tbuckley/cabot-search huggingface dataset:
Area Deprivation Index and Melanoma Thickness in Veterans
Authors: Alejandra K. Moncayo, Jacqueline M. Ferguson, Mathew P. Dizon, Linden Huhmann, Daniel Y. Kim, Nhan Do, Mary T. Brophy, Thomas F. Osborne, Allyson C. Spence, Nathanael R. Fillmore, Susan M. Swetter, Rebecca I. Hartman
Journal: JAMA Dermatology (2025)

The US Veterans Health Administration (VHA) provides comprehensive medical care for enrolled veterans. Differences in melanoma diagnosis, associated with individual-level factors, have been previously published. The area deprivation index (ADI) ranks a neighborhood's level of deprivation and can inform whether the characteristics of a patient's area of residence can contribute to delayed diagnosis, measured by melanoma thickness. To evaluate if neighborhood deprivation is associated with thicker (greater than 2 mm) cutaneous melanoma diagnosis after controlling for individual-level characteristics in the US veteran population. This national cohort study used data from the US Veterans Eligibility Trends and Statistics database, the Veterans Affairs Cancer Registry, and veterans' electronic health care records. Veterans enrolled at the VHA who were diagnosed with melanoma from October 1, 2013, to December 31, 2019, were included. Data analysis conducted from September 2023 to July 2024. Quintiles of ranked neighborhood deprivation measured by the nationwide ADI. Generalized Poisson models were used to calculate the risk of a thick cutaneous melanoma diagnosis, defined by the American Joint Committee on Cancer Staging Manual eighth edition staging as a Breslow thickness greater than 2 mm (ie, T3 to T4 disease). Of 7249 veterans with a melanoma diagnosis included in the study, 6988 (96.4%) were male, and the mean (SD) age was 68.9 (12.2) years. A total of 856 (11.8%) lived in the least deprived neighborhoods (quintile 1: ADI of 1-20) and 1205 (16.6%) lived in the most deprived neighborhoods (quintile 5: ADI of 81-100) nationwide. The risk of thicker melanoma at diagnosis increased with measured deprivation in the neighborhood. There was a 33% increased risk of thicker melanoma (greater than 2 mm) in veterans in quintile 5 compared with those in quintile 1 of ADI (adjusted risk ratio, 1.33; 95% CI, 1.05-1.68). In this national cohort study of US veterans with melanoma, neighborhood-level deprivation at time of diagnosis was independently associated with thicker melanoma at diagnosis after controlling for individual-level factors and tumor characteristics. These findings underscore the significant association between neighborhood deprivation and melanoma diagnosis.
siRNA-AGO2 complex inhibits bacterial gene translation: A promising therapeutic strategy for superbug infection
Authors: Chen Wang, Wangjian Sheng, Yu Zhou, Xudong Hang, Jiayi Zhao, Yuanyuan Gu, Xiangfeng Meng, Yuefan Bai, Weili Li, Yujing Zhang, Linlin Zhang, Jing Yu, Zhen Zhou, Xiaona Li, Haorui Sun, Yanhong Xue, Tao Xu, Ke Zen, Hong Ling, Chen-Yu Zhang, Hongkai Bi, Huan Wang
Journal: Cell Reports Medicine (2025)

Silencing resistance genes of pathogenic bacteria by RNA interference (RNAi) is a potential strategy to fight antibiotic-resistant bacterial infections. Currently, RNAi cannot be achieved in bacteria due to the lack of RNA-induced silencing complex machinery and the difficulty of small interfering RNA (siRNA) delivery. Here, we show that exosomal siRNAs can be efficiently delivered into bacterial cells and can silence target genes primarily through translational repression without mRNA degradation. The exosomal Argonaute 2 (AGO2) protein forms a complex with siRNAs, which is essential for bacterial gene silencing. Both in vitro and in vivo-generated exosome-packaged siRNAs resensitize methicillin-resistant Staphylococcus aureus (MRSA) to methicillin treatment by silencing the mecA gene, which is the primary beta-lactam resistance determinant of MRSA. This approach significantly enhances the therapeutic effect in a mouse model of MRSA infection. In summary, our study provides a method for siRNA delivery to bacteria that may facilitate the treatment of antibiotic-resistant bacterial infection.
Human Papillomavirus Vaccination and Actinic Keratosis Burden
Authors: Emily Wenande, Anna Hastrup, Stine Wiegell, Peter A. Philipsen, Niels Bech Thomsen, Shadmehr Demehri, Susanne K. Kjaer, Merete Haedersdal
Journal: JAMA Dermatology (2025)

The substantial morbidity and socioeconomic costs associated with actinic keratosis (AK) management represent major public health concerns. Anecdotal evidence suggests that human papillomavirus (HPV) vaccination may offer therapeutic and preventive effects against AK and keratinocyte carcinomas (KCs). To investigate the effect of HPV vaccination on burden of disease in immunocompetent patients with high numbers of AK. The VAXAK trial was a parallel-design, double-blind, randomized sham-controlled clinical trial with 12 months' follow-up. This single-center trial was conducted at the Department of Dermatology, Bispebjerg University Hospital in Copenhagen, Denmark, between May 2021 and June 2024. Eligible participants were immunocompetent adults with 15 or more clinical AK lesions in a 50 cm2 to 100 cm2 test area on the head, trunk, or extremities. Participants were randomized 1:1 to blinded, 9-valent alphapapillomavirus vaccine or sham vaccine (isotonic sodium chloride solution), each administered intramuscularly at 0, 2, and 6 months. Thick AKs (Olsen grade II-III) received cryotherapy at months 6 and 9; test areas were otherwise untreated during the study. The preselected primary outcome was the percentage reduction in baseline AKs assessed 2, 6, 9, and 12 months after first vaccination. Secondary outcomes included total AK number, thick lesions, new AKs, and rate of incident KCs over 12 months. Participants were selected by consecutive sampling of 163 screened patients following exclusion of 93 individuals due to ineligibility or patients opting out. Among 70 enrolled participants (median [IQR] age, 75.50 [69.00-79.00] years; 47 [67%] male), 69 completed the study. Median (IQR) AK reductions were higher in the HPV-vaccinated vs sham group, shown consistently over the study period (month 2: 35% [25%-44%] vs 25% [18%-33%]; P = .03; month 6: 47% [33%-53%] vs 29% [16%-44%]; P = .01; month 9: 58% [37%-63%] vs 42% [33%-56%]; P = .09; month 12: 58% [47%-69%] vs 47% [32%-65%]; P = .05). Total AK numbers were correspondingly lower in the HPV-vaccinated group (median [IQR] at month 6: 14.00 [11.00-16.00] vs 17.00 [12.00-23.00]; P = .01; month 12: 10.00 [6.00-24.00] vs 16.00 [8.50-21.00]; P = .02). Coincidingly, fewer thick AKs were observed in the HPV-vaccinated group (median [IQR] at month 6: 5.00 [3.00-7.00] vs 6.50 [3.75-10.00]; P = .02; month 12: 3.00 [2.00-5.00] vs 5.00 [2.50-8.50]; P = .049). In contrast, no significant differences in rates of new AKs (1-2 AK[s] per month) or KC numbers overall or per participant were identified during the 12-month trial. In this randomized clinical trial, standard alphapapillomavirus vaccination was found to reduce AK burden in immunocompetent individuals with multiple lesions. HPV-targeted vaccines may be useful for management of AK, a chronic, relapsing disease and the most common precancer in fair-skinned populations. ClinicalTrials.gov Identifier: NCT05202860.
Quantitative Protein Expression of Antibody-Drug Conjugate Targets in EGFR Mutated and Wild-Type Non-Small Cell Lung Cancer
Authors: Ioannis P. Trontzas, Mengni He, Anna Wurtz, Charles J. Robbins, Nathaniel Robinson, Katherine Bates, Matthew Liu, Thazin N. Aung, Liam Scott, Nay Chan, Sneha Burela, Jacob Schillo, Daniel C. Liebler, Salisha Hill, Ryan D. Morrison, Ioannis Vathiotis, Konstantinos N. Syrigos, Sarah B. Goldberg, Katerina Politi, David L. Rimm
Journal: Clinical Cancer Research (2025)

Antibody-drug conjugates (ADCs) are a promising approach for the management of patients with non-small cell lung cancer (NSCLC). However, only a small subset of patients derive benefit from these therapies. We employed quantitative immunofluorescence (QIF) assays to measure the levels of four ADC target proteins (HER2, TROP2, HER3, EGFR) in three NSCLC tissue microarray cohorts stratified according to EGFR mutation (EGFRmut (n=83), EGFRwt (n=128), and EGFR unknown (n=232)). Assay limits were established by mass spectrometry on standard cell lines. All four targets demonstrated a broad and comparable dynamic range of expression in all three cohorts. High proportions of cases were above assay limits for all targets. Comparison of target expression showed a significant association of HER2 with EGFR expression and a non-significant association with EGFR mutation (p=0.0005 and 0.14, respectively). TROP2 expression was not associated with EGFR expression or mutation. HER3 demonstrated a significant negative correlation with EGFR mutation, but no significant association with EGFR expression (p<0.0001 and 0.9869, respectively). EGFR expression was significantly associated with EGFR mutation (p=0.047). ADC targets are highly expressed in NSCLC, implying that the benefit from these agents may be broad. Benefit from these therapies may go beyond mutation status and fully quantitative approaches may help to select patients for ADC targeting. Inter-target correlation may provide insight on the underlying signaling pathways and/or treatment-related resistant mechanisms. In the future, QIF may be a valuable tool to select ADC treatment sequence.
The cost of US funding cuts
Authors: None The Lancet Healthy Longevity
Journal: The Lancet Healthy Longevity (2025)

On Jan 20, 2025, Donald Trump was inaugurated as the President of the USA for the second time. Since then, multiple funding cuts to health programmes and health research in the name of cost saving have been instigated. Diversity, equity, inclusion, and accessibility (DEIA) initiatives have also been banned, prompting extensive discussion about the implications for research and health. The situation continues to unfold as legal challenges are mounted and the Trump administration continues to make changes, meaning that further updates are likely by the time of this Editorial's publication.
<i>Notes from the Field</i>: Detection of Vaccine-Derived Poliovirus Type 2 in Wastewater — Five European Countries, September–December 2024
Authors: Shahin Huseynov, Eugene Saxentoff, Sabine Diedrich, Javier Martin, Magdalena Wieczorek, Maria Cabrerizo, Soile Blomqvist, Jaume Jorba, José Hagan
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
<i>Notes From the Field</i>: Enhanced Identification of Tobacco Use Among Adult Medicaid Members — King County, Washington, 2016–2023
Authors: Amber K. Sabbatini, Austin Craig, Eli Kern, Susan Hernandez, Caroline Brazeel, Alexandra Kearly, Madison Hluchan, Orobosa Idehen, Elizabeth Courtney-Long, Corinne Husten, Brian S. Armour
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Regulatory considerations for successful implementation of digital endpoints in clinical trials for drug development
Authors: Gül Erdemli, Tina Murphy, Sarah Walinsky
Journal: npj Digital Medicine (2025)

Regulatory acceptance of Digital Health Technology (DHT) -derived endpoints can be a long, multifaceted and costly process. Success relies on establishing a global strategy as part of the development program including health authority consultations to ensure alignment with regulatory requirements. In this manuscript, the authors provide stepwise guidance for successful implementation of DHT-derived endpoints in clinical trials for drug development.
Harnessing myeloid cells in cancer
Authors: Su-Yeon Park, Ekaterina Pylaeva, Vikas Bhuria, Adriana Rosa Gambardella, Giovanna Schiavoni, Dimitrios Mougiakakos, Sung-Hoon Kim, Jadwiga Jablonska
Journal: Molecular Cancer (2025)

Cancer-associated myeloid cells due to their plasticity play dual roles in both promoting and inhibiting tumor progression. Myeloid cells with immunosuppressive properties play a critical role in anti-cancer immune regulation. Cells of different origin, such as tumor associated macrophages (TAMs), tumor associated neutrophils (TANs), myeloid derived suppressor cells (also called MDSCs) and eosinophils are often expanded in cancer patients and significantly influence their survival, but also the outcome of anti-cancer therapies. For this reason, the variety of preclinical and clinical studies to modulate the activity of these cells have been conducted, however without successful outcome to date. In this review, pro-tumor activity of myeloid cells, myeloid cell-specific therapeutic targets, in vivo studies on myeloid cell re-polarization and the impact of myeloid cells on immunotherapies/genetic engineering are addressed. This paper also summarizes ongoing clinical trials and the concept of chimeric antigen receptor macrophage (CAR-M) therapies, and suggests future research perspectives, offering new opportunities in the development of novel clinical treatment strategies.
Idiopathic Pulmonary Fibrosis Mortality by Industry and Occupation — United States, 2020–2022
Authors: Jacek M. Mazurek, Girija Syamlal, David N. Weissman
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Idiopathic pulmonary fibrosis (IPF), a progressive lung disease characterized by scarring and worsening lung function, has a poor prognosis. A recent systematic review estimated that 21% of IPF deaths might be attributable to occupational exposures. To describe IPF mortality among U.S. residents aged ≥15 years who were ever employed, by industry and occupation, CDC conducted an exploratory analysis of 2020-2022 multiple cause-of-death data. During 2020-2022, a total of 67,843 (39,712 [59%] male and 28,131 [41%] female) decedents had IPF, suggesting that during this 3-year period, 8,340 IPF deaths in males and 5,908 deaths in females might have been associated with occupational exposures. By industry group, the highest proportionate mortality ratios among males were among those employed in utilities (1.15) and among females, were among those employed in public administration (1.12). By occupation group, the highest IPF mortality rates among males were among community and social services workers (1.23) and among females among farming, fishing, and forestry workers (1.24). Estimates of elevated IPF mortality among workers in specific industries and occupations warrant confirmation, control of known exposure-related risk factors, and continued surveillance to better understand the full range of occupational exposures that might increase risk for developing IPF.
Implementing large language models in healthcare while balancing control, collaboration, costs and security
Authors: Fabio Dennstädt, Janna Hastings, Paul Martin Putora, Max Schmerder, Nikola Cihoric
Journal: npj Digital Medicine (2025)

Integrating Large Language Models (LLMs) into healthcare promises substantial advancements but requires careful consideration of technical, ethical, and regulatory challenges. Closed LLMs of private companies offer ease of deployment but pose risks related to data privacy and vendor dependence. Open LLMs deployed on local hardware enable greater model customization but demand resources and technical expertise. Balancing these approaches, with collaboration among clinicians, researchers, and companies is crucial to ensure effective, secure, and ethical implementation.
Genome assembly of the maize B chromosome provides insight into its epigenetic characteristics and effects on the host genome
Authors: Qian Liu, Yang Liu, Congyang Yi, Zhi Gao, Zeyan Zhang, Congle Zhu, James A. Birchler, Fangpu Han
Journal: Genome biology (2025)

B chromosomes contribute to the genetic variation in numerous eukaryotes. Yet their genetic and epigenetic characteristics, as well as their effects on the host genome remain poorly understood. Here, we present a comprehensive genome assembly of diploid maize B73 with two copies of B chromosomes using long-read sequencing. We annotate a total of 1124 high-confidence protein-coding genes and 119,579,190 bp repeat elements representing 88.55% of the B chromosome assembly. Using CENH3 ChIP-seq data, we accurately determined the position of the B chromosome centromere, which features a unique monomer-composed satellite array distinct from that found on the chromosome arms. Our research provides detailed genetic and epigenetic maps of the B chromosome, shedding light on its molecular landscape, including DNA sequence composition, DNA methylation patterns, histone modifications, and R-loop distributions across various chromatin regions. Consistent with the cytological morphology of the B chromosome, the less condensed euchromatin regions displayed high levels of H3K4me3, H3K9ac, gene expression, and dense R-loop distributions. DNA methylation on the B chromosome was primarily observed at CG sites. The centromeric region is notably enriched with H3K4me3 and H3K9ac histone modifications and has lower CHG methylation compared to the pericentromeric regions. Moreover, our findings reveal that B chromosome accumulation affects R-loop formation on A chromosomes, and exerts tissue-specific influences on A chromosome gene expression. The accurate assembly and detailed epigenetic maps of the maize B chromosome will help understand the drive mechanism, reveal its conflict with the host genome, and accelerate the construction of artificial chromosomes.
<i>Alcaligenes faecalis</i> promotes colitis to colorectal cancer transition through IgA+ B cell suppression and vinculin acetylation
Authors: Jing Zheng, Chishun Zhou, Zizheng Li, Xin Jin, Yihua Zou, Shasha Bai, Huanjin Zheng, Weichao Ling, Yiru Zhao, Ying Wang, Rong Zhang, Zhongqiu Liu, Linlin Lu
Journal: Gut Microbes (2025)

Lymphoid tissue-resident commensal bacteria (LRC), a subtype of gut microbiota essential for inflammation-associated carcinogenesis, predominantly attribute to colorectal cancer(CRC), whereas its role was largely unknown. Herein, we found Alcaligenes faecalis (A. faecalis), the main LRC embedded in Peyer's patches, was abundantly enriched in colitis, adenoma, and stage-dependently observed in CRC tissues. Interestingly, A. faecalis alone can not affect intestinal homeostasis, while during colitis, A. faecalis significantly translocated from Peyer's patches to colon, remarkably attenuated immune response abilities of B cells, T cells, and DC cells in PPs, consequently impeded IgA+ B cells homing. Meanwhile, during colitis, the ectopia of A. faecalis in colon tissues, promoted vinculin acetylation by A. faecalis-derived metabolite acetic acid, which impeded intestinal barrier via hindering the binding of vinculin to β-catenin. Our study revealed A. faecalis not only suppress mucosal immune responses via reducing IgA+ B cells in Peyer's patches but also disrupt intestinal barrier via increasing vinculin acetylation, ultimately promoting inflammation-to-cancer transition in CRC.
Mitochondria-enriched hematopoietic stem cells exhibit elevated self-renewal capabilities, thriving within the context of aged bone marrow
Authors: Haruhito Totani, Takayoshi Matsumura, Rui Yokomori, Terumasa Umemoto, Yuji Takihara, Chong Yang, Lee Hui Chua, Atsushi Watanabe, Takaomi Sanda, Toshio Suda
Journal: Nature Aging (2025)
Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19
Authors: Rebeka Fekete, Alba Simats, Eduárd Bíró, Balázs Pósfai, Csaba Cserép, Anett D. Schwarcz, Eszter Szabadits, Zsuzsanna Környei, Krisztina Tóth, Erzsébet Fichó, János Szalma, Sára Vida, Anna Kellermayer, Csaba Dávid, László Acsády, Levente Kontra, Carlos Silvestre-Roig, Judit Moldvay, János Fillinger, Attila Csikász-Nagy, Tibor Hortobágyi, Arthur Liesz, Szilvia Benkő, Ádám Dénes
Journal: Nature Neuroscience (2025)

COVID-19 is associated with diverse neurological abnormalities, but the underlying mechanisms are unclear. We hypothesized that microglia, the resident immune cells of the brain, are centrally involved in this process. To study this, we developed an autopsy platform allowing the integration of molecular anatomy, protein and mRNA datasets in postmortem mirror blocks of brain and peripheral organ samples from cases of COVID-19. We observed focal loss of microglial P2Y12R, CX3CR1-CX3CL1 axis deficits and metabolic failure at sites of virus-associated vascular inflammation in severely affected medullary autonomic nuclei and other brain areas. Microglial dysfunction is linked to mitochondrial injury at sites of excessive synapse and myelin phagocytosis and loss of glutamatergic terminals, in line with proteomic changes of synapse assembly, metabolism and neuronal injury. Furthermore, regionally heterogeneous microglial changes are associated with viral load and central and systemic inflammation related to interleukin (IL)-1 or IL-6 via virus-sensing pattern recognition receptors and inflammasomes. Thus, SARS-CoV-2-induced inflammation might lead to a primarily gliovascular failure in the brain, which could be a common contributor to diverse COVID-19-related neuropathologies.
The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells
Authors: Nariaki Asada, Pauline Ginsberg, Hans-Joachim Paust, Ning Song, Jan-Hendrik Riedel, Jan-Eric Turner, Anett Peters, Anna Kaffke, Jonas Engesser, Huiying Wang, Yu Zhao, Robin Khatri, Philipp Gild, Roland Dahlem, Björn-Philipp Diercks, Sarada Das, Zoya Ignatova, Tobias B. Huber, Immo Prinz, Nicola Gagliani, Hans-Willi Mittrücker, Christian F. Krebs, Ulf Panzer
Journal: Nature Immunology (2025)

Tissue-resident memory T (TRM) cells are a specialized T cell population that reside in tissues and provide a rapid protective response upon activation. Here, we showed that human and mouse CD4+ TRM cells existed in a poised state and stored messenger RNAs encoding proinflammatory cytokines without protein production. At steady state, cytokine mRNA translation in TRM cells was suppressed by the integrated stress response (ISR) pathway. Upon activation, the central ISR regulator, eIF2α, was dephosphorylated and stored cytokine mRNA was translated for immediate cytokine production. Genetic or pharmacological activation of the ISR-eIF2α pathway reduced cytokine production and ameliorated autoimmune kidney disease in mice. Consistent with these results, the ISR pathway in CD4+ TRM cells was downregulated in patients with immune-mediated diseases of the kidney and the intestine compared to healthy controls. Our results indicated that stored cytokine mRNA and translational regulation in CD4+ TRM cells facilitate rapid cytokine production during local immune response.