@article {pmid40376505,
year = {2025},
author = {Li, Y and Zheng, J and Mlacha, YP and Lu, S and Abdulla, S and Li, Q and Yan, G and Zhou, X and Xiao, N and Githu, V and Gavana, T and Chaki, P and Bi, P and Sui, Y and Wang, Y and Wang, D},
title = {Impact of Implementation Interruptions of 1,7-Malaria Reactive Community-Based Testing and Response Approach on Malaria Control Efforts - Southern Tanzania.},
journal = {China CDC weekly},
volume = {7},
number = {18},
pages = {628-634},
pmid = {40376505},
issn = {2096-7071},
abstract = {INTRODUCTION: Surveys from the China-Tanzania Malaria Control Project demonstrated that the 1,7-malaria Reactive Community-Based Testing and Response (1,7-mRCTR) approach significantly reduced malaria incidence rates. However, implementation was disrupted by security concerns, infectious disease outbreaks, and supply shortages. This study evaluates how these interruptions affected intervention effectiveness to inform future malaria control strategies.

METHODS: The study employed a two-phased design: Phase I (2016-2018) and Phase II (2019-2021). Weekly malaria incidence rates per 100 people were calculated from cases reported by local health facilities in the intervention areas during both phases. Seasonal and trend decomposition using loess (STL) and interrupted time series modeling with piecewise linear regression were used to evaluate the impact of disruptions on 1,7-mRCTR implementation effectiveness.

RESULTS: In Tanzania's 1,7-mRCTR areas, malaria incidence peaked during November-December and June-July. Phase I's 8-month interruption reversed the weekly trend from a 0.17% decline to a 0.58% increase (P=0.001). After resumption, incidence dropped 8.96% (P=0.039) and maintained a 0.39% long-term decline (P=0.003). Even with seasonal adjustment, the interruption slowed the weekly decline from 0.08% to 0.07% (P=0.003). Phase II showed a similar pattern: a one-week interruption caused a 0.70% drop (P=0.007) but shifted the trend from a 0.02% decline to a 0.08% increase (P=0.001). After resumption, interventions stabilized the decline at 0.11% weekly (P=0.001).

CONCLUSIONS: This research demonstrates that Tanzania's malaria incidence is closely linked to seasonal patterns and consistent intervention efforts. Phase I's 8-month security-related interruption reduced 1,7-mRCTR effectiveness by 12.5%, while Phase II's 3-month pandemic-induced interruption caused only short-term fluctuations with minimal long-term impact. Rapid resumption of interventions after disruptions allowed for prompt recovery, highlighting the importance of adaptive strategies to maintain progress toward malaria control goals.},
}

@article {pmid40376501,
year = {2025},
author = {Wang, S and Ding, W and Lu, S and Li, L and Qian, F and Chen, C and Liu, L and Cai, Y and Liu, X and Perez, S and Frutos, R and Yao, H and Zhou, Y and Ye, C and Wu, D and Li, S and Kwete, XJ and Sui, Y and Wang, D},
title = {China's Malaria R&D Innovations: A Scoping Review from 2013-2023.},
journal = {China CDC weekly},
volume = {7},
number = {18},
pages = {635-643},
pmid = {40376501},
issn = {2096-7071},
abstract = {Malaria remains a major global health challenge. Understanding the research progress of the potential innovative tools is important for malaria elimination. This scoping review aims to explore China's research and development (R&D) advances from 2013-2023 in addressing the current challenges and contributing to global malaria elimination. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), this review searched the English and Simplified Chinese data sources from five databases. A total of 11,112 English articles and 2,944 Chinese articles were retrieved. After screening, 44 English and 13 Chinese articles were included. Key advancements were identified in three domains: vector control, pathogen screening and diagnosis, and prevention and treatment. Innovations in vector control include studies such as the use of Serratia strains and symbiont-mediated RNAi approaches to block malaria transmission. Advances in pathogen screening and diagnosis feature biosensor development, AI monitoring technologies, and novel amplification gene and nucleic acid detection technologies. In prevention and treatment, artemisinin-based combination therapies (ACTs) remain a cornerstone, with additional progress in industrial pharmaceuticals and technologies already in field and semi-field-testing stages. This review underscores the importance of leveraging China's R&D capacity to meet global challenges. To maximize impact, we call for global attention to strengthening international collaboration with China in malaria R&D to accelerate the commercialization, regulatory approval, and large-scale deployment of innovations.},
}

@article {pmid40374764,
year = {2025},
author = {Kwak, JW and Houghton, AM},
title = {Targeting neutrophils for cancer therapy.},
journal = {Nature reviews. Drug discovery},
volume = {},
number = {},
pages = {},
pmid = {40374764},
issn = {1474-1784},
abstract = {Neutrophils are among the most abundant immune cell types in the tumour microenvironment and have been associated with poor outcomes across multiple cancer types. Yet despite mounting evidence of their role in tumour progression, therapeutic strategies targeting neutrophils have only recently gained attention and remain limited in scope. This is probably due to the increasing number of distinct neutrophil subtypes identified in cancer and the limited understanding of the mechanisms by which these subsets influence tumour progression and immune evasion. In this Review, we discuss the spectrum of neutrophil subtypes - including those with antitumour activity - and their potential to polarize towards tumour-suppressive phenotypes. We explore the molecular pathways and effector functions by which neutrophils modulate cancer progression, with an emphasis on identifying tractable therapeutic targets. Finally, we examine emerging clinical trials aimed at modulating neutrophil lineages and consider their implications for patient outcomes.},
}

@article {pmid40373766,
year = {2025},
author = {Sajadi, MM and Abbasi, A and Tehrani, ZR and Siska, C and Clark, R and Chi, W and Seaman, MS and Mielke, D and Wagh, K and Liu, Q and Jumpa, T and Ketchem, RR and Nguyen, DN and Tolbert, WD and Pierce, BG and Atkinson, B and Deming, D and Sprague, M and Asakawa, A and Ferrer, D and Dunn, Y and Calvillo, S and Yin, R and Guest, JD and Korber, B and Mayer, BT and Sato, AH and Ouyang, X and Foulke, S and Habibzadeh, P and Karimi, M and Aslanabadi, A and Hojabri, M and Saadat, S and Zareidoodeji, R and Kędzior, M and Pozharski, E and Heredia, A and Chen, H and Montefiori, D and Ferrari, G and Pazgier, M and Lewis, GK and Jardine, JG and Lusso, P and DeVico, A},
title = {A comprehensive engineering strategy improves potency and manufacturability of a near pan-neutralizing antibody against HIV.},
journal = {Structure (London, England : 1993)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.str.2025.04.016},
pmid = {40373766},
issn = {1878-4186},
abstract = {Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential to prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials with "first-generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" antibodies will be required for optimal clinical utility, while preserving or enhancing Current Good Manufacturing Practices (cGMP) manufacturing capability. Here, we report the engineering of an anti-CD4-binding site (CD4bs) bnAb, N49P9.3. Through a series of rational modifications, we produced a variant, N49P9.6-FR-LS, that demonstrates enhanced potency, superior antiviral activity in combination with other bnAbs, low polyreactivity, and longer circulating half-life. Additional engineering for manufacturing produced a final variant, eN49P9, with properties conducive to cGMP production. Overall, these efforts demonstrate the feasibility of developing enhanced anti-CD4bs bnAbs with greatly improved antiviral properties as well as potential translational value.},
}

@article {pmid40373748,
year = {2025},
author = {Kublin, JG},
title = {Antibiotics fire up inflammation to cool vaccine responsiveness.},
journal = {Cell host & microbe},
volume = {33},
number = {5},
pages = {618-620},
doi = {10.1016/j.chom.2025.04.015},
pmid = {40373748},
issn = {1934-6069},
mesh = {Humans ; *Anti-Bacterial Agents/adverse effects ; *Inflammation/chemically induced/immunology ; *Rabies Vaccines/immunology/administration & dosage ; *Gastrointestinal Microbiome/drug effects/immunology ; Vaccination ; Animals ; },
abstract = {In this issue of Cell Host & Microbe, Feng et al. find that broad-spectrum antibiotics perturbed the ecology of the gut microbiome in individuals receiving a rabies vaccine, resulting in systemic inflammatory responses. Such inflammation is hypothesized to alter immune homeostasis with consequences for immunological responsiveness to vaccination.},
}

Humans
*Anti-Bacterial Agents/adverse effects
*Inflammation/chemically induced/immunology
*Rabies Vaccines/immunology/administration & dosage
*Gastrointestinal Microbiome/drug effects/immunology
Vaccination
Animals

@article {pmid40373198,
year = {2025},
author = {Davis, MR and Kufel, JE and Kufel, WD and McCreary, EK and Oleksiuk, LM and Ours, R and Pham, CU and Ross, JK and Smith, EA and Trisler, MJ and Tverdek, F},
title = {You've Got a Friend in Me: Curbside Questions Infectious Diseases Clinicians Ask Infectious Diseases Pharmacists.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf250},
pmid = {40373198},
issn = {1537-6591},
abstract = {This multicenter study highlights the critical role of ID pharmacists in supporting ID consult services, with 89% of 1,518 curbside inquiries from ID clinicians resulting in clinical management changes as recommended by the pharmacist. These findings emphasize the necessity of ID pharmacists in optimizing multidisciplinary patient care.},
}

@article {pmid40373114,
year = {2025},
author = {Caniels, TG and Prabhakaran, M and Ozorowski, G and MacPhee, KJ and Wu, W and van der Straten, K and Agrawal, S and Derking, R and Reiss, EIMM and Millard, K and Turroja, M and Desrosiers, A and Bethony, J and Malkin, E and Liesdek, MH and van der Veen, A and Klouwens, M and Snitselaar, JL and Bouhuijs, JH and Bronson, R and Jean-Baptiste, J and Gajjala, S and Rikhtegaran Tehrani, Z and Benner, A and Ramaswami, M and Duff, MO and Liu, YW and Sato, AH and Kim, JY and Baken, IJL and Mendes Silva, C and Bijl, TPL and van Rijswijk, J and Burger, JA and Cupo, A and Yasmeen, A and Phulera, S and Lee, WH and Randall, KN and Zhang, S and Corcoran, MM and Regadas, I and Sullivan, AC and Brown, DM and Bohl, JA and Greene, KM and Gao, H and Yates, NL and Sawant, S and Prins, JM and Kootstra, NA and Kaminsky, SM and Barin, B and Rahaman, F and Meller, M and Philiponis, V and Laufer, DS and Lombardo, A and Mwoga, L and Shotorbani, S and Holman, D and Koup, RA and Klasse, PJ and Karlsson Hedestam, GB and Tomaras, GD and van Gils, MJ and Montefiori, DC and McDermott, AB and Hyrien, O and Moore, JP and Wilson, IA and Ward, AB and Diemert, DJ and de Bree, GJ and Andrews, SF and Caskey, M and Sanders, RW},
title = {Precise targeting of HIV broadly neutralizing antibody precursors in humans.},
journal = {Science (New York, N.Y.)},
volume = {},
number = {},
pages = {eadv5572},
doi = {10.1126/science.adv5572},
pmid = {40373114},
issn = {1095-9203},
abstract = {A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01B, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, that target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.},
}

@article {pmid40373112,
year = {2025},
author = {Willis, JR and Prabhakaran, M and Muthui, M and Naidoo, A and Sincomb, T and Wu, W and Cottrell, CA and Landais, E and deCamp, AC and Keshavarzi, NR and Kalyuzhniy, O and Lee, JH and Murungi, LM and Ogonda, WA and Yates, NL and Corcoran, MM and Phulera, S and Musando, J and Tsai, A and Lemire, G and Sein, Y and Muteti, M and Alamuri, P and Bohl, JA and Holman, D and Himansu, S and Leav, B and Reuter, C and Lin, LA and Ding, B and He, C and Straus, WL and MacPhee, KJ and Regadas, I and Nyabundi, DV and Chirchir, R and Anzala, A and Kimotho, JN and Kibet, C and Greene, K and Gao, H and Beatman, E and Benson, K and Laddy, D and Brown, DM and Bronson, R and Baptiste, J and Gajjala, S and Rikhtegaran-Tehrani, Z and Benner, A and Ramaswami, M and Lu, D and Alavi, N and Amirzehni, S and Kubitz, M and Tingle, R and Georgeson, E and Phelps, N and Adachi, Y and Liguori, A and Flynn, C and McKenney, K and Zhou, X and Owuor, DC and Owuor, S and Kim, SY and Duff, M and Kim, JY and Gibson, G and Baboo, S and Diedrich, J and Schiffner, T and Shields, M and Matsoso, M and Santos, J and Syvertsen, K and Kennedy, A and Schroeter, M and Vekemans, J and Yates, J and Paulson, JC and Hyrien, O and McDermott, AB and Maenetje, P and Nyombayire, J and Karita, E and Ingabire, R and Edward, V and Muturi-Kioi, V and Maenza, J and Shapiro, AE and McElrath, MJ and Edupuganti, S and Taylor, BS and Diemert, D and Ozorowski, G and Koup, RA and Montefiori, D and Ward, AB and Hedestam, GK and Tomaras, G and Hunt, DJ and Muema, D and Sok, D and Laufer, DS and Andrews, SF and Nduati, EW and Schief, WR},
title = {Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.},
journal = {Science (New York, N.Y.)},
volume = {},
number = {},
pages = {eadr8382},
doi = {10.1126/science.adr8382},
pmid = {40373112},
issn = {1095-9203},
abstract = {A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States and IAVI-G003 in Rwanda and South Africa, we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI-G002). The vaccines were generally safe and well tolerated, except 18% of IAVI-G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM, and heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development. The results establish clinical proof of concept that heterologous boosting can advance bnAb-precursor maturation and demonstrate bnAb priming in Africa where the HIV burden is highest.},
}

@article {pmid40372917,
year = {2025},
author = {Alassaf, M and Madan, A and Ranganathan, S and Marschall, S and Wong, JJ and Goldberg, ZH and Brent, AE and Rajan, A},
title = {Adipocyte metabolic state regulates glial phagocytic function.},
journal = {Cell reports},
volume = {44},
number = {5},
pages = {115704},
doi = {10.1016/j.celrep.2025.115704},
pmid = {40372917},
issn = {2211-1247},
abstract = {Excess dietary sugar profoundly impacts organismal metabolism and health, yet it remains unclear how metabolic adaptations in adipose tissue influence other organs, including the brain. Here, we show that a high-sugar diet (HSD) in Drosophila reduces adipocyte glycolysis and mitochondrial pyruvate uptake, shifting metabolism toward fatty acid oxidation and ketogenesis. These metabolic changes trigger mitochondrial oxidation and elevate antioxidant responses. Adipocyte-specific manipulations of glycolysis, lipid metabolism, or mitochondrial dynamics non-autonomously modulate Draper expression in brain ensheathing glia, key cells responsible for neuronal debris clearance. Adipocyte-derived ApoB-containing lipoproteins maintain basal Draper levels in glia via LpR1, critical for effective glial phagocytic activity. Accordingly, reducing ApoB or LpR1 impairs glial clearance of degenerating neuronal debris after injury. Collectively, our findings demonstrate that dietary sugar-induced shifts in adipocyte metabolism substantially influence brain health by modulating glial phagocytosis, identifying adipocyte-derived ApoB lipoproteins as essential systemic mediators linking metabolic state with neuroprotective functions.},
}

@article {pmid40372253,
year = {2025},
author = {Elkholi, IE and Robert, A and Malouf, C and Wu, JL and Kuasne, H and Drapela, S and Macleod, G and Hébert, S and Pacis, A and Calderon, V and Kleinman, CL and Gomes, AP and Alvarez, JV and Aguirre-Ghiso, JA and Park, M and Angers, S and Côté, JF},
title = {Targeting the Dependence on PIK3C3-mTORC1 Signaling in Dormancy-Prone Breast Cancer Cells Blunts Metastasis Initiation.},
journal = {Cancer research},
volume = {},
number = {},
pages = {OF1-OF20},
doi = {10.1158/0008-5472.CAN-23-2654},
pmid = {40372253},
issn = {1538-7445},
support = {25244//Cancer Research Society (CRS)/ ; FDN-143281//Canadian Institutes of Health Research (CIHR)/ ; PJT-156086//Canadian Institutes of Health Research (CIHR)/ ; //Canadian Cancer Society (CCS)/ ; R01CA292658//National Cancer Institute (NCI)/ ; CA109182//National Cancer Institute (NCI)/ ; CA253977//National Cancer Institute (NCI)/ ; CA284085//National Cancer Institute (NCI)/ ; P30CA013330//National Cancer Institute (NCI)/ ; RSG-22-164-01-MM//American Cancer Society (ACS)/ ; //Fonds de Recherche du Québec - Santé (FRQS)/ ; //Quebec Breast Cancer Foundation/ ; //Compute Canada (Calcul Canada)/ ; //Calcul Quebec/ ; //Fonds de Recherche du Québec - Santé (FRQS)/ ; //Institut de Recherche Clinique De Montréal Foundation/ ; //Peter Quinlan Postdoctoral research Fellowship in Oncology/ ; //Miles for Moffit/ ; //The Mark Foundation Aspire Program/ ; //The Gurwin Foundation/ ; //U.S. Department of Defense (DOD)/ ; //Melanoma Research Alliance (MRA)/ ; //Rose C. Falkenstein Chair in Cancer Research/ ; //Samuel Waxman Cancer Research Foundation (SWCRF)/ ; //Diane and Sal Guerrera Chair in Cancer Genetics/ ; //Canada Research Chairs (Chaires de recherche du Canada)/ ; },
abstract = {Halting breast cancer metastatic relapse following primary tumor removal remains challenging due to a lack of specific vulnerabilities to target during the clinical dormancy phase. To identify such vulnerabilities, we conducted genome-wide CRISPR screens on two breast cancer cell lines with distinct dormancy properties: 4T1 (short-term dormancy) and 4T07 (prolonged dormancy). The dormancy-prone 4T07 cells displayed a unique dependency on class III PI3K (PIK3C3). Unexpectedly, 4T07 cells exhibited higher mechanistic target of rapamycin complex 1 (mTORC1) activity than 4T1 cells due to lysosome-dependent signaling occurring at the cell periphery. Pharmacologic inhibition of PIK3C3 suppressed this phenotype in the 4T1-4T07 models as well as in human breast cancer cell lines and a breast cancer patient-derived xenograft. Furthermore, inhibiting PIK3C3 selectively reduced metastasis burden in the 4T07 model and eliminated dormant cells in a HER2-dependent murine breast cancer dormancy model. These findings suggest that PIK3C3-peripheral lysosomal signaling to mTORC1 may represent a targetable axis for preventing dormant cancer cell-initiated metastasis in patients with breast cancer. Significance: Dormancy-prone breast cancer cells depend on the class III PI3K to mediate peripheral lysosomal positioning and mTORC1 hyperactivity, which can be targeted to blunt breast cancer metastasis.},
}

@article {pmid40372237,
year = {2025},
author = {Hullar, MA and Kahsai, OJ and Hill, C and Levy, L and Malen, RC and Curtis, KR and Ammar, H and Sillah, A and Reedy, AM and Lampe, JW and Ogino, S and Potter, JD and Newcomb, PA and Phipps, AI},
title = {Highly sensitive DNA testing of Fusobacterium nucleatum (Fn) in colorectal tumors.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-1020},
pmid = {40372237},
issn = {1538-7755},
abstract = {BACKGROUND: Fusobacterium nucleatum (Fn) has been associated with risk of colorectal cancer (CRC), poorer CRC survival, and tumor attributes. Accurate and sensitive detection of Fn in tumor tissue is critical to evaluating their role in CRC.

METHODS: We developed a droplet digital PCR (ddPCR) assay for detecting Fn, using the transcription termination/anti-termination gene (nusG) normalized for host tissue (solute carrier organic anion transporter family member 2A1, SLCO2A1). We assayed Fn(nusG), in matched tumor and normal tissue, for 613 participants in the Seattle site of the Colon Cancer Family Registry (SCCFR). We used logistic regression to determine the odds of Fn enrichment in tumor tissue according to tumor site and stage, adjusting for age, sex, and body mass index.

RESULTS: The limit of quantitation for Fn(nusG) was 4.1 copies/10 ng host tissue. Detection of Fn was quenched and more poorly detected at low levels in FFPE tissues using qPCR. There was low agreement between qPCR and ddPCR (Cohen's kappa = 0.46). Fn(nusG) was detected in tumor (21%) and normal (10%) tissue and enriched in 19% of tumors. Individuals with tumors enriched in Fn were more likely to be female (59% vs. 48%, respectively, p=0.04) with proximal colon tumors (57% vs 43%, p=0.026). In multivariable-adjusted analyses, proximal colon tumors were significantly associated with Fn enrichment (odds ratio vs. rectal tumors: 1.86; 95% CI: 1.11 to 3.24).

CONCLUSIONS: We established a sensitive and specific method to detect Fn enrichment in human tissues.

IMPACT: ddPCR enhanced detection of Fn(nusG) for studies targeting tumor-associated bacteria.},
}

@article {pmid40371912,
year = {2025},
author = {Wesselink, E and Thomas, CE and Takashima, Y and Mizuno, H and Buchanan, DD and Qu, C and Hsu, L and Dias Costa, A and Ugai, S and Zhong, Y and Huyghe, JR and Thomas, S and Gallinger, S and Grant, RC and Le Marchand, L and Masugi, Y and van Duijnhoven, FJ and Ugai, T and Ogino, S and Nowak, JA and Peters, U and Phipps, AI},
title = {Associations between calcium intake and T cell infiltration in colorectal tumours.},
journal = {Cancer prevention research (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1158/1940-6207.CAPR-25-0023},
pmid = {40371912},
issn = {1940-6215},
abstract = {Higher T cell infiltration in colorectal tumours has been associated with better prognosis. Evidence indicates that calcium signalling is essential for T cells functioning. However, as it is unknown whether calcium intake influences T cell infiltration, we investigated the association of calcium intake with T cell subsets in the tumour microenvironment of colorectal cancer. In total, 943 participants from three cohort studies, for which data on tumour infiltrating T cells and calcium intake was available, were included for these analyses. Immune cell infiltration was quantified by digital image analyses with machine learning algorithms using a customized 9-plex multispectral immunofluorescence assay (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, DAPI). Associations between pre-diagnostic calcium intake and densities of non-overlapping subsets of epithelial and stromal tissue area T cells were assessed using multivariable binary or ordinal logistic regression analyses. A higher dietary calcium intake was positively associated with CD3+CD4-CD8- double negative T cells density in the epithelial (OR 1.57; 95% CI 1.13-2.24) and stromal (OR 1.24; 95%CI 1.06-1.45) tumour tissue area. No other statistically significant associations were observed after correcting for multiple testing. In conclusion, dietary calcium intake was associated with a higher density of CD4-CD8- double negative T cells in the epithelial and stromal tumour tissue area, but not with infiltration of CD4+ or CD8+ T cells. More research is needed to further unravel the role of calcium in tumour immune profiles and associations with clinical outcomes. Our findings offer a promising basis for further research.},
}

@article {pmid40369385,
year = {2025},
author = {Manohar, PM and Peterson, LM and Jenkins, IC and Wu, QV and Kurland, BF and Novakova-Jiresova, A and Muzi, M and Chen, DL and Specht, JM and Dintzis, S and Kinahan, PE and Mankoff, DA and Linden, HM},
title = {[18 F]-Fluoroestradiol PET (FES-PET) and [18 F] Flurodeoxyglucose PET (FDG-PET) Imaging May Aid in Managing Therapy in Patients with Metastatic Lobular Breast Cancer.},
journal = {Molecular imaging and biology},
volume = {},
number = {},
pages = {},
pmid = {40369385},
issn = {1860-2002},
abstract = {AIM: This study examines the combination of FES-PET and FDG-PET as complementary imaging for detection of metastatic ILC.

METHODS: We retrospectively evaluated FES and FDG uptake in patients with metastatic ILC from an estrogen receptor (ER) positive primary tumor. We classified lesions into three categories (FES high/FDG low, FES high/FDG high, FES low/FDG low) using SUVmax cut-off values of 1.5 for FES and 5.0 for FDG. Qualitative evaluation included examination of the difference in the extent of disease between FES and FDG.

RESULTS: Of the 38 patients, 82% had FES uptake in all tumor sites identified by FDG, with 18% lacking FES uptake in at least one lesion. Mean (range) SUVmax for FES and FDG was 4.0 (0.67-10.6) and 4.6 (1.3-12.5), respectively. The majority of ILC patients (25/38), had lesions with FES high/FDG low uptake, consistent with the strongly ER + indolent nature of ILC. Patients with disease classified as FES high/FDG low had longer median overall survival (OS) (3.2 years) and progression-free survival (PFS) (1.5 years) than FES high/FDG high (OS = 2.1 years and PFS = 0.46 years). The median overall OS for all patients was 3.0 years (95% CI 2.5, 4.8) and PFS of 1.3 years (95% CI 0.6, 2.5). 8 patients (21%) had qualitatively more extensive disease by FES-PET.

CONCLUSIONS: Our findings suggest that both FES-PET and FDG-PET can identify metastatic ILC and be useful in detecting the pattern and extent of disease. The imaging combination provides additional information for prognosis and clinical decision making, balancing suitability for endocrine therapy and aggressiveness/indolence of disease.},
}

@article {pmid40368142,
year = {2025},
author = {Friedman, RK and Heath, AS and Huffman, JE and Baker, JT and Hasbani, NR and Gagliano Taliun, SA and Chen, MH and Howard, TE and Lewis, JP and Pankratz, N and Patil, S and Reiner, AP and Thibord, F and Yanek, LR and Yao, J and Chen, HH and Curran, JE and Faraday, N and Guo, X and Wheeler, MM and Ryan, KA and Zhou, X and Cho, K and Almasy, L and Auer, PL and Becker, LC and Wilson, PWF and Boerwinkle, E and O'Connell, JR and Rich, SS and Samuels, DC and , and , and , and Blangero, J and Fornage, M and Kooperberg, C and Mathias, RA and Mitchell, BD and Rotter, JI and Johnson, AD and Smith, NL and Coban-Akdemir, ZH and Below, JE and Morrison, AC and Johnsen, JM and de Vries, PS},
title = {Genetic study of von Willebrand factor antigen levels ≤ 50 IU/dL identifies variants associated with increased risk of VWD and bleeding.},
journal = {Journal of thrombosis and haemostasis : JTH},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtha.2025.04.029},
pmid = {40368142},
issn = {1538-7836},
abstract = {BACKGROUND: von Willebrand disease (VWD) is a common inherited bleeding disorder caused by low levels or activity of circulating von Willebrand factor (VWF). Genetic susceptibility to VWF antigen (VWF:Ag) below normal (≤50 IU/dL) in the general population is underexplored.

METHODS: To identify genetic variants influencing VWF:Ag levels ≤50 IU/dL, we performed a genome-wide association study in 926 cases with VWF:Ag levels ≤50 IU/dL and 12,846 controls from 7 studies from the TOPMed program. We then examined whether genome-wide significant findings were also associated with clinical diagnosis of VWD in 5 biobanks with 708 VWD cases and 1,286,069 controls, and with 6 bleeding and thrombotic disorders in FinnGen.

RESULTS: Variants at two loci were associated (P<5×10[-9]) with VWF:Ag levels ≤50 IU/dL: ABO and VWF. The VWF index variant, p.Tyr1584Cys, is a rare (0.22%) missense variant with odds ratio (OR) of 78.58, while the ABO index variant is a common intronic variant with a smaller effect (OR=2.52). Notably, both VWF (OR=7.16) and ABO (OR=1.57) variants were also associated (P<0.025) with diagnosed VWD. Among p.Tyr1584Cys heterozygotes, the penetrance of VWF:Ag levels ≤50 IU/dL was 24.2% and the penetrance of diagnosed VWD was 0.3%. p.Tyr1584Cys was associated (P<0.0042) with increased odds of heavy menstrual bleeding (OR=1.27), iron deficiency anemia (OR=1.55), and intrapartum hemorrhage (OR=2.20), but decreased odds of deep vein thrombosis (OR=0.54).

CONCLUSIONS: While p.Tyr1584Cys currently has conflicting interpretations of pathogenicity, our results suggest that it is a low penetrance pathogenic variant that contributes to VWF:Ag levels ≤50 IU/dL, bleeding, and VWD.},
}

@article {pmid40368025,
year = {2025},
author = {Park, ER and Kirchhoff, AC and Mitchell, CO and Durieux, N and Foor, A and Kuhlthau, K and Perez, GK and Ards, L and Alston, S and Armstrong, GT and Vaca Lopez, PL and McDonald, A and Nolan, VG and Levy, DE and Leisenring, WM and Galbraith, AA and Nathan, PC and Vukadinovich, C and Cooper, CL and Donelan, K},
title = {Assessing the effect of virtual navigation interventions to improve health insurance literacy and decrease financial burden in cancer survivors: The HINT II study protocol.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {107952},
doi = {10.1016/j.cct.2025.107952},
pmid = {40368025},
issn = {1559-2030},
abstract = {BACKGROUND: Childhood cancer survivors often face high healthcare costs to monitor and manage new or lasting effects of their treatment. Enhancing survivors' health insurance literacy (HIL) - the knowledge, ability, and confidence in enrolling in and navigating health plans - is vital for minimizing financial burden. Few studies have assessed the effect of a health insurance navigation program on improving HIL among survivors. We present the protocol for an ongoing randomized controlled trial (RCT) assessing the effectiveness of two health insurance navigation programs (HINT-S and HINT-A) on improving HIL, financial burden, out-of-pocket costs, and healthcare utilization for adult survivors of childhood cancer.

METHODS: This three-arm RCT assesses the effectiveness of two digitally delivered health insurance navigation interventions and enhanced usual care (EUC) on improving HIL at six and 12 months in a national cohort of childhood cancer survivors. While HINT-S is composed of five synchronous, navigator-led sessions, HINT-A is an asynchronous, prerecorded set of five videos. EUC participants receive only a health insurance informational booklet. Financial burden, medical out-of-pocket costs, and healthcare utilization (receipt of preventive care, recommended screenings/vaccinations, and acute care) are assessed at 12 months. Moderators to the interventions' effectiveness will be investigated, as well as implementation outcomes (feasibility, acceptability, appropriateness, fidelity, and cost-effectiveness).

CONCLUSIONS: There is a strong need for interventions to improve cancer survivors' HIL, helping them navigate the complexity of the U.S. healthcare system. This trial will elucidate the potential effectiveness and implementation of health insurance navigation programs that may benefit many cancer survivors.

TRIAL REGISTRATION: NCT05527392.},
}

@article {pmid40367160,
year = {2025},
author = {Stepanov, I and Gottshall, NR and Ahmadianyazdi, A and Sinha, D and Lockhart, EJ and Nguyen, TNH and Hassan, S and Horowitz, LF and Yeung, RS and Gujral, TS and Folch, A},
title = {Low-cost robotic manipulation of live microtissues for cancer drug testing.},
journal = {Science advances},
volume = {11},
number = {20},
pages = {eads1631},
pmid = {40367160},
issn = {2375-2548},
mesh = {Humans ; *Robotics/economics/instrumentation ; Drug Screening Assays, Antitumor/methods/economics/instrumentation ; *Antineoplastic Agents/pharmacology ; *Neoplasms/drug therapy/pathology ; Lab-On-A-Chip Devices ; },
abstract = {The scarcity of human biopsies available for drug testing is a paramount challenge for developing therapeutics, disease models, and personalized treatments. Microtechnologies that combine the microscale manipulation of tissues and fluids offer the exciting possibility of miniaturizing both disease models and drug testing workflows on scarce human biopsies. Unfortunately, these technologies presently require microfluidic devices or robotic dispensers that are not widely accessible. We have rapidly prototyped an inexpensive platform based on an off-the-shelf robot that can microfluidically manipulate live microtissues into/out of culture plates without using complicated accessories such as microscopes or pneumatic controllers. The robot integrates complex functions with a simple, cost-effective, and compact construction, allowing placement inside a tissue culture hood for sterile workflows. We demonstrated a proof-of-concept cancer drug evaluation workflow of potential clinical utility using patient tumor biopsies with multiple drugs on 384-well plates. Our user-friendly, low-cost platform promises to make drug testing of microtissues broadly accessible to pharmaceutical, clinical, and biological laboratories.},
}

Humans
*Robotics/economics/instrumentation
Drug Screening Assays, Antitumor/methods/economics/instrumentation
*Antineoplastic Agents/pharmacology
*Neoplasms/drug therapy/pathology
Lab-On-A-Chip Devices

@article {pmid40366394,
year = {2025},
author = {Hardy, S and Chhan, CB and Davis, AR and McGuire, AT},
title = {Viral Entry.},
journal = {Current topics in microbiology and immunology},
volume = {},
number = {},
pages = {},
doi = {10.1007/82_2025_300},
pmid = {40366394},
issn = {0070-217X},
abstract = {Epstein-Barr virus chiefly infects B cells and epithelial cells but is capable of infecting other cell types in the human host. Host cell entry is a complex process mediated by several viral glycoproteins that define tropism and mediate membrane fusion. This chapter will review what is known about the function of viral glycoproteins in the entry process, explore the nature of interactions between viral glycoproteins and host cell receptors, and highlight gaps in knowledge about the entry process that remain to be filled.},
}

@article {pmid40365909,
year = {2025},
author = {Levy, JA and Kazemian, E and Ramin, C and Loroña, NC and Nadri, M and Gasho, JO and Silos, KD and Nikolova, AP and Dey, D and Siegel, EM and Gigic, B and Hardikar, S and Byrd, DA and Toriola, AT and Ose, J and Li, CI and Shibata, D and Ulrich, CM and Tamarappoo, BK and Atkins, KM and Figueiredo, JC},
title = {Subclinical Atherosclerosis and Cardiovascular Events Among Patients With Colorectal Cancer.},
journal = {Cancer medicine},
volume = {14},
number = {10},
pages = {e70938},
pmid = {40365909},
issn = {2045-7634},
support = {P30CA042014//National Cancer Institute of the National Institutes of Health/ ; R01CA160684//National Cancer Institute of the National Institutes of Health/ ; R01CA189184//National Cancer Institute of the National Institutes of Health/ ; R01CA207371//National Cancer Institute of the National Institutes of Health/ ; R01CA215134//National Cancer Institute of the National Institutes of Health/ ; R01CA254108//National Cancer Institute of the National Institutes of Health/ ; R03CA270473//National Cancer Institute of the National Institutes of Health/ ; U01CA206110//National Cancer Institute of the National Institutes of Health/ ; U01CA246659//National Cancer Institute of the National Institutes of Health/ ; },
mesh = {Humans ; Male ; Female ; *Colorectal Neoplasms/complications/epidemiology/therapy ; Middle Aged ; Aged ; Prospective Studies ; *Atherosclerosis/epidemiology/etiology ; *Cardiovascular Diseases/epidemiology/etiology ; Risk Factors ; Positron Emission Tomography Computed Tomography ; Coronary Vessels/diagnostic imaging ; },
abstract = {BACKGROUND: Prior studies have documented that patients with colorectal cancer (CRC) are at an increased risk of cardiovascular disease (CVD).

OBJECTIVES: To examine coronary artery calcium (CAC) as a marker of subclinical atherosclerosis and its association with major adverse cardiovascular events (MACE) in patients with CRC across the cancer treatment trajectory.

METHODS: Adults with newly diagnosed CRC were enrolled in the prospective ColoCare study from 2017 to 2024. CAC was measured from routine diagnostic computed tomography (CT) and positron emission tomography-CT scans at CRC diagnosis until 5 years post-diagnosis. Atherosclerosis was defined as the presence of CAC. We used multivariable-adjusted Fine and Gray models to assess the association between CAC and MACE risk, accounting for competing risks.

RESULTS: Among 300 CRC patients, the most common CVD risk factors at cancer diagnosis were hypertension (37%), hyperlipidemia (24%), and diabetes (14%). During follow-up (median = 5.3 years), 75 (25%) individuals experienced MACE: stroke (3%), new/worsening HF (9%), HF exacerbation requiring hospitalization (2%), coronary revascularization (3%), and death (19%). Among individuals with imaging at baseline (n = 101), 37 (36.6%) had CAC, and statins were not prescribed in 11 (55.0%) patients with moderate/high CAC. For those with serial imaging (n = 61), 31.1% showed worsening CAC and 3% developed new CAC. Baseline CAC conferred a higher risk of MACE (HR = 4.79; 95% CI: 1.05-21.75, p = 0.04) after accounting for cancer-related deaths as a competing risk.

CONCLUSIONS: Subclinical atherosclerosis and MACE are common among patients with CRC. Integrating CAC from routine cancer imaging can identify patients who may benefit from cardio-preventive treatment.},
}

Humans
Male
Female
*Colorectal Neoplasms/complications/epidemiology/therapy
Middle Aged
Aged
Prospective Studies
*Atherosclerosis/epidemiology/etiology
*Cardiovascular Diseases/epidemiology/etiology
Risk Factors
Positron Emission Tomography Computed Tomography
Coronary Vessels/diagnostic imaging

@article {pmid40365115,
year = {2025},
author = {Restar, AJ and Lucas, R and Nfn, S and Alpert, AB and Phipps, A and Wang, G and Operario, D and Radix, A and van der Merwe, LA and Lindström, S and Everhart, A and Gamarel, KE and Streed, CG},
title = {Underinvested, Under-Referred, and Underserved: Applying a Gender Equity Continuum Framework in Cancer Control Continuum Programs and Policies to Expand to Transgender and Nonbinary Populations.},
journal = {JCO oncology advances},
volume = {2},
number = {1},
pages = {e2400023},
pmid = {40365115},
issn = {2994-9750},
abstract = {Gender-inclusive and gender-specific approaches are critically needed in cancer control continuum services to recognize and meet the needs of transgender and nonbinary (trans) populations. Current research, programs, and policies largely cater to cisgender populations and subscribe to a binary, gendered cisnormative ideology, both within health care systems and insurance policies, leaving trans people's cancer prevention and treatment needs neglected. Such disparities can be attributed to the significant gap in funding and research to address trans cancer prevention and treatment. We discuss the research, program, and policy implications of cisnormative practices and provide recommendations for promoting gender-inclusive and specific services across the cancer control continuum with the goal of eliminating cancer disparities and improving cancer outcomes for people of all gender groups, including trans populations.},
}

@article {pmid40364978,
year = {2025},
author = {Alavattam, KG and Dickson, BM and Hirano, R and Dell, R and Tsukiyama, T},
title = {ChIP-seq Data Processing and Relative and Quantitative Signal Normalization for Saccharomyces cerevisiae.},
journal = {Bio-protocol},
volume = {15},
number = {9},
pages = {e5299},
pmid = {40364978},
issn = {2331-8325},
abstract = {Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) is a widely used technique for genome-wide analyses of protein-DNA interactions. This protocol provides a guide to ChIP-seq data processing in Saccharomyces cerevisiae, with a focus on signal normalization to address data biases and enable meaningful comparisons within and between samples. Designed for researchers with minimal bioinformatics experience, it includes practical overviews and refers to scripting examples for key tasks, such as configuring computational environments, trimming and aligning reads, processing alignments, and visualizing signals. This protocol employs the sans-spike-in method for quantitative ChIP-seq (siQ-ChIP) and normalized coverage for absolute and relative comparisons of ChIP-seq data, respectively. While spike-in normalization, which is semiquantitative, is addressed for context, siQ-ChIP and normalized coverage are recommended as mathematically rigorous and reliable alternatives. Key features • ChIP-seq data processing workflow for Linux and macOS integrating data acquisition, trimming, alignment, processing, and multiple forms of signal computation, with a focus on reproducibility. • ChIP-seq signal generation using siQ-ChIP to quantify absolute IP efficiency-providing a rigorous alternative to spike-in normalization-and normalized coverage for relative comparisons. • Broad applicability demonstrated with Saccharomyces cerevisiae (experimental) and Schizosaccharomyces pombe (spike-in) data but suitable for ChIP-seq in any species. • In-depth notes and troubleshooting guide users through setup challenges and key concepts in basic bioinformatics, data processing, and signal computation. Graphical overview Flowchart depicting ChIP-seq data processing steps covered in this protocol.},
}

@article {pmid40364850,
year = {2025},
author = {Rubinstein, S and Mohsin, A and Banerjee, R and Ma, W and Mishra, S and Kwok, M and Yang, P and Warner, JL and Cowan, AJ},
title = {Summarizing clinical evidence utilizing large language models for cancer treatments: a blinded comparative analysis.},
journal = {Frontiers in digital health},
volume = {7},
number = {},
pages = {1569554},
pmid = {40364850},
issn = {2673-253X},
abstract = {BACKGROUND: Concise synopses of clinical evidence support treatment decision-making but are time-consuming to curate. Large language models (LLMs) offer potential but they may provide inaccurate information. We objectively assessed the abilities of four commercially available LLMs to generate synopses for six treatment regimens in multiple myeloma and amyloid light chain (AL) amyloidosis.

METHODS: We compared the performance of four LLMs: Claude 3.5, ChatGPT 4.0; Gemini 1.0 and Llama-3.1. Each LLM was prompted to write synopses for six regimens. Two hematologists independently assessed accuracy, completeness, relevance, clarity, coherence, and hallucinations using Likert scales. Mean scores with 95% confidence intervals (CI) were calculated across all domains and inter-rater reliability was evaluated using Cohen's quadratic weighted kappa.

RESULTS: Claude demonstrated the highest performance in all domains, outperforming the other LLMs in accuracy: mean Likert score 3.92 (95% CI 3.54-4.29); ChatGPT 3.25 (2.76-3.74); Gemini 3.17 (2.54-3.80); Llama 1.92 (1.41-2.43);completeness: mean Likert score 4.00 (3.66-4.34); GPT 2.58 (2.02-3.15); Gemini 2.58 (2.02-3.15); Llama 1.67 (1.39-1.95); and extentofhallucinations: mean Likert score 4.00 (4.00-4.00); ChatGPT 2.75 (2.06-3.44); Gemini 3.25 (2.65-3.85); Llama 1.92 (1.26-2.57). Llama performed considerably poorer across all the studied domains. ChatGPT and Gemini had intermediate performance. Notably, none of the LLMs registered perfect accuracy, completeness, or relevance.

CONCLUSION: Claude performed at a consistently higher level than other LLMs, all tested LLMs required careful editing from a domain expert to become usable. More time will be needed to determine the suitability of LLMsto independently generate clinical synopses.},
}

@article {pmid40364846,
year = {2025},
author = {Battisti, P and Ykema, MR and Kasal, DN and Jennewein, MF and Beaver, S and Weight, AE and Hanson, D and Singh, J and Bakken, J and Cross, N and Fusco, P and Archer, J and Reed, S and Gerhardt, A and Julander, JG and Casper, C and Voigt, EA},
title = {A bivalent self-amplifying RNA vaccine against yellow fever and Zika viruses.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1569454},
pmid = {40364846},
issn = {1664-3224},
mesh = {Animals ; *Zika Virus/immunology ; *Zika Virus Infection/prevention & control/immunology ; Antibodies, Neutralizing/immunology/blood ; Mice ; *Yellow fever virus/immunology ; Antibodies, Viral/immunology/blood ; *Yellow Fever/prevention & control/immunology ; Mice, Inbred C57BL ; Cricetinae ; *Viral Vaccines/immunology ; Female ; Mesocricetus ; CD8-Positive T-Lymphocytes/immunology ; *Yellow Fever Vaccine/immunology ; Immunogenicity, Vaccine ; },
abstract = {INTRODUCTION: Yellow fever (YFV) and Zika (ZIKV) viruses cause significant morbidity and mortality, despite the existence of an approved YFV vaccine and the development of multiple ZIKV vaccine candidates to date. New technologies may improve access to vaccines against these pathogens. We previously described a nanostructured lipid carrier (NLC)-delivered self-amplifying RNA (saRNA) vaccine platform with excellent thermostability and immunogenicity, appropriate for prevention of tropical infectious diseases.

METHODS: YFV and ZIKV prM-E antigen-expressing saRNA constructs were created using a TC-83 strain Venezuelan equine encephalitis virus-based replicon and complexed with NLC by simple mixing. Monovalent and bivalent vaccine formulations were injected intramuscularly into C57BL/6 mice and Syrian golden hamsters, and the magnitude, durability, and protective efficacy of the resulting immune responses were then characterized.

RESULTS AND DISCUSSION: Monovalent vaccines established durable neutralizing antibody responses to their respective flaviviral targets, with little evidence of cross-neutralization. Both vaccines additionally elicited robust antigen-reactive CD4[+] and CD8[+] T cell populations. Notably, humoral responses to YFV saRNA-NLC vaccination were comparable to those in YF-17D-vaccinated animals. Bivalent formulations established humoral and cellular responses against both viral targets, commensurate to those established by monovalent vaccines, without evidence of saRNA interference or immune competition. Finally, both monovalent and bivalent vaccines completely protected mice and hamsters against lethal ZIKV and YFV challenge. We present a bivalent saRNA-NLC vaccine against YFV and ZIKV capable of inducing robust and efficacious neutralizing antibody and cellular immune responses against both viruses. These data support the development of other multivalent saRNA-based vaccines against infectious diseases.},
}

Animals
*Zika Virus/immunology
*Zika Virus Infection/prevention & control/immunology
Antibodies, Neutralizing/immunology/blood
Mice
*Yellow fever virus/immunology
Antibodies, Viral/immunology/blood
*Yellow Fever/prevention & control/immunology
Mice, Inbred C57BL
Cricetinae
*Viral Vaccines/immunology
Female
Mesocricetus
CD8-Positive T-Lymphocytes/immunology
*Yellow Fever Vaccine/immunology
Immunogenicity, Vaccine

@article {pmid40360879,
year = {2025},
author = {Wang'ondu, RW and Ashcraft, E and Chang, TC and Roberts, KG and Brady, SW and Fan, Y and Evans, W and Relling, MV and Crews, KR and Yang, J and Yang, W and Pounds, S and Wu, G and Devidas, M and Maloney, K and Mattano, L and Schore, RJ and Angiolillo, A and Larsen, E and Salzer, W and Burke, MJ and Loh, ML and Jeha, S and Pui, CH and Inaba, H and Cheng, C and Mullighan, CG},
title = {Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {40360879},
issn = {1476-5551},
support = {P30 CA021765 and R35 CA197695//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; U10 CA98543, U10 CA180886, U10 CA98413, U10 CA180899, U24 CA114766, U24-CA196173//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; American Society of Hematology Minority Hematology Fellow award//American Society of Hematology (ASH)/ ; },
abstract = {Genomic alterations of IKZF1 are common and associated with adverse clinical features in B-progenitor acute lymphoblastic leukemia (B-ALL). The relationship between the type of IKZF1 alteration, B-ALL genomic subtype and outcome are incompletely understood. B-ALL subtype and genomic alterations were determined using transcriptome and genomic sequencing, and SNP microarray analysis in 688 pediatric patients with B-ALL in the St. Jude Total Therapy XV and 16 studies. IKZF1 alterations were identified in 115 (16.7%) patients, most commonly in BCR::ABL1 (78%) and CRLF2-rearranged, BCR::ABL1-like B-ALL (70%). These alterations were associated with 5-year cumulative incidence of relapse (CIR) of 14.8 ± 3.3% compared to 5.0 ± 0.9% for patients without any IKZF1 alteration (P < 0.0001). In separate multivariable analyses adjusting for genetic subtype groups and other factors, IKZF1 deletions of exons 4-7 (P = 0.0002), genomic IKZF1[plus] with any IKZF1 deletion (P = 0.006) or with focal IKZF1 deletion (P = 0.0007), and unfavorable genomic subtypes (P < 0.005) were independently adverse prognostic factors. Associations of genomic IKZF1[plus] and exon 4-7 deletions with adverse outcomes were confirmed in an independent cohort. The type of IKZF1 alteration, together with the subtype, are informative for risk stratification and to predict response in patients with B-ALL.},
}

@article {pmid40359708,
year = {2025},
author = {Gouda, MA and Voss, MH and Tawbi, H and Gordon, M and Tykodi, SS and Lam, ET and Vaishampayan, U and Tannir, NM and Chaves, J and Nikolinakos, P and Fan, A and Lee, R and McDermott, D and Shapiro, GI and Gandhi, L and Bhatia, S and Katragadda, V and Meric-Bernstam, F},
title = {A phase I/II study of the safety and efficacy of telaglenastat (CB-839) in combination with nivolumab in patients with metastatic melanoma, renal cell carcinoma, and non-small-cell lung cancer.},
journal = {ESMO open},
volume = {10},
number = {5},
pages = {104536},
doi = {10.1016/j.esmoop.2025.104536},
pmid = {40359708},
issn = {2059-7029},
abstract = {BACKGROUND: Telaglenastat (CB-839) is a glutaminase 1 inhibitor that targets the dysregulation in glutamine metabolism in cancer cells and the tumor microenvironment. Preclinical data suggested that the combination of telaglenastat with programmed cell death protein 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) antibodies can lead to enhanced immune response against cancer.

PATIENTS AND METHODS: We designed a phase I/II trial to investigate the safety and efficacy of telaglenastat combined with nivolumab in patients with advanced solid tumors. Dose escalation was carried out using a 3 + 3 design with two dose levels for telaglenastat (600 mg and 800 mg twice daily). Nivolumab was given at a fixed dose of 240 mg by intravenous infusion on days 1 and 15 of a 28-day cycle in all patients. Expansion in phase II was planned using Simon's two-stage design in disease- and prior therapy-specific cohorts.

RESULTS: We included a total of 118 patients across different cohorts. The most frequently reported adverse events were fatigue (42.4%; n = 50), nausea (39%; n = 46), and photophobia (32.2%; n = 38). In the response-assessable analysis set (including 107 patients in dose expansion and recommended phase II dose of dose escalation), the overall response rate (ORR) was 8.4% (n = 9). The ORR was 24% in 25 patients with clear-cell renal cell carcinoma (ccRCC) who were checkpoint inhibitor-naïve, 5.9% in 17 patients with ccRCC after nivolumab, 0% in 9 patients with ccRCC after other prior anti-PD-1/PD-L1, 5.4% in 37 patients with melanoma after anti-PD-1/PD-L1, and 0% in 19 patients with non-small-cell lung cancer after anti-PD-1/PD-L1.

CONCLUSIONS: Telaglenastat in combination with nivolumab was generally well tolerated. The combination did not show a pattern of efficacy across different study cohorts.},
}

@article {pmid40359110,
year = {2025},
author = {Gen, R and Addetia, A and Asarnow, D and Park, YJ and Quispe, J and Chan, MC and Brown, JT and Lee, J and Campbell, MG and Lapointe, CP and Veesler, D},
title = {SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals.},
journal = {Cell reports},
volume = {44},
number = {5},
pages = {115696},
doi = {10.1016/j.celrep.2025.115696},
pmid = {40359110},
issn = {2211-1247},
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats-natural reservoirs of sarbecoviruses with a markedly different innate immune system than humans. We reveal that nsp1 potently inhibits translation in Rhinolophus lepidus bat cells, which belong to the same genus as known sarbecovirus reservoir hosts. We determined a cryoelectron microscopy structure of nsp1 bound to the R. lepidus 40S ribosomal subunit, showing that it blocks the mRNA entry channel by targeting a highly conserved site among mammals. Accordingly, we found that nsp1 blocked protein translation in mammalian cells from several species, underscoring its broadly inhibitory activity and conserved role in numerous SARS-CoV-2 hosts. Our findings illuminate the arms race between coronaviruses and mammalian host immunity, providing a foundation for understanding the determinants of viral maintenance in bat hosts and spillover.},
}

@article {pmid40358923,
year = {2025},
author = {Yorke, AA and Schandorf, MT and Quaye, ANM and Twum, PT and Sengupta, B and Nkansah-Poku, K and Kplorfia, JA and Fagestrom, J},
title = {Empowering young minds through STEM education: Engaging high schoolers in Ghana through medical physics.},
journal = {Journal of applied clinical medical physics},
volume = {},
number = {},
pages = {e70126},
doi = {10.1002/acm2.70126},
pmid = {40358923},
issn = {1526-9914},
abstract = {PURPOSE: To promote diversity in Science, Technology, Engineering, and Mathematics (STEM), an educational presentation and hands-on session was organised to raise awareness of STEM career opportunities among high school girls to introduce the students to the field of medical physics.

MATERIALS AND METHODS: The study involved 65 first-year Senior High School girls, aged 13-16, pursuing general science in Accra, Ghana. This initiative, organised by the Girls Excellence Movement (GEM) in collaboration with a United States (US) institution, implemented the "heroes in radiation oncology" program, which included a relatable presentation and hands-on experience in simulation to treatment planning activities. The program's effectiveness was assessed through pre-and post-assessment surveys, and a thematic analysis of student feedback.

RESULTS: Participants' awareness of career fields showed an interest in traditional healthcare professions (92%) and engineering (73.8%), with minimal medical physics awareness (12.3%). Post-presentation survey showed a significant change in participants' perception of medical physics 87.3%. Thematic analysis revealed increased awareness, understanding, and interest, dispelled misconceptions about radiation safety, and highlighted the interdisciplinary nature and career opportunities. The presentation was successful in inspiring participants and expanding their perspectives on medical physics.

CONCLUSION: The program raised awareness of medical physics among participants, many of whom were previously unfamiliar with the field. Participants reported a newfound understanding of the interdisciplinary nature of medical physics, its connections to biology, mathematics, and engineering.This program can easily be reproduced in community and school outreaches.},
}

@article {pmid40358803,
year = {2025},
author = {Krisch, JM and Ermoian, RP and Indelicato, DJ and Lee, JY and Perentesis, JP and Perkins, SM and Laack, NN and Chang, JH and MacEwan, IJ and Wolden, SL and Wang, D and Yock, TI and Aridgides, PD},
title = {Outcomes following radiation therapy for embryonal tumor with multilayered rosettes (ETMR): results from the Pediatric Proton/Photon Consortium Registry (PPCR).},
journal = {Journal of neuro-oncology},
volume = {},
number = {},
pages = {},
pmid = {40358803},
issn = {1573-7373},
abstract = {PURPOSE: Embryonal tumor with multilayered rosettes (ETMR) is a rare pediatric CNS embryonal tumor with poor survival. The Pediatric Proton/Photon Consortium Registry (PPCR) was queried for outcomes data from prospectively consenting pediatric patients with ETMR treated with proton radiation therapy (RT).

METHODS: 20 patients (2013-2021) at 9 institutions had ETMR; 2 with prior RT were excluded from statistical analyses (PPCR ETMR, N = 18). Overall Survival (OS) and Event Free Survival (EFS) analyses were performed using the Kaplan-Meier method and log-rank values. Median follow-up was calculated using the reverse Kaplan-Meier method.

RESULTS: Median age at RT was 3.0 years (1.7-12.2); median follow-up was 55.5 months (2.6-119.4). 8 patients (44%) expired and 6 patients (33%) are surviving ≥ 55 months. 11 (61%) patients received systemic therapy with stem cell support. The majority (89%) had focal RT (median dose 54 Gy), while 2 patients received craniospinal irradiation (CSI, 30.6-36 Gy). 4-year OS and EFS were 59.6% and 54.2%, respectively. Local control (LC) at 4 years was 81%. No differences in OS or EFS were observed for receipt of systemic therapy with stem cell support (p = 0.361, p = 0.57), progression prior to RT (p = 0.127, p = 0.18), or surgery to RT ≥ 200 days (p = 0.35, p = 0.254). Symptomatic radionecrosis was not reported.

CONCLUSION: Focal proton RT provided effective local control as part of multimodality therapy for ETMR, with encouraging survival for this rare and often infant age tumor. Outcomes for CSI were limited to 2 patients treated upfront, and 1 patient receiving salvage CSI for disseminated relapse after focal RT who is surviving > 1 year.

TRIAL REGISTRATION: DFCI protocol 12-103, clinicaltrials.gov NCT01696721, date of registration 9/27/2012.},
}

@article {pmid40357548,
year = {2025},
author = {Blair, KM and Bohinc, DJ and Bane, KL and Warnock, M and Abuaita, B and Gura, C and Grinsztejn, E and Marshall, SH and Wilson, BM and Bonomo, RA and Tambralli, A and Knight, JS and O'Riordan, MX and Lawrence, DA and Stavrou, EX and Sandkvist, M},
title = {Acinetobacter Baumannii Secreted Protease CpaA Inhibits Factor XII-Mediated Bradykinin Generation and Neutrophil Activation.},
journal = {Circulation research},
volume = {},
number = {},
pages = {},
doi = {10.1161/CIRCRESAHA.124.324764},
pmid = {40357548},
issn = {1524-4571},
abstract = {BACKGROUND: FXII (coagulation factor XII) is best known for its roles in the contact and kallikrein-kinin pathways. FXII is converted to its active enzyme (FXIIa [activated factor XII]) by PKa (plasma kallikrein) or its unique ability to autoactivate on bacterial or other biologic surfaces. In vivo, FXIIa initiates the intrinsic coagulation pathway and promotes inflammation by reciprocal activation of prekallikrein, which cleaves HK (high-molecular-weight kininogen) to liberate bradykinin. CpaA (coagulation targeting metallo-endopeptidase of A baumannii) is a secreted metalloprotease identified in a human clinical isolate of Acinetobacter baumannii that cleaves FXII at O-linked glycosylated sites, inhibiting contact activation. While CpaA facilitates a modest in vivo fitness advantage in mice, the role of CpaA in human infection remains unclear. As such, the objectives of this study were to characterize the structural details of the interaction between CpaA, FXII, and the KKSs (kallikrein-kinin systems) and to determine the downstream consequences on thromboinflammatory responses.

METHODS: The effect of purified CpaA on the coagulant activity of FXII and the generation of bradykinin was characterized. Neutrophil signaling, flow cytometry, and functional assays were performed to define how CpaA-mediated cleavage of FXII affects innate immune functions. Bacterial killing by human neutrophils was performed with wild-type and mutant A baumannii strains lacking CpaA.

RESULTS: We found that CpaA cleaves both FXII zymogen and FXIIa but not beta Factor XII. However, cleavage of FXIIa by CpaA does not significantly inhibit its clotting activity, demonstrating that CpaA does not inactivate FXIIa, but rather prevents activation of zymogen FXII. CpaA also cleaves HK, resulting in reduced kallikrein activation and bradykinin generation. We previously identified that zymogen FXII interacts with the urokinase receptor on neutrophils and upregulates neutrophil activation. Here, we demonstrate that CpaA cleaves neutrophil FXII, resulting in reduced Akt2 phosphorylation, chemotaxis, oxidative burst, and neutrophil extracellular trap formation. Importantly, CpaA decreases the human neutrophil killing efficiency of A baumannii in culture.

CONCLUSIONS: These data identify a role for FXII in responding to bacterial infection and suggest that by inhibiting the contact and KKSs and impairing neutrophil activation, CpaA may blunt the innate immune response and help prevent the elimination of A baumannii from the human host.},
}

@article {pmid40357217,
year = {2025},
author = {Kuczmarski, TM and Lynch, RC},
title = {Optimizing therapy for relapsed/refractory classic Hodgkin lymphoma in the era of PD-1 blockade.},
journal = {HemaSphere},
volume = {9},
number = {5},
pages = {e70110},
pmid = {40357217},
issn = {2572-9241},
}

@article {pmid40355027,
year = {2025},
author = {Phelan, R and Rotz, S and Dandoy, CE and Auletta, JJ and Badia, P and Bhatt, NS and Ballard, SA and Blacken, R and Daraiseh, NM and Desmond, C and Dunseath, C and Epling, P and Flesch, L and Huber, J and Jenssen, K and Kapadia, M and Kent, G and Klunk, A and Kusnier, K and Lehmann, L and Liberio, N and Maier, S and Myers, KC and O'Connor, G and Pai, A and Tarquini, S and Fitch, TJ and Hartley, D},
title = {Multicenter Study on Caregiver Experiences in Pediatric Hematopoietic Stem Cell Transplantation: Part II. Treatment Challenges, Communication Barriers, and Caregiver-Driven Approaches to Mitigation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.04.012},
pmid = {40355027},
issn = {2666-6367},
abstract = {Hematopoietic stem cell transplantation (HSCT) is a life-saving yet complex treatment for pediatric patients that introduces significant physical, emotional, and logistical challenges for caregivers. This multicenter, prospective qualitative longitudinal study explored caregiver experiences across four time points: pre-transplant (n=47), 30 days post-transplant (n=43), 100 days post-transplant (n=34), and six months post-transplant (n=26). Forty-nine caregivers participated in semi-structured interviews, which were transcribed and thematically analyzed. This manuscript encompasses the following themes that emerged from the interviews: treatment-related side effects and complications, communication gaps, and the impact of the COVID-19 pandemic. Caregiver priorities evolved over time, shifting from managing acute complications such as pain, infections, mucositis, and medication administration to addressing longer-term concerns like developmental delays, nutritional rehabilitation, and psychosocial adaptation. Caregivers reported challenges such as information overload, inconsistent messaging, and limited preparation for transitions in care. They employed various strategies to cope, including advocacy, peer support, and the use of healthcare team resources. These findings highlight the importance of stage-specific, tailored interventions to support caregivers throughout the HSCT journey. Clear communication, accessible education, and coordinated multidisciplinary care are essential to fostering caregiver resilience and improving patient and family-centered outcomes.},
}

@article {pmid40350587,
year = {2025},
author = {Sala, M and Roos, CR and Kober, H and Bricker, JB and Stern, CM and Plutchik, J and John, M and Haeny, AM and Feldman, JM and Aslan, M and Hay, JL and Forman, EM},
title = {Combining Cognitive-Behaviour Therapy With Mindfulness Training in a Digital Intervention for Binge Eating Disorder: A Single-Session Pilot Trial.},
journal = {European eating disorders review : the journal of the Eating Disorders Association},
volume = {},
number = {},
pages = {},
doi = {10.1002/erv.3204},
pmid = {40350587},
issn = {1099-0968},
support = {K23AT012126/AT/NCCIH NIH HHS/United States ; },
abstract = {OBJECTIVE: Delivering a single-session treatment digitally can offer increased accessibility. We developed and tested a single-session digital intervention for binge-eating disorder (BED) combining cognitive behavioural therapy (CBT) and mindfulness training.

METHOD: English-speaking adults who met criteria for BED were recruited nationally. Participants completed a 60-min digital single-session intervention for BED. Our primary outcome was to evaluate initial acceptability (usability, overall satisfaction, engagement, visual appeal of content, understandability of programme material, desire to continue the programme, and overall helpfulness) and feasibility (intervention completion). We also evaluated changes in binge eating episodes, assessed via the Eating Disorder Examination Questionnaire (EDE-Q) objective binge eating episodes question, and eating disorder symptoms, assessed via the EDE-Q and Binge Eating Scale (BES). Acceptability measures were administered immediately after the completion of the digital module, while the BES and EDE-Q were administered at pre-treatment and at 1-month follow-up.

RESULTS: All participants (N = 21) completed the intervention. Ratings for acceptability were excellent, with averages above a four on a five-point Likert scale on ratings for all dimensions. Participants reported large and significant decreases in binge eating episodes (d = 0.86) and BES scores (d = 0.91) as well as medium and significant decreases in global eating disorder symptoms at 1-month follow-up (d = 0.55).

DISCUSSION: Results from this pilot suggest promising acceptability and feasibility for a single session of Mindful Courage for BED. This single session also appears to be preliminarily efficacious in reducing binge eating.},
}

@article {pmid40349288,
year = {2025},
author = {Mauro, M and Radich, J and Jain, P and Sequeira, D and Bellanti, F and Douer, D},
title = {Pharmacokinetic profile of novel reduced-dose Danziten[™] (nilotinib tablets) versus Tasigna[®] (nilotinib capsules): in vivo bioequivalence and population pharmacokinetic analysis.},
journal = {Cancer chemotherapy and pharmacology},
volume = {95},
number = {1},
pages = {56},
pmid = {40349288},
issn = {1432-0843},
mesh = {Humans ; Therapeutic Equivalency ; Male ; Female ; Tablets ; Adult ; Capsules ; *Pyrimidines/pharmacokinetics/administration & dosage ; Food-Drug Interactions ; Biological Availability ; Models, Biological ; Middle Aged ; Young Adult ; Fasting ; Cross-Over Studies ; Dose-Response Relationship, Drug ; Administration, Oral ; },
abstract = {PURPOSE: To evaluate single dose pharmacokinetics (PK) of novel reduced-dose film coated Danziten[™] (nilotinib tablets) using a population PK approach, establish bioequivalence vs. Tasigna[®] (nilotinib capsules) and investigate food effects on PK of both formulations.

METHODS: A population PK model evaluating nilotinib capsules (300 or 400 mg) or tablets (142 or 190 mg) was developed using data from 14 single dose studies and > 30,000 plasma samples from healthy men and women. Steady-state nilotinib concentration-time profiles following twice daily dosing with various treatment and food conditions were simulated using a randomly sampled dataset of 50 subjects.

RESULTS: PK was characterized by a 2-compartment model with linear elimination and zero-order absorption with lag time. Bioequivalence was met for all steady state exposure metrics for both doses under fasted conditions. A milligram strength for nilotinib tablets ~ 50% lower than that for capsules resulted in bioequivalent nilotinib exposures. Administration with a low-fat meal under modified fasting conditions increased the bioavailability (BA) of 142 mg and 190 mg nilotinib tablets by 26.0% and 29.3%, respectively, vs. fasting; values for 300 mg and 400 mg capsules were 56.8% and 60.7%. Administration with a high-fat meal under modified fasting conditions increased the BA of 142 and 190 mg nilotinib tablets by 48.6% and 52.2%, respectively; values for 300 and 400 mg capsules were 180.6% and 183.3%.

CONCLUSION: Nilotinib tablets 142 and 190 mg provide bioequivalent exposures to 300 mg and 400 mg capsules under fasted conditions and substantially smaller effects of food on exposure.},
}

Humans
Therapeutic Equivalency
Male
Female
Tablets
Adult
Capsules
*Pyrimidines/pharmacokinetics/administration & dosage
Food-Drug Interactions
Biological Availability
Models, Biological
Middle Aged
Young Adult
Fasting
Cross-Over Studies
Dose-Response Relationship, Drug
Administration, Oral

@article {pmid39670372,
year = {2025},
author = {Ramwala, OA and Lowry, KP and Hippe, DS and Unrath, MPN and Nyflot, MJ and Mooney, SD and Lee, CI},
title = {ClinValAI: A framework for developing Cloud-based infrastructures for the External Clinical Validation of AI in Medical Imaging.},
journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing},
volume = {30},
number = {},
pages = {215-228},
doi = {10.1142/9789819807024_0016},
pmid = {39670372},
issn = {2335-6936},
mesh = {Humans ; *Cloud Computing ; *Algorithms ; *Computational Biology ; Female ; *Artificial Intelligence ; *Diagnostic Imaging/standards/statistics & numerical data ; Workflow ; Mammography/statistics & numerical data/standards/methods ; Breast Neoplasms/diagnostic imaging ; Validation Studies as Topic ; },
abstract = {Artificial Intelligence (AI) algorithms showcase the potential to steer a paradigm shift in clinical medicine, especially medical imaging. Concerns associated with model generalizability and biases necessitate rigorous external validation of AI algorithms prior to their adoption into clinical workflows. To address the barriers associated with patient privacy, intellectual property, and diverse model requirements, we introduce ClinValAI, a framework for establishing robust cloud-based infrastructures to clinically validate AI algorithms in medical imaging. By featuring dedicated workflows for data ingestion, algorithm scoring, and output processing, we propose an easily customizable method to assess AI models and investigate biases. Our novel orchestration mechanism facilitates utilizing the complete potential of the cloud computing environment. ClinValAI's input auditing and standardization mechanisms ensure that inputs consistent with model prerequisites are provided to the algorithm for a streamlined validation. The scoring workflow comprises multiple steps to facilitate consistent inferencing and systematic troubleshooting. The output processing workflow helps identify and analyze samples with missing results and aggregates final outputs for downstream analysis. We demonstrate the usability of our work by evaluating a state-of-the-art breast cancer risk prediction algorithm on a large and diverse dataset of 2D screening mammograms. We perform comprehensive statistical analysis to study model calibration and evaluate performance on important factors, including breast density, age, and race, to identify latent biases. ClinValAI provides a holistic framework to validate medical imaging models and has the potential to advance the development of generalizable AI models in clinical medicine and promote health equity.},
}

Humans
*Cloud Computing
*Algorithms
*Computational Biology
Female
*Artificial Intelligence
*Diagnostic Imaging/standards/statistics & numerical data
Workflow
Mammography/statistics & numerical data/standards/methods
Breast Neoplasms/diagnostic imaging
Validation Studies as Topic

@article {pmid40347455,
year = {2025},
author = {Schenk, JM and Gulati, R and Beatty, SJ and Plymate, S and Lin, DW and Dash, A and Porter, MP and Vandoren, M and Wright, JL and Neuhouser, ML},
title = {Reduced adipose tissue with limited loss of lean mass after weight loss: results from the Prostate Active Lifestyle Study.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djaf113},
pmid = {40347455},
issn = {1460-2105},
abstract = {Adiposity reduction has both cancer-specific and overall health benefits for patients with overweight or obesity. However, the indiscriminate loss of lean mass accompanying weight loss remains a concern for older cancer patients. Body composition was evaluated in the Prostate Active Lifestyle Study, a randomized controlled weight loss trial targeting caloric restriction and increased physical activity among patients with prostate cancer (PCa) and overweight or obesity on active surveillance. Compared to control, the intervention statistically significantly decreased total fat (-3.4%; 95%CI: -5.3%, -1.5%), android fat (-2.0%; 95%CI: -3.6%, -0.4%), and visceral adipose tissue mass (-613 g; 95%CI: -894 g, -331 g) (all 2-sided p < .001) with no difference in lean mass (p = .70) and a statistically significant increase in lean-to-fat ratio (0.40; 95%CI: 0.06, 0.73; 2-sided p = .02). Weight loss interventions incorporating diet and physical activity among patients with PCa and overweight or obesity can yield statistically significant reductions in adiposity while limiting lean mass loss.},
}

@article {pmid40346049,
year = {2025},
author = {Pasvolsky, O and Dima, D and Feng, L and Dong, W and Richards, T and Davis, JA and Afrough, A and Vazquez-Martinez, M and Sannareddy, A and Goel, U and Banerjee, R and Khouri, J and Cervoni, F and Gaballa, MR and Lieberman-Cribbin, A and Rana, MS and Julian, K and Ferreri, CJ and Shune, L and DeJarnette, S and Bhurtel, E and Susanibar Adaniya, S and Portuguese, A and Hosoya, H and Mikkilineni, L and Kaur, G and Rossi, A and Herr, MM and Schrum, D and Lin, C and Raza, S and Lin, Y and Midha, S and Omar, N and Atarsh, S and McGuirk, J and Sborov, D and Voorhees, P and Anwer, F and Alsina, M and Freeman, C and Garfall, AL and Razzo, BM and Sidana, S and Cowan, AJ and Anderson, LD and Hansen, DK and Richard, S and Patel, KK and Lee, HC and Grajales-Cruz, A},
title = {Outcomes of elderly patients with relapsed refractory multiple myeloma (RRMM) treated with teclistamab: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {92},
pmid = {40346049},
issn = {2044-5385},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA281756/CA/NCI NIH HHS/United States ; NCI Grant P30 CA016672//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; NCI (R01CA281756-01A1)//U.S. Department of Health & Human Services | NIH | NIH Clinical Center (Clinical Center)/ ; },
mesh = {Humans ; *Multiple Myeloma/drug therapy/mortality/pathology ; Aged ; Male ; Female ; Aged, 80 and over ; Middle Aged ; Retrospective Studies ; *Antibodies, Bispecific/therapeutic use/adverse effects/administration & dosage ; Treatment Outcome ; United States ; Adult ; *Antineoplastic Agents, Immunological/therapeutic use/adverse effects ; Age Factors ; },
abstract = {Teclistamab, a BCMA-directed bispecific antibody, received regulatory approval for relapsed/refractory multiple myeloma (RRMM) based on the MajesTEC-1 study. Despite the fact that myeloma is primarily a cancer of elderly adults, only 15% of MajesTEC-1 participants (n = 24) were ≥75 years old. In this multicenter retrospective study, we report real-world outcomes of a large cohort of older RRMM patients treated with teclistamab. Of 385 analyzed patients, 83 (22%) were in the older group (age ≥75) and 302 (78%) in the younger group (age <75). Compared to the younger group, the older group had less adverse baseline disease characteristics, including a lower incidence of high-risk cytogenetics (44.6% vs. 57.9%, p = 0.03) and extramedullary disease (22% vs. 40%, p = 0.02). There were no significant differences in rates of any-grade CRS (52% vs. 59%, p = 0.27), any-grade ICANS (19% vs. 13%, p = 0.12), and overall response rate (62% vs. 53%, p = 0.17) between the older and younger groups. In multivariable analysis, age was not significantly associated with survival outcomes. Our findings suggest that teclistamab is safe and efficacious in well-selected patients ≥75 years old, and advanced age alone should not preclude teclistamab administration.},
}

Humans
*Multiple Myeloma/drug therapy/mortality/pathology
Aged
Male
Female
Aged, 80 and over
Middle Aged
Retrospective Studies
*Antibodies, Bispecific/therapeutic use/adverse effects/administration & dosage
Treatment Outcome
United States
Adult
*Antineoplastic Agents, Immunological/therapeutic use/adverse effects
Age Factors

@article {pmid40346033,
year = {2025},
author = {Mihalas, AB and Arora, S and O'Connor, SA and Feldman, HM and Cucinotta, CE and Mitchell, K and Bassett, J and Kim, D and Jin, K and Hoellerbauer, P and Delegard, J and Ling, M and Jenkins, W and Kufeld, M and Corrin, P and Carter, L and Tsukiyama, T and Aronow, B and Plaisier, CL and Patel, AP and Paddison, PJ},
title = {KAT5 regulates neurodevelopmental states associated with G0-like populations in glioblastoma.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4327},
pmid = {40346033},
issn = {2041-1723},
support = {R01 CA295090/CA/NCI NIH HHS/United States ; R01 CA190957/CA/NCI NIH HHS/United States ; S10 OD026919/OD/NIH HHS/United States ; R01CA190957//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; R01NS119650//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R35 GM139429/GM/NIGMS NIH HHS/United States ; T32CA080416//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R21 CA232244/CA/NCI NIH HHS/United States ; R01 NS119650/NS/NINDS NIH HHS/United States ; P30CA15704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; T32 CA080416/CA/NCI NIH HHS/United States ; },
mesh = {*Glioblastoma/pathology/genetics/metabolism ; Humans ; *Histone Acetyltransferases/metabolism/genetics ; *Brain Neoplasms/pathology/genetics/metabolism ; Cell Line, Tumor ; Neoplastic Stem Cells/metabolism/pathology ; Animals ; Gene Expression Regulation, Neoplastic ; Neural Stem Cells/metabolism ; Mice ; Cell Proliferation ; Proto-Oncogene Proteins c-myc/metabolism/genetics ; },
abstract = {Quiescence cancer stem-like cells may play key roles in promoting tumor cell heterogeneity and recurrence for many tumors, including glioblastoma (GBM). Here we show that the protein acetyltransferase KAT5 is a key regulator of transcriptional, epigenetic, and proliferative heterogeneity impacting transitions into G0-like states in GBM. KAT5 activity suppresses the emergence of quiescent subpopulations with neurodevelopmental progenitor characteristics, while promoting GBM stem-like cell (GSC) self-renewal through coordinately regulating E2F- and MYC- transcriptional networks with protein translation. KAT5 inactivation significantly decreases tumor progression and invasive behavior while increasing survival after standard of care. Further, increasing MYC expression in human neural stem cells stimulates KAT5 activity and protein translation, as well as confers sensitivity to homoharringtonine, to similar levels to those found in GSCs and high-grade gliomas. These results suggest that the dynamic behavior of KAT5 plays key roles in G0 ingress/egress, adoption of quasi-neurodevelopmental states, and aggressive tumor growth in gliomas.},
}

*Glioblastoma/pathology/genetics/metabolism
Humans
*Histone Acetyltransferases/metabolism/genetics
*Brain Neoplasms/pathology/genetics/metabolism
Cell Line, Tumor
Neoplastic Stem Cells/metabolism/pathology
Animals
Gene Expression Regulation, Neoplastic
Neural Stem Cells/metabolism
Mice
Cell Proliferation
Proto-Oncogene Proteins c-myc/metabolism/genetics

@article {pmid40344957,
year = {2025},
author = {Rugo, HS and Bardia, A and Gradishar, WJ and Hamilton, EP and Hurvitz, SA and Jhaveri, K and Mahtani, R and Tolaney, SM},
title = {Expert consensus on treating HR+/HER2- metastatic breast cancer based on real-world practice patterns observed in the RETRACT survey of US oncologists.},
journal = {Breast (Edinburgh, Scotland)},
volume = {82},
number = {},
pages = {104485},
doi = {10.1016/j.breast.2025.104485},
pmid = {40344957},
issn = {1532-3080},
abstract = {Hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2-mBC) is incurable, but recent progress has been made in developing new treatment options and the treatment landscape is rapidly shifting. There are published recommendations for treatment choices and sequencing to help guide oncologists in treating HR+/HER2-mBC, but little evidence has been published regarding real-world practice patterns. The REal-world TReatment patterns And Considerations of Toxicity in HR+/HER2-mBC (RETRACT) survey was designed to evaluate real-world practice patterns in the testing and management of this disease by US oncologists. The survey questions were answered via an online platform and the data were anonymized before analysis. A total of 150 oncologists practicing at academic and community centers completed the survey. The results showed this sample of oncologists largely followed recommended best practices for testing biomarkers, selecting treatments, and managing adverse events. However, several items did show substantial minorities of oncologists not in alignment with recommendations in areas including the definition and treatment of visceral crisis, ideal treatment for patients with endocrine resistance, the routine use of next-generation sequencing for biomarker testing, and the use of prophylactic measures for treatment-related adverse events in patients receiving alpelisib.},
}

@article {pmid40344546,
year = {2025},
author = {Check, DK and Li, Z and Shibeika, S and Sloan, CE and Sitlinger, A and Zullig, LL and Graf, SA and Blalock, DV},
title = {Receipt of Alcohol Screening, Brief Intervention, and Treatment Among US Adults With and Without a History of Cancer.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2401030},
doi = {10.1200/OP-24-01030},
pmid = {40344546},
issn = {2688-1535},
abstract = {PURPOSE: Many cancer survivors consume alcohol above recommended limits, increasing their risk of recurrence, second cancers, and cancer-related mortality. Alcohol screening, brief intervention, and referral to treatment (SBIRT) is a guideline-recommended strategy for reducing unhealthy alcohol consumption among adult primary care patients. To our knowledge, no prior studies have evaluated SBIRT's reach among cancer survivors.

METHODS: We conducted a cross-sectional study of adults who completed the National Survey on Drug Use and Health from 2015 to 2022. We examined past-year receipt of alcohol screening and-among respondents who endorsed unhealthy alcohol use-brief intervention and treatment. All outcomes were examined among cancer survivors and those with no cancer history. We used modified Poisson regression to assess the associations of cancer history with each outcome, adjusting for sociodemographic characteristics.

RESULTS: The cohort included 86,410 respondents with no history of cancer and 9,963 cancer survivors. The percentages of respondents endorsing past-year receipt of alcohol screening (approximately 40%), brief intervention (approximately 8%), and treatment (approximately 2%) were similarly low in both groups. After adjustment, there was a small but statistically significant difference in alcohol screening, with cancer survivors more likely than people without a history of cancer to receive alcohol screening (adjusted risk ratio [aRR], 1.07; 95% CI, 1.02 to 1.13). Among those with unhealthy alcohol use, cancer survivors were no more or less likely than people without a history of cancer to receive brief alcohol intervention (aRR, 1.00; 95% CI, 0.93 to 1.07) or alcohol treatment (aRR, 0.92; 95% CI, 0.47 to 1.69).

CONCLUSION: Results reveal an important opportunity to improve SBIRT uptake across the board and especially for cancer survivors, who are at increased risk of alcohol-related adverse health effects and, potentially, more motivated to change cancer-related health behaviors.},
}

@article {pmid40343485,
year = {2025},
author = {Yang, H and Luo, K and Peters, BA and Wang, Y and Zhang, Y and Daviglus, M and Pirzada, A and Cordero, C and Yu, B and Burk, RD and Kaplan, R and Qi, Q},
title = {Diet, Gut Microbiota, and Histidine Metabolism Toward Imidazole Propionate Production in Relation to Type 2 Diabetes.},
journal = {Diabetes care},
volume = {},
number = {},
pages = {},
doi = {10.2337/dc24-2816},
pmid = {40343485},
issn = {1935-5548},
support = {R01DK119268/DK/NIDDK NIH HHS/United States ; R01HL140976/HL/NHLBI NIH HHS/United States ; },
abstract = {OBJECTIVE: To examine associations of serum imidazole propionate (ImP), histidine, and their ratio with incident type 2 diabetes (T2D) and related dietary and gut microbial factors in U.S. Hispanic/Latino people.

RESEARCH DESIGN AND METHODS: In the Hispanic Community Health Study/Study of Latinos, we evaluated serum ImP, histidine, and ImP-to-histidine ratio at baseline (2008-2011) and their cross-sectional associations with dietary intake and prospective associations with incident T2D over ∼12 years (n = 4,632). In a subsample with gut microbiota data during a follow-up visit (2016-2018), we examined gut microbial species associated with serum ImP and their potential interactions with dietary intake.

RESULTS: Serum ImP and ImP-to-histidine ratio were positively associated with incident T2D (hazard ratio [95% CI] = 1.17 [1.00-1.36] and 1.33 [1.14-1.55], respectively, comparing highest and lowest tertiles), whereas histidine was inversely associated with incident T2D (hazard ratio = 0.75 [95% CI 0.64-0.86]). A higher amount of fiber intake was associated with lower serum ImP level and ImP-to-histidine ratio, whereas histidine intake was not associated with serum ImP level in the overall sample. Fifty-three bacterial species, including 19 putative ImP producers, were associated with serum ImP. Histidine intake was positively associated with serum ImP and ImP-to-histidine ratio only in participants with a high ImP-associated gut microbiota score (P = 0.03 and 0.02, respectively, for interaction). The associations of fiber intake with serum ImP and ImP-to-histidine ratio were partly mediated by ImP-associated gut microbiota (proportion mediated = 31.4% and 19.8%, respectively).

CONCLUSIONS: This study suggested an unfavorable relationship between histidine metabolism toward ImP production, potentially regulated by dietary intake and gut microbiota, and risk of T2D in U.S. Hispanics/Latino people.},
}

@article {pmid40342410,
year = {2025},
author = {Zhang, T and Gentry, CA and Kuderer, NM and Lyman, GH and Ng, B and Michailidou, D},
title = {Association of SSRI and SNRI use with incidence of cardiovascular events in veterans with giant cell arteritis and polymyalgia rheumatica.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1509941},
pmid = {40342410},
issn = {1664-3224},
mesh = {Humans ; *Polymyalgia Rheumatica/drug therapy/epidemiology/complications ; Male ; Female ; Aged ; *Giant Cell Arteritis/drug therapy/epidemiology/complications ; *Selective Serotonin Reuptake Inhibitors/therapeutic use/adverse effects ; Incidence ; Veterans ; *Serotonin and Noradrenaline Reuptake Inhibitors/therapeutic use/adverse effects ; *Cardiovascular Diseases/epidemiology/etiology ; Aged, 80 and over ; Middle Aged ; United States/epidemiology ; },
abstract = {The leading cause of death in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) is cardiovascular disease. The objective of this study was to determine whether the use of selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) in veterans with GCA and PMR could have a cardio-modulatory effect as compared to nonuse. Patients with GCA and PMR were identified through the Veterans Affairs Informatics and Computing Infrastructure. After a 2:1 propensity score matching for SSRI or SNRI users, we identified nonusers with similar covariates. We then applied a multivariate logistic regression (MLR), to calculate the odds ratio (OR) for cardiovascular event (CVE) outcomes within 5 years after the index date. Related hazard ratios (HR) were also calculated to validate the discovery of our findings. We identified 2249 patients with GCA and 3906 patients with PMR. Among patients with GCA, 174 (27%) SSRI users had incident cardiovascular disease as compared to 47 (28%) SNRI users and 277 (19%) nonusers; in the PMR cohort, 108 (13%) were SSRI users compared to 71 (15%) SNRI users and 255 (11%) nonusers. The adjusted ORs of the CVE outcome associated with venlafaxine (2.44, p=0.01) and sertraline (1.45, p=0.04) were significantly greater than 1 in GCA, with similar results observed in the PMR cohort (2.01, p=0.02, and 1.45, p=0.04, respectively). Cox-regression analysis was also conducted, and the hazard ratios were qualitatively consistent with the MLR analysis. In conclusion, the adjusted risk of CVE in patients with GCA or PMR using either venlafaxine or sertraline was higher than that in the non-exposed groups.},
}

Humans
*Polymyalgia Rheumatica/drug therapy/epidemiology/complications
Male
Female
Aged
*Giant Cell Arteritis/drug therapy/epidemiology/complications
*Selective Serotonin Reuptake Inhibitors/therapeutic use/adverse effects
Incidence
Veterans
*Serotonin and Noradrenaline Reuptake Inhibitors/therapeutic use/adverse effects
*Cardiovascular Diseases/epidemiology/etiology
Aged, 80 and over
Middle Aged
United States/epidemiology

@article {pmid40341939,
year = {2025},
author = {Byun, J and Han, Y and Choi, J and Sun, R and Shaw, VR and Zhu, C and Xiao, X and Lusk, C and Badr, H and Lee, HS and Jang, HJ and Li, Y and Lim, H and Long, E and Liu, Y and Kachuri, L and Walsh, KM and Wiencke, JK and Albanes, D and Lam, S and Tardon, A and Neuhouser, ML and Barnett, MJ and Chen, C and Bojesen, S and Brenner, H and Landi, MT and Johansson, M and Risch, A and Wichmann, HE and Bickeböller, H and Christiani, DC and Rennert, G and Arnold, S and Field, JK and Shete, S and Le Marchand, L and Liu, G and Andrew, AS and Zienolddiny, S and Grankvist, K and Johansson, M and Caporaso, N and Taylor, F and Lazarus, P and Schabath, MB and Aldrich, MC and Patel, A and Lin, X and Zanetti, KA and Harris, CC and Chanock, S and McKay, J and Schwartz, AG and Hung, RJ and Amos, CI and , },
title = {Genome-wide association study for lung cancer in 6531 African Americans reveals new susceptibility loci.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf059},
pmid = {40341939},
issn = {1460-2083},
support = {U19CA203654//the National Institutes of Health (NIH)/ ; RR170048//Cancer Prevention Research Interest of Texas (CPRIT)/ ; },
abstract = {Despite lung cancer affecting all races and ethnicities, disparities are observed in incidence and mortality rates among different ethnic groups in the United States. Non-Hispanic African Americans had a high incidence rate of lung cancer at 55.8 per 100 000 people, as well as the highest death rate at 37.2 per 100 000 people from 2016 to 2020. While previous genome-wide association studies (GWAS) have identified over 45 susceptibility risk loci that influence lung cancer development, few GWAS have investigated the etiology of lung cancer in African Americans. To address this gap in knowledge, we conducted GWAS of lung cancer focused on studying African Americans, comprising 2267 lung cancer cases and 4264 controls. We identified three loci associated with lung cancer, one with lung adenocarcinoma, and four with lung squamous cell carcinoma in this population at the genomic-wide significance level. Among them, three novel loci were identified near VWF at 12p13.31 for overall lung cancer and GACAT3 at 2p24.3 and LMAN1L at 15q24.1 for lung squamous cell carcinoma. In addition, we confirmed previously reported risk loci with known or new lead variants near CHRNA5 at 15q25.1 and CYP2A6 at 19q13.2 associated with lung cancer and TRIP13 at 5p15.33 and ERC1 at 12p13.33 associated with lung squamous cell carcinoma. Further multi-step functional analyses shed light on biological mechanisms underlying these associations of lung cancer in this population. Our study highlights the importance of ancestry-specific studies for the potential alleviation of lung cancer burden in African Americans.},
}

@article {pmid40341199,
year = {2025},
author = {Ajani, JA and D'Amico, TA and Bentrem, DJ and Corvera, CU and Das, P and Enzinger, PC and Enzler, T and Gerdes, H and Gibson, MK and Grierson, P and Gupta, G and Hofstetter, WL and Ilson, DH and Jalal, S and Kim, S and Kleinberg, LR and Klempner, S and Lacy, J and Lee, B and Licciardi, F and Lloyd, S and Ly, QP and Matsukuma, K and McNamara, M and Merkow, RP and Miller, AM and Mukherjee, S and Mulcahy, MF and Perry, KA and Pimiento, JM and Reddi, DM and Reznik, S and Roses, RE and Strong, VE and Su, S and Uboha, N and Wainberg, ZA and Willett, CG and Woo, Y and Yoon, HH and McMillian, NR and Stein, M},
title = {Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {5},
pages = {169-191},
doi = {10.6004/jnccn.2025.0022},
pmid = {40341199},
issn = {1540-1413},
mesh = {Humans ; *Stomach Neoplasms/therapy/diagnosis/pathology/mortality ; *Medical Oncology/standards/methods ; Biomarkers, Tumor/analysis ; Prognosis ; Neoplasm Staging ; },
abstract = {Gastric cancer is the fifth leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improve survival, and enhance the quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing has had a significant impact on clinical practice and patient care. Targeted therapies have demonstrated encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. This selection from the NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer highlights recommendations for biomarker testing and discusses updates for the treatment of advanced disease, including peritoneal carcinoma as only disease and unresectable locally advanced, recurrent, or metastatic disease.},
}

Humans
*Stomach Neoplasms/therapy/diagnosis/pathology/mortality
*Medical Oncology/standards/methods
Biomarkers, Tumor/analysis
Prognosis
Neoplasm Staging

@article {pmid40341193,
year = {2025},
author = {Tsang, TK and Rojas, DP and Xu, F and Xu, Y and Zhu, X and Halloran, ME and Longini, IM and Yang, Y},
title = {Estimating transmissibility of Zika virus in Colombia in the presence of surveillance bias.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {4299},
pmid = {40341193},
issn = {2041-1723},
mesh = {Humans ; *Zika Virus Infection/transmission/epidemiology/virology ; Colombia/epidemiology ; Female ; Adolescent ; Male ; Adult ; *Zika Virus/physiology ; Young Adult ; Bayes Theorem ; Disease Outbreaks ; Middle Aged ; Child ; Population Surveillance ; Bias ; Microcephaly/epidemiology/virology ; },
abstract = {The 2015-2016 Zika virus outbreak in the Americas presented significant challenges in understanding the transmission dynamics due to substantial reporting biases, as women of reproductive age (15-39 years) were disproportionately represented in the surveillance data when public awareness of relationship between Zika and microcephaly increased. Using national surveillance data from Colombia during July 27, 2015-November 21, 2016, we developed a Bayesian hierarchical modeling framework to reconstruct the true numbers of symptomatic cases and estimate transmission parameters while accounting for differential reporting across age-sex groups. Our model revealed that the detection rate of symptomatic cases among women of reproductive age was 99% (95% CI: 98.7-100), compared to 85.4% (95% CI: 84.7-86.1) in other demographic groups. After correcting for these biases, our results showed that females aged 15-39 years remained 82.8% (95% CI: 80.2-85.2%) more susceptible to Zika symptomatic infection than males of the same age, independent of differential reporting areas. Departments with medium-high altitude, medium-high population density, low coverage of forest, or high dengue incidence from 2011-2015 exhibited greater Zika risk. This study underscores the importance of accounting for surveillance biases in epidemiological studies to better understand factors influencing Zika transmission and to inform disease control and prevention.},
}

Humans
*Zika Virus Infection/transmission/epidemiology/virology
Colombia/epidemiology
Female
Adolescent
Male
Adult
*Zika Virus/physiology
Young Adult
Bayes Theorem
Disease Outbreaks
Middle Aged
Child
Population Surveillance
Bias
Microcephaly/epidemiology/virology

@article {pmid40340857,
year = {2025},
author = {Kumar, SK and Callander, NS and Adekola, K and Anderson, LD and Baljevic, M and Baz, R and Campagnaro, E and Costello, C and D'Angelo, C and Derman, B and Devarakonda, S and Elsedawy, N and Godara, A and Godby, K and Hillengass, J and Holmberg, L and Htut, M and Huff, CA and Hultcrantz, M and Kang, Y and Larson, S and Lee, HC and Liedtke, M and Martin, T and Omel, J and Robinson, T and Rosenberg, A and Schroeder, MA and Sherbenou, D and Suvannasankha, A and Valent, J and Varshavsky-Yanovsky, AN and Vogl, D and Kovach, E and Kumar, R},
title = {NCCN Guidelines® Insights: Multiple Myeloma, Version 1.2025.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {5},
pages = {132-140},
doi = {10.6004/jnccn.2025.0023},
pmid = {40340857},
issn = {1540-1413},
mesh = {Humans ; *Multiple Myeloma/diagnosis/therapy ; *Medical Oncology/standards ; },
abstract = {The NCCN Guidelines for Multiple Myeloma (MM) provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with MM. These NCCN Guidelines Insights highlight the important updates and changes specific to systemic therapy for patients with newly diagnosed as well as previously treated MM included in Version 1.2025 of the NCCN Guidelines for MM.},
}

Humans
*Multiple Myeloma/diagnosis/therapy
*Medical Oncology/standards

@article {pmid40340130,
year = {2025},
author = {Ujjani, C and Wang, H and Broome, C and Gopal, AK and Smith, SD and Lai, C and Shadman, M and Leslie, L and Warren, EH and Lynch, R and Swanson, N and Grossfeld, T and Cheson, BD and Dunleavy, K},
title = {Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.04.004},
pmid = {40340130},
issn = {2152-2669},
abstract = {BACKGROUND: Bruton tyrosine kinase (BTK) inhibitors are approved in several B-cell malignancies, including the recent authorization of zanubrutinib for relapsed or refractory follicular lymphoma (FL).

METHODS: Based on preclinical studies demonstrating synergy with ibrutinib and the B-cell lymphoma (BCL)-2 inhibitor, venetoclax, in FL cell lines, we conducted a multicenter phase Ib/II study evaluating this combination in relapsed or refractory FL.

RESULTS: The recommended phase 2 dose was ibrutinib 560 mg and venetoclax 600 mg. There was no evidence of clinical tumor lysis syndrome, despite the omission of a venetoclax ramp up. At a median duration of therapy of 6 months, the most common adverse events were low grade diarrhea (83%), infection (75%), and rash (58%). Amongst the 24 patients enrolled, the overall and complete response (CR) rates were 63% and 21%. At a median follow up of 6.9 months, the median progression-free survival was 8.2 months, and the median duration of CR (n = 5) was 38 months.

CONCLUSION: The combination of a BTK and BCL2 inhibitor is efficacious in relapsed/refractory FL and represents a unique dual-targeted approach warranting further investigation.},
}

@article {pmid40339592,
year = {2025},
author = {Escrivá-de-Romani, S and Cejalvo, JM and Alba, E and Friedmann, J and Rodríguez-Lescure, Á and Savard, MF and Pezo, RC and Gion, M and Ruiz-Borrego, M and Hamilton, E and Pluard, T and Webster, M and Beeram, M and Linden, H and Saura, C and Shpektor, D and Salim, B and Harvey, P and Hurvitz, SA},
title = {Zanidatamab plus palbociclib and fulvestrant in previously treated patients with hormone receptor-positive, HER2-positive metastatic breast cancer: primary results from a two-part, multicentre, single-arm, phase 2a study.},
journal = {The Lancet. Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1470-2045(25)00140-8},
pmid = {40339592},
issn = {1474-5488},
abstract = {BACKGROUND: New HER2-targeted regimens, including chemotherapy-free options, are needed for metastatic breast cancer. In an ongoing, two-part, phase 2a study, we assessed the safety and antitumour activity of zanidatamab, a HER2-targeted bispecific antibody, plus palbociclib and fulvestrant, in heavily pretreated patients with hormone receptor-positive, HER2-positive advanced or metastatic breast cancer.

METHODS: This multicentre, single-arm, two-part, phase 2a study is being conducted at 13 university hospitals, cancer centres, or research institutes in Spain, Canada, and the USA. Eligible patients were adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, and with pathologically confirmed unresectable or metastatic breast cancer, assessed locally to be hormone receptor-positive and HER2-positive, with disease progression during or after previous HER2-targeted therapies. Patients were enrolled in part 1, part 2, or part 1 followed by part 2. In part 1, patients received starting doses of zanidatamab (20 mg/kg intravenously once every 2 weeks on days 1 and 15 of a 28-day cycle) with palbociclib (125 mg orally once a day on days 1-21 of each cycle) and fulvestrant (500 mg intramuscular injection once every 2 weeks for the first three doses [cycle 1: days 1 and 15, cycle 2: day 1], then once every 4 weeks [all subsequent cycles: day 1]). In part 1, primary endpoints were safety of the triplet combination and confirmation of recommended doses for part 2. In part 2, patients received the recommended doses confirmed in part 1, and the primary endpoint was progression-free survival at 6 months. Safety and progression-free survival were assessed in all enrolled patients who received any dose of zanidatamab, palbociclib, or fulvestrant. Patients in part 1 who were treated at the recommended doses were analysed together with the patients in part 2. This study is registered with ClinicalTrials.gov, NCT04224272, and is active with recruitment completed.

FINDINGS: Overall, 51 patients (49 [96%] female and two [4%] male; median age 54·0 [46·0-62·0] years; 42 [82%] White) were enrolled: eight in part 1 (June 10, 2020-Feb 7, 2021) and 43 in part 2 (Feb 8, 2021-Oct 31, 2022). All 51 patients had received study treatment at the data cutoff (Aug 3, 2023); median follow-up was 16·1 months (IQR 9·9-23·4) and the median duration of triplet regimen treatment was 7·4 months (3·4-14·8). The median number of previous HER2-targeted therapies was 4 (IQR 3-4). 12 (24%) of 51 patients had previously received trastuzumab deruxtecan. The planned starting drug doses administered in part 1 of the study were confirmed as the recommended doses for part 2. All 51 patients were treated at the recommended doses. All 51 patients had at least one treatment-related adverse event of any grade, with diarrhoea being the most common (41 [80%] patients, with 34 [67%] having grade 1-2 events). Grade 3 or 4 treatment-related adverse events occurred in 34 (67%) patients, with neutropenia being the most common (26 [51%] patients). One (2%) patient had a serious grade 3 treatment-related adverse event of increased transaminases. No treatment-related deaths occurred. In the overall sample (N=51), progression-free survival at 6 months was 66·7% (95% CI 52·1-79·2).

INTERPRETATION: Zanidatamab plus palbociclib and fulvestrant was generally safe and showed promising antitumour activity, supporting further evaluation of this chemotherapy-free triplet regimen.

FUNDING: Zymeworks, Jazz Pharmaceuticals, and Pfizer.},
}

@article {pmid40339051,
year = {2025},
author = {Burger, R and Bell-Mandla, N and Harper, A and Richardson, S and Kanema, S and Thomas, R and Mwenge, L and Wilson, E and Floyd, S and Bock, P and Ayles, H and Fidler, S and Hayes, R and Hauck, K and , },
title = {Does enhanced HIV prevention, diagnosis, and linkage to care reduce hospitalisation in high HIV-burden communities in Zambia and South Africa? findings from the HPTN 071 (PopART) randomised trial.},
journal = {PLOS global public health},
volume = {5},
number = {5},
pages = {e0004373},
pmid = {40339051},
issn = {2767-3375},
abstract = {ClinicalTrials.gov NCT01900977.},
}

@article {pmid40339010,
year = {2025},
author = {Ely, ZA and Kulstad, ZJ and Gunaydin, G and Addepalli, S and Verzani, EK and Casarrubios, M and Clauser, KR and Wang, X and Lippincott, IE and Louvet, C and Schmitt, T and Kapner, KS and Agus, MP and Hennessey, CJ and Cleary, JM and Hadrup, SR and Klaeger, S and Su, J and Jaeger, AM and Wolpin, BM and Raghavan, S and Smith, EL and Greenberg, PD and Aguirre, AJ and Abelin, JG and Carr, SA and Jacks, T and Freed-Pastor, WA},
title = {Pancreatic cancer-restricted cryptic antigens are targets for T cell recognition.},
journal = {Science (New York, N.Y.)},
volume = {388},
number = {6747},
pages = {eadk3487},
doi = {10.1126/science.adk3487},
pmid = {40339010},
issn = {1095-9203},
mesh = {*Pancreatic Neoplasms/immunology/therapy/genetics ; Humans ; *Antigens, Neoplasm/immunology/genetics ; *Histocompatibility Antigens Class I/immunology ; *T-Lymphocytes, Cytotoxic/immunology ; *Peptides/immunology ; Organoids/immunology ; Receptors, Antigen, T-Cell/immunology ; Antigen Presentation ; Cell Line, Tumor ; },
abstract = {Translation of the noncoding genome in cancer can generate cryptic (noncanonical) peptides capable of presentation by human leukocyte antigen class I (HLA-I); however, the cancer specificity and immunogenicity of noncanonical HLA-I-bound peptides (ncHLAp) are incompletely understood. Using high-resolution immunopeptidomics, we discovered that cryptic peptides are abundant in the pancreatic cancer immunopeptidome. Approximately 30% of ncHLAp exhibited cancer-restricted translation, and a substantial subset were shared among patients. Cancer-restricted ncHLAp displayed robust immunogenic potential in a sensitive ex vivo T cell priming platform. ncHLAp-reactive, T cell receptor-redirected T cells exhibited tumoricidal activity against patient-derived pancreatic cancer organoids. These findings demonstrate that pancreatic cancer harbors cancer-restricted ncHLAp that can be recognized by cytotoxic T cells. Future therapeutic strategies for pancreatic cancer, and potentially other solid tumors, may include targeting cryptic antigens.},
}

*Pancreatic Neoplasms/immunology/therapy/genetics
Humans
*Antigens, Neoplasm/immunology/genetics
*Histocompatibility Antigens Class I/immunology
*T-Lymphocytes, Cytotoxic/immunology
*Peptides/immunology
Organoids/immunology
Receptors, Antigen, T-Cell/immunology
Antigen Presentation
Cell Line, Tumor

@article {pmid40338545,
year = {2025},
author = {Schoen, MW and Doherty, J and Eaton, D and Khan, S and Candelieri, D and Fedele, N and Baxi, P and Wynveen, M and Pickett, C and Wilson, RJ and Stackable, K and Ingram, K and Karunanandaa, K and Agarwal, R and Rajasekhar, A and Riekhof, F and Govindan, S and Cheranda, N and Knoche, EM and Etzioni, RD and Montgomery, RB},
title = {Treatment Patterns and Survival Among Veterans With De Novo Metastatic Hormone-Sensitive Prostate Cancer.},
journal = {JAMA network open},
volume = {8},
number = {5},
pages = {e259433},
pmid = {40338545},
issn = {2574-3805},
mesh = {Humans ; Male ; Aged ; Retrospective Studies ; Cross-Sectional Studies ; *Veterans/statistics & numerical data ; *Prostatic Neoplasms/mortality/drug therapy/pathology ; Docetaxel/therapeutic use ; *Androgen Antagonists/therapeutic use ; Middle Aged ; United States/epidemiology ; Aged, 80 and over ; *Androgen Receptor Antagonists/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; },
abstract = {IMPORTANCE: Combination therapy for metastatic hormone-sensitive prostate cancer (mHSPC) has been widely adopted, yet clinical use and outcomes are unknown. Furthermore, optimal therapy is uncertain due to lack of direct comparison of androgen receptor pathway inhibitors (ARPIs) and docetaxel in high-volume disease.

OBJECTIVE: To evaluate the use of combination therapy and its association with overall survival among patients with mHSPC and to compare ARPIs vs docetaxel doublet therapy by volume of disease.

This retrospective cross-sectional study was conducted in the US Veterans Health Administration among 6216 US veterans with de novo mHSPC from January 1, 2013, to December 31, 2022, treated with androgen deprivation therapy (ADT) within 3 months of diagnosis. Treatments for mHSPC were collected within 4 months of ADT. Volume of disease was assessed from radiology report review. Data were analyzed from July 2023 to October 2024.

MAIN OUTCOMES AND MEASURES: Overall survival (OS) and clinical progression-free survival (PFS), indicated by time to castration resistance or death.

RESULTS: Among 6216 male veterans with mHSPC (mean [SD] age, 73.9 [9.7] years), use of combination therapy increased from 344 of 637 veterans (54.0%) in 2020 to 465 of 737 veterans (63.1%) in 2022. Among 4106 veterans treated from 2017 to 2022, combination therapy was associated with longer OS (40.3 [95% CI, 38.0-42.1] months vs 33.0 [95% CI, 31.2-35.1] months; hazard ratio [HR], 0.80 [95% CI, 0.74-0.87]) and was used more frequently among younger veterans with fewer comorbidities. Among 1174 veterans with high-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (32.3 [95% CI, 29.5-35.3] months vs 34.7 [95% CI, 31.7-37.1] months; HR, 1.06 [95% CI, 0.91-1.23]); however, ARPIs were associated with longer PFS (18.7 [95% CI, 17.1-20.9] months vs 16.0 [95% CI, 14.0-17.7] months; HR, 0.80 [95% CI, 0.70-0.91]; P = .001). In a multivariable model of high-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (adjusted HR, 0.89 [95% CI, 0.76-1.05]). Among 366 veterans with low-volume mHSPC, there was no difference in OS between ARPIs and docetaxel (68.4 [95% CI, 52.6 months to not reached] months vs 55.3 [95% CI, 41.7-78.9] months; HR, 0.81 [95% CI, 0.58-1.13]), but ARPIs were associated with longer PFS (39.7 [95% CI, 34.3-52.9] months vs 24.0 [95% CI, 20.3-32.9] months; HR, 0.57 [95% CI, 0.43-0.76]).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of veterans with de novo mHSPC, use of combination therapies increased over time and were associated with longer survival compared with ADT monotherapy. In both high- and low-volume mHSPC, no differences in OS were observed between ARPI and docetaxel combinations; however, ARPIs had longer PFS. Future research into the role of docetaxel is needed to elucidate the benefit of chemotherapy in mHSPC.},
}

Humans
Male
Aged
Retrospective Studies
Cross-Sectional Studies
*Veterans/statistics & numerical data
*Prostatic Neoplasms/mortality/drug therapy/pathology
Docetaxel/therapeutic use
*Androgen Antagonists/therapeutic use
Middle Aged
United States/epidemiology
Aged, 80 and over
*Androgen Receptor Antagonists/therapeutic use
Antineoplastic Combined Chemotherapy Protocols/therapeutic use

@article {pmid40337764,
year = {2025},
author = {Damle, SR and Pillarisetty, VG and Safyan, RA and Chiorean, EG},
title = {A new dawn in cancer immunotherapy: the promise of mutant KRAS-specific vaccines.},
journal = {Translational gastroenterology and hepatology},
volume = {10},
number = {},
pages = {20},
pmid = {40337764},
issn = {2415-1289},
}

@article {pmid40337301,
year = {2025},
author = {Eckardt, JN and Hahn, W and Ries, RE and Chrost, SD and Winter, S and Stasik, S and Röllig, C and Platzbecker, U and Müller-Tidow, C and Serve, H and Baldus, CD and Schliemann, C and Schäfer-Eckart, K and Hanoun, M and Kaufmann, M and Burchert, A and Schetelig, J and Bornhäuser, M and Wolfien, M and Meshinchi, S and Thiede, C and Middeke, JM},
title = {Age-stratified machine learning identifies divergent prognostic significance of molecular alterations in AML.},
journal = {HemaSphere},
volume = {9},
number = {5},
pages = {e70132},
pmid = {40337301},
issn = {2572-9241},
abstract = {Risk stratification in acute myeloid leukemia (AML) is driven by genetics, yet patient age substantially influences therapeutic decisions. To evaluate how age alters the prognostic impact of genetic mutations, we pooled data from 3062 pediatric and adult AML patients from multiple cohorts. Signaling pathway mutations dominated in younger patients, while mutations in epigenetic regulators, spliceosome genes, and TP53 alterations became more frequent with increasing age. Machine learning models were trained to identify prognostic variables and predict complete remission and 2-year overall survival, achieving area-under-the-curve scores of 0.801 and 0.791, respectively. Using Shapley (SHAP) values, we quantified the contribution of each variable to model decisions and traced their impact across six age groups: infants, children, adolescents/young adults, adults, seniors, and elderly. The highest contributions to model decisions among genetic variables were found for alterations of NPM1, CEBPA, inv(16), and t(8;21) conferring favorable risk and alterations of TP53, RUNX1, ASXL1, del(5q), -7, and -17 conferring adverse risk, while FLT3-ITD had an ambiguous role conferring favorable treatment responses yet poor overall survival. Age significantly modified the prognostic value of genetic alterations, with no single alteration consistently predicting outcomes across all age groups. Specific alterations associated with aging such as TP53, ASXL1, or del(5q) posed a disproportionately higher risk in younger patients. These results challenge uniform risk stratification models and highlight the need for context-sensitive AML treatment strategies.},
}

@article {pmid40335656,
year = {2025},
author = {Harris, K},
title = {An uneasy truce between population health and the gene pools within our bodies.},
journal = {Nature reviews. Genetics},
volume = {},
number = {},
pages = {},
pmid = {40335656},
issn = {1471-0064},
}

@article {pmid40334068,
year = {2025},
author = {Muhsen, IN and Roloff, GW and Faramand, RG and Othman, T and Valtis, YK and Kopmar, NE and Dekker, SE and Connor, M and Mercadal, S and O'Connor, TE and Dykes, KC and Ahmed, M and Jeyakumar, N and Zhang, A and Miller, K and Sutherland, KC and Guzowski, C and Gupta, VK and Majhail, NS and Battiwalla, M and Solh, MM and Malik, SA and Mathews, J and Oliai, C and Shaughnessy, PJ and Mountjoy, L and Lee, CJ and Logan, AC and Tsai, SB and Leonard, JT and Schwartz, MS and Sasine, JP and Kumaran, M and Frey, NV and Park, JH and Koura, D and Cassaday, RD and Shah, BD and Aldoss, I and Muffly, LS and Hill, LC},
title = {Outcomes of Brexucabtagene Autoleucel in Relapsed/Refractory Acute Lymphoblastic Leukemia Patients with CNS Involvement.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015779},
pmid = {40334068},
issn = {2473-9537},
abstract = {Relapsed/Refractory (r/r) B-cell acute lymphoblastic leukemia patients with central nervous system involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor T-cell (CAR T-cell) clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with r/r B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in CNS B-ALL patients utilizing data from the Real-World Outcomes Collaborative for CAR T in ALL (ROCCA) consortium. Of 189 patients infused, 31 had CNS-2 (presence of blasts in CSF with < 5 WBC/uL) or CNS-3 (presence of blasts with >5 WBC/uL and/or clinical signs/symptoms) disease pre-apheresis and are the focus of this report. The median age was 46.5 years (range, 24-76), and 58.1% were males. Most (87.1%) received bridging therapy. Following brexu-cel, 21 of 24 with CNS restaging (87.5%) achieved CNS-1. Additionally, 28 of 30 evaluable patients achieved marrow complete remission (CR); 25 were MRD-negative. No statistically significant differences were seen in progression-free survival (PFS) or overall survival (OS) following brexu-cel among patients with or without CNS involvement. Similarly, grade 3-4 immune effector cell associated neurotoxicity syndrome (ICANS) occurred similarly in patients with (35.5%) and without CNS disease (30%). In conclusion, our data suggest that brexu-cel results in high response rates in CNS B-ALL patients with toxicity comparable to patients without CNS involvement.},
}

@article {pmid40334067,
year = {2025},
author = {Shadman, M and Burke, JM and Cultrera, J and Yimer, HA and Zafar, SF and Misleh, J and Rao, SS and Farber, CM and Cohen, AC and Yao, H and Idoine, A and An, Q and Flinn, IW and Sharman, JP},
title = {Zanubrutinib is well tolerated and effective in CLL/SLL patients intolerant of ibrutinib/acalabrutinib: Updated results.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015493},
pmid = {40334067},
issn = {2473-9537},
abstract = {Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib revolutionized chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment, although treatment-related toxicities limit the use of some BTK inhibitors. Zanubrutinib, a potent next-generation BTK inhibitor, has higher selectivity than ibrutinib or acalabrutinib. The ongoing phase 2, single-arm BGB-3111-215 study investigates the safety and efficacy of zanubrutinib in patients with B-cell malignancies who are intolerant of ibrutinib and/or acalabrutinib. Here, results in patients with CLL/SLL are presented. Patients received zanubrutinib 160 mg BID or 320 mg QD. With a 34.5-month median follow-up, 71 patients (ibrutinib intolerant only, n=44; acalabrutinib intolerant only, n=17; ibrutinib and acalabrutinib intolerant, n=10) received ≥1 zanubrutinib dose. On zanubrutinib, 54% (28/52) of ibrutinib-intolerant patients and 70% (19/27) of acalabrutinib-intolerant patients experienced no recurrence of intolerance AEs; 60% and 72% of intolerance AEs did not recur, respectively. Of recurrent ibrutinib-intolerance AEs, 64% were lower grade; 44% of acalabrutinib-intolerance AEs were lower grade. No intolerance AEs recurred at a higher grade with zanubrutinib. The most common recurrent ibrutinib-intolerance and acalabrutinib-intolerance AEs were fatigue and diarrhea, respectively. The most common TEAEs with zanubrutinib were fatigue (32%), COVID-19 (28%), and diarrhea and contusion (each 24%). Grade ≥3 TEAEs occurred in 61%, serious TEAEs in 32%, and TEAEs leading to discontinuation in 11%. Of 67 efficacy-evaluable patients, 94% experienced disease control: 30% had a best response of stable disease and 64% had a partial or complete response. These data demonstrate that patients intolerant of ibrutinib/acalabrutinib may benefit from switching to zanubrutinib therapy. ClinicalTrials.gov: NCT04116437.},
}

@article {pmid40333962,
year = {2025},
author = {Zheng, D and van den Heuvel, A and Balog, J and Willemsen, IM and Kloet, S and Tapscott, SJ and Mahfouz, A and van der Maarel, SM},
title = {DUX4 activates common and context-specific intergenic transcripts and isoforms.},
journal = {Science advances},
volume = {11},
number = {19},
pages = {eadt5356},
pmid = {40333962},
issn = {2375-2548},
mesh = {*Homeodomain Proteins/genetics/metabolism ; Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism/pathology ; Animals ; Protein Isoforms/genetics/metabolism ; Mice ; *DNA, Intergenic/genetics ; Transcriptome ; Humans ; Myoblasts/metabolism ; Gene Expression Regulation, Developmental ; Muscle, Skeletal/metabolism ; },
abstract = {DUX4 regulates the expression of genic and nongenic elements and modulates chromatin accessibility during zygotic genome activation in cleavage stage embryos. Its misexpression in skeletal muscle causes facioscapulohumeral dystrophy (FSHD). By leveraging full-length RNA isoform sequencing with short-read RNA sequencing of DUX4-inducible myoblasts, we elucidate an isoform-resolved transcriptome featuring numerous unannotated isoforms from known loci and novel intergenic loci. While DUX4 activates similar programs in early embryos and FSHD muscle, the isoform usage of known DUX4 targets is notably distinct between the two contexts. DUX4 also activates hundreds of previously unannotated intergenic loci dominated by repetitive elements. The transcriptional and epigenetic profiles of these loci in myogenic and embryonic contexts indicate that the usage of DUX4-binding sites at these intergenic loci is influenced by the cellular environment. These findings demonstrate that DUX4 induces context-specific transcriptomic programs, enriching our understanding of DUX4-induced muscle pathology.},
}

*Homeodomain Proteins/genetics/metabolism
Muscular Dystrophy, Facioscapulohumeral/genetics/metabolism/pathology
Animals
Protein Isoforms/genetics/metabolism
Mice
*DNA, Intergenic/genetics
Transcriptome
Humans
Myoblasts/metabolism
Gene Expression Regulation, Developmental
Muscle, Skeletal/metabolism

@article {pmid40333666,
year = {2025},
author = {Olivieri, DJ and Eastment, MC and Mugisha, N and Menon, MP},
title = {Correlates of cervical cancer awareness among women aged 30-49 in five sub-Saharan African nations: Evidence from the Demographic and Health Survey (DHS)-2017-2023.},
journal = {PLOS global public health},
volume = {5},
number = {5},
pages = {e0003344},
pmid = {40333666},
issn = {2767-3375},
abstract = {Cervical cancer is the leading cause of cancer-related mortality in low- and middle-income countries (LMICs). Prior studies associate high cervical cancer awareness with reductions in cervical cancer incidence. In this study, we utilize nationally representative Demographic and Health Surveys Program (DHS) to analyze correlates of cervical cancer awareness to inform global strategies. All DHS surveys between 2017-2023 were queried for questions on cervical cancer awareness. Socio-demographic variables (e.g., age, marital status), socioeconomic variables (e.g., education, wealth, literacy) and variables pertaining to healthcare decision making, distance traveled, intimate partner violence (IPV), and female genital mutilation/circumcision (FGC/M)) were extracted. Sample weights were applied, and logistic regressions were performed. Variables with p < 0.20 were included in multivariate analysis. Data was obtained from 30,214 women aged 30-49 years old living in Benin, Cameroon, Madagascar, Mauritania, and Mozambique, 19,403 of whom were asked questions on cervical cancer awareness. Cervical cancer awareness varied from 53% in Cameroon to 12% in Benin. Literacy, frequency of watching television, mobile telephone ownership, visiting a local healthcare facility and hormonal contraceptive use were associated with increased cervical cancer awareness, while lack of healthcare decision making independence was associated with decreased awareness after multivariate adjustment. Women who experienced emotional IPV were associated with increased awareness in Cameroon. Less than 4% of all women were screened for cervical cancer. Given the known association between awareness and screening, targeted efforts to increase awareness among women without communication modalities has the potential to reduce global cervical cancer disparities. Potential strategies include co-locating cervical cancer awareness programs with public health programs and implementing large-scale telecommunication outreach programs to improve awareness.},
}

@article {pmid40329475,
year = {2025},
author = {Sullivan, SD and Grueger, J and Sullivan, AP and Ramsey, SD},
title = {The consequences of pharmaceutical tariffs in the United States.},
journal = {Journal of managed care & specialty pharmacy},
volume = {},
number = {},
pages = {1-4},
doi = {10.18553/jmcp.2025.25090},
pmid = {40329475},
issn = {2376-1032},
abstract = {The Trump Administration has threatened to impose tariffs on imported branded, generic, and biosimilar pharmaceutical products. Although specific details regarding the exact rates and implementation timeline remain unclear, the administration has indicated that these tariffs will be substantial. Tariffs can create supply chain disruptions, increase costs, limit patient access to essential medications, and negatively impact research and innovation. Rather than punitive tariffs, industrial policy options and collaborative international treaties may better serve US economic and public health interests and lead to a more secure and consistent domestic supply of critical medicines.},
}

@article {pmid40329098,
year = {2025},
author = {Bulteel, AJB and Barnum, K and Datta, S and Dodge, LE and Lake, L and Elavalakanar, P and Lam, BD and Patell, R},
title = {Clinician characteristics associated with use of risk assessment models for venous thromboembolism and bleeding in hospitalized patients.},
journal = {Annals of hematology},
volume = {},
number = {},
pages = {},
pmid = {40329098},
issn = {1432-0584},
support = {DD20-2002/CC/CDC HHS/United States ; },
}

@article {pmid40328984,
year = {2025},
author = {Abernethy, NF and McCloskey, K and Trahey, M and Rinn, L and Broder, G and Andrasik, M and Laborde, R and McGhan, D and Spendolini, S and Marimuthu, S and Kanzmeier, A and Hanes, J and Kublin, JG},
title = {Rapid development of a registry to accelerate COVID-19 vaccine clinical trials.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {251},
pmid = {40328984},
issn = {2398-6352},
support = {UM1AI068614//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1AI068635//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
abstract = {Response to the SARS-Cov-2 pandemic required the unprecedented, rapid activation of the COVID-19 Prevention Network (CoVPN) representing hundreds of sites conducting vaccine clinical trials. The CoVPN Volunteer Screening Registry (VSR) collected participant information, distributed qualified candidates across sites, and monitored enrollment progress. The system consisted of three web-based interfaces. The Volunteer Questionnaire flowed into a secure database. The Site Portal supported volunteer selection, analytics, and enrollment. The Administrative Portal enabled dynamic analytic reports by geography, clinical trial, and site, including volunteering rates over time. The VSR collected over 650,000 volunteers, serving a key role in the recruitment of diverse participants for multiple Phase 3 clinical trials. Over 47% of the 166,729 volunteers selected for screening represented prioritized groups. The success of the VSR demonstrates how digital tools can be rapidly yet safely integrated into an accelerated clinical trial setting. We summarize the development of the system and lessons learned for pandemic preparedness.},
}

@article {pmid40328898,
year = {2025},
author = {Zamora, D and Xie, H and Wong, E and Santiano, C and Vivas-Jimenez, A and Sadowska-Klasa, A and Kampouri, E and Stevens-Ayers, T and Ueda Oshima, M and Leisenring, WM and Hill, JA and Boeckh, M},
title = {ELISPOT as a predictor of clinically significant cytomegalovirus infection after hematopoietic cell transplantation in letermovir recipients.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {40328898},
issn = {1476-5365},
support = {T32 AI118690/AI/NIAID NIH HHS/United States ; K23AI163343//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; K23AI163343//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; K23AI163343//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {We examined cytomegalovirus-specific cell-mediated immunity (CMV-CMI) to pp65 and IE-1 at 100 days after hematopoietic cell transplantation (HCT) following discontinuation of letermovir prophylaxis using ELISPOT (T-SPOT®.CMV, Oxford-Immunotec, Abingdon, UK). We compared ELISPOT results to a laboratory-developed intracellular cytokine staining (ICS) assay and characterized thresholds for the prediction of late clinically significant (cs)CMV infection using receiver operating characteristic analysis. We identified factors associated with high (i.e., at or above threshold) CMV-CMI to both antigens. ELISPOT correlated well with polyfunctional CMV-specific T-cell immunity by ICS. We defined thresholds of 67 and 4 spots per 250,000 cells for pp65 and IE-1, respectively, for predicting late csCMV infection. PBSC graft source, CMV seropositive donor, and/or CMV reactivation in the first 100 days post-HCT were associated with high CMV-CMI to pp65 and/or IE-1. Patients with high CMV-CMI to both antigens at day 100 had a lower incidence of late csCMV infection, however, late changes in immunosuppression affected risk prediction. Clinical risk factors (e.g., early CMV infection, acute graft-versus-host disease) predicted late csCMV and improved the predictive value of CMV-CMI testing. Thus, standardized CMV-CMI, after HCT, combined with clinical factors can be used to accurately stratify the risk of late csCMV infection after letermovir prophylaxis.},
}

@article {pmid40328734,
year = {2025},
author = {Chehayeb, RJ and Odzer, N and Albany, RA and Ferrucci, L and Sarpong, D and Perez-Escamilla, R and Lewis, JB and Phipps, AI and Meisner, A and Pusztai, L},
title = {Breastfeeding attributable fraction of triple negative breast cancer in the US.},
journal = {NPJ breast cancer},
volume = {11},
number = {1},
pages = {40},
pmid = {40328734},
issn = {2374-4677},
abstract = {Rates of triple negative breast cancer (TNBC) are higher in Black women than in non-Hispanic White women. Breastfeeding duration and younger age at first birth are known risk factors for TNBC and vary by race. To quantify the contribution of these risk factors to disparities in TNBC, we calculated the population-attributable fraction (PAF). A PubMed search was performed to identify relevant studies and pooled odds ratios for breastfeeding for < 6 months and age at first birth < 25 years were calculated. PAF was calculated using the Levin formula. PAF of breastfeeding for < 6 months was 12% (95% confidence interval (CI) 5-20%) among White women and 15% (95%CI 3-26%) among Black women. We estimate that up to 15% of annual new TNBC in Black women and 12% in White women might be avoided by supporting breastfeeding. Policies supporting breastfeeding could hence reduce TNBC incidence and lessen racial disparities.},
}

@article {pmid40328293,
year = {2025},
author = {Davis, CP and Fest, S and Cushing-Haugen, K and Kensler, TW and Chavarro, JE and Harris, HR},
title = {Dietary patterns and age at menarche in a prospective study of girls in the USA.},
journal = {Human reproduction (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/humrep/deaf072},
pmid = {40328293},
issn = {1460-2350},
support = {//Breast Cancer Research Foundation/ ; U01 HL145386/NH/NIH HHS/United States ; T32 CA094880/NH/NIH HHS/United States ; //Breast Cancer Research Foundation/ ; U01 HL145386/NH/NIH HHS/United States ; T32 CA094880/NH/NIH HHS/United States ; },
abstract = {STUDY QUESTION: Are dietary patterns associated with age at menarche after accounting for BMI-for-age (BMIz) and height?

SUMMARY ANSWER: We observed associations between both the Alternative Healthy Eating Index (AHEI) and the Empirical Dietary Inflammatory Pattern (EDIP) and age at menarche.

WHAT IS KNOWN ALREADY: Dietary patterns have been sparsely examined in relation to age at menarche and no studies have examined the association between the AHEI, a healthier diet, and EDIP, a pro-inflammatory diet, and menarche.

STUDY DESIGN, SIZE, DURATION: The Growing Up Today Study (GUTS) is a prospective cohort of children ages 9-14 years at study enrollment. GUTS enrolled in two waves with enrollment beginning in 1996 (GUTS1) and 2004 (GUTS2). For this analysis, GUTS1 and GUTS2 participants were followed through 2001 and 2008, respectively.

We included 7530 participants who completed food frequency questionnaire(s) (FFQ) prior to menarche who then self-reported age at menarche during study follow-up. Cox proportional hazard models were used to calculate multivariable hazard ratios (HRs) and 95% CIs for the associations between two dietary patterns, the AHEI and EDIP, and age at menarche, with and without adjustment for time-varying BMIz and height.

Six thousand nine hundred ninety-two participants (93%) reported menarche during the study period. On average, participants completed the baseline FFQ 1.75 years prior to menarche. Participants in the highest quintile of AHEI diet score (indicating a healthier diet) were 8% less likely to attain menarche within the next month compared to those in the lowest quintile (95% CI = 0.85-0.99; Ptrend = 0.03). This association remained after adjustment for BMIz and height (corresponding HR = 0.93; 95% CI = 0.86-1.00; Ptrend = 0.04). Participants in the highest quintile of the EDIP score (i.e. most inflammatory diet), were 15% more likely to attain menarche in the next month relative to those in the lowest quintile (95% CI = 1.06-1.25; Ptrend = 0.0004), and the association remained following adjustment for BMIz and height (corresponding HR = 1.15; 95% CI = 1.06-1.25; Ptrend = 0.0004).

Self-reported questionnaires are subject to some error; however, given our prospective study design it is likely this error is non-differential with respect to the outcome.

Our findings of an association between both the AHEI and EDIP and age at menarche indicate that diet quality may play a role in age at menarche independent of BMI or height.

This work was supported by the Breast Cancer Research Foundation. The GUTS is supported by the National Institutes of Health U01 HL145386. C.P.D. was supported by National Institutes of Health T32 CA094880. The authors have no conflicts of interest to disclose.

TRIAL REGISTRATION NUMBER: N/A.},
}

@article {pmid40327712,
year = {2025},
author = {Jia, C and Peters, BA and Usyk, M and Wang, Z and Hanna, DB and Sharma, A and Anastos, K and Kaplan, R and Burk, R and Qi, Q},
title = {Associations of fecal and blood microbiota-related metabolites with gut microbiota and type 2 diabetes in HIV infection.},
journal = {AIDS (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAD.0000000000004231},
pmid = {40327712},
issn = {1473-5571},
abstract = {OBJECTIVES: Assess the relationships of gut microbiota (GMB)-related metabolites in feces and blood with GMB and type 2 diabetes (T2D) in the context of HIV infection, the presence of which could disrupt host metabolism.

DESIGN: We conducted a cross-sectional study among 111 women with HIV (WWH) and 56 women without HIV (WWOH) in the MACS/WIHS Combined Cohort Study.

METHODS: We measured 62 targeted metabolites in both feces and plasma and examined their associations with GMB composition (243 species) and prevalent T2D.

RESULTS: We observed 44 metabolites with detection rates ≥25% in both feces and plasma. Correlations between fecal and plasma metabolites were stronger in WWOH than in WWH (median r: 0.13 vs. 0.04). Fecal metabolites showed stronger correlations with GMB than plasma metabolites among all participants (median r [IQR] of measured vs. GMB-predicted metabolites: 0.24 [0.11, 0.33] vs. 0.08 [-0.03, 0.24]; P = 0.002), and the difference in this comparison was more pronounced in WWOH compared to WWH. We found a moderate consistency for the associations of fecal and plasma metabolites with T2D in WWH (r for effect sizes of fecal and plasma metabolites on T2D = 0.36; P = 0.03), but not in WWOH (r = 0.13; P = 0.45). Fecal and plasma kynurenate, a tryptophan catabolism metabolite, showed opposite associations with T2D, with a positive association for plasma (OR: 2.54, 95% CI: [1.28-5.76]; P = 0.01) and an inverse association for feces (0.59 [0.27-1.23]; P = 0.18) in WWH.

CONCLUSIONS: Fecal metabolites are more strongly associated with GMB than plasma metabolites, especially among WWOH. HIV infection might also influence associations of fecal and plasma metabolites with T2D.},
}

@article {pmid40327300,
year = {2025},
author = {Hamilton, EP and Jeselsohn, RM and Vahdat, LT and Hurvitz, SA},
title = {PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor Degraders for Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.},
journal = {Targeted oncology},
volume = {},
number = {},
pages = {},
pmid = {40327300},
issn = {1776-260X},
abstract = {The estrogen receptor (ER) signaling pathway is a key driver of breast cancer, primarily through the activation of genes that promote tumor cell survival and growth. The recommended first-line treatment for ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer is endocrine therapy plus a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. However, most patients experience disease progression, and there is no clear standard of care in the second-line setting. Thus, novel treatments in the advanced setting are needed. In this narrative review, we describe the unique mechanisms of action of a new class of drugs called PROteolysis TArgeting Chimera (PROTAC) ER degraders. Unlike other ER-targeted therapies, these small molecules harness the body's primary intracellular natural protein disposal machinery, the ubiquitin-proteasome system, to directly induce ER degradation. Vepdegestrant (ARV-471) is the furthest advanced PROTAC ER degrader currently in clinical development. Preclinical data demonstrate increased tumor growth inhibition with vepdegestrant alone or in combination with CDK4/6 inhibitors compared with the selective ER degrader fulvestrant. In a first-in-human phase 1/2 clinical study, vepdegestrant administered orally as monotherapy or in combination with palbociclib showed promising clinical activity and a favorable safety profile in patients with heavily pretreated ER+/HER2- advanced breast cancer. Several other PROTAC ER degraders (AC699, ERD-3111, ERD-4001, and HP568) are in early development and have demonstrated activity in preclinical breast cancer models, with some recently entering clinical trials. The data highlight the potential for PROTAC ER degraders to be a new backbone therapy in breast cancer.},
}

@article {pmid40325041,
year = {2025},
author = {Langowski, MD and Francica, JR and Roederer, AL and Hurlburt, NK and Rodarte, JV and Da Silva Pereira, L and Flynn, BJ and Bonilla, B and Dillon, M and Kiyuka, P and Ravichandran, R and Weidle, C and Carter, L and Rao, M and Matyas, GR and Pepper, M and Idris, AH and Seder, RA and Pancera, M and King, NP},
title = {Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {87},
pmid = {40325041},
issn = {2059-0105},
support = {INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; INV-010680/GATES/Gates Foundation/United States ; DGE-1762114//National Science Foundation/ ; },
abstract = {A vaccine that provides robust, durable protection against malaria remains a global health priority. Although a breakthrough in the fight against malaria has recently been achieved by the licensure of two vaccines based on the circumsporozoite protein (CSP), the effectiveness and durability of protection can still be improved. Both vaccines contain a portion of CSP that does not include epitopes targeted by recently identified, potently protective monoclonal antibodies, suggesting that newer immunogens can expand the breadth of immunity and potentially increase protection. Here we explored >100 alternative CSP-based immunogens and evaluated the immunogenicity and protection of a large number of candidates, comparing several to the licensed R21 vaccine. The data highlight several general features that improve the stability and immunogenicity of CSP-based vaccines, such as inclusion of the C-terminal domain and high-density display on protein nanoparticle scaffolds. We also identify antigen design strategies that do not warrant further exploration, such as synthetic repeat regions that include non-native repeat cadences. The benchmark R21 vaccine outperformed our best immunogen for immunogenicity and protection. Overall, our data provide valuable insights on the inclusion of junctional region epitopes that will guide the development of potent and durable vaccines against malaria.},
}

@article {pmid40323670,
year = {2025},
author = {Rodríguez-Díaz, CE and Zangeneh, SZ and Chen, YO and Guo, X and Tsuyuki, K and Ransome, Y and Friedman, RK and Srithanaviboonchai, K and Roberts, ST and Mimiaga, MJ and Mayer, KH and Safren, SA},
title = {The Longitudinal Impact of Psychosocial Syndemic Variables on Adherence to Antiretroviral Therapy Among People With HIV in Brazil, Thailand, and Zambia: An Analysis by HIV Transmission Groups in HPTN 063.},
journal = {AIDS education and prevention : official publication of the International Society for AIDS Education},
volume = {37},
number = {2},
pages = {89-106},
doi = {10.1521/aeap.2025.37.2.89},
pmid = {40323670},
issn = {1943-2755},
mesh = {Humans ; Male ; *HIV Infections/drug therapy/psychology/epidemiology/transmission ; Thailand/epidemiology ; Zambia/epidemiology ; Female ; Adult ; Longitudinal Studies ; Brazil/epidemiology ; *Medication Adherence/psychology ; *Syndemic ; *Anti-HIV Agents/therapeutic use ; Homosexuality, Male/psychology/statistics & numerical data ; Middle Aged ; Substance-Related Disorders/psychology/epidemiology ; Heterosexuality/psychology/statistics & numerical data ; Cross-Sectional Studies ; Young Adult ; },
abstract = {In the field of HIV prevention and care, most studies of HIV syndemic problems are cross-sectional, few differentiate by HIV transmission groups, and few focus on people living with HIV (PWH). We analyzed one-year longitudinal data of 692 sexually active PWH (heterosexual men [HM], heterosexual women [HW], and men who have sex with men [MSM]) in care from Brazil, Thailand, and Zambia. Syndemic scores (0-3+) included stimulant use, polydrug use, depression, alcohol use, and fear of discrimination. Overall, syndemic scores were associated with lower ART adherence over time, but this differed across sexual transmission categories. For HM and HW, those with 2 or 3+ syndemic problems had lower odds of ART adherence than those with none. However, for MSM, the association between syndemic scores and ART adherence was not significant. While syndemic problems generally predicted suboptimal ART adherence among PWH, the association appears nuanced across subgroups.},
}

Humans
Male
*HIV Infections/drug therapy/psychology/epidemiology/transmission
Thailand/epidemiology
Zambia/epidemiology
Female
Adult
Longitudinal Studies
Brazil/epidemiology
*Medication Adherence/psychology
*Syndemic
*Anti-HIV Agents/therapeutic use
Homosexuality, Male/psychology/statistics & numerical data
Middle Aged
Substance-Related Disorders/psychology/epidemiology
Heterosexuality/psychology/statistics & numerical data
Cross-Sectional Studies
Young Adult

@article {pmid40323243,
year = {2025},
author = {Yu, JB and Grew, D and Sculley, E and Siva, S and Hardcastle, N and Tang, C and Yang, J and Kim, M and Lo, SS},
title = {Practical Considerations for the Treatment of Primary Renal Cell Carcinoma With SABR.},
journal = {Practical radiation oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.prro.2025.03.007},
pmid = {40323243},
issn = {1879-8519},
}

@article {pmid40321251,
year = {2025},
author = {Deslandes, B and Wu, X and Lee, MA and Goudswaard, LJ and Jones, GW and Gsur, A and Lindblom, A and Ogino, S and Vymetalkova, V and Wolk, A and Wu, AH and Huyghe, JR and Peters, U and Phipps, AI and Thomas, CE and Pai, RK and Grant, RC and Buchanan, DD and Yarmolinsky, J and Gunter, MJ and Zheng, J and Hazelwood, E and Vincent, EE},
title = {Transcriptome-wide Mendelian randomisation exploring dynamic CD4+ T cell gene expression in colorectal cancer development.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40321251},
support = {HHSN268201200008C/HL/NHLBI NIH HHS/United States ; U01 CA167551/CA/NCI NIH HHS/United States ; R01 CA081488/CA/NCI NIH HHS/United States ; U01 CA122839/CA/NCI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; HHSN268201200008I/HL/NHLBI NIH HHS/United States ; U19 CA148107/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Recent research has identified a potential protective effect of higher numbers of circulating lymphocytes on colorectal cancer (CRC) development. However, the importance of different lymphocyte subtypes and activation states in CRC development and the biological pathways driving this relationship remain poorly understood and warrant further investigation. Specifically, CD4+ T cells - a highly dynamic lymphocyte subtype - undergo remodelling upon activation to induce the expression of genes critical for their effector function. Previous studies investigating their role in CRC risk have used bulk tissue, limiting our current understanding of the role of these cells to static, non-dynamic relationships only.

METHODS: Here, we combined two genetic epidemiological methods - Mendelian randomisation (MR) and genetic colocalisation - to evaluate evidence for causal relationships of gene expression on CRC risk across multiple CD4+ T cell subtypes and activation stage. Genetic proxies were obtained from single-cell transcriptomic data, allowing us to investigate the causal effect of expression of 1,805 genes across five CD4+ T cell activation states on CRC risk (78,473 cases; 107,143 controls). We repeated analyses stratified by CRC anatomical subsites and sex, and performed a sensitivity analysis to evaluate whether the observed effect estimates were likely to be CD4+ T cell-specific.

RESULTS: We identified six genes with evidence (FDR-P<0.05 in MR analyses and H4>0.8 in genetic colocalisation analyses) for a causal role of CD4+ T cell expression in CRC development - FADS2, FHL3, HLA-DRB1, HLA-DRB5, RPL28, and TMEM258. We observed differences in causal estimates of gene expression on CRC risk across different CD4+ T cell subtypes and activation timepoints, as well as CRC anatomical subsites and sex. However, our sensitivity analysis revealed that the genetic proxies used to instrument gene expression in CD4+ T cells also act as eQTLs in other tissues, highlighting the challenges of using genetic proxies to instrument tissue-specific expression changes.

CONCLUSIONS: Our study demonstrates the importance of capturing the dynamic nature of CD4+ T cells in understanding disease risk, and prioritises genes for further investigation in cancer prevention research.},
}

@article {pmid40313741,
year = {2025},
author = {Barrero, DJ and Hedouin, S and Mao, Y and Asbury, CL and Stergachis, A and O'Toole, E and Biggins, S},
title = {Centromeres in the thermotolerant yeast K. marxianus mediate attachment to a single microtubule.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40313741},
issn = {2693-5015},
support = {DP5 OD029630/OD/NIH HHS/United States ; R35 GM134842/GM/NIGMS NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; },
abstract = {Eukaryotic chromosome segregation requires spindle microtubules to attach to chromosomes through kinetochores. The chromosomal locus that mediates kinetochore assembly is the centromere and is epigenetically specified in most organisms by a centromeric histone H3 variant called CENP-A. An exception to this is budding yeast which have short, sequenced-defined point centromeres. In S. cerevisiae, a single CENP-A nucleosome is formed at the centromere and is sufficient for kinetochore assembly. The thermophilic budding yeast Kluyveromyces marxianus also has a point centromere but its length is nearly double the S. cerevisiae centromere and the number of centromeric nucleosomes and kinetochore attachment sites is unknown. Purification of native kinetochores from K. marxianus yielded a mixed population, with one subpopulation that appeared to consist of doublets, making it unclear whether K. marxianus shares the same attachment architecture as S. cerevisiae. Here, we demonstrate that though the doublet kinetochores have a functional impact on kinetochore strength, kinetochore localization throughout the cell cycle appears conserved between these two yeasts. In addition, whole spindle electron tomography demonstrates that a single microtubule binds to each chromosome. Single-molecule nucleosome mapping analysis suggests the presence of a single centromeric nucleosome. Taken together, we propose that the K. marxianus point centromere assembles a single centromeric nucleosome that mediates attachment to one microtubule.},
}

@article {pmid40323013,
year = {2025},
author = {Garcia, NMG and Becerra, JN and Srinivasan, S and McKinney, BJ and DiMarco, AV and Wu, F and Fitzgibbon, M and Alvarez, JV},
title = {APOBEC3 activity promotes the survival and evolution of drug-tolerant persister cells during EGFR inhibitor resistance in lung cancer.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-24-0442},
pmid = {40323013},
issn = {2767-9764},
abstract = {APOBEC mutagenesis is one of the most common endogenous sources of mutations in human cancer and is a major source of genetic intratumor heterogeneity. High levels of APOBEC mutagenesis are associated with poor prognosis and aggressive disease across diverse cancers, but the mechanistic and functional impacts of APOBEC mutagenesis on tumor evolution and therapy resistance remain relatively unexplored. To address this, we investigated the contribution of APOBEC mutagenesis to acquired therapy resistance in a model of EGFR-mutant non-small cell lung cancer. We find that inhibition of EGFR in lung cancer cells leads to a rapid and pronounced induction of APOBEC3 expression and activity. Functionally, APOBEC expression promotes the survival of drug-tolerant persister cells (DTPs) following EGFR inhibition. Constitutive expression of APOBEC3B alters the evolutionary trajectory of acquired resistance to the EGFR inhibitor gefitinib, making it more likely that resistance arises through de novo acquisition of the T790M gatekeeper mutation and squamous transdifferentiation during the DTP state. APOBEC3B expression is associated with increased expression of the squamous cell transcription factor deltaNp63 and squamous cell transdifferentiation in gefitinib-resistant cells. Knockout of p63 in gefitinib-resistant cells reduces the expression of the deltaNp63 target genes IL1alpha/beta and sensitizes these cells to the third-generation EGFR inhibitor osimertinib. These results suggest that APOBEC activity promotes acquired resistance by facilitating evolution and transdifferentiation in DTPs, and suggest that approaches to target deltaNp63 in gefitinib-resistant lung cancers may have therapeutic benefit.},
}

@article {pmid40321654,
year = {2025},
author = {Alvarez, CS and Kaplan, RC and Camargo, MC and Avilés-Santa, ML and Daviglus, M and Garcia-Bedoya, O and Isasi, CR and Pattany, MS and Thyagarajan, B and Talavera, GA and Graubard, BI and McGlynn, KA},
title = {Associations of Helicobacter pylori with metabolic dysfunction-associated steatotic liver disease and related conditions: cross-sectional results from the Hispanic Community Health Study/Study of Latinos.},
journal = {Lancet regional health. Americas},
volume = {41},
number = {},
pages = {100953},
pmid = {40321654},
issn = {2667-193X},
abstract = {BACKGROUND: Hispanic/Latino populations have been reported to have high rates of both metabolic dysfunction-associated steatotic liver disease (MASLD) and Helicobacter pylori infection. Several observational studies, predominantly from Asian populations, have suggested a link between these conditions. Thus, the primary objective of the current study was to examine the association between H. pylori and MASLD and secondarily, to assess its association with related conditions in the Hispanic Community Health Study/Study of Latinos.

METHODS: In this cross-sectional study, a total of 16,144 participants with baseline data on H. pylori serology were included. Based on weighted statistics, the median age was 40 years [interquartile range (IQR): 28, 52]; 52.2% women (n = 9661) and 47.8% men (n = 6483). Participants' Hispanic/Latino heritage included 37.6% Mexicans (n = 6397), 20.1% Cubans (n = 2307), 15.8% Puerto Ricans (n = 2663), 10.0% Dominicans (n = 1447), 7.4% Central Americans (n = 1710), 4.9% South Americans (1052). MASLD was estimated using the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI). Other conditions examined were obesity, central obesity, diabetes and metabolic syndrome. Multivariable logistic regression models were used to calculate the ratios of (adjusted) prevalences (RP) and 95% confidence intervals (CI) for the overall association of H. pylori seropositivity with MASLD and related conditions. Analyses were also stratified by Hispanic/Latino heritage.

FINDINGS: The overall prevalence of MASLD ranged from 47% (FLI) to 65% (HSI). After accounting for age, sex, education, and other key variables, the analysis found a modest association between H. pylori seropositivity and MASLD as determined by HSI (RP: 1.06, 95% CI: 1.02-1.10) overall, and among individuals of Puerto Rican and Mexican heritages. Furthermore, an overall association between H. pylori seropositivity and obesity was observed (RP: 1.09, 95% CI: 1.02-1.16).

INTERPRETATION: This study provides support for a positive association of H. pylori seropositivity with MASLD and obesity among Hispanic/Latino populations. However, given the exploratory nature of these findings, caution is warranted in their interpretation. Further research is necessary to establish causality and examine potential mechanisms of these associations.

FUNDING: The Hispanic Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), San Diego State University (N01-HC65237), and University of Illinois at Chicago (HHSN268201300003I). The following Institutes/Centers/Offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, United States, the National Institute of Deafness and Other Communications Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements. This study was also funded in part by the Intramural Research Program of the National Cancer Institute.},
}

@article {pmid40321290,
year = {2025},
author = {Samandari, T and Achola, M and Hutter, JN and Mboya, G and Otieno, W and Kee, JJ and Huang, Y and Aponte, JJ and Ockenhouse, CF and Lee, CK and Polakowski, L and Yacovone, M and Tapley, A and Dadabhai, S and Mkhize, NN and Kaldine, H and Bhebhe, S and Moore, PL and Hural, J and Garrett, N and Kublin, JG},
title = {Neutralizing Antibody Responses After mRNA COVID-19 Booster Vaccination are Unaffected by Parasitemia in a Malaria-Endemic Setting.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40321290},
support = {T32 AI007044/AI/NIAID NIH HHS/United States ; UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1 AI068618/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {Subclinical malaria may reduce the immunogenicity of mRNA vaccines. We evaluated neutralizing antibody responses in adults with (n=87) and without (n=221) PCR-confirmed Plasmodium falciparum who received a COVID-19 booster. Similar boosted ID50 geometric mean titers >22,000 in parasitemic and non-parasitemic participants suggests that COVID-19 mRNA vaccine responses are not impaired.},
}

@article {pmid40321081,
year = {2025},
author = {Lottermoser, JA and Liu, H and Bai, J and Hu, Z and Dittman, JS},
title = {Complexin gains effective access to the assembling SNAREs via its membrane-binding C-terminal domain.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP286500},
pmid = {40321081},
issn = {1469-7793},
support = {NS116747/NS/NINDS NIH HHS/United States ; NS127534/NS/NINDS NIH HHS/United States ; R56NS128048//National Science Foundation/ ; },
abstract = {The conserved presynaptic SNARE-binding protein complexin (Cpx) promotes Ca[2+]-triggered synaptic vesicle (SV) fusion and inhibits spontaneous fusion at some synapses. A membrane-binding motif in the C-terminal domain (CTD) of Cpx plays a critical role in Cpx function, but it remains unclear whether the CTD participates in Cpx regulation of synaptic transmission beyond targeting Cpx to membranes. We examined the impact of the Caenorhabditis elegans CPX-1 CTD in vivo and found that this domain profoundly boosted the efficiency of CPX-1-mediated inhibition of spontaneous SV fusion as a function of protein abundance at the synapse. Removing the C-terminal half of CPX-1 and substituting it with the SV protein RAB-3 was able to fully restore both the fusogenic and inhibitory functions of CPX-1 whereas other SV proteins failed to restore CPX-1 function with the same efficiency regardless of abundance. These results indicate that regulation of spontaneous SV fusion requires a specific interaction of CPX-1 with the SV membrane. We propose that Cpx cannot efficiently access assembling SNAREs from the cytoplasm and that interactions of its CTD with the SV membrane guide Cpx to these sites of SNARE assembly. KEY POINTS: Complexin (Cpx) regulates presynaptic SNARE assembly to control synaptic transmission. A membrane curvature-sensing motif within the Cpx C-terminal domain (CTD) recruits Cpx to vesicles. Replacement of the CTD with the synaptic vesicle protein Rab3 can restore full Cpx function whereas other vesicle proteins fail to substitute regardless of abundance. The efficiency of Cpx-mediated inhibition of synaptic vesicle fusion is profoundly enhanced by the specific localization supplied by its CTD. These results suggest that Cpx reaches the assembling SNARE complexes via its specific CTD-membrane interactions and these SNAREs are inaccessible from the cytoplasmic compartment.},
}

@article {pmid40320146,
year = {2025},
author = {Su, CT and Saber, W and Bansal, A and Li, L and Nakamura, R and Cutler, C and Roth, JA and Wright, W and Steuten, L and Ramsey, SD},
title = {Out-of-Pocket Expenditures and Financial Hardship Among Patients with Myelodysplastic Syndrome Undergoing Allogeneic Transplant or Hypomethylating Agent / Supportive Care (BMT CTN 1102).},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.04.015},
pmid = {40320146},
issn = {2666-6367},
abstract = {INTRODUCTION: The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1102 trial demonstrated that allogeneic hematopoietic cell transplantation (HCT) was associated with superior overall survival compared to non-HCT approaches among elderly patients with higher-risk myelodysplastic syndrome (MDS). The trial included an ancillary cost diary component to assess the out-of-pocket (OOP) expenditures and financial hardship in the post-HCT period through three phased surveys for up to 19 months after enrollment.

OBJECTIVE: The purpose of the study is to assess the OOP costs and financial hardship experienced by participants of BMT CTN 1102.

STUDY DESIGN: BMT CTN 1102 assigned participants to Donor and No-Donor arms based on donor availability. Participants could additionally enroll in the ancillary cost diary component, with a total of 138 participants returning 267 surveys across three survey waves at 1-, 7-, and 19-months after enrollment. As participants who underwent HCT returned 78% (207/267) of the total surveys, we report on the collected data descriptively.

RESULTS: Participants who underwent HCT had high levels of monthly OOP expenditure ($1126, $812, $442) and financial hardship (47%, 53%, 57%) across the three survey waves. For reference, participants who did not undergo HCT generally reported lower levels of OOP expenditure ($478, $845, $256) and financial hardship (37%, 55%, 46%).

CONCLUSION: Among BMT CTN 1102 participants, those who underwent HCT reported high levels of OOP expenditures and financial hardship for up to 19 months after enrollment. Ongoing routine assessment of patient-level OOP expenditures and financial burden may be helpful in the post-HCT survivorship period.},
}

@article {pmid40319195,
year = {2025},
author = {Merkel, EC and Meyer, CL and Yusuf, RA and Morrison, CF and Kelly, DL and Levine, DR and LeBlanc, TW and Ullrich, CK and El-Jawahri, A},
title = {What do pediatric transplant physicians think about palliative care? Results from a national survey study.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {40319195},
issn = {1476-5365},
abstract = {The benefits of palliative care (PC) for hematopoietic cell transplant (HCT) patients are well established, however, uptake in pediatric HCT remains limited. To understand pediatric transplant physicians' attitudes towards PC, we conducted a cross-sectional study with a 28-question survey. A composite score and regression model identified factors associated with positive attitudes towards subspecialty PC. Ninety-eight participants reported caring for pediatric patients. Most (81%) trust PC clinicians to care for their patients, yet 33% feel PC clinicians lack enough HCT knowledge to counsel patients. Nearly half (46%) see the name "PC" as a barrier to referral. Multivariable analysis showed that spiritual practice (β = 1.53, p = 0.029), <10 years of clinical practice (β = 2.23, p = 0.007), and perceived PC quality (β = 0.73, p < 0.001) were associated with a more positive attitude towards PC. More training in PC (β = -2.70, p = 0.003) and a higher sense of ownership over PC issues (β = -0.51, p = 0.001) were associated with a more negative attitude towards subspecialty PC. These findings highlight barriers to pediatric HCT and PC collaboration, including concerns about PC team knowledge of HCT and patient perceptions. While most pediatric transplant physicians trust PC to enhance patient care, interventions are needed to improve collaboration.},
}

@article {pmid40319052,
year = {2025},
author = {Olivieri, DJ and Berridge-Green, A and Othus, M and Radich, JP and Advani, AS and Erba, HP and Walter, RB},
title = {Biobanking and consent to future biospecimen use among adults enrolled in SWOG trials from 2000 to 2024.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {85},
pmid = {40319052},
issn = {2044-5385},
support = {U10 CA180819/CA/NCI NIH HHS/United States ; U10 CA180888/CA/NCI NIH HHS/United States ; ASH HONORS Award (DJO)//American Society of Hematology (ASH)/ ; U10-CA180888, U10-CA180819//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
}

@article {pmid40318950,
year = {2025},
author = {Grivas, P and Aragon-Ching, JB and Bellmunt, J and Loriot, Y and Climent Duran, MA and Sridhar, SS and Su, PJ and Park, SH and Kopyltsov, E and Yamamoto, Y and Jacob, N and Hoffman, J and Tyroller, K and Manitz, J and Kearney, M and Schlichting, M and Powles, T},
title = {Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Long-term Analyses of Patient-reported Outcomes and Quality-adjusted Time Without Symptoms or Toxicity from the JAVELIN Bladder 100 Trial.},
journal = {European urology oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euo.2025.04.004},
pmid = {40318950},
issn = {2588-9311},
abstract = {BACKGROUND AND OBJECTIVE: In JAVELIN Bladder 100, avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival versus BSC alone, with no detrimental impact on quality of life (QOL), in patients with advanced urothelial carcinoma without progression following first-line platinum-based chemotherapy. We report long-term analyses of patient-reported outcomes (PROs) in patients treated with avelumab (any duration or ≥12 mo) and a post hoc analysis comparing quality-adjusted time without symptoms or toxicity (Q-TWiST) between arms.

METHODS: PROs were assessed using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQol 5-level EQ-5D (EQ-5D-5L). Q-TWiST was calculated as the utility-weighted sum of mean time in three health states: time with all-cause grade 3/4 toxicity prior to progression, time without grade 3/4 toxicity or symptoms of progression, and time after progression.

KEY FINDINGS AND LIMITATIONS: In the overall avelumab plus BSC arm (n = 350) and the subgroup treated for ≥12 mo (n = 118), completion rates for PRO assessments during treatment were >80%. FBlSI-18 total and EQ-5D-5L index scores remained stable throughout 24 mo of treatment, with no clinically important changes from baseline. The mean Q-TWiST was 18.46 mo with avelumab plus BSC versus 15.13 mo with BSC alone (22% relative improvement). Limitations include open-label trial design and small patient numbers at later cycles.

Patients receiving avelumab had preserved health-related QOL and control of cancer-related symptoms with manageable toxicity, further supporting avelumab first-line maintenance as the recommended treatment for advanced urothelial carcinoma not progressed after platinum-based chemotherapy.},
}

@article {pmid40318860,
year = {2025},
author = {Tembhare, P and Chen, X and Chan, JKC and Wood, B and Naresh, KN},
title = {Fifth edition WHO classification: precursor lymphoid neoplasms, acute leukaemias of mixed or ambiguous lineage, myeloid/lymphoid neoplasms, and histiocytic and dendritic cell neoplasms, including strategies for application in resource-limited settings.},
journal = {Journal of clinical pathology},
volume = {},
number = {},
pages = {},
doi = {10.1136/jcp-2025-210135},
pmid = {40318860},
issn = {1472-4146},
abstract = {The fifth edition of the WHO classification of haematolymphoid tumours (WHO-HEM5) introduces significant updates to the classification of acute lymphoblastic leukaemia, ALAL (including mixed phenotype acute leukaemia (MPAL)), myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK), and histiocytic and dendritic cell neoplasms, reflecting the advances in the understanding of the genetic basis of these diseases. This review provides an overview of these changes, highlighting a shift to a more refined molecular-genetic approach. The incorporation of newly recognised genetic subtypes into the classification scheme underscores the evolving landscape of these entities. Challenges in diagnosing ALAL/MPAL and MLN-TK are discussed, along with recent insights into histiocytic and dendritic cell neoplasms, including newly defined entities such as ALK-positive histiocytosis.The review also explores the practical implications of WHO-HEM5, particularly in resource-limited settings, where comprehensive molecular testing may be unavailable. While morphology and immunohistochemistry remain essential diagnostic tools, strategic use of flow cytometry and targeted fluorescence in situ hybridisation can facilitate risk-adapted classification and improve survival in regions with limited resources and therapeutic options. Future large-scale studies are necessary to establish the diagnostic and prognostic value of these newly genetically defined entities for diverse healthcare environments, and to standardise guidelines in refining disease classification and optimising patient outcomes.},
}

@article {pmid40318736,
year = {2025},
author = {Lee, SJ and Pavletic, S and Blazar, BR and Yao, Y and Ji, R and Marshall, K and Cutler, C and , },
title = {Belumosudil for Chronic Graft-Versus-Host Disease: Analysis of Long-Term Results From the KD025-208 and ROCKstar Studies.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.04.020},
pmid = {40318736},
issn = {2666-6367},
abstract = {BACKGROUND: Belumosudil is an oral selective rho-associated coiled-coil-containing protein kinase-2 (ROCK2) inhibitor approved for the treatment of chronic graft-versus-host disease (cGVHD) following an allogeneic hematopoietic cell transplant (alloHCT) in patients aged ≥12 years after failure of ≥2 prior systemic lines of therapy (LOTs). The KD025-208 (NCT02841995) and KD025-213 (ROCKstar; NCT03640481) studies demonstrated that belumosudil was well tolerated, with clinically meaningful responses in patients with cGVHD. KD025-217 (NCT05305989) is a follow-up study that evaluated extended treatment with belumosudil in patients enrolled in the parent studies, KD025-208 and ROCKstar.

OBJECTIVE: This pooled analysis reports the long-term follow-up (overall median follow-up duration of 31.4 months) results from these studies in patients with cGVHD.

STUDY DESIGN: The study included a total of 208 patients across 3 cohorts. Cohort 1 (n=95) received belumosudil 200 mg once daily, cohort 2 (n=92) received belumosudil 200 mg twice daily and cohort 3 (n=21) received belumosudil 400 mg once daily. The primary end point was best overall response rate (ORR). Duration of response (DOR), failure-free survival (FFS) and time to next treatment (TTNT) were also evaluated in this analysis.

RESULTS: The best ORR in the modified intent-to-treat (mITT) population was 72%. The median DOR for the responder population was 62.3 weeks (range, 36.1-82.6 weeks). The median FFS in the mITT population was 15.1 months (range, 11.3-20.6 months). The 1- and 2-year FFS rates were 56% and 40%, respectively. The median TTNT was 22.1 months (range, 15.2-40.3 months), where 47% of patients received a new systemic therapy for cGVHD by 36 months.

CONCLUSION: When compared with the published data, the long-term results from this pooled analysis of these two phase 2 studies demonstrated belumosudil was associated with durable responses, and it remained well tolerated with no new safety concerns.},
}

@article {pmid40313749,
year = {2025},
author = {Chanda, A and Song, Y and Nazir, J and Lin, C and Cheng, A and Sargent, J and Sikora, AE},
title = {Bridging Gaps in Antibody Responses and Animal Welfare: Assessing Blood Collection Methods and Vaginal Immunity in Mice Immunized with Intranasal Gonococcal Vaccines.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40313749},
issn = {2693-5015},
support = {R01 AI117235/AI/NIAID NIH HHS/United States ; },
abstract = {Assessing antibody titers and functional responses is essential for evaluating vaccine efficacy, yet the impact of blood collection methods on these immunological assessments remains unclear. Retro-orbital (RO) blood collection is commonly used but significant complications can occur. Increasingly, investigators have adopted alternative blood collection approaches, such as saphenous vein (SV) sampling to improve laboratory animal welfare. This study compared RO and SV sampling in the development of a Neisseria gonorrhoeae (Ng) vaccine, evaluating Adhesin Complex Protein (ACP) and multiple transferable resistance (Mtr) E protein (MtrE) as antigen candidates. Epitope mapping revealed that ACP and MtrE possess multiple, highly accessible B-cell and T-cell epitope clusters, reinforcing their immunological potential. Following intranasal immunization with rACP, rACP+CpG, and rMtrE+CpG, we assessed the specificity, magnitude, kinetics, and functional quality of immune responses elicited by the immunization regimens. Out of 45 comparisons, only eight significant differences were detected in antibody titers, while the human serum bactericidal assays revealed no differences between RO and SV in antigen-immunized groups. However, antibodies elicited by rACP alone or ACP+CpG in SV samples restored 30.05% and 75.2% of human lysozyme hydrolytic activity compared to 19.3 and 59.9 % in RO, respectively suggesting that SV sampling may be more reliable for assessing functional antibody responses. Beyond its immunological advantages, SV sampling reduces stress, minimizes ocular trauma, and improves animal welfare, making it a viable alternative to RO collection. Given its widespread use in vaccine research, standardizing SV sampling could improve data reliability, ethical compliance, and translational relevance in preclinical studies.},
}

@article {pmid40317503,
year = {2025},
author = {Christie, JR and Romine, P and Eddy, K and Chen, DL and Daher, O and Abdelrazek, M and Malthaner, RA and Qiabi, M and Nayak, R and Kinahan, P and Nair, VS and Mattonen, SA},
title = {Thorax-encompassing multi-modality PET/CT deep learning model for resected lung cancer prognostication: A retrospective, multicenter study.},
journal = {Medical physics},
volume = {},
number = {},
pages = {},
doi = {10.1002/mp.17862},
pmid = {40317503},
issn = {2473-4209},
support = {//Gerald C. Baines Foundation/ ; //London Health Sciences Foundation/ ; 152218//Cancer Research Society/ ; //Natural Sciences and Engineering Research Council of Canada/ ; 2020-06498//Discovery Grants program/ ; //Lawson Health Research Institute's Internal Research Fund (IRF)/ ; T32CA009515/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Patients with early-stage non-small cell lung cancer (NSCLC) typically receive surgery as their primary form of treatment. However, studies have shown that a high proportion of these patients will experience a recurrence after their resection, leading to an increased risk of death. Cancer staging is currently the gold standard for establishing a patient's prognosis and can help clinicians determine patients who may benefit from additional therapy. However, medical images which are used to help determine the cancer stage, have been shown to hold unutilized prognostic information that can augment clinical data and better identify high-risk NSCLC patients. There remains an unmet need for models to incorporate clinical, pathological, surgical, and imaging information, and extend beyond the current staging system to assist clinicians in identifying patients who could benefit from additional therapy immediately after surgery.

PURPOSE: We aimed to determine whether a deep learning model (DLM) integrating FDG PET and CT imaging from the thoracic cavity along with clinical, surgical, and pathological information can predict NSCLC recurrence-free survival (RFS) and stratify patients into risk groups better than conventional staging.

MATERIALS AND METHODS: Surgically resected NSCLC patients enrolled between 2009 and 2018 were retrospectively analyzed from two academic institutions (local institution: 305 patients; external validation: 195 patients). The thoracic cavity (including the lungs, mediastinum, pleural interfaces, and thoracic vertebrae) was delineated on the preoperative FDG PET and CT images and combined with each patient's clinical, surgical, and pathological information. Using the local cohort of patients, a multi-modal DLM using these features was built in a training cohort (n = 225), tuned on a validation cohort (n = 45), and evaluated on testing (n = 35) and external validation (n = 195) cohorts to predict RFS and stratify patients into risk groups. The area under the curve (AUC), Kaplan-Meier curves, and log-rank test were used to assess the prognostic value of the model. The DLM's stratification performance was compared to the conventional staging stratification.

RESULTS: The multi-modal DLM incorporating imaging, pathological, surgical, and clinical data predicted RFS in the testing cohort (AUC = 0.78 [95% CI:0.63-0.94]) and external validation cohort (AUC = 0.66 [95% CI:0.58-0.73]). The DLM significantly stratified patients into high, medium, and low-risk groups of RFS in both the testing and external validation cohorts (multivariable log-rank p < 0.001) and outperformed conventional staging. Conventional staging was unable to stratify patients into three distinct risk groups of RFS (testing: p = 0.94; external validation: p = 0.38). Lastly, the DLM displayed the ability to further stratify patients significantly into sub-risk groups within each stage in the testing (stage I: p = 0.02, stage II: p = 0.03) and external validation (stage I: p = 0.05, stage II: p = 0.03) cohorts.

CONCLUSION: This is the first study to use multi-modality imaging along with clinical, surgical, and pathological data to predict RFS of NSCLC patients after surgery. The multi-modal DLM better stratified patients into risk groups of poor outcomes when compared to conventional staging and further stratified patients within each staging classification. This model has the potential to assist clinicians in better identifying patients that may benefit from additional therapy.},
}

@article {pmid40316478,
year = {2025},
author = {Cavanaugh, D and Holt, SK and Dwyer, E and Petersen, E and Gore, JL and Schade, GR and Grivas, P and Hsieh, AC and Lee, JK and Montgomery, B and Schweizer, MT and Yezefski, T and Yu, EY and Chen, JJ and Liao, JJ and Weg, E and Zeng, J and Jannat, S and Berry, DL and Master, VA and Garcia, JM and Reed, MJ and Bentov, I and Wright, JL and Psutka, SP},
title = {Prospective evaluation of comprehensive geriatric assessments in multidisciplinary bladder cancer care and implications for personalized vulnerability phenotyping.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2025.03.025},
pmid = {40316478},
issn = {1873-2496},
abstract = {PURPOSE: Frailty predicts adverse outcomes in bladder cancer (BC). Current guidelines endorse completion of Comprehensive Geriatric Assessments (CGAs) in older adults prior to treatment election to objectively measure frailty, however, these are rarely performed in urologic practice due to inadequate resources. We hypothesized CGA implementation would be feasible and identify multifaceted vulnerabilities beyond standard risk assessments in a multidisciplinary BC clinic and developed a novel method to visualize "vulnerability phenotypes" to guide supportive interventions.

METHODS: Adults with BC were prospectively enrolled (June, 2020-July, 2021). Initially, patients underwent standard of care (SOC) risk assessment (N = 27). Subsequently, patients completed CGAs augmented with body composition assessments (N = 67). CGA completion time, rates, and patient-reported burden were assessed. Interdependence of CGA domains were quantified using Spearman correlation coefficients and compared decisional conflict and regret between arms. Vulnerability phenotypes were visualized using Spider Plots, generated in R. Clinical and survival associations with CGAs were evaluated using Cox proportional hazards models.

RESULTS: 94 patients were enrolled with a median age of 72 years. Instrument completion in the CGA cohort was 79% to 100%. 91% of patients reported CGA completion was at most minimally burdensome. CGAs identified vulnerabilities including 31% vulnerable-to-moderately frail, 21% with mild-to-severe depression, 3% with mild-moderate dementia, and 40% at risk for malnutrition-malnourished. Frailty measures across instruments were weakly correlated (rho <0.4). In this heterogeneous cohort, vulnerability domains were not significantly associated with decisional conflict/regret, survival, nor complication rates after treatment. A novel Spider Plot tool is proposed to facilitate communication of the dominant vulnerability-driving individual risks.

CONCLUSIONS: CGAs can be successfully incorporated into uro-oncology practice with low perceived burden, identifying key vulnerabilities with implications for clinical care. Weak correlations across instruments support the value of gathering information across discrete domains. We present a novel approach to visually characterize personalized vulnerability phenotypes.},
}

@article {pmid40315850,
year = {2025},
author = {Wu, W and Ahmad, K and Henikoff, S},
title = {Chromatin-bound U2AF2 splicing factor ensures exon inclusion.},
journal = {Molecular cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molcel.2025.04.013},
pmid = {40315850},
issn = {1097-4164},
abstract = {Most mRNA splicing occurs co-transcriptionally, but it is unclear how splicing factors accurately select exons for inclusion. Using CUT&RUN profiling in K562 cells, we demonstrate that three splicing factors-SF3B1, U2AF1, and U2AF2-bind near active promoters of intron-containing and intronless genes, implying their association with the general transcriptional machinery. RNase A treatment reduces factor binding at promoters, indicating that these proteins interact with nascent transcripts. Strikingly, the U2AF2 protein also accumulates throughout intron-containing gene bodies and requires histone H3-lysine36 trimethylation but not nascent transcripts or persistent RNA polymerase II. Chromatin-bound U2AF2 preferentially binds to exons of highly expressed, exon-dense genes, with greater occupancy at exons skipped after U2AF2 knockdown, suggesting that U2AF2 enhances exon selection accuracy. U2AF2-targeted genes include those encoding splicing factors, where it improves splicing accuracy and efficiency. Our findings provide a mechanistic basis for the homeostatic regulation of efficient co-transcriptional splicing by chromatin-bound U2AF2.},
}

@article {pmid40315406,
year = {2025},
author = {Chen, W and Chang, TC and Rabin, KR and Raetz, EA and Devidas, M and Hunger, SP and Ramirez, NC and Mullighan, CG and Loh, ML and Wu, G},
title = {Performance of Two-Phase Designs for the Time-to-Event Outcome and a Case Study Assessing the Relapse Risk Associated With B-ALL Subtypes.},
journal = {JCO clinical cancer informatics},
volume = {9},
number = {},
pages = {e2400223},
pmid = {40315406},
issn = {2473-4276},
mesh = {Humans ; Case-Control Studies ; *Research Design ; Computer Simulation ; *Neoplasm Recurrence, Local ; },
abstract = {PURPOSE: To reduce costs in genomic studies of time-to-event phenotypes like survival, researchers often sequence a subset of samples from a larger cohort. This process usually involves two phases: first, collecting inexpensive variables from all samples, and second, selecting a subset for expensive measurements, for example, sequencing-based biomarkers. Common two-phase designs include nested case-control and case-cohort designs. Additional designs include sampling subjects based on follow-up time, like extreme case-control designs. Recently an optimal two-phase design using a maximum likelihood-based method was proposed, which could accommodate arbitrary sample selection in the second phase. However, direct comparisons of this optimal design with others in terms of power and computational cost is lacking.

METHODS: This study performs a direct evaluation of typical two-phase designs, including Tao's optimal design, on type I error, power, effect size estimation, and computational time, using both simulated and real data sets.

RESULTS: Results show that the optimal design had the highest power and accurate effect size estimation under the Cox regression model. Surprisingly, logistic regression achieved similar power with much lower computational cost than a more sophisticated method. The study further applied these methods to the MP2PRT study, reporting hazard ratios of cancer subtypes on relapse risk.

CONCLUSION: Recommendations for selecting two-phase designs and analysis methods are regarding power, bias of estimated effect size, and computational time.},
}

Humans
Case-Control Studies
*Research Design
Computer Simulation
*Neoplasm Recurrence, Local

@article {pmid40315399,
year = {2025},
author = {Carlsson, SV and Barata, PC and Bryce, AH and George, DJ and Gillessen, S and Loeb, S and Montgomery, B and Morris, D and Riaz, IB and Palapattu, G and Schoen, MW and Washington Iii, SL and Cornell, B and Levine, R and Aggarwal, P and McGowan, T and Cotter, M and Thompson, B and Devgan, G and Russell, D and Kuperman, G and Lenero, E and Iwata, K and Miyahira, AK and Soule, HR and Carithers, G and Oh, WK and Agarwal, N},
title = {Prostate Cancer Foundation White Paper on Combination Therapy for Metastatic Hormone-Sensitive Prostate Cancer.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500050},
doi = {10.1200/OP-25-00050},
pmid = {40315399},
issn = {2688-1535},
abstract = {Despite several randomized controlled trials demonstrating the benefits of combination therapies for metastatic hormone-sensitive prostate cancer (mHSPC), a significant treatment gap persists. This initiative by the Prostate Cancer Foundation (PCF) convened stakeholders from academia, community practices, industry, and patient advocacy groups to address critical challenges in mHSPC care. Expert discussions and a review of real-world evidence and meta-analyses informed the development of strategies to improve care delivery. Evaluation of the data from global registries, such as IRONMAN, and large community databases was used to assess treatment utilization patterns and disparities. Combination therapies with two agents-androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI)-or three agents-ADT + ARPI + docetaxel-demonstrate significant survival improvements while preserving quality of life for patients with mHSPC, yet adoption remains inconsistent. Of the eligible patients, 20%-60% remain undertreated, with geographic, financial, and systemic barriers contributing to inconsistencies in care. Younger, White, urban-dwelling patients with fewer comorbidities are more likely to receive combination treatment, highlighting disparities across populations. Meta-analyses identified a lack of standardization due to varying inclusion criteria and comparators across trials. Real-world evidence underscored disparities influenced by geographic location, practice type, and access to specialty care. Initiatives such as the PANTHER study highlight improved outcomes in Black patients treated with combination therapies, emphasizing the importance of including diverse populations in clinical trials. To bridge gaps in care, this initiative prioritizes awareness, standardization, and equitable access to evidence-based therapies. Proposed solutions include targeted knowledge dissemination strategies, development of educational resources, and advocacy for policy changes to promote guideline-concordant care. By leveraging collaborative efforts, organizations, including PCF, can contribute to enhancing survival outcomes and quality of life for all patients with mHSPC.},
}

@article {pmid40315333,
year = {2025},
author = {Geiger, RA and Khera, D and Tenthorey, JL and Kochs, G and Graf, L and Emerman, M and Malik, HS},
title = {Heterozygous and generalist MxA super-restrictors overcome breadth-specificity trade-offs in antiviral restriction.},
journal = {Science advances},
volume = {11},
number = {18},
pages = {eadu0062},
pmid = {40315333},
issn = {2375-2548},
mesh = {*Myxovirus Resistance Proteins/genetics/metabolism/chemistry ; Humans ; Influenza A Virus, H5N1 Subtype ; *Antiviral Agents/pharmacology ; Thogotovirus ; },
abstract = {Antiviral restriction factors such as MxA (myxovirus resistance protein A) inhibit many viruses. Viral escape drives restriction factors to evolve rapidly at virus-binding interfaces to regain defense. Here, we explore how antiviral proteins balance restricting many viruses with evolving specificity against individual viruses. Human MxA uses its rapidly evolving loop L4 as the specificity determinant for orthomyxoviruses such as thogotovirus (THOV) and influenza (IAV). Previous combinatorial mutagenesis of rapidly evolving residues in human MxA loop L4 identified THOV "super-restrictors" and suggested an antiviral breadth-specificity trade-off. Using a modified combinatorial mutagenesis strategy, we find super-restrictor MxA variants specific to H5N1 IAV. A single L4 residue underlies the MxA breadth-specificity trade-off. However, rare "generalist" super-restrictors or a heterozygous combination of more common "specialist" super-restrictors can overcome the breadth-specificity trade-off. Our findings suggest that at least two strategies enable restriction factors such as MxA to increase their restriction of diverse viruses to overcome breadth-specificity trade-offs, which might be pervasive in host-virus conflicts.},
}

*Myxovirus Resistance Proteins/genetics/metabolism/chemistry
Humans
Influenza A Virus, H5N1 Subtype
*Antiviral Agents/pharmacology
Thogotovirus

@article {pmid40314975,
year = {2025},
author = {Zheng, Y and Ahmad, K and Henikoff, S},
title = {Total whole-arm chromosome losses predict malignancy in human cancer.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {18},
pages = {e2505385122},
doi = {10.1073/pnas.2505385122},
pmid = {40314975},
issn = {1091-6490},
support = {Henikoff//Howard Hughes Medical Institute (HHMI)/ ; HG012797//HHS | National Institutes of Health (NIH)/ ; },
mesh = {Humans ; *Neoplasms/genetics/pathology ; *Aneuploidy ; Centromere/genetics/metabolism ; Histones/genetics/metabolism ; },
abstract = {Aneuploidy is observed as gains or losses of whole chromosomes or chromosome arms and is a common hallmark of cancer. Whereas models for the generation of aneuploidy in cancer invoke mitotic chromosome segregation errors, whole-arm losses might occur simply as a result of centromere breakage. We recently showed that elevated RNA Polymerase II level over the S-phase-dependent histone genes predicts rapid recurrence of human meningioma and is correlated with total whole-arm losses relative to gains. To explain this imbalance in arm losses over gains, we have proposed that histone overexpression at S-phase competes with the histone H3 variant CENP-A, resulting in centromere breaks and whole-arm losses. To test whether centromere breaks alone can drive aneuploidy, we ask whether total whole-arm aneuploids can predict outcomes across different cancer types in large RNA and whole-genome sequencing databanks. We find that total whole-arm losses generally predict outcome, suggesting that centromere breakage is a major initiating factor leading to aneuploidy and the resulting changes in the selective landscape that drive most cancers. We also present evidence that centromere breakage alone is sufficient to account for whole-arm losses and gains, contrary to mitotic spindle error models for the generation of aneuploidy. Our results suggest that therapeutic intervention targeting histone overexpression has the potential to reduce aneuploidy and slow cancer progression.},
}

Humans
*Neoplasms/genetics/pathology
*Aneuploidy
Centromere/genetics/metabolism
Histones/genetics/metabolism

@article {pmid40311704,
year = {2025},
author = {Alfaifi, SA and Louie, AV and Siva, S and Guckenberger, M and Videtic, GMM and Higgins, KA and Alshafa, F and AlGhamdi, H and Gillespie, EF and Stephans, K and Mula-Hussain, L and Harrow, S and Palma, DA},
title = {International Patterns of Practice for Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: Are We All in Sync?: Global patterns of practice for SABR for early-stage NSCLC.},
journal = {International journal of radiation oncology, biology, physics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ijrobp.2025.04.022},
pmid = {40311704},
issn = {1879-355X},
abstract = {PURPOSE: To generate an understanding of the similarities and variations in international practice patterns for stereotactic ablative radiotherapy (SABR) in early-stage non-small cell lung cancer (NSCLC).

METHODS: An online survey was conducted from October to December 2023, addressing general clinical and technical considerations for lung SABR, and for 5 specific anatomical NSCLC locations (peripheral, abutting chest wall, near brachial plexus, central, and ultra-central). Invitations to participate were extended through email and were distributed on social media.

RESULTS: The survey was completed by 255 radiation oncologists, each representing a single institution across 51 countries. Respondents reported treating a median of 20 cases annually. A total of 38% of participants reported using single-fraction SABR, and 54% applied an upper limit on the maximum dose (Dmax). Among those who applied a Dmax limit, 58% reported a Dmax threshold at ≥130% of the prescription, though this limit varied by region and national economy status. Respondents from low- and middle-income countries were less likely to set a Dmax limit at ≥130% (30% vs. 66%, p < 0.01) and less likely to use single-fraction SABR (14% vs. 44%, p < 0.01). Higher annual SABR patient volumes were associated with higher Dmax adoption (г = 0.23, p < 0.01). Across the 5 clinical scenarios presented; 57 distinct dose regimens were recommended. The most common regimen in each scenario was: 54 Gy in 3 fractions for peripheral tumors, 50 Gy in 5 fractions for apical, central, and abutment of chest wall, and 60 Gy in 8 fractions for ultra-central tumors. Approximately two-thirds of practices recommend a biologically effective dose (BED10) <100 Gy for one or more anatomical sites.

CONCLUSION: The findings reveal considerable variation in global SABR practice. These differences highlight the need for further data to guide prescription practices, and an international experts' consensus may be beneficial to standardize practice.},
}

@article {pmid40311075,
year = {2025},
author = {Sharma, R and Holtzman, NG and Pusic, I and Cutler, CS and Treister, N and Mehta, RS and Alousi, AS and Vigneswaran, N and Javaid, A and Boksa, FA and Mody, DP and Costa-da-Silva, AC and Schueller, O and Macé, S and Yao, Y and Ji, R and Hu, B and Marshall, K and Blazar, BR and Lee, SJ and Pavletic, SZ and Mays, JW},
title = {Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016170},
pmid = {40311075},
issn = {2473-9537},
abstract = {Belumosudil (KD025), an oral, selective, Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) inhibitor, is approved for third-line treatment of chronic graft-versus-host disease (cGVHD). Previous studies demonstrated that ROCK2 inhibition reduces blood interleukin (IL)-17 activity and promotes regulatory T-cell (Treg) recovery. However, these studies did not evaluate immune responses within cGVHD-affected tissues. This study assessed tissue-level immune dynamics in 20 subjects with oral cGVHD from the phase 2 ROCKstar trial, before and after 6 months of belumosudil treatment, focusing on key effector sites (oral mucosa [OM], minor salivary glands [MSG], and skin) and peripheral blood. Following belumosudil treatment, reduction in collagen was observed in OM in parallel with decreased IL-17+ cell frequency in both OM (n = 14 pairs) and MSG (n = 11 pairs). IL-17 was primarily produced by non-T cells in the oral tissues. Immune cell frequencies in the OM decreased following treatment, while CD4 Tregs increased in both MSG and blood. Per overall or mouth-specific clinical response criteria, responders to belumosudil exhibited a reduction in collagen type I and IL-17 in OM. Additionally, salivary transforming growth factor β1 (TGF)-β1, a critical driver of fibrosis, decreased significantly, with a strong correlation observed between TGF-β1 and IL-17 levels. These findings illustrate the tissue-level response to belumosudil therapy and suggest that there is a reduction in tissue fibrosis and inflammation, thereby highlighting the therapeutic impact of ROCK2 inhibition in mitigating cGVHD. The ROCKstar study was registered at www.clinicaltrials.gov as NCT03640481.},
}

@article {pmid40309186,
year = {2025},
author = {Andrews, SS and Brent, R},
title = {Individual yeast cells signal at different levels but each with good precision.},
journal = {Royal Society open science},
volume = {12},
number = {4},
pages = {241025},
pmid = {40309186},
issn = {2054-5703},
abstract = {Different isogenic cells exhibit different responses to the same extracellular signals. Several authors assumed that this variation arose from stochastic signalling noise with the implication that single eukaryotic cells could not detect their surroundings accurately, but work by us and others has shown that the variation is dominated instead by persistent cell-to-cell differences. Here, we analysed previously published data to quantify the sources of variation in pheromone-induced gene expression in Saccharomyces cerevisiae. We found that 91% of response variation was due to stable cell-to-cell differences, 8% from experimental measurement error, and 1% from signalling noise and expression noise. Low noise enabled precise signalling; individual cells could transmit over 3 bits of information through the pheromone response system and so respond differently to eight different pheromone concentrations. Additionally, if individual cells could reference their responses against constitutively expressed proteins, then cells could determine absolute pheromone concentrations with 2 bits of accuracy. These results help explain how individual yeast cells can accurately sense and respond to different extracellular pheromone concentrations.},
}

@article {pmid40308027,
year = {2025},
author = {Gomez, RA and Hou, J and Gersuk, VH and Chow, IT and Farrington, ML and Robinson, D and Kwok, WW},
title = {Ara h 2105-124-Specific TH2A Cells Drive Peanut Allergy in DRB1*15:01 Individuals: A Detailed Epitope Analysis.},
journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology},
volume = {},
number = {},
pages = {},
doi = {10.1111/cea.70072},
pmid = {40308027},
issn = {1365-2222},
support = {U19 AI135817/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: The IgE-mediated CD4 T-cell response to peanut (Arachis hypogaea) is heterogeneous, yet TH2 cells remain central drivers of pathology. This study aimed to dissect this complexity at the epitope level by focusing on the HLA-DRB1*15:01-DRB5*01:01 haplotype. Specifically, we examined how distinct epitope-specific T-cell subsets shape the immunological landscape of peanut allergy in peanut-allergic (PA) versus non-peanut-allergic (NPA) individuals.

METHODS: Using in vitro and ex vivo MHC-II tetramer approaches, the phenotype, frequency, function, and transcriptome of CD4 T-cell responses to novel Ara h epitopes were assessed. Bulk RNA sequencing further characterised these T cells, allowing identification of subsets associated with TH2 polarisation in PA individuals.

RESULTS: Eleven HLA-DRB1*15:01 and DRB5*01:01-restricted epitopes were identified in Ara h 1, 2, 3, 6, 7, and 8 using tetramer-guided epitope mapping on cell lines, followed by ex vivo validation in peripheral blood. T-cell phenotype was epitope-dependent, with a distinct TH2A population specific to the epitope Ara h 2105-124 (Ara h 2 p14) detected only in PA donors. These TH2A cells were phenotypically and transcriptionally distinct, marked by high CRTH2/CD161, low CD27, IL-5 production, and gene enrichment in cytokine signalling and lipid metabolism. Other epitope-specific T-cell subsets displayed more heterogeneous gene profiles related to immune activation, differentiation, and antigen presentation, underscoring the complexity of peanut-specific responses even within a single HLA haplotype.

CONCLUSION: These findings reveal that the strong TH2 bias in DRB1*15:01-DRB5*01:01 PA individuals arises from a distinct subset of Ara h 2 p14-specific TH2A cells characterised by a specialised metabolic and cytokine signalling program. At the same time, the functional diversity observed in non-Ara h 2 p14 subsets highlights the potential for leveraging these populations in tolerance-promoting therapies. Understanding the epitope-level heterogeneity of peanut-specific T-cells provides insight into the epitope-specific mechanisms driving peanut allergy and has potential implications for therapeutic interventions.},
}

@article {pmid40307656,
year = {2025},
author = {Keiser, E and Corbett, AM and Chido-Amajuoyi, O and Antoine, A and Stehman, C and Dorn, I and Goines, D and LoConte, NK},
title = {Acceptability of Stool-Based DNA Colorectal Cancer Screening among Black/African-American Patients Served by Federally Qualified Health Centers.},
journal = {Journal of cancer education : the official journal of the American Association for Cancer Education},
volume = {},
number = {},
pages = {},
pmid = {40307656},
issn = {1543-0154},
support = {UWCCC: University of Wisconsin Carbone Cancer Center Support Grant P30 CA014520/CA/NCI NIH HHS/United States ; },
abstract = {Colorectal cancer (CRC) has an increased burden among Black/African-American populations. Following the COVID-19 pandemic, home-based CRC screening options are being used more frequently. We conducted focus groups to understand the acceptability of stool-based DNA testing for CRC screening in this population. Ten focus groups about the acceptability of various CRC screening modalities were held with Black/African-American participants at two federally qualified health centers (FQHCs) in Milwaukee, Wisconsin. Participants were separated into focus groups based on age and gender. Thematic analysis was carried out using NVivo. Across the groups, there were a total of 79 participants, of which 40.5% were aged 40-50 years ("younger participants"), 59.5% aged > 50 years ("older participants"), 53.2% male, and 46.8% female. Overall, knowledge was low regarding perceived risk of CRC. There was limited awareness of CRC screening options among younger patients and widespread lack of knowledge about stool-based DNA testing. Most respondents preferred colonoscopy as their first-choice screening test but were open to other screening tests. Stool-based DNA tests were more preferred among younger participants but was felt to be acceptable across all groups. Given the low awareness/knowledge of screening modalities identified in our study, educational interventions and shared decision making by primary care providers are needed.},
}

@article {pmid40307080,
year = {2025},
author = {Melão, BVLA and Assel, M and Pere, M and Nalavenkata, S and Touijer, KA and Laudone, VP and Lin, DW and Rivas, JG and Bjartell, A and Carlsson, SV},
title = {Assessment of postoperative practices and discharge recommendations after radical prostatectomy.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2025.03.027},
pmid = {40307080},
issn = {1873-2496},
abstract = {PURPOSE: Consistent, accurate postoperative guidance is crucial for early recovery and patient satisfaction in urology, especially for radical prostatectomy (RP) patients. However, patients often receive inconsistent information, highlighting the need for standardized, evidence-based postoperative care guidelines.

MATERIALS AND METHODS: We conducted a comprehensive review and evaluation of current postoperative practices for RP. This involved (1) reviewing existing discharge information at Josie Robertson Surgery Center, Memorial Sloan Kettering Cancer Center to identify areas of improvement; (2) systematically evaluating inconsistencies in discharge instructions and their impact on patient care; (3) distributing an anonymous survey to urologists in the US and Europe via REDCap to gather insights into global postoperative care practices. The survey included questions on various aspects of postoperative care, such as catheter use, medication regimens, dietary restrictions, and physical activity guidelines.

RESULTS: We received 247 survey responses. Despite some consensus on certain postoperative practices and recommendations, significant variability existed, underscoring the lack of standardized guidelines. Notable differences were observed between US and European cohorts, particularly in postoperative length of stay and discharge practices. Only 1.4% of US responders discharged patients 3 or more days postsurgery compared to 46% in Europe. Variability was also noted in recommendations for erectile function medications and postoperative activity restrictions.

CONCLUSION: This study underscores the significant variability in postoperative care recommendations for RP and the urgent need for standardized, evidence-based guidelines. Implementing such guidelines will enhance patient recovery, satisfaction, and overall outcomes, improving postoperative care across various surgical procedures.},
}

@article {pmid40306967,
year = {2025},
author = {Parihar, AS and Pant, N and Heidari, P and Fong, L and Iravani, A},
title = {Approaches to Imaging Immune Activation Using PET.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.124.268289},
pmid = {40306967},
issn = {1535-5667},
abstract = {This review explores the role of PET in imaging immune activation, particularly in oncology. [18]F-FDG is widely used for assessing treatment response to immunotherapies and can demonstrate unique response patterns as well as immune-related adverse events. However, because of the limited specificity of [18]F-FDG, newer PET radiopharmaceuticals targeting specific cellular or subcellular components of the immune system have been developed that can provide more precise information. The development of immune-specific PET radiopharmaceuticals offers significant potential for improving immune monitoring in both clinical practice and research.},
}

@article {pmid40305682,
year = {2025},
author = {Chappidi, MR and Newcomb, LF and Zheng, Y and Liu, M and Schenk, JM and Zhu, K and de la Calle, CM and Brooks, JD and Carroll, PR and Dash, A and Filson, CP and Gleave, ME and Liss, MA and Martin, F and McKenney, JK and Morgan, TM and Wagner, AA and Nelson, PS and Lin, DW},
title = {Magnetic Resonance Imaging at second surveillance biopsy after diagnosis in patients with Grade Group 1 prostate cancer in the Canary Prostate Active Surveillance Study.},
journal = {The Journal of urology},
volume = {},
number = {},
pages = {101097JU0000000000004592},
doi = {10.1097/JU.0000000000004592},
pmid = {40305682},
issn = {1527-3792},
abstract = {PURPOSE: No clear guidelines exist regarding MRI use after confirmatory biopsy during active surveillance (AS). Our objective was to evaluate MRI performance after confirmatory biopsy in patients with vs. without prior MRI-informed biopsy.

METHODS: Patients in Canary PASS with Gleason grade group (GG) 1 disease undergoing MRI-informed Biopsy 2, defined as second surveillance biopsy after diagnosis, were separated into prior vs. no prior MRI-informed biopsy groups. Primary outcome was reclassification (≥GG2) at MRI-informed Biopsy 2. Reclassification rates and location (systematic cores, targeted cores, both) were compared between groups. Univariable and multivariable logistic regression identified predictors of reclassification.

RESULTS: Patients with (n=101) vs. without (n=103) prior MRI-informed biopsy had lower reclassification rates at Biopsy 2 (21% vs. 36%, p=0.017) and lower GG at reclassification (95% vs. 73% of reclassifications to GG2, p=0.039). In multivariable modeling, PI-RADS 4-5 at MRI-informed Biopsy 2 was associated with increased odds of reclassification (OR=2.04 95%CI [1.04-4.05]). The negative predictive value of MRI at Biopsy 2 was 87% (95%CI[78-96]) and 73% (95%CI[61-85]) in with vs. without prior MRI groups, respectively. Reclassification location was identified by targeted cores only in 36% vs. 19% of patients with vs. without prior MRI, respectively (p=0.4). Reclassification location was identified by systematic cores only in 36% vs. 58% of patients with vs. without prior MRI, respectively (p=0.4).

CONCLUSIONS: These results support MRI use at Biopsy 2 and suggest negative surveillance MRI should not replace Biopsy 2. Both targeted and systematic cores should be taken at Biopsy 2 in patients with and without prior MRI on AS.},
}

@article {pmid40305509,
year = {2025},
author = {Gabel, AM and Crosse, EI and Belleville, AE and Hogg, SJ and McKellar, SA and Abdel-Wahab, O and Thomas, JD and Bradley, RK},
title = {Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment.},
journal = {PloS one},
volume = {20},
number = {4},
pages = {e0321148},
pmid = {40305509},
issn = {1932-6203},
mesh = {*Tumor Microenvironment/immunology/genetics ; Animals ; Humans ; Mice ; *RNA-Binding Proteins/genetics/metabolism/immunology ; Cell Line, Tumor ; CD8-Positive T-Lymphocytes/immunology ; Female ; Interferon-gamma/pharmacology ; *Neoplasms/immunology/genetics/pathology ; Gene Expression Regulation, Neoplastic ; Mice, Inbred C57BL ; Antigen Presentation ; },
abstract = {Exploiting the immune system to eradicate cancer cells is an area of intense clinical study. However, the mechanisms that shape the tumor-immune microenvironment are incompletely understood. Here, we identify Muscleblind-like (MBNL) proteins as novel modulators of the tumor-immune microenvironment across diverse cancers. We demonstrate that loss of tumor MBNL expression results in an attenuated response to interferon gamma and reduced tumor antigen presentation in melanoma, breast cancer, and colorectal cancer cells. Parallel experiments in a syngeneic mouse melanoma model revealed that MBNL loss reduces tumor cell killing by CD8 + T cells in vitro and facilitates tumor escape from cytotoxic CD8 + T cell infiltration in vivo. Finally, we extended these studies to 29 human cancer types to find that MBNL expression levels are strongly associated with gene expression signatures of T cell tumor infiltration. These insights suggest that MBNL proteins play important roles in shaping the immune landscape across diverse malignancies.},
}

*Tumor Microenvironment/immunology/genetics
Animals
Humans
Mice
*RNA-Binding Proteins/genetics/metabolism/immunology
Cell Line, Tumor
CD8-Positive T-Lymphocytes/immunology
Female
Interferon-gamma/pharmacology
*Neoplasms/immunology/genetics/pathology
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Antigen Presentation

@article {pmid40305026,
year = {2025},
author = {Montano-Campos, JF and Hahn, EE and Haupt, EC and Radich, J and Bansal, A},
title = {Oncologist-Patient Concordance and Treatment Adherence in Chronic Myeloid Leukemia.},
journal = {JAMA network open},
volume = {8},
number = {4},
pages = {e258039},
pmid = {40305026},
issn = {2574-3805},
}

@article {pmid40304602,
year = {2025},
author = {Kopyeva, I and Bretherton, RC and Ayers, JL and Yu, M and Grady, WM and DeForest, CA},
title = {Matrix Stiffness and Biochemistry Govern Colorectal Cancer Cell Growth and Signaling in User-Programmable Synthetic Hydrogels.},
journal = {ACS biomaterials science & engineering},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsbiomaterials.4c01632},
pmid = {40304602},
issn = {2373-9878},
abstract = {Colorectal cancer (CRC) studies in vitro have been conducted almost exclusively on 2D cell monolayers or suspension spheroid cultures. Though these platforms have shed light on many important aspects of CRC biology, they fail to recapitulate essential cell-matrix interactions that often define in vivo function. Toward filling this knowledge gap, synthetic hydrogel biomaterials with user-programmable matrix mechanics and biochemistry have gained popularity for culturing cells in a more physiologically relevant 3D context. Here, using a poly(ethylene glycol)-based hydrogel model, we systematically assess the role of matrix stiffness and fibronectin-derived RGDS adhesive peptide presentation on CRC colony morphology and proliferation. Highlighting platform generalizability, we demonstrate that these hydrogels can support the viability and promote spontaneous spheroid or multicellular aggregate formation of six CRC cell lines that are commonly utilized in biomedical research. These gels are engineered to be fully degradable via a "biologically invisible" sortase-mediated reaction, enabling the triggered recovery of single cells and spheroids for downstream analysis. Using these platforms, we establish that substrate mechanics play a significant role in colony growth: soft conditions (∼300 Pa) encourage robust colony formation, whereas stiffer (∼2 kPa) gels severely restrict growth. Tuning the RGDS concentration did not affect the colony morphology. Additionally, we observe that epidermal growth factor receptor (EGFR) signaling in Caco-2 cells is influenced by adhesion ligand identity─whether the adhesion peptide was derived from collagen type I (DGEA) or fibronectin (RGDS)─with DGEA yielding a marked decrease in the level of downstream protein kinase phosphorylation. Taken together, this study introduces a versatile method to culture and probe CRC cell-matrix interactions within engineered 3D biomaterials.},
}

@article {pmid40304595,
year = {2025},
author = {Abrams, HR and Saifee, NH and Miller, WS and Cortez, A and Hasan, RA and Panch, SR and Fertrin, KY},
title = {Alloimmunization as a barrier to gene therapy in sickle cell disease.},
journal = {Transfusion},
volume = {},
number = {},
pages = {},
doi = {10.1111/trf.18266},
pmid = {40304595},
issn = {1537-2995},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; },
abstract = {Alloimmunization is prevalent in patients with sickle cell disease (SCD) and can be a barrier to gene therapy (GT) due to the necessary transfusion support for successful stem cell collection and infusion. We estimate that standard-of-care GT for an adult with SCD will require an average of 35-45 units of red blood cells over a 6-month period. Institutions should actively plan for these transfusion needs and share information to inform national consensus policies on the management of alloimmunization during GT.},
}

@article {pmid40304490,
year = {2025},
author = {Owen, MC and Zhou, Y and Dudley, H and Feehley, T and Hahn, A and Yokoyama, CC and Axelrod, ML and Lin, C-Y and Wang, D and Janowski, AB},
title = {Novel murine model of human astrovirus infection reveals cardiovascular tropism .},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0024025},
doi = {10.1128/jvi.00240-25},
pmid = {40304490},
issn = {1098-5514},
abstract = {UNLABELLED: Astroviruses are a common cause of gastrointestinal disease in humans and have been linked to fatal cases of encephalitis. A major barrier to the study of human-infecting astroviruses is the lack of an in vivo model as previous attempts failed to identify a host that supports viral replication. We describe a novel murine model of infection using astrovirus VA1/HMO-C (VA1), an astrovirus with high seroprevalence in humans. VA1 is cardiotropic, and viral RNA levels peak in the heart tissue 7 days post-inoculation in multiple different murine genetic backgrounds. Infectious VA1 particles could be recovered from heart tissue 3 and 5 days post-inoculation. Viral capsid was detected intracellularly in the heart tissue by immunostaining, and viral RNA was detected in cardiac myocytes, endocardium, and endothelial cells based on fluorescent in situ hybridization and confocal microscopy. Histologically, we identified inflammatory infiltrates consistent with myocarditis in some mice, with viral RNA colocalizing with the infiltrates. These foci contained CD3 +T cells and CD68 +macrophages. Viral RNA levels increased by >10 fold in the heart tissue or serum samples from Rag1 or Stat1 knockout mice, demonstrating the role of both adaptive and innate immunity in the response to VA1 infection. Based on the in vivo tropisms, we tested cardiac-derived primary cells and determined that VA1 can replicate in primary human cardiac endothelial cells, suggesting a novel cardiovascular tropism in human cells. This novel in vivo model of a human-infecting astrovirus enables further characterization of the host immune response and reveals a new cardiovascular tropism of astroviruses.

IMPORTANCE: Astroviruses routinely cause infections in humans; however, few methods were available to study these viruses. Here, we describe the first animal system to study human-infecting astroviruses by using mice. We demonstrate that mice are susceptible to astrovirus VA1, a strain that commonly infects humans and has been linked to fatal brain infections. The virus infects the heart tissue and is associated with inflammation. When mice with impaired immune systems were infected with VA1, they were found to have higher amounts of the virus in their hearts and blood. We found that VA1 can infect cells from human blood vessels of the heart, which is associated with human health. This model will enable us to better understand how astroviruses cause disease and how the immune system responds to infection. Our findings also suggest that astroviruses could be linked to cardiovascular diseases, including in humans.},
}