocrine gene expression including targets of ASCL1. Chemoresistance following USP22 loss reflects attenuated DNA damage-driven phosphorylation events and apoptosis, in conjunction with increased expression of glycolysis and hypoxia-related genes. Glycolysis program upregulation may reflect a targetable vulnerability, as inhibition of GLUT1 re-sensitizes USP22-null tumors to chemotherapy.},
}

@article {pmid42414619,
year = {2026},
author = {Theodore, DA and Mayer, BT and Rolle, CP and DeJesus, E and Ackerman, ME and Seaman, MS and Weiner, JA and Mohri, H and Huang, Y and Gray, B and Chang, J and Gerber, MW and Yu, J and Luo, Y and Padte, NN and Yin, MT and Barin, B and Greene, R and Palmer, S and Pazmino, A and Benitez, J and Dorr, C and McNairy, M and DiRenzo, J and Orzell, CV and Ho, DD and Hyrien, O and Sobieszczyk, ME},
title = {Bispecific 10E8.4/iMab broadly neutralizing antibody in people with or without HIV-1: a partially randomized phase 1 trial.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42414619},
issn = {1546-170X},
support = {INV-032929/GATES/Gates Foundation/United States ; INV-036842/GATES/Gates Foundation/United States ; INV-036842/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; INV-032929/GATES/Gates Foundation/United States ; },
abstract = {Broadly neutralizing antibodies (bnAbs) are a promising tool for HIV prevention and treatment. Here we conducted a first-in-human, phase 1 trial of the bispecific 10E8.4/iMab antibody, which consists of a 10E8.4 arm binding the HIV-1 envelope glycoprotein membrane-proximal external region and an ibalizumab (iMab) arm binding the human CD4 molecule. 10E8.4/iMab was administered intravenously (IV) or subcutaneously (SC). Safety/tolerability within 2 weeks of 10E8.4/iMab administration (primary outcome) and the pharmacokinetics (PK), antiviral activity, induction of anti-10E8.4/iMab antibodies, longitudinal CD4[+] and CD8[+] T cell counts and long-term safety (secondary outcomes) were evaluated. 54 participants living with HIV (PLWH) or without HIV (PLWoH) received 10E8.4/iMab or placebo. In arm 1, PLWoH received 10E8.4/iMab 0.3 mg kg[-1] IV, 1 mg kg[-1] SC, or 1 mg kg[-1] IV (n = 3 each). In arm 2, PLWoH received 10E8.4/iMab 3 mg kg[-1] IV, 10 mg kg[-1] IV or 30 mg kg[-1] IV (n = 6 each). In arms 3/3a, PLWH received 10E8.4/iMab 10 mg kg[-1] IV (n = 3) or 30 mg kg[-1] IV (n = 6). In arm 4, PLWoH were randomized to receive 10E8.4/iMab or placebo 2.5 mg kg[-1] SC or 10 mg kg[-1] SC (n = 9 each). Participants in arms 1-3 were not randomized. No treatment-related serious adverse events (AEs) or AEs ≥ grade 3 were reported. The most common solicited AEs were tenderness (10/54, 18.5%), fatigue (18/54, 33.3%) and headache (12/54, 22.2%). Related grade 2 local and systemic solicited AEs occurred in one and six participants, respectively. Three of nine PLWH developed a generalized rash 8-12 days after infusion that resolved within 9-16 days. The primary objective of the study to evaluate the safety/tolerability of 10E8.4/iMab was met. These data support further study of 10E8.4/iMab to expand HIV treatment and prevention options. ClinicalTrials.gov: NCT03875209 .},
}

@article {pmid42415858,
year = {2026},
author = {Vo, PT and Orozco, JJ and Sandmaier, BM},
title = {Radioimmunotherapy as a targeted strategy of reduced-intensity conditioning for allogeneic transplantation in leukemia.},
journal = {Frontiers in oncology},
volume = {16},
number = {},
pages = {1846420},
pmid = {42415858},
issn = {2234-943X},
abstract = {Reduced-intensity conditioning (RIC) has expanded the use of allogeneic hematopoietic transplant (allo-HCT) as a potentially curative treatment of a variety of hematological cancers including acute myeloid leukemia (AML) by reducing treatment-related morbidity and mortality. However, the RIC allo HCT success is limited by relapse, especially for patients with adverse molecular/cytogenetics or with measurable residual disease (MRD) at the time of HCT. Radioimmunotherapy (RIT) potentially improves the efficacy of RIC by enhancing the cytoreductive effect with the ability to deliver targeted radiation to sites of hematopoietic malignancy while sparing nonhematopoietic organs. In clinical trials using different combinations of targeting antibodies and radionuclides, reliable radiation targeting to marrow and spleen has been consistently demonstrated. Toxicity is often predictable and organ-specific with hepatic toxicity most commonly limiting the therapeutic dose. In this article, we review the rationale for combining RIT with RIC and discuss antigen selection and distinct properties of β- and α-emitting radionuclides. We also summarize clinical experience combining fludarabine-based RIC regimens with RIT and provide emerging directions, including the development of α-emitter platforms. Available data suggest that RIT may potentially improve disease control while maintaining the tolerability of RIC. Because the majority of the current evidence involves early-phase studies, additional prospective evaluation is needed before radioimmunotherapy can be considered a standard component of conditioning.},
}

@article {pmid42416089,
year = {2026},
author = {Gelderblom, HC and Gray, G and Kelley, B},
title = {Breaking the sound barrier: global monoclonal antibody pharmacoequity.},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1845146},
pmid = {42416089},
issn = {2296-2360},
abstract = {Monoclonal antibodies represent one of biomedicine's greatest successes, yet global access remains profoundly inequitable, with low- and middle-income countries bearing the brunt of limited access. This perspective proposes that long-acting infectious disease mAbs, starting with WHO-recommended nirsevimab for RSV prevention, could catalyze transformation by connecting with existing WHO Essential Medicines List mAbs. Picture two static half-circles: WHO Essential Medicines List mAbs with proven value but limited access, and infectious disease prevention mAbs with transformative potential. Connected, they form a complete wheel capable of rolling toward the aspirations of global pharmacoequity. HIV antiretroviral therapy demonstrates precedent-costs declined 100-fold through political mobilization, not technological breakthroughs.},
}

@article {pmid42402217,
year = {2026},
author = {Minami, CA and Jager, LR and Lorentzen, EH and Shadyab, AH and Krok-Schoen, JL and Nazmus Saquib, AT and King, JJ and Anderson, GL and King, TA and Mittendorf, EA},
title = {Worsening frailty and declining quality of life in older survivors of non-metastatic breast cancer.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag218},
pmid = {42402217},
issn = {1460-2105},
abstract = {Breast cancer treatment can worsen frailty, but the impact of this decline on long-term quality of life (QoL) remains uncertain. We identified women ≥65 years old with non-metastatic breast cancer from the Life and Longevity after Cancer survivorship cohort of the Women's Health Initiative. We examined the association between clinically-significant worsening of frailty, measured by a validated claims-based index one year post-diagnosis, and long-term decline in QoL, assessed on a ten-point scale 4 to 6 years post-diagnosis. Among 1,061 eligible patients, 692 (65.2%) were robust (not living with frailty), 343 (32.3%) were living with pre-frailty, and 26 (2.5%) were living with frailty at cancer diagnosis. Clinically-significant worsening of frailty occurred in 19.5% of patients. In fully adjusted models, worsening frailty was significantly associated with long-term QoL declines (Odds Ratio 1.48; 95% Confidence Interval [1.07 to 2.04]). These findings highlight the need for interventions to prevent worsening frailty during breast cancer treatment.},
}

@article {pmid42405616,
year = {2026},
author = {Abramson, JS and Straus, DJ and Bartlett, NL and Burke, JM and Lynch, RC and Domingo Domenech, E and Hess, B and Schuster, SR and Linhares, Y and Gandhi, M and Shah, HR and Jurczak, W and Re, A and Hahn, U and Prince, HM and Guo, W and Davis, G and Ho, L and Fanale, M and Yasenchak, CA and Lee, HJ},
title = {Study of brentuximab vedotin combination treatment in people with early-stage Hodgkin lymphoma: a plain language summary.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/14796694.2026.2693614},
pmid = {42405616},
issn = {1744-8301},
}

@article {pmid42406686,
year = {2026},
author = {Orvain, C and Othus, M and Byelykh, M and Schoch, G and Davis, C and Sandmaier, BM and Walter, RB},
title = {Pre- and post-transplant serum albumin levels and outcomes after allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia.},
journal = {Leukemia & lymphoma},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/10428194.2026.2695317},
pmid = {42406686},
issn = {1029-2403},
abstract = {Hypoalbuminemia has been repeatedly linked to increased non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT); a recent analysis also suggested an association with relapse risk. To evaluate the relationship between hypoalbuminemia, NRM, and relapse, we assessed its prognostic role in 1258 adults with MDS (myelodysplastic neoplasm)/AML or AML allografted while in remission between 2006 and 2023. After multivariable adjustment, low pre-HCT serum albumin levels were statistically significantly associated with NRM (hazard ratio [HR] = 0.67, p = 0.028), relapse-free survival (RFS; HR = 0.73, p = 0.005), and overall survival (OS; HR = 0.72, p = 0.007) but not relapse (HR = 0.77, p = 0.070). A day-28 landmark analysis showed day +28 hypoalbuminemia to be associated with NRM (HR = 0.31, p < 0.001), RFS (HR = 0.67, p < 0.001), and OS (HR = 0.52, p < 0.001) but not relapse (HR = 1.08, p = 0.6). Together, our data indicate that pre- and post-HCT serum albumin levels are independently associated with NRM and survival in AML patients undergoing allogeneic HCT.},
}

@article {pmid42406881,
year = {2026},
author = {Shi, C and Collins, JM and Ekanayaka, A and Stewart, JD and Conneely, KN and Huang, DY and Jung, SY and Manson, JE and Schwartz, GG and Silverman, AJ and Vitolins, MZ and Williamson, MR and Reiner, AP and Smith, RL and Whitsel, EA},
title = {Indoor Radon Concentrations and Hematologic Traits in the Women's Health Initiative.},
journal = {Epidemiology (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/EDE.0000000000002020},
pmid = {42406881},
issn = {1531-5487},
abstract = {BACKGROUND: We examined radon's association with the complete blood count and leukocyte differential to better understand radon-related risks of stroke and myocardial infarction (MI) previously observed in the Women's Health Initiative (WHI).

METHODS: We conducted a repeated measures analysis in this prospective cohort of post-menopausal women enrolled in 1993-1998 and examined at 5 visits over 19 years in 40 US clinical centers (n=154,630). We estimated indoor radon concentrations (pCi/L) at time-varying, geocoded addresses of participants (1993-2013) by linking them to the US Geological Survey Radon Index (1993) zoned by US Environmental Protection Agency Action Levels. We estimated covariate-adjusted, longitudinal associations of radon concentrations with complete blood count components using linear mixed-effects models. In a subset (n=6,313), we evaluated cross-sectional associations with the complete blood count differential using multivariate compositional data analysis.

RESULTS: At 2-4 and >4 pCi/L, adjusted mean (95% confidence interval) leukocytes were 48 (33, 63) and 78 (58, 98) cells/μL lower than at <2 pCi/L, while platelets, hematocrit, and hemoglobin were higher: 315 (-280, 910) and 2,033 (1,248, 2,818) cells/μL; 0.27% (0.24%, 0.30%) and 0.23% (0.19%, 0.27%); and 0.09 (0.08, 0.10) and 0.09 (0.07, 0.10) g/dL. Nonlinear spline models of the Radon Index revealed similar associations. Lymphocyte percentages were lower and other percentages were higher at higher (>4 pCi/L) vs. lower (<2 pCi/L) radon concentrations in nonlinear compositional data analysis.

CONCLUSION: The radon-related cardiovascular implications of these modest, pro-thrombotic, myeloid shifts in the complete blood count/differential among postmenopausal women in the WHI remain unknown.},
}

@article {pmid42397196,
year = {2026},
author = {Singh Mahla, R},
title = {Comment on: Distinct cytokine and cytokine receptor expression patterns characterise different forms of myositis.},
journal = {Rheumatology (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/rheumatology/keag349},
pmid = {42397196},
issn = {1462-0332},
}

@article {pmid42399473,
year = {2026},
author = {Zadoroznyj, A and Eriksson, P and Bernardo, C and Tran, L and Mattsson, CA and Flaig, TW and Seiler, R and Tangen, CM and Black, PC and Lerner, SP and McConkey, DJ and Höglund, M and Liedberg, F and Sjödahl, G},
title = {Proliferation- and cytotoxic immune signatures identify chemotherapy-responsive bladder tumors in a molecular subtype dependent manner.},
journal = {NPJ precision oncology},
volume = {10},
number = {1},
pages = {},
pmid = {42399473},
issn = {2397-768X},
support = {847583//European Union's Horizon 2020 research and innovation programme/ ; CAN 2022/1971//Swedish Cancer Society/ ; },
abstract = {Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) has been the standard care for muscle-invasive bladder cancer (MIBC) for two decades. One third of NAC-treated patients achieve pathologic complete response (pT0N0), a proxy for improved survival after RC. Predicting response already at transurethral resection of bladder tumor (TUR-BT) would enable selective use of NAC, minimizing exposure to ineffective therapy. We aimed to identify tumor mRNAs associated with response across multiple transcriptomic studies, prioritizing subsequent biomarkers for validation. Three NAC-treated cohort with tumor transcriptomic profiles were included. Differential mRNA-expression analysis and subtype classification according to the Lund Taxonomy were performed. Within each cohort and subtype, genes were ranked by differential expression, and integrated into a meta rank-score. Survival associations of top genes in the NAC-cohorts were used to select candidate biomarkers for protein validation. Proliferation/late cell-cycle gene predicted response in Urothelial-like subtype and cytotoxic T- and NK-cell-related genes predicted response in Basal/Squamous tumors. These findings were validated by immunostainings for CCNB1 and NKG7, respectively. This integrative framework suggests a complex picture in which two NAC-predictive signals identify responders in a subtype dependent manner. The framework can be updated as new datasets become available, providing dynamic exploration of NAC-predictive biomarkers in MIBC.},
}

@article {pmid42400043,
year = {2026},
author = {Wang, Y and Xue, X and Usyk, M and Sharma, A and Anastos, K and Post, WS and Hodis, HN and Wang, Z and Witt, MD and Rinaldo, CR and Brown, TT and Palella, FJ and Gange, S and Kuniholm, MH and Sha, BE and Caron, P and Gerszten, RE and Clish, CB and Guillemette, C and Burk, RD and Kaplan, RC and Qi, Q and Hanna, DB and Peters, BA},
title = {Multi-omics profiles of sex hormone-binding globulin are associated with subclinical atherosclerosis in men with HIV.},
journal = {Genome medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13073-026-01709-8},
pmid = {42400043},
issn = {1756-994X},
support = {R01HL095129/HL/NHLBI NIH HHS/United States ; K01HL169019/HL/NHLBI NIH HHS/United States ; R01HL148094/HL/NHLBI NIH HHS/United States ; R01HL140976/HL/NHLBI NIH HHS/United States ; K01HL137557/HL/NHLBI NIH HHS/United States ; K01HL160146/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Sex hormones and HIV infection both influence cardiovascular health. However, the association between sex hormones and subclinical atherosclerosis is not fully understood, especially in the context of HIV.

METHODS: Among 321 men (65% with HIV) from the MACS/WIHS Combined Cohort Study, we measured 14 serum sex hormones and sex hormone-binding globulin (SHBG), assessed carotid artery plaque (IMT > 1.5 mm) using high-resolution B-mode ultrasound, and performed metagenomic sequencing on stool samples. In 312 men, we measured 986 plasma metabolites via liquid chromatography-tandem mass spectrometry and 2883 plasma proteins using the Olink Explore 3072 platform. In stratified analyses of men with (MWH) and without HIV (MWOH) and adjusting for covariates and multiple testing, we (1) examined associations of sex hormones with plaque; (2) characterized multi-omics profiles related to sex hormones; and (3) generated sex hormone-related omics scores via linear combination of related species, metabolites, and proteins, respectively, to explore whether these sex hormone-related multi-omics profiles were associated with plaque.

RESULTS: Median age of participants was 62 years (interquartile range: 58-68), and 31.5% had carotid artery plaque. Sex hormones were differentially associated with plaque in MWH and MWOH. In MWH, an inverse association was observed between SHBG and plaque (OR = 0.60 per 1-SD increase, 95% CI: 0.41, 0.90). Furthermore, higher SHBG levels were associated with overall gut microbial composition, lower abundance of species from genera Prevotella, Fibrobacter and Coprococcus, higher levels of certain metabolites (primarily lipid and carnitine metabolites) and proteins enriched in the cell-cell adhesion pathway. Some SHBG-related species (e.g., Mediterranea massiliensis), metabolites (e.g., phosphatidylcholine-based lipids) and proteins (e.g., enriched in immune response pathway) were also associated with plaque in MWH. All three SHBG-related omics scores were inter-correlated and inversely associated with plaque in MWH. In MWOH, estrone-sulfate was positively associated with plaque (OR = 3.80, 95% CI: 1.41, 10.22) but not with any species, metabolites or proteins.

CONCLUSIONS: Higher SHBG, and related microbial species, circulating metabolites, and proteins, were inversely associated with carotid artery plaque. These findings suggested that SHBG may play a protective role in subclinical atherosclerosis in MWH.},
}

@article {pmid42401524,
year = {2026},
author = {Danquah, SA and Sullivan, LB},
title = {Mitochondria produce lactate to vent redox pressure.},
journal = {Trends in endocrinology and metabolism: TEM},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tem.2026.06.005},
pmid = {42401524},
issn = {1879-3061},
abstract = {Conventionally viewed as a waste product or a cytosolic pyruvate source, recent findings suggest that lactate may also directly contribute to mitochondrial oxidative metabolism. Using an intramitochondrial lactate biosensor, Rauseo et al. instead find that energized mitochondria are producers of lactate, which buffers mitochondrial redox to mitigate reactive oxygen species production.},
}

@article {pmid42395085,
year = {2026},
author = {Zhang, X and Yang, B and Boden-Albala, B and Anton-Culver, H and Allison, M and Van Horn, L and Madsen, TE and Malik, S and Manson, JE and Neuhouser, ML and Reiner, AP and Wong, ND and Liu, S},
title = {Intake of B vitamins and their circulating levels in relation to incident stroke in women and men: Findings from two national prospective cohorts in the United States.},
journal = {American journal of preventive cardiology},
volume = {28},
number = {},
pages = {101534},
pmid = {42395085},
issn = {2666-6677},
abstract = {BACKGROUND: Evidence linking different B vitamins to stroke risk remains sparse, particularly regarding long-term intake and dose-response thresholds in populations fortified with folic acids.

OBJECTIVE: To prospectively investigate the associations of long-term intake of B vitamins and their circulating levels with incident stroke.

METHODS: Using a validated food frequency questionnaire, we assessed intake of B vitamins among 121,565 participants in the Women's Health Initiative (WHI). We also examined circulating levels of B vitamins in relation to stroke risk among 99,660 All of Us Research Program (AoU) participants. Multivariable Cox models estimated hazard ratios (HRs) and their 95 % confidence intervals (CIs).

RESULTS: In WHI (6803 incident stroke cases; median follow-up: 18.4 years), higher long-term intakes of thiamin, riboflavin, niacin, pyridoxine, and folate were significantly associated with lower stroke risk, with HRs (95 % CI) of 0.84 (0.76, 0.92), 0.90 (0.81, 0.99), 0.80 (0.72, 0.88), 0.88 (0.80, 0.96), and 0.88 (0.80, 0.97) comparing the highest to the lowest quintiles, respectively. Most B vitamins exhibited reverse J-shaped associations, whereas folate showed a linear inverse relationship up to at least 2000 dietary folate equivalent (DFE)/day. In AoU (5163 incident stroke cases; median follow-up: 5.7 years), higher plasma folate and pyridoxine were associated with lower risk (HRs: 0.86 and 0.50, respectively).

CONCLUSIONS: In two large prospective cohorts of US adults, higher intake of thiamin, riboflavin, niacin, pyridoxine, and folate, as well as higher circulating concentrations of pyridoxine and folate, were associated with a lower risk of stroke, even after folic acid fortification.},
}

@article {pmid42394610,
year = {2026},
author = {Al-Husseini, JK and Upreti, M and Ha, JH and Fong, EM and Spindler, A and Baker, CJ and Koos, DS and Abruzzo, T and Zhang, M and Krieger, MD and Hauptman, JS and Moats, R and Johal, MS and Chiarelli, PA},
title = {Tunable Nanoparticle Thin-Film Reveals Distance Dependence of Auger-Mediated Radiation Enhancement in Diffuse Midline Glioma.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.6c05629},
pmid = {42394610},
issn = {1936-086X},
abstract = {Metallic nanoparticles (NPs) enhance radiotherapy through photoelectric absorption and Auger electron cascades, yet the effective spatial range over which these low-energy electrons induce biological damage remains poorly defined. Quantifying nanoscale energy deposition is essential for rational therapeutic design and safe clinical translation. Here, we establish a self-assembled polyelectrolyte-nanoparticle-cell architecture enabling nanometer-precision control of NP-cell separation (25-100 nm) to directly probe distance-dependent radiation enhancement. Layer-by-layer assembly produced uniform interfaces confirmed by spectroscopy, ellipsometry, electron microscopy, atomic force microscopy, and microgravimetry. Using human microglial (HMC3) and diffuse intrinsic pontine glioma (SU-DIPG-IV) cells, we quantified intracellular reactive oxygen species generation and γH2AX-marked DNA double-strand breaks following [137]Cs γ-irradiation. Cells positioned 25.9 nm from the NP layer exhibited significantly increased DNA damage relative to NP-free controls, whereas damage progressively decreased with increasing separation, yielding a 250% differential effect between 25.9 and 97.5 nm. Modality-dependent attenuation profiles were observed across γ-ray, X-ray, and electron irradiation. These findings define the effective nanoscale interaction radius governing NP-mediated Auger enhancement and establish a technique for the interrogation of light-matter interactions for therapeutic energy deposition.},
}

@article {pmid42394871,
year = {2026},
author = {Shatila, M and Cruz, CC and Varatharajalu, K and Urias Rivera, AC and Abdul-Baki, K and Takigawa, K and Gupta, T and Baerman, E and Lu, L and Jeong-Ah Lee, I and Salim, H and Menon, R and Sullivan, A and Vemulapalli, V and Natha, C and Khan, A and Grivas, P and Faleck, D and Dougan, M and Thomas, AS and Wang, Y},
title = {Validation of the immune-mediated colitis endoscopic score using a retrospective cohort of patients with immune-mediated colitis.},
journal = {iGIE : innovation, investigation and insights},
volume = {5},
number = {2},
pages = {136-144.e5},
pmid = {42394871},
issn = {2949-7086},
abstract = {BACKGROUND AND AIMS: Immune-mediated colitis (IMC) is a challenging adverse effect of immune checkpoint inhibitor therapy, often leading to treatment interruption or discontinuation. Current IMC endoscopic scoring systems were adapted from those used for inflammatory bowel disease but fail to fully capture IMC. The newly proposed IMC endoscopic score (IMCES) seeks to help guide prognosis and treatment. We aimed to validate IMCES and explore its association with IMC clinical severity and outcomes.

METHODS: This single-center retrospective study included patients with IMC who received immune checkpoint inhibitors and underwent endoscopic evaluation. IMCESs were calculated on the basis of 10 gross endoscopic features, as previously reported. Patients were divided into those with IMCES <4 and IMCES ≥4. Primary end points were selective immunosuppressive therapy (SIT) use, hospitalization, and clinical and endoscopic remission.

RESULTS: We evaluated 807 patients, including the 308 previously used to develop IMCES, with 499 in a validation cohort. We found that IMCES ≥4 was associated with need for steroids and SIT (P < .05). Patients with IMCES ≥4 also tended to be hospitalized more often and longer (P < .05). Including ulceration as a criterion in IMCES strengthened these associations. Clinical symptoms had lower specificities for being associated with SIT use (26.8% for diarrhea, 64.6% for colitis) compared to IMCES ≥4 (91.5%).

CONCLUSIONS: IMCES ≥4 had a high specificity for the need for SIT and was associated with worse outcomes. Given the importance of risk stratification in the treatment of IMC to inform the early introduction of SIT, IMCES may be a powerful clinical tool to estimate prognosis and guide management but requires further validation.},
}

@article {pmid42391404,
year = {2026},
author = {Garcia, MA and Farrell-Sherman, A and Aydin, B and Zhuo, J and Fray, EJ and Zinsser, AM and Lai, J and Sowers, K and Li, H and Lopez, BM and Abeyta-Lopez, A and Chu, T and Lubbeck, D and Chae, M and Bachmann, N and Varriale, J and Westfall, DH and Hoh, R and Dalhuisen, T and Simonetti, FR and Peluso, MJ and Deeks, SG and Siliciano, RF and Cohn, LB and Siliciano, JD},
title = {Inhibitory potential of autologous neutralizing antibodies sets quantitative limits on the rebound-competent HIV-1 reservoir.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {27},
pages = {e2608337123},
doi = {10.1073/pnas.2608337123},
pmid = {42391404},
issn = {1091-6490},
support = {UM1AI164560//Delaney AIDS Research Enterprise (DARE)/ ; UM1AI64565//HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases (DMID)/ ; INV-002707/GATES/Gates Foundation/United States ; K23AI157875//HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases (DMID)/ ; P30AI094189//JHU | Center for AIDS Research, Johns Hopkins University (JHU CFAR)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Antibodies, Neutralizing/immunology ; *HIV-1/immunology/genetics/physiology ; *HIV Infections/immunology/virology/drug therapy ; *HIV Antibodies/immunology ; CD4-Positive T-Lymphocytes/virology/immunology ; Immunoglobulin G/immunology ; Viral Load ; },
abstract = {HIV-1 cure requires preventing viral rebound after treatment interruption, but quantitative criteria defining the rebound-competent reservoir are lacking. We studied individuals undergoing observational treatment interruption without confounding interventions to identify virologic and immunologic determinants of rebound. In 9 of 13 participants, rebound viruses were genetically identical or similar to proviruses in circulating resting CD4[+] T-cells. We found no evidence of recombination among rebound sequences. Instead, resistance to autologous neutralizing antibodies (aNAbs) was a critical determinant of viral rebound. Increased suppression of viral outgrowth by contemporaneous IgG isolated from plasma was correlated with longer time to rebound. Using inhibitory potential (IP), the log reduction in single-round infection at physiologic IgG concentrations, we defined quantitative limits governing rebound-competency with respect to contemporaneous aNAbs. Contemporaneous IgG antibodies inhibited different reservoir variants with a wide range of IP values (0.4 to 8.2 logs), whereas rebound viruses were minimally inhibited (0.5 to 2.8 logs), indicating that inhibition by even up to 2.8 logs (631-fold) cannot prevent rebound. Longitudinal analyses revealed that waning aNAb potency over time on antiretroviral therapy (ART) allows previously neutralized variants to gain rebound potential, consistent with the finding that rebound can come from variants deposited in the reservoir at different pre-ART time points. Thus, rebound competency is a dynamic, immune-governed property defined by quantitative immunologic constraints, including those exerted by aNAbs.},
}

Humans
*Antibodies, Neutralizing/immunology
*HIV-1/immunology/genetics/physiology
*HIV Infections/immunology/virology/drug therapy
*HIV Antibodies/immunology
CD4-Positive T-Lymphocytes/virology/immunology
Immunoglobulin G/immunology
Viral Load

@article {pmid42392158,
year = {2026},
author = {Gaballa, MR and Julian, K and Afrough, A and Hansen, DK and Goel, U and De Menezes Silva Corraes, A and Dima, D and Rana, MS and Hosoya, H and Mikkilineni, L and Fogel, L and Raza, S and Banerjee, R and Zanwar, SS and Pasvolsky, O and Sannareddy, A and Borogovac, A and Davis, JA and Green, K and Biran, N and Zolotov, E and Herr, MM and Shune, L and Bhurtel, E and DeJarnette, S and Atrash, S and Ferreri, CJ and Richards, T and Abid, MB and Bal, S and Ali, HM and Ye, JC and Richard, S and Kaur, G and Shain, KH and Castaneda-Puglianini, OA and Harada, K and De Avila, G and Rossi, AC and Hassan, H and Anderson, LD and Voorhees, P and Khouri, J and Sidana, S and Portuguese, AJ and Janakiram, M and Lee, HC and Lin, Y and Grajales-Cruz, AF and Patel, KK and Sborov, DW},
title = {Real-World Outcomes with BCMA- and GPRC5D-Targeting Bispecific Antibodies in Plasma Cell Leukemia.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026020826},
pmid = {42392158},
issn = {2473-9537},
abstract = {Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as 'active' (≥5% circulating plasma cells within 30 days of BsAb initiation) or 'historical'. In a heavily pretreated population, patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging therapy to CAR-T (Tal Bridge, 11%). Cytokine release syndrome (CRS) was grade 1-2 in 56% and grade 3-4 in 4%, whereas neurotoxicity was grade 1-2 in 16% and grade 3-4 in 5%. Among 110 evaluable patients, the overall response rate (ORR) was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS of 1.2 and 1.6 months and mOS of 8.1 and 3.6 months, respectively (P=0.007, P=0.023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P<0.001, P=0.002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were safe in PCL, with talquetamab showing superior outcomes compared with BCMA-directed BsAbs.},
}

@article {pmid42392183,
year = {2026},
author = {Krakow, EF and Bleakley, M},
title = {Minor histocompatibility antigen TCR-T.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025018015},
pmid = {42392183},
issn = {2473-9537},
abstract = {Minor histocompatibility antigens (MiHA) are polymorphic peptides presented by HLA molecules on recipient cells in allogeneic hematopoietic cell transplantation (allo-HCT) and are derived from proteins with genetic variants that differ between recipient and donor. Following allo-HCT, hematopoietic-restricted MiHA enable selective targeting of residual recipient-derived hematopoiesis, including malignant cells. Advances in engineering T cells with high-affinity MiHA-specific T-cell receptors (TCR; TCR-T) are enabling clinical translation of MiHA T cell immunotherapy. Early-phase trials of HA-1 and HA-2-specific TCR-T demonstrate safety, persistence, and durable anti-leukemic activity in high-risk or relapsed disease. To accelerate translation, the field should expand TCR-T development to additional MiHA targets to broaden HLA and population coverage, integrate MiHA genotyping into donor selection, and devise platform trials to include patients with various MiHA/HLA genotypes and to efficiently test combination therapies. MiHA-directed TCR-T represents a genetically precise, potentially routine HCT adjunct that promises to fortify graft-versus-leukemia effects and improve relapse-free survival.},
}

@article {pmid42392870,
year = {2026},
author = {Tolmeijer, SH and Maurice-Dror, C and Sandhu, S and de la Calle, CM and Kollmannsberger, C and Adil, M and Wang, CK and Murtha, AJ and Donnellan, G and van Erp, NP and Mehra, N and Hofman, MS and Azad, AA and Davis, ID and Bergman, AM and Zwart, W and van der Zande, K and Seymour, L and Black, PC and Akbari, V and Cordova, L and Lansdorp, PM and Jones, SJ and Nelson, PS and Castro, E and Schrader, KA and Ha, G and Cheng, HH and Ost, P and Olmos, D and Chi, KN and Pritchard, CC and Wyatt, AW},
title = {Germline CDK12 variants in aggressive prostate cancer.},
journal = {Cancer discovery},
volume = {},
number = {},
pages = {},
doi = {10.1158/2159-8290.CD-26-0084},
pmid = {42392870},
issn = {2159-8290},
abstract = {CDK12 mutations occur in 2-7% of metastatic prostate cancers (mPCa) and are considered to be exclusively somatic. Here, we identified five patients with mPCa (ages 44-62) harboring germline CDK12 truncating variants among 4,535 tested (0.1%). All had CDK12-driven cancers defined by an additional somatic CDK12 variant and the CDK12-specific hallmark genomic instability signature characterized by hundreds of tandem duplications. Two patients had multiple independent CDK12-driven tumors with distinct secondary somatic CDK12 variants. Germline CDK12 truncating variants were enriched in mPCa compared to gnomAD V4.1.0 controls (n=807,162; odds ratio 11.4, 95% CI 3.6-27.8) and V2.1.1 non-cancer controls (n=134,187; odds ratio 29.6; 95% CI 6.8-28.6). Family history revealed multiple related individuals with prostate or ovarian cancer, and germline variant inheritance was confirmed in the two tested pedigrees. Our data suggest that germline CDK12 truncating variants are a rare driver of lethal mPCa.},
}

@article {pmid42393431,
year = {2026},
author = {Abbadi, J and Velayutham, R and Annan, AC and Nikpoor, AR and Ahmadi, M and Rocha, BGS and Farriester, JW and Reel, JM and Holland, EC and Szulzewsky, F and Birbrair, A and Fung, KM and Talbot, S and Cox, MA},
title = {Macrophage-secreted brain-derived neurotrophic factor promotes tumor growth in triple-negative breast cancer by inducing axonogenesis.},
journal = {Cell death and differentiation},
volume = {},
number = {},
pages = {},
pmid = {42393431},
issn = {1476-5403},
support = {P20GM103639//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {Tumor-infiltrating nerves play critical roles in promoting tumor growth and progression; however, the mechanisms that drive tumor innervation remain unclear. Upon transformation, tumors recruit surrounding peripheral nerves into the tumor microenvironment (TME) to obtain their own innervation, a process called axonogenesis. While in vitro studies suggest tumor cell-derived neurotrophins, such as brain-derived neurotrophic factor (BDNF), drive axonogenesis, this has yet to be demonstrated in vivo. During wound healing, macrophages are the primary source of neurotrophins. Given the critical role of macrophages in breast cancer growth, we investigated whether these immune cells drive tumor axonogenesis in breast tumors in vivo. Syngeneic Py230 mouse triple-negative breast cancer (TNBC) cells were transplanted into intact mice and mice lacking immune-derived BDNF. Bone marrow-derived macrophages from either wild-type or immune-BDNF-deficient mice were transplanted into tumor-bearing recipients to determine if macrophage-derived BDNF was sufficient to restore tumor growth and innervation. We found that transplanted TNBC cannot grow in the absence of immune-derived BDNF, and that depletion of macrophages from the TME compromises tumor innervation. Remarkably, the introduction of wild-type macrophages restores tumor growth and innervation in mice lacking immune-derived BDNF, demonstrating that macrophages are both necessary and sufficient for tumor axonogenesis in vivo. In the absence of sensory tumor innervation, tumor growth was significantly reduced. Moreover, targeting BDNF signaling diminished TNBC growth and innervation. Our findings identify macrophages as the critical source of BDNF driving axonogenesis in breast cancer and suggest that selectively targeting BDNF signaling could provide a novel therapeutic strategy for treating TNBC through compromising tumor innervation.},
}

@article {pmid42394524,
year = {2026},
author = {Hameed, SA and Niyogusaba, T and Ojia, JA and Al-Zubi, S and Nyakato, C and Olds, P and Asombang, A and Parikh, A and Buwambaza, SS},
title = {Colorectal cancer care in Uganda: a narrative review and case-based health needs assessment from Mbarara Regional Referral Hospital.},
journal = {Global health action},
volume = {19},
number = {1},
pages = {2694008},
doi = {10.1080/16549716.2026.2694008},
pmid = {42394524},
issn = {1654-9880},
mesh = {Humans ; Uganda ; *Colorectal Neoplasms/therapy/diagnosis ; *Needs Assessment ; Referral and Consultation ; Health Services Accessibility ; Palliative Care/organization & administration ; },
abstract = {Colorectal cancer (CRC) is an important cause of cancer-related morbidity and mortality in both Sub-Saharan Africa (SSA) and Uganda. Despite national progress in cancer awareness and policy development, CRC care remains limited by resource constraints. CRC serves as an ideal lens for assessing health system resiliency, as it spans the care continuum. This review searched PubMed from inception through December 2025 for Uganda specific articles on CRC and analyzed 13 peer-reviewed articles to describe the current state of CRC care in Uganda, with insights from a health needs assessment (HNA) conducted at Mbarara Regional Referral Hospital (MRRH).Across Uganda, CRC diagnosis and treatment are hindered by insufficient endoscopic and pathology capacity, medication stockouts, and inconsistent access to immunohistochemistry and molecular testing. Screening programs remain underdeveloped due to inadequate resources for follow-up diagnostics. At MRRH, chemotherapy and surgery are available but constrained by equipment shortages, long wait times, and limited workforce despite rising patient volumes. Palliative care remains a strength, supported by national morphine availability and the efforts of Hospice Africa Uganda, though integration within oncology clinics remains incomplete. Improvement to CRC care will require expanding diagnostic infrastructure, digitizing health records, workforce development, and strengthening supply-chain management. Addressing chemotherapy and medication stockouts represents a tangible, near-term step toward improving quality of care. Experience from MRRH demonstrates both the challenges and opportunities to scaling cancer care in resource-limited settings and provides an illustrative example, albeit limited as a single-institution review, for addressing CRC systems across Uganda.},
}

Humans
Uganda
*Colorectal Neoplasms/therapy/diagnosis
*Needs Assessment
Referral and Consultation
Health Services Accessibility
Palliative Care/organization & administration

@article {pmid42384816,
year = {2026},
author = {Hollis, JA and Stonick, JA and Topalidou, I and Young, JM and Moens, CB and Lehrbach, NJ and Campbell, MG and Malik, HS},
title = {Remote homology and functional genetics unmask deeply preserved Scm3/HJURP orthologs in metazoans.},
journal = {Science advances},
volume = {12},
number = {27},
pages = {eaeg5356},
pmid = {42384816},
issn = {2375-2548},
mesh = {Animals ; Centromere/metabolism/genetics ; Caenorhabditis elegans/genetics/metabolism ; Zebrafish/genetics ; *DNA-Binding Proteins/genetics/metabolism/chemistry ; Amino Acid Sequence ; Caenorhabditis elegans Proteins/genetics/metabolism/chemistry ; Centromere Protein A/metabolism/genetics ; Models, Molecular ; Evolution, Molecular ; *Chromosomal Proteins, Non-Histone/genetics/metabolism/chemistry ; },
abstract = {In most animals and fungi, centromere identity and function depend on the Scm3/Holliday junction recognition protein (HJURP) chaperone, which deposits CENPA at centromeres. However, Scm3/HJURP orthologs appeared to be missing in insects, nematodes, many vertebrates, and other metazoans, suggesting radical chaperone replacement in these lineages. Here, we combine remote homology detection, AlphaFold-based structural modeling, and functional genetics in zebrafish and Caenorhabditis elegans to identify previously unknown Scm3/HJURP orthologs that localize to centromeres and whose loss causes catastrophic mitotic failure. We further show that Drosophila CAL1, long considered a functional analog, is instead a highly diverged Scm3/HJURP ortholog. Despite rapid primary-sequence divergence, predicted and known structures reveal a broadly conserved CENPA-H4-binding scm3 fold across fungi, vertebrates, nematodes, insects, and most metazoans. Our work demonstrates how rapid divergence can obscure the broad conservation of essential centromere machinery and provides a generalizable strategy for unmasking missing orthologs.},
}

Animals
Centromere/metabolism/genetics
Caenorhabditis elegans/genetics/metabolism
Zebrafish/genetics
*DNA-Binding Proteins/genetics/metabolism/chemistry
Amino Acid Sequence
Caenorhabditis elegans Proteins/genetics/metabolism/chemistry
Centromere Protein A/metabolism/genetics
Models, Molecular
Evolution, Molecular
*Chromosomal Proteins, Non-Histone/genetics/metabolism/chemistry

@article {pmid42385358,
year = {2026},
author = {Hamilton, BK and Onstad, L and Carpenter, PA and Pidala, J and Chen, G and Cutler, C and El Jurdi, N and Farhadfar, N and Juckett, M and Kitko, CL and Lee, CJ and Lee, SJ},
title = {Clinical Predictors of Response in Chronic Graft-Versus-Host Disease: Results From the "Predicting the Quality of Response to Specific Treatments (PQRST)" Trial.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70427},
pmid = {42385358},
issn = {1096-8652},
support = {CA118953/NH/NIH HHS/United States ; },
abstract = {Despite significant progress in chronic GVHD therapies, challenges remain in understanding pleomorphic phenotypes and varying responses to treatment. The aim of this study was to identify predictors of treatment response. We conducted a prospective, observational cohort study of patients beginning first-, second-, or third-line systemic therapy for chronic GVHD with defined agents. We describe best and 6-month response rates, failure-free survival (FFS), and clinical predictors of response. Best response rates were 60%-70% to index therapies, which subsequently declined to 40% at 6 months. Similarly, failure-free survival at 6 months was 66%, but dropped to 41% at 18 months and did not vary based on agent or line of therapy. No clear clinical predictors of FFS or survival were identified. Patient-reported fatigue was associated with NIH response, but we did not find any other clinical predictors of response. Six-month responders were associated with higher FFS at 1 year. When patients were responding to therapy, more than one organ improved. Conversely, one organ usually accounted for patients progressing. In the contemporary era, we demonstrate high but not durable responses across all agents and the first three lines of therapy. There remain large variations in practice, and no specific patterns of agents used, organ responsiveness, or overall responsiveness were identified. Additional study is needed to identify clinical and biologic phenotypes and define predictors of treatment response. Trial Registration: clinicaltrials.gov identifier: NCT04431479.},
}

@article {pmid42386083,
year = {2026},
author = {Zhang, Y and Li, Y and Xue, X and Wang, T and Moon, JY and Isasi, CR and Yu, B and Rohan, TE and Kaplan, RC and Qi, Q},
title = {Height variation independent of known genetic variants and health in later life: a cohort study.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {101425},
doi = {10.1016/j.ajcnut.2026.101425},
pmid = {42386083},
issn = {1938-3207},
abstract = {BACKGROUND: Adult-attained height is associated with later-life health, but it reflects both genetic and non-genetic influences. The health implications of height variation not explained by known common height-associated genetic variants remain unclear.

OBJECTIVE: To examine associations of residual height (height variation independent of known genetic variants) with multiple disease incidence and all-cause mortality in later life.

METHODS: In this cohort study of 407,366 adults of European ancestry (aged 40-70) in UK Biobank (2006-2010), sex- and age-specific genetically predicted height was estimated from 9,863 height-associated variants, adjusted for 30 principal components of ancestry. Residual height was calculated as the difference between observed and genetically predicted height. Plasma proteomics (2,054 proteins; Olink[TM] Explore) were profiled. Deaths and 49 incident diseases were ascertained through national registries. Multivariable Cox models estimated associations of residual height and related proteins with disease incidence and mortality.

RESULTS: Higher residual height (mean [SD], 0.0 [4.8]) was associated with more favorable self-reported pre-adulthood exposures (e.g., later birth years, no maternal smoking around birth, being breastfed as a baby, no adoption experience, and lower childhood adversity scores) and lower hazard ratios of 32 out of 49 diseases (median follow-up=∼12.5 years). Using participants with residual height within ±0.5 SDs from the mean as reference, those with residual height <-2 SDs had higher adjusted hazard ratios of mortality (1.61; 95% confidence interval 1.50, 1.72), multimorbidity (1.28; 1.12, 1.46), cardiovascular disease (1.45; 1.32, 1.60), psychiatric/neurological disease (1.38; 1.28, 1.48), and other disease categories (e.g., diabetes, digestive, and musculoskeletal diseases). In contrast, higher genetically predicted height was associated with higher incidence of 19 diseases, including subtypes of cancer, non-atherosclerotic cardiovascular diseases, and musculoskeletal diseases, as well as higher all-cause mortality. We identified 806 plasma proteins related to inflammation, immune response, and autophagy via TNF, NF-κB, PI3K-Akt, and JAK-STAT signaling pathways, which were associated with residual height and multiple diseases and mortality.

CONCLUSION: Higher residual height was associated with lower disease incidence and mortality, with associations distinct from those for genetically predicted height.},
}

@article {pmid42386722,
year = {2026},
author = {Neidlinger, P and Lenz, T and Foersch, S and Loeffler, CML and Clusmann, J and Gustav, M and Shaktah, LA and Langer, R and Dislich, B and Boardman, LA and French, AJ and Goode, EL and Gsur, A and Brezina, S and Gunter, MJ and Steinfelder, R and Behrens, HM and Röcken, C and Harrison, T and Peters, U and Phipps, AI and Curigliano, G and Fusco, N and Marra, A and Hoffmeister, M and Brenner, H and Kather, JN},
title = {A deep learning framework for efficient pathology image analysis.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42386722},
issn = {2041-1723},
support = {(DECADE, 70115166)//Deutsche Krebshilfe (German Cancer Aid)/ ; EXC 2050/2 - Project ID 390696704, (TRR 412/1, 535081457; SFB 1709/1 2025, 533056198)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; (SECAI, 57616814)//Deutscher Akademischer Austauschdienst (German Academic Exchange Service)/ ; (BELLADONNA, BCRF-25-225)//Breast Cancer Research Foundation (BCRF)/ ; (Leeds Biomedical Research Centre, NIHR203331)//DH | National Institute for Health Research (NIHR)/ ; },
mesh = {*Deep Learning ; Humans ; *Image Processing, Computer-Assisted/methods ; *Neoplasms/pathology/diagnostic imaging ; },
abstract = {Artificial intelligence has transformed digital pathology by enabling biomarker prediction from high-resolution whole-slide images. However, current methods are computationally inefficient, processing thousands of redundant tiles per slide and requiring complex aggregation models. We introduce EAGLE (Efficient Approach for Guided Local Examination), a deep learning framework that emulates pathologists by selectively analyzing informative regions. EAGLE combines task-agnostic tile selection with detailed feature extraction and is benchmarked against leading slide- and tile-level foundation models across 43 tasks from nine cancer types spanning morphology, biomarker prediction, treatment response and prognosis. EAGLE outperforms patch aggregation methods by up to 23% and achieves the highest overall classification performance. It processes one slide in 2.27 s, reducing computational time by more than 99% compared with existing models. This efficiency supports rapid and auditable workflows by enabling review of the exact tiles used for each prediction and reducing dependence on high-performance computing. By reliably identifying informative regions and minimizing artifacts, EAGLE provides robust and auditable outputs, supported by systematic negative controls and attention concentration analyses. Its unified embedding enables rapid slide search, integration into multi-omics pipelines and emerging clinical foundation models.},
}

*Deep Learning
Humans
*Image Processing, Computer-Assisted/methods
*Neoplasms/pathology/diagnostic imaging

@article {pmid42387202,
year = {2026},
author = {Huang, IJ and Baek, GT and Wu, QV and Chen, GZ and Marzouk, O and Cohen, J and Kwok, M and Banerjee, R and Cicero, K and Basom, R and Holmberg, L and Gopal, AK and Qiao, Y and Cowan, AJ and Portuguese, AJ},
title = {Impact of doublet post-transplant maintenance on outcomes in multiple myeloma: A propensity score matching analysis.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {42387202},
issn = {1476-5365},
abstract = {Post-transplant maintenance therapy is a cornerstone of care for transplant-eligible patients with multiple myeloma (MM). While lenalidomide/bortezomib has been used as maintenance, clinical trials suggest that doublet maintenance may provide additional benefit, particularly in high-risk disease. Real-world evidence remains limited. We conducted a single-center retrospective analysis of patients with MM who underwent single autologous stem cell transplantation (ASCT) followed by maintenance therapy between 2015 and 2023. Doublet maintenance was defined as ≥2 agents and monotherapy maintenance as a single agent; dexamethasone was excluded from both definitions. The primary outcomes were event-free survival (EFS) and overall survival (OS). To mitigate treatment allocation bias, propensity score matching (PSM) was used to generate a pseudopopulation of monotherapy maintenance patients with characteristics comparable to those receiving doublet therapy. A total of 410 patients were included (doublet, n = 80; monotherapy, n = 330). The most common doublet and monotherapy regimens were bortezomib-lenalidomide (n = 46, 58%) and lenalidomide (n = 159, 48%), respectively. In the PSM analysis, doublet maintenance was associated with superior EFS (HR 0.58, p = 0.022; aHR 0.48, p = 0.007) and OS (HR 0.45, p = 0.022; aHR 0.47, p = 0.029). In this real-world analysis, doublet maintenance after ASCT was associated with superior EFS and OS, supporting broader consideration of this approach in MM.},
}

@article {pmid42388439,
year = {2026},
author = {Leng, JX and Arshad, M and Carpenter, DJ and Qazi, J and Huang, C and Serra, L and Vaios, E and Reitman, ZJ and Floyd, SR and Kirkpatrick, JP and Fecci, PE and Chmura, SJ and Hong, JC and Sperduto, PW and Salama, JK and Mullikin, TC},
title = {Impact of Radionecrosis and Local Recurrence on Overall Survival After Stereotactic Radiosurgery for Brain Metastases.},
journal = {Advances in radiation oncology},
volume = {11},
number = {11},
pages = {102098},
pmid = {42388439},
issn = {2452-1094},
abstract = {PURPOSE: Radionecrosis (RN) is a dose-limiting toxicity after stereotactic radiosurgery (SRS) for brain metastases and is hard to differentiate from treated tumor progression. The outcomes of patients with RN following SRS are poorly described, particularly compared with those with local central nervous system progression. Therefore, we characterize outcomes of patients who developed RN versus those with treated tumor recurrence in the absence of out-of-field intracranial progression after SRS.

METHODS AND MATERIALS: This cohort study included patients who completed an initial course of SRS between 2015 and 2020. The primary outcome was overall survival (OS) by the presence of RN or treated tumor local recurrence (LR), analyzed using the Kaplan-Meier method. Binomial logistic regression was used to test parameters associated with RN or LR.

RESULTS: A total of 1383 patients were included; 758 (55%) were women, and the median age was 63.4 years. Common primaries were lung (n = 757, 55%), breast (203, 15%), and melanoma (118, 9%). At a median follow-up of 8.7 months, 143 patients (10%) had concern for intracranial progression or RN at irradiated sites. Following a multidisciplinary evaluation, 96 patients were ultimately diagnosed with RN and 47 with LR. Patients with LR were diagnosed earlier after SRS than those with RN (median 5.8 vs 8.3 months; P = .0087), and they had worse OS than those with RN (median 15.2 vs 40.4 months; P < .001). Patients symptomatic for either LR or RN presented earlier after SRS than asymptomatic patients and had worse OS. In binomial logistic regression, RN was associated with single-fraction SRS (odds ratio [OR], 0.38; P = .012), receipt of immunotherapy after SRS (OR, 0.32; P < .014), and a longer interval from SRS (OR, 0.94; P = .028).

CONCLUSIONS: In this multi-institutional cohort study of brain metastasis patients treated with SRS, those with RN had a significantly better OS than those with LR. These data inform surveillance, diagnosis, and prognosis of these patients.},
}

@article {pmid42389189,
year = {2026},
author = {Singh, P and Wright, JH and Smythe, KS and Fukuda, B and Hung, LH and Yeung, CCS and Yeung, KY},
title = {Graphical and interactive spatial proteomics image analysis workflow.},
journal = {GigaByte (Hong Kong, China)},
volume = {2026},
number = {},
pages = {gigabyte186},
pmid = {42389189},
issn = {2709-4715},
abstract = {Spatial proteomics provides a spatially resolved view of protein expression and localization within cells and tissues by mapping the location and abundance of proteins. There is a need for fully-integrated end-to-end imaging workflows for spatial proteomic analysis that are flexible, reproducible, and support graphical and interactive visualizations. We present a modular and interactive spatial proteomic image analysis workflow with individual containerized steps that empowers biomedical researchers to reproducibly execute and customize complex analyses. Our workflow consists of cell segmentation, unsupervised clustering with optional batch correction, validation of clusters on the image, and cell type clustering results visualization. A form-based graphical interface can be utilized to execute and customize multi-step workflows with a single click or interactively adjust image processing steps within the workflow, apply workflows to various datasets, and modify input parameters as needed. We illustrated the functionality of our workflow using human normal tonsil and colorectal cancer tissues stained by high-plex immunohistochemistry.},
}

@article {pmid42389526,
year = {2026},
author = {Toumi, R and Guenette, SJ and Oda, SK},
title = {Fusion protein-mediated costimulation in engineered T cells: from intrinsic signaling to tumor microenvironment rewiring.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1819470},
pmid = {42389526},
issn = {1664-3224},
mesh = {Humans ; *Tumor Microenvironment/immunology ; *T-Lymphocytes/immunology/metabolism/transplantation ; Animals ; Signal Transduction/immunology ; *Receptors, Chimeric Antigen/immunology/genetics/metabolism ; *Neoplasms/immunology/therapy ; *Immunotherapy, Adoptive/methods ; Lymphocyte Activation/immunology ; *Recombinant Fusion Proteins/immunology/genetics ; Receptors, Antigen, T-Cell/genetics/immunology/metabolism ; },
abstract = {Adoptive T cell therapies have markedly improved outcomes in hematologic malignancies but their efficacy in solid tumors can be diminished by a hostile tumor microenvironment that impedes sustained therapeutic responses. Beyond challenges such as limited trafficking and antigen heterogeneity, engineered T cells face suppressive myeloid and stromal populations, inhibitory checkpoint ligand interactions, and metabolically hostile niches that collectively diminish effector function and persistence. To overcome these barriers, a new generation of fusion protein-based costimulatory strategies has emerged that couple ligand-guided sensing of the tumor microenvironment with modular control of T cell activation and fate. This review examines how conventional and non-canonical costimulatory modules, when incorporated into chimeric antigen receptor (CAR) and T cell receptor (TCR) architectures, modulate T cell differentiation and function within the tumor site. It further analyzes how membrane-anchored and secreted fusion proteins enable engineered T cells to activate dendritic cells, reprogram myeloid cells, and convert poorly inflamed tumors into treatment-responsive environments. Together, these advances establish a design framework in which fusion protein-based receptors and ligands enhance T cell function and remodel the tumor microenvironment, thereby expanding the therapeutic potential of adoptive T cell therapy for solid tumors.},
}

Humans
*Tumor Microenvironment/immunology
*T-Lymphocytes/immunology/metabolism/transplantation
Animals
Signal Transduction/immunology
*Receptors, Chimeric Antigen/immunology/genetics/metabolism
*Neoplasms/immunology/therapy
*Immunotherapy, Adoptive/methods
Lymphocyte Activation/immunology
*Recombinant Fusion Proteins/immunology/genetics
Receptors, Antigen, T-Cell/genetics/immunology/metabolism

@article {pmid42389828,
year = {2026},
author = {Ortiz-Maldonado, V and Liang, EC and Huang, JJ and Jeon, Y and Hirayama, AV and Kimble, EL and Portuguese, AJ and Khouderchah, C and Braathen, K and Torkelson, A and Kirchmeier, D and Shadman, M and Maloney, DG and Riddell, SR and Turtle, CJ and Gauthier, J},
title = {A novel dose-dense strategy for CD19-directed CAR T-cell therapy is associated with durable responses without increased toxicity in patients with B-cell non-Hodgkin lymphoma.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.300321},
pmid = {42389828},
issn = {1592-8721},
abstract = {CD19-directed chimeric antigen receptor (CAR) T-cell therapy induces durable remissions in only 30-40% of patients with relapsed or refractory (R/R) B-cell non- Hodgkin lymphoma (B-NHL), highlighting a major need to improve outcomes. In dose-escalation studies, higher CAR T-cell doses improved tumor control but caused prohibitive toxicities. Having established the maximum tolerated JCAR014 dose in patients with B-NHL at 2 x 106 CAR+ cells/kg, we hypothesized that a second infusion at day 14 ("dose-dense") at the same dose and without repeat lymphodepletion, would be safe and enhance antitumor efficacy. We report outcomes from the pilot dose-dense cohort of a phase 1/2 trial (ClinicalTrials.gov identifier: NCT01865617) with 8-year follow-up. Two CAR T-cell products, each containing 2 x 106 CAR+ cells/kg, were manufactured for all 20 treated patients; 17 received both infusions. Any-grade cytokine release syndrome (CRS) and neurotoxicity (NT) occurred in 10 (59%) and 3 (18%) of dose-dense patients, respectively, and-except for one grade 2 CRS-events followed the first infusion only. Despite no additional lymphodepletion, CAR T-cell re-expansion after the second infusion occurred in 16 (94%) patients. By Lugano criteria, overall and complete response rates were 47% (8/17) and 41% (7/17), respectively. Among responders, the 8-year durationof- response rate was 63% (95% CI: 37-100), comparing favorably with the 26% (95% CI: 14-48) observed in patients treated with a single infusion. In conclusion, early redosing on day 14 was feasible, safe and led to durable responses in patients with R/R B-NHL.},
}

@article {pmid42390889,
year = {2026},
author = {Ramsey, DC and Shulman, DS and Zhou, GC and Cameron, D and Geiger, E and Howell, RM and Krull, K and Murphy, AJ and Ness, KK and Turcotte, LM and Raskin, KA and Srivastava, DK and Yasui, Y and Chow, EJ and Armstrong, GT and Weil, BR and Dubois, SG and Weldon, CB},
title = {Long-term outcomes of evolving treatment regimens in Ewing sarcoma survivors diagnosed 1970-1999: A report from the Childhood Cancer Survivor Study.},
journal = {Cancer},
volume = {132},
number = {14},
pages = {e70504},
doi = {10.1002/cncr.70504},
pmid = {42390889},
issn = {1097-0142},
support = {//American Lebanese Syrian Associated Charities/ ; CA21765/CA/NCI NIH HHS/United States ; CA55727/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Sarcoma, Ewing/drug therapy/mortality ; Female ; Male ; Child ; Child, Preschool ; Adolescent ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Neoplasms, Second Primary/epidemiology/mortality ; *Bone Neoplasms/drug therapy/mortality ; Adult ; Young Adult ; *Cancer Survivors/statistics & numerical data ; Infant ; Treatment Outcome ; },
abstract = {BACKGROUND: Survivors of Ewing sarcoma (EWS) are at significant long-term risk of treatment- and disease-related complications. The purpose of this study was to characterize long-term outcomes in EWS survivors according to treatment regimen.

METHODS: Five-year survivors of EWS diagnosed between 1970 and 1999 from the Childhood Cancer Survivor Study were included. Late mortality (>5 years from diagnosis), subsequent malignant neoplasms (SMNs), and severe to fatal chronic health conditions (CHCs) by chemotherapy regimen were compared. Patients were compared to siblings via cumulative incidence and proportional hazards models. Standardized mortality ratios (SMRs) compared late mortality between survivors and the general population.

RESULTS: Survivors (N = 739) had higher all-cause (SMR, 6.16; 95% CI, 5.36-7.05), SMN-related (SMR, 9.24; 95% CI, 6.92-12.08), cardiac-related (SMR, 4.53; 95% CI, 2.81-6.93), and noncardiopulmonary health-related (SMR, 2.04; 95% CI, 1.25-3.15) mortality compared with the general population. Compared with siblings (N = 5040), survivors had an increased risk of developing CHCs (any: hazard ratio [HR], 5.49; 95% CI, 4.58-6.59; cardiovascular: HR, 4.59; 95% CI, 3.67-5.74; neurological: HR, 2.82; 95% CI, 1.72-4.63; respiratory: HR, 5.37; 95% CI, 2.76-10.5; renal: HR, 4.61; 95% CI, 2.26-9.40). Between chemotherapy groups within EWS, there were no statistically significant differences in all-cause, SMN-caused, or health-related late mortality and the risk of developing SMNs or CHCs (any, cardiovascular, neurological, or respiratory), except that the vincristine, doxorubicin, and cyclophosphamide (VDC) plus ifosfamide and etoposide (IE) group had a higher risk of renal complications (HR, 2.55; 95% CI, 1.07-11.7; 30-year incidence was 0.56% for VDC and 3.2% for VDC/IE).

CONCLUSIONS: No differences in late mortality, SMNs, and most CHCs were observed between patients who received VDC versus VDC/IE. Aging EWS survivors' elevated risk of morbidity and mortality underscores the need for lifelong survivorship care and therapies that reduce the risk for late effects.},
}

Humans
*Sarcoma, Ewing/drug therapy/mortality
Female
Male
Child
Child, Preschool
Adolescent
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Neoplasms, Second Primary/epidemiology/mortality
*Bone Neoplasms/drug therapy/mortality
Adult
Young Adult
*Cancer Survivors/statistics & numerical data
Infant
Treatment Outcome

@article {pmid42391037,
year = {2026},
author = {Lotan, Y and Luu, M and Liu, M and Tikhonekov, S and Kobayashi, T and Ahdoot, M and Kim, HL and Porten, S and Peers, G and Kita, Y and Daskivich, T and Murakami, K and Sakatani, T and Pagano, I and Zheng, Y and Zhang, Z and Furuya, H and Rosser, CJ},
title = {Clinical Validation of a Multiplex Urine Biomarker Assay for Surveillance of Recurrent Bladder Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-26-1407},
pmid = {42391037},
issn = {1557-3265},
abstract = {BACKGROUND: More than 50% of patients with non-muscle invasive bladder cancer (NMIBC) experience recurrence, requiring lifelong surveillance with repeated cystoscopy. Given the invasive nature and cost of cystoscopy, accurate non-invasive tools are needed to support risk-adapted monitoring. We evaluated the ability of Oncuria-Monitor to detect recurrent bladder cancer (BC) during surveillance.

METHODS: Between February 2017 and August 2020, six medical centers in the United States and Japan prospectively enrolled 300 patients with a history of BC, generating 1,248 serial urine samples. Participants were divided into training and validation cohorts. At each surveillance visit over two years, urine samples were analyzed in a blinded manner using Oncuria-Monitor and BladderChek™, alongside urine cytology. Test performance was compared with cystoscopy and histopathology-confirmed recurrence.

RESULTS: Recurrent BC was identified in 31% (93/300) of participants, with 143 total recurrences during follow-up, including 90 tumors in the validation cohort. In the validation cohort, Oncuria-Monitor achieved a sensitivity of 85.6% (95% CI: 78.1-92.2%) and negative predictive value (NPV) of 93.0% (95% CI: 89.2-96.4%). In comparison, BladderChek™ demonstrated a sensitivity of 20.0% and NPV of 88.0%, while urine cytology showed a sensitivity of 36.9% and NPV of 91.6%. The number needed to evaluate to detect one recurrence was 3 for both cystoscopy and Oncuria-Monitor, compared with 15 for BladderChek™ and 8 for cytology.

CONCLUSIONS: In this prospective study, Oncuria-Monitor demonstrated clinically actionable performance, enabling a rule-out strategy that could safely reduce cystoscopy in approximately 25% of surveillance visits. These findings support a paradigm shift toward biomarker-guided, risk-adapted surveillance in BC.},
}

@article {pmid42391046,
year = {2026},
author = {Kaiser, AJ and Readshaw, JJ and Doyle, LA and Puiu, M and Kelly, A and McGuire, SF and Acosta, JP and Vu, D and Nelson, A and Smith, DL and Araújo-Bazán, L and Arias-Palomo, E and Luyten, YA and Stoddard, BL and Blower, TR and Kaiser, BK},
title = {Multiple forms of protein-protein and DNA binding are exhibited by BrxC from the BREX phage restriction system.},
journal = {Nucleic acids research},
volume = {54},
number = {12},
pages = {},
doi = {10.1093/nar/gkag651},
pmid = {42391046},
issn = {1362-4962},
support = {R35 GM148166/GM/NIGMS NIH HHS/United States ; R15 GM140375/GM/NIGMS NIH HHS/United States ; //New England Biolabs/ ; //Fred Hutchinson Cancer Center/ ; BB/T008695/1//Biotechnology and Biological Sciences Research Council Newcastle-Liverpool-Durham Doctoral Training Partnership/ ; BB/Y003659/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; PID2023-152248NB-I00//Lister Institute Prize Fellowship/ ; //MICIU/AEI/10.13039/501100011033/ ; //ERDF, EU/ ; P30 CA015704-40//Cancer Center Support/ ; },
mesh = {Protein Binding ; *Bacteriophages/genetics ; Adenosine Triphosphate/metabolism ; *DNA-Binding Proteins/metabolism/chemistry/genetics ; *DNA/metabolism ; *Adenosine Triphosphatases/metabolism/chemistry/genetics ; DNA Methylation ; *Bacterial Proteins/metabolism/chemistry/genetics ; Models, Molecular ; Protein Multimerization ; },
abstract = {Bacteriophage exclusion (BREX) defense systems restrict phage infection via inhibition of phage DNA replication, while also modifying and protecting the bacterial genome. Type I BREX systems encode six conserved proteins, including a site-specific DNA methyltransferase. Host methylation requires a subset of BREX proteins, whereas phage restriction generally requires them all, suggesting that distinct but overlapping complexes mediate these activities. Full details of the mechanism and regulation of BREX remain to be understood. Here, we characterize the behavior and structures of the conserved BrxC AAA+ ATPase protein. BrxC forms multiple assemblages-various self-associating multimers, as well as a complex with BrxB-PglZ-that can be uncoupled via distinct point mutations, leading to differing effects on host methylation versus phage restriction. BrxC's self-association, as well as its ability to bind DNA, is regulated by ATP binding and hydrolysis; BrxA and BrxB appear to also regulate those behaviors. These collective results suggest that BrxC may play a key role in controlling the two activities of BREX, with BrxB, BrxC, and PglZ forming a core complex, and the equilibrium among competing assemblies containing those proteins modulating the balance between idling and activated restrictive states.},
}

Protein Binding
*Bacteriophages/genetics
Adenosine Triphosphate/metabolism
*DNA-Binding Proteins/metabolism/chemistry/genetics
*DNA/metabolism
*Adenosine Triphosphatases/metabolism/chemistry/genetics
DNA Methylation
*Bacterial Proteins/metabolism/chemistry/genetics
Models, Molecular
Protein Multimerization

@article {pmid42391096,
year = {2026},
author = {Crew, KD and Anderson, GL and Arnold, KB and Dzingle, S and Michel, A and DeLucie, M and Law, CW and Pruthi, S and Sandoval Leon, AC and Shirley, R and Grosse Perdekamp, MT and Colonna, SV and Krisher, SL and King, TA and Yee, LD and Ballinger, TJ and Braun-Inglis, C and Mangino, DA and Wisinski, KB and DeYoung, CA and Ross, M and Floyd, JD and Kaster, A and VanderWalde, LH and Saphner, TJ and Zarwan, C and Lo, S and Graham, C and Conlin, AK and Yost Butler, K and Agnese, DM and Jernigan, C and Hershman, DL and Neuhouser, ML and Zell, JA and Arun, B and Kukafka, R},
title = {Cluster randomized controlled trial of decision support for breast cancer chemoprevention, MiCHOICE.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag216},
pmid = {42391096},
issn = {1460-2105},
abstract = {INTRODUCTION: Breast cancer chemoprevention is underutilized among high-risk women. We examined whether decision support could increase informed decision-making.

METHODS: We conducted a cluster randomized controlled trial to evaluate the effect of a patient-facing decision aid (RealRisks) and provider tool (BNAV) compared to standard education on the number of women with high-risk breast lesions making informed choices. Questionnaires were administered at baseline, 6 and 12 months. The primary outcome was chemoprevention informed choice (defined as adequate knowledge and attitudes congruent with decision) at 6 months. Secondary endpoints included breast cancer risk perceptions, worry, chemoprevention knowledge, decision conflict, and chemoprevention decision.

RESULTS: Across 31 randomized sites, we enrolled 210 providers, who were primarily breast health specialists. Twenty-four sites (14 intervention, 10 control) enrolled 412 patients. Among 287 patients evaluable for the primary outcome, there were no significant differences in informed choice between the intervention and control arms at 6 months (35% vs 27%, respectively; p = 0.20) and 12 months (37% vs 25%, respectively; p = 0.05). At 6 months, women in the intervention compared to control arm were more likely to have accurate breast cancer risk perceptions (31% vs 21%, respectively; p = 0.03) and adequate chemoprevention knowledge (33% vs 23%, respectively; p = 0.04). At 12 months, 52% of women in the control and 50% in the intervention arm self-reported initiating chemoprevention.

CONCLUSION: Decision support led to modest improvements in accurate risk perceptions and chemoprevention knowledge, but not informed choice. Relatively high chemoprevention uptake was achieved among women with high-risk breast lesions managed mainly by breast health specialists.

TRIAL REGISTRATION: NCT04496739.},
}

@article {pmid41649873,
year = {2026},
author = {Munzur, AD and Herberts, C and Kwan, EM and Emmett, L and Sandhu, S and Buteau, JP and Iravani, A and Joshua, AM and Francis, RJ and Lee, ST and Scott, AM and Martin, AJ and Stockler, MR and Zhang, AY and Williams, SG and Bernales, CQ and Donnellan, G and Koudjanian, M and Parekh, K and Bacon, JVW and Karsan, A and Azad, AA and Davis, ID and Hofman, MS and Wyatt, AW},
title = {Clonal Hematopoiesis after 177Lu-PSMA-617 Radioligand Therapy in Prostate Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {32},
number = {13},
pages = {2644-2652},
doi = {10.1158/1078-0432.CCR-25-4001},
pmid = {41649873},
issn = {1557-3265},
support = {//Prostate Cancer Foundation (PCF)/ ; //Cancer Research Society (CRS)/ ; //Terry Fox Research Institute (TFRI)/ ; 707339//Canadian Cancer Society (CCS)/ ; 2016274//National Health and Medical Research Council (NHMRC)/ ; //BC Cancer Foundation/ ; //University of British Columbia (UBC)/ ; },
mesh = {Humans ; Male ; *Dipeptides/adverse effects/administration & dosage/therapeutic use ; *Heterocyclic Compounds, 1-Ring/adverse effects/administration & dosage/therapeutic use ; *Prostatic Neoplasms, Castration-Resistant/pathology/radiotherapy/genetics/drug therapy/blood ; *Clonal Hematopoiesis/radiation effects/drug effects/genetics ; *Radioisotopes/adverse effects ; Aged ; *Lutetium ; Taxoids/adverse effects/administration & dosage ; *Radiopharmaceuticals/adverse effects/administration & dosage ; Middle Aged ; Mutation ; Prostate-Specific Antigen ; },
abstract = {PURPOSE: Clonal hematopoiesis (CH) is a precursor state linked to risk of hematologic neoplasms and may be exacerbated by radiation exposure. We aimed to compare CH prevalence after the new radioligand therapy 177Lu-PSMA-617 versus the alternative standard-of-care cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer (mCRPC).

EXPERIMENTAL DESIGN: This post hoc correlative analysis used serial blood samples from TheraP (ANZUP 1603), a randomized phase II trial in docetaxel-refractory mCRPC. Cell-free DNA and leukocyte DNA underwent error-corrected deep targeted sequencing. CH mutations were called at variant allele frequency (VAF) ≥0.25%. Variants detected at progression but undetected at baseline were defined as treatment-emergent CH. A total of 178 patients had a baseline sample; 107 (60 177Lu-PSMA-617; 47 cabazitaxel) had paired baseline-progression samples (median interval, 29 vs. 27 weeks).

RESULTS: Baseline CH was detected in 77% (138/178) of patients, with similar prevalence and gene distribution between arms. Treatment-emergent CH occurred more often after 177Lu-PSMA-617 than cabazitaxel [62% (37/60) vs. 40% (19/47); P = 0.03], and 83% (121/146) of all emergent mutations were detected after 177Lu-PSMA-617. The DNA damage response gene PPM1D accounted for 42% (51/121) of 177Lu-PSMA-617-emergent mutations, with odds ratios of 3.2 for any treatment-emergent CH and 5.4 for PPM1D, relative to cabazitaxel. CH clones expanded more frequently and to a greater magnitude with 177Lu-PSMA-617 (proportion expanding, 70.9% vs. 29.5%; P = 7.5 × 10-5), and increases in maximal CH VAF correlated with the number of 177Lu-PSMA-617 cycles received (+2.9% per cycle; P = 0.002).

CONCLUSIONS: 177Lu-PSMA-617 strongly promotes CH, supporting integration of longitudinal monitoring for long-term hematologic sequelae as radioligand therapy is implemented earlier in prostate cancer care. See related commentary by Lückerath et al., p. 2527.},
}

Humans
Male
*Dipeptides/adverse effects/administration & dosage/therapeutic use
*Heterocyclic Compounds, 1-Ring/adverse effects/administration & dosage/therapeutic use
*Prostatic Neoplasms, Castration-Resistant/pathology/radiotherapy/genetics/drug therapy/blood
*Clonal Hematopoiesis/radiation effects/drug effects/genetics
*Radioisotopes/adverse effects
Aged
*Lutetium
Taxoids/adverse effects/administration & dosage
*Radiopharmaceuticals/adverse effects/administration & dosage
Middle Aged
Mutation
Prostate-Specific Antigen

@article {pmid42377120,
year = {2026},
author = {Iravani, A},
title = {Salvage Radiotherapy Decision-making in the Era of Molecular Imaging: Insights from EMPIRE-2.},
journal = {Radiology},
volume = {319},
number = {3},
pages = {e260977},
doi = {10.1148/radiol.260977},
pmid = {42377120},
issn = {1527-1315},
}

@article {pmid42377436,
year = {2026},
author = {Chalian, M and Alipour, E and Pooyan, A and Haseli, S and Shomal Zadeh, F and Park, C and Mantilla, JG and Jones, AD and Schaub, SK and Cranmer, LD and Kinahan, PE and Nyflot, MJ},
title = {MRI-Based radiomic signature for predicting pathologic treatment response to neoadjuvant chemoradiotherapy and radioimmunotherapy in soft tissue sarcoma.},
journal = {Skeletal radiology},
volume = {},
number = {},
pages = {},
pmid = {42377436},
issn = {1432-2161},
abstract = {BACKGROUND: Prediction of treatment outcomes is essential for improving clinical management, particularly in patients with soft tissue sarcoma, where treatment options remain suboptimal. Given the limitations of current therapies, there is increasing interest in combining neoadjuvant radiotherapy with immunotherapy, referred to as neoadjuvant radioimmunotherapy (NRIT). We aim to develop a predictive model for assessing pathologic treatment response in patients undergoing NRIT or chemoradiotherapy, integrating radiomic features with radiologist assessments, clinical data, and pathology findings.

MATERIALS AND METHODS: Radiomic and semantic features were extracted from pre- and post-treatment MRI scans. The XGBoost algorithm was used for feature selection and model development. Models included a model based on clinical variables and semantic features, a model based on radiomic features and clinical features and a model using all available features.

RESULTS: Study cohort included 213 patients (mean age of 54 years, male/female of 1.6). There were 17 patients in the prospective arm. The best model used all radiomic, clinical, and semantics features. It achieved an area under the receiver operating characteristic curve (AUC) of 0.72 (95% CI = 0.51-0.89) on the hold-out testing set.

CONCLUSION: Multi-modal radiomic-based models are effective in identifying patients at higher risk of non-response to neoadjuvant therapy. Furthermore, the performance of multi-modal radiomics-based models exceeded those based solely on radiologist evaluations. Our findings underscore the potential of radiomics in enhancing precision medicine by enabling identification of treatment response in STS patients undergoing NRIT before surgical excision of the tumor.},
}

@article {pmid42379250,
year = {2026},
author = {Bingham, NE and Boiko, JR and Jones, DC and Wong, D and Khong, T and Mithraprabhu, S and Ensbey, KS and Elz, AE and Newell, EW and Spencer, A and Hill, GR},
title = {Spatial transcriptomics identifies a suppressive, T-cell excluded tumor microenvironment in extramedullary myeloma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026020500},
pmid = {42379250},
issn = {2473-9537},
abstract = {Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor outcomes due to aggressive disease kinetics and therapy resistance. The bone marrow (BM) tumour microenvironment (TME) promotes cell survival and drug resistance in marrow restricted MM, but little is known about the TME in EMD. To characterize the tissue architecture of these tumors, we performed spatial transcriptomics on tumour biopsies. Like BM-restricted MM, we identified significant inter-patient heterogeneity in plasma cell (PC) expression profiles, although still maintaining a characteristic plasma cell transcriptome. The TME was dominated by macrophages with a suppressive "M2" phenotype. CD8+ T-cells frequently expressed exhaustion markers LAG3 and TIGIT, consistent with a suppressive TME. We identified three recurrent TME niches based on immune-cell composition: immune excluded, immune suppressed and immune permissive. The immune excluded niche comprised the bulk of tumors, reflecting spatial exclusion of immune cells. The suppressive extracellular matrix from abundant tumour-associated fibroblasts in the immune suppressive niche may further contribute to T-cell exclusion. Cell-cell interaction modelling revealed a complex, bidirectional network: PC modulated the TME through PGE2 and VEGFB, while receiving canonical pro-survival signals through CD38, CXCR4 and BCMA. Notably, TME cells, particularly fibroblasts and macrophages, are predicted to collectively promote the suppressive macrophage phenotype and fibrotic extracellular matrix, reinforcing an immunosuppressive milieu that supports local disease progression. These findings reveal the spatial organization of EMD, highlighting niche substitution rather than niche independence, and identify clinically tractable microenvironmental niches and signaling networks in this high-risk myeloma subset.},
}

@article {pmid42379983,
year = {2026},
author = {Cassano, RC and Banerjee, R and Afrough, A and Portuguese, AJ and Thakur, R and Cicero, K and Kwok, M and Foster, L and Buda, G and Meletath, S and Galimberti, S and Serviddio, G and Dhodapkar, MV and Dima, D},
title = {MRD in multiple myeloma: Moving from "minimal" to "measurable".},
journal = {Blood reviews},
volume = {},
number = {},
pages = {101413},
doi = {10.1016/j.blre.2026.101413},
pmid = {42379983},
issn = {1532-1681},
abstract = {The assessment of minimal residual disease (MRD) is an important prognostic factor in hematologic malignancies, including multiple myeloma (MM). Historically defined as cancer cells undetectable by conventional morphology, MRD is now more appropriately termed measurable residual disease, reflecting its quantitative and clinically actionable nature. Advances in next-generation flow cytometry and next-generation sequencing have enabled detection of disease at sensitivities as low as 10[-6] and even 10[-7], redefining the concept of complete response. Nonetheless, challenges remain regarding assay sensitivity, standardization, and interpretation of results. Achieving MRD-negativity is a strong and independent predictor of improved survival outcomes in both newly diagnosed and relapsed/refractory MM. Consequently, MRD negativity has increasingly been accepted by regulatory agencies as an intermediate endpoint supporting accelerated drug approval. This review summarizes MRD detection methodologies, clinically relevant thresholds, and therapeutic implications, highlighting the paradigm shift from "minimal" to measurable residual disease.},
}

@article {pmid42380658,
year = {2026},
author = {Steichen, JM and Madden, PJ and Flynn, CT and Phulera, S and Shil, M and Kalyuzhniy, O and Liguori, A and Kifude, C and Sewall, LM and Cottrell, CA and Ma, KM and Baboo, S and Diedrich, JK and McKenney, K and deCamp, AC and Carnathan, DG and Phung, I and Ramezani-Rad, P and Marina-Zárate, E and Freeman, B and Xie, Z and Lee, JH and Sincomb, T and Phelps, N and Lu, D and Goodwin, D and Tingle, R and Adachi, Y and Alavi, N and Tran, J and Tran, AS and Nascimento, A and Sovie, C and Bader, DLV and Voic, H and Zhou, X and Pixton, G and Walsh, A and Melo, MB and Schiffner, T and Batista, FD and Burton, DR and Irvine, DJ and Paulson, JC and Yates, JR and Ozorowski, G and Ward, AB and Silvestri, G and Crotty, S and Schief, WR},
title = {Vaccination elicits HIV broadly neutralizing antibodies in primates.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-026-10837-5},
pmid = {42380658},
issn = {1476-4687},
abstract = {The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been proposed as templates for vaccine development[1-6]. Germline-targeting is a conceptually radical vaccine design approach to elicit bnAbs, aiming to prime rare bnAb-precursor B cells possessing pre-determined human genetic and structural features shared with template bnAbs, and then guide B cell affinity maturation to potent bnAb evolution with heterologous boosters[7-11]. Although the approach has shown promise in clinical[12-17] and pre-clinical[18-34] studies, it faces many immunological challenges and, to date, has not succeeded in generating bnAbs in humans or nontransgenic animals. Here, we report an adjuvanted protein germline-targeting vaccine tested in outbred nonhuman primates that generated bnAb-class memory B cells and sera capable of neutralizing diverse HIV clinical isolates. bnAb lineages were generated in ≥50% of animals, achieving up to 67% neutralization breadth compared to the reference bnAb. Vaccine-induced bnAbs exhibited precise structural mimicry of human bnAb interactions with HIV envelope (Env), matching the germline-targeting predictions. Furthermore, serum bnAb activity developed in 44% of animals and in the most striking instance reached titers expected to confer protection against diverse HIV isolates. These results demonstrate proof of principle that germline-targeting vaccines can reproducibly elicit prespecified classes of bnAbs to prespecified epitopes under endogenous conditions, supporting further optimization of this approach for HIV vaccine development.},
}

@article {pmid42382044,
year = {2026},
author = {Torabi, A and Love, J and Wu, D and Hirayama, A and Naresh, K},
title = {Epigenetics as a mechanism of lineage extinction and relapse of B-cell lymphoma treated with CD19 CAR T-cell therapy.},
journal = {Blood neoplasia},
volume = {3},
number = {3},
pages = {100251},
pmid = {42382044},
issn = {2950-3280},
}

@article {pmid42383153,
year = {2026},
author = {Liu, J and Nolin, AC and Unnithan, S and Erkanli, A and Penvose, K and Atkins, S and Holtzman, S and Chess, I and Vattakalam, A and Blank, SV and Wright, JD and Albright, BB and Hazelton, WD and Myers, ER and Havrilesky, LJ},
title = {Endometrial thickness in patients with postmenopausal bleeding and endometrial cancer: A retrospective cohort study.},
journal = {Gynecologic oncology reports},
volume = {66},
number = {},
pages = {102135},
pmid = {42383153},
issn = {2352-5789},
abstract = {OBJECTIVE: Updated ACOG guidelines recommend a combined approach of transvaginal ultrasound (TVUS) and endometrial sampling for evaluation of most postmenopausal bleeding (PMB). Although prior studies investigating the reliability of TVUS suggest that non-endometrioid endometrial cancer subtypes present with thinner endometrium, some included cases with incomplete endometrial visualization. We therefore evaluated endometrial thickness (ET) by cancer subtype while controlling for incomplete endometrial visualization.

METHODS: We performed a retrospective cohort study of patients with PMB who underwent TVUS followed by tissue-confirmed endometrial cancer at three academic centers (2013-2022). Cancers were classified as endometrioid or non-endometrioid (serous, clear cell, carcinosarcoma, undifferentiated). Fibroid presence, endometrial visualization, and race/ethnicity were recorded. Patients with incomplete endometrial visualization were excluded from endometrial thickness analysis. Appropriate nonparametric statistical comparisons were performed.

RESULTS: Among 171 analysis-eligible patients (121 endometrioid, 50 non-endometrioid), non-endometrioid cancers were more common among non-Hispanic Black (53%) than non-Hispanic White (20%) or Hispanic patients (25%). Patients with non-endometrioid cancers were more likely to have incompletely visualized endometria (34% vs 9.1%, p < 0.01). Among patients with complete visualization, mean ET did not differ between endometrioid and non-endometrioid cancers (16.9 vs 19.5 mm) or by race/ethnicity. ET ≤4 mm occurred in 5.6% of cancers with fully visualized endometria, without differences between subtypes.

CONCLUSION: When endometrium was fully visualized, non-endometrioid cancers did not present with thinner ET than endometrioid cancers, and a 4 mm cutoff may miss 5.6% of cancers. Incomplete visualization, more common in non-endometrioid disease, may lead to additional missed diagnoses, supporting universal endometrial sampling for PMB.},
}

@article {pmid42383436,
year = {2026},
author = {Jones, SMW and Keegan, THM and Hahn, EE and Nichols, HB and O'Meara, ES and Figueroa Gray, M and Wernli, KJ and Sauder, CAM and Kirchhoff, AC and Laurent, CA and Kushi, LH and Chubak, J},
title = {Test-Retest Reliability and Mode Effects on Single-Item and Multi-Item Measures in a Survey of Adolescent and Young Adults with Cancer.},
journal = {Journal of adolescent and young adult oncology},
volume = {},
number = {},
pages = {21565333251414792},
doi = {10.1177/21565333251414792},
pmid = {42383436},
issn = {2156-535X},
abstract = {PURPOSE: This project examined test-retest reliability and survey mode administration across single-item and multi-item measures among adolescent and young adult (AYA) cancer survivors.

METHODS: Forty-six AYAs randomly assigned to survey mode (phone, online, and paper) completed the survey and were invited to complete the survey again 1 week later.

RESULTS: Mode effects were found on 6% of single-items and 25% of multi-item scores. Reliability was low for 52% of single-items and 8% of multi-item scores.

CONCLUSION: Multi-item measures should generally be used over single-item measures due to better reliability, but single-item measures may be preferable when mode effects are large.},
}