tbuckley/cabot-search huggingface dataset:
Tumor immune microenvironment delineates progression trajectories of distinct nasopharyngeal carcinoma phenotypes
Authors: Eugenia Li Ling Yeo, Boon Hao Hong, Shi Hui Tay, Jialing Neo, Enya Hui Wen Ong, Wen Min Chow, Kah Min Tan, Kar Perng Low, Adelene Yen Ling Sim, Tianzhu Lu, Xin Zhang, Luo Huang, Janice Ser Huey Tan, Joseph Tien Seng Wee, Yoke Lim Soong, Kam Weng Fong, Terence Wee Kiat Tan, Sze Yarn Sin, Xin Xiu Sam, Jacqueline Siok Gek Hwang, Tony Kiat Hon Lim, Jia-Ying Joey Lee, Lit-Hsin Loo, Khee Chee Soo, Narayanan Gopalakrishna Iyer, Kwok Seng Loh, Joshua K Tay, Jianjun Liu, Mei Kim Ang, Joe Poh Sheng Yeong, Jin Xin Bei, Sze Huey Tan, Darren Wan Teck Lim, Melvin Lee Kiang Chua
Journal: Cell Reports Medicine (2025)

We investigate the molecular landscape of locally advanced nasopharyngeal carcinoma (LA-NPC) subtypes: limited (L), ascending (A), descending (D), and ascending-descending (AD). Using a cohort of 994 patients, we perform germline and somatic whole-exome sequencing (WES), transcriptomic profiling, multiplex immunohistochemistry (mIHC), and spatial histopathological analyses of tumor whole-slide images (WSIs). Germline WES reveals the most variants in AD subtypes, but somatic WES shows no subtype-specific mutations. Transcriptomics reveals higher extracellular matrix (ECM) gene expression in A and AD subtypes and higher immune gene expression in D and AD subtypes, agreeing with deconvolution and mIHC. Tumor immune microenvironment (TIME) of node-negative (N0) and node-positive (N+) L subtypes, considered early nasopharyngeal carcinoma (NPC), resembles A and D subtypes, respectively, suggesting distinct evolutionary trajectories. Spatial WSI analyses identify the most immune-dense tumors among D subtypes and association of TIME with disease-free survival in AD subtypes. These findings highlight the TIME's role in LA-NPC progression and its potential impact on treatment strategies.
Correction: Transcription of HIV-1 at sites of intact latent provirus integration
Authors: Ana Rafaela Teixeira, Cintia Bittar, Gabriela S. Silva Santos, Thiago Y. Oliveira, Amy S. Huang, Noemi Linden, Isabella A.T.M. Ferreira, Tetyana Murdza, Frauke Muecksch, R. Brad Jones, Marina Caskey, Mila Jankovic, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2025)
Utility of sentinel lymph node biopsy for acral lentiginous melanoma in the contemporary era: a national cohort analysis
Authors: Mohammad S Farooq, Neha Shafique, Gracia M Vargas, Alexander H R Varey, Serigne N Lo, Emily Y Chu, Michael E Ming, John T Miura, Giorgos C Karakousis
Journal: Journal of the American Academy of Dermatology (2025)
Subset of Child-Pugh Score 7 Shows Comparable Survival Outcomes to Child-Pugh Score 6 in Hepatocellular Carcinoma Patients Treated with Atezolizumab and Bevacizumab
Authors: Jaejun Lee, Keungmo Yang, Ji Won Han, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, Hee Sun Cho, Hyun Yang, Si Hyun Bae, Ji Hoon Kim, Heechul Nam, Chang Wook Kim, Hae Lim Lee, Hee Yeon Kim, Sung Won Lee, Ahlim Lee, Do Seon Song, Myeong Jun Song, Soon Woo Nam, Jung Hyun Kwon, Soon Kyu Lee
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Given the limited data on the effectiveness of Atezolizumab plus Bevacizumab (Ate/Bev) in HCC patients with a Child-Pugh score (CPS) of 7, this study aims to evaluate the treatment’s efficacy in this population and identify specific CPS 7 subgroups that may benefit from it. Experimental Design: This study included patients with advanced HCC who received Ate/Bev as first-line therapy between September 2020 and December 2023 at seven university hospitals. The primary outcome was OS, while secondary outcomes included PFS and treatment response. Results: Among the 374 included patients, those with CPS 5 (n=169) demonstrated the highest OS and PFS, followed by patients with CPS 6 (n=105) and CPS 7 (n=100) (P&amp;lt;0.05). For the variables comprising CPS, the HR for OS increased with elevated TB levels and was lower in patients with mild ascites (P&amp;lt;0.05). The HR for OS tended to increase as albumin levels dropped to 2.8 g/dL. Based on these findings, CPS 7 patients were further classified into two subgroups: favorable (TB &amp;lt;2 mg/dL, 3.5 ≥ Alb ≥ 2.8 g/dL, mild ascites, and absence of hepatic encephalopathy) and unfavorable (other CPS 7). Compared to patients with CPS 6, those in the favorable CPS 7 group exhibited comparable OS and PFS, while unfavorable CPS 7 patients had significantly lower OS and PFS (P&amp;lt;0.05). These findings were consistently observed in the multivariate analysis. Conclusions: This study suggests that Ate/Bev treatment can be effective in subset of CPS 7 patients, highlighting the potential to broaden treatment eligibility for this population.
A phase II study of neoadjuvant GVAX and cyclophosphamide combined with nivolumab and SBRT followed by surgery in borderline resectable pancreatic adenocarcinoma
Authors: Parul Agarwal, Matthew Guo, Kabeer Munjal, Hanfei Qi, Rose Parkinson, Anna Ferguson, Christina Mitchell, Jeanne Harrison, Robert A. Anders, Elizabeth D. Thompson, Hao Wang, Ana De Jesus, Lei Zheng, Jin He, Richard Burkhart, Amol Narang, Ben George, Elizabeth M. Jaffee, Mark Yarchoan, Daniel Laheru, Arsen Osipov
Journal: Clinical Cancer Research (2025)

Abstract Purpose: BR-PDAC is treated with perioperative chemotherapy and surgical resection +/- SBRT, but long-term survival is rare. GVAX is a GM-CSF- secreting vaccine that activates T-cell immunity against tumor-associated antigens. This multi- center phase II clinical trial evaluated the safety and immune effects of GVAX/Cy/nivolumab and SBRT on the PDAC TME. Methods: Patients received neoadjuvant mFOLFIRINOX or gemcitabine/nab-paclitaxel if intolerant to mFOLFIRINOX followed by combination immunotherapy and SBRT before surgical resection. The primary endpoint was CD8+ T-cell density in surgical specimens compared with in historical controls treated with neoadjuvant mFOLFIRINOX and SBRT. Pathologic response rate, overall survival, and exploratory immune evaluation of the TME is also reported. Results: 31 patients were enrolled from January 2018 to July 2021. 18 patients received at least one dose of combined immunotherapy. Fourteen patients underwent definitive surgical resection and one complete pathologic complete response was observed. At a median follow-up of 19.5 months, median OS was 20.4 months (95% CI 18.2, NA). There was no difference in the mean CD8 T cell density between study patients as compared to historical control patients. Nonsignificant increases in the abundance score for specific immune cell subsets were observed in responders as compared to non-responders. Conclusions: The addition of combined immunotherapy and SBRT was safe and feasible in this patient population. No difference was observed in the mean CD8 T cell density between study patients and historical controls. These findings support the need for better characterization of how neoadjuvant immunotherapy may shift the phenotype of the PDAC TME.
Facts &amp; Hopes: towards the next quantum leap in melanoma
Authors: Keith T. Flaherty, Andrew E. Aplin, Michael A. Davies, Nir Hacohen, Meenhard Herlyn, Dave Hoon, Patrick Hwu, Michal Lotem, James Mulé, Jennifer A. Wargo, David E. Fisher
Journal: Clinical Cancer Research (2025)

Abstract Outcomes from advanced melanoma, the deadliest of the skin cancers arising from melanocytes and capable of widely metastasizing, have greatly improved with death rates decreasing for AJCC stage 4 melanoma patients by 3-5 percent annually over the past 10 years (1,2). This improvement is a result of advances in both targeted therapy and immunotherapy (Fig 1). BRAF and MEK inhibitors for advanced melanoma have led the way for targeted cancer strategies and first- in-class approvals for immune checkpoint blockers targeting CTLA4, PD1, and LAG3, T cell engager therapy targeting the antigen gp100 and tumor-infiltrating lymphocyte therapy (3). All of the preceding have contributed to enhanced outcomes including long-term durable responses in up to half of patients with advanced disease. In addition, adjuvant and neoadjuvant approaches are reducing the risk of relapse in patients with stage II and III disease. Because of its immunogenicity and defined targetable mutations, melanoma drug development has led the way for novel approaches in cancer research. Yet additional approaches are needed for patients with recurrent or non-responsive disease or rare subtypes including mucosal, acral and uveal melanomas. Progress in modified T cells, including TCR, CAR-T and CRISPR gene editing strategies holds promise for future therapeutics. Continued understanding of the molecular and immune tumor microenvironment and heterogeneity, understanding the microbiome and numerous diverse approaches to topics ranging from prevention, to mechanisms of treatment resistance and novel therapeutic approaches, will optimize opportunities to further decrease melanoma mortality.
Let’s go WILD: Increasing Inclusivity in Theories of Developmental Psychology
Authors: Kim A Bard, Heidi Keller, David A Leavens
Journal: Behavioral and Brain Sciences (2025)

Abstract Most scientists are aware that developmental databases derive primarily from Western, middle-class samples, but fewer are cognizant that developmental theories can be similarly biased. There is urgency in revising developmental theories, both scientifically (embracing diversity is essential to the study of human psychology) and applied (it is damaging to apply WEIRD standards/methods/theories to evaluate development in the multitude of non-WEIRD contexts). We evaluate the extent to which two prominent developmental theories are inclusive. We find that Shared Intentionality Theory is based on a WEIRD bias in the foundational databases: the core constructs lack culturally diverse data, undermining claims that this theory explains human-general social cognition. In Attachment Theory, we illuminate the lack of inclusivity in the core assumptions and resulting claims of the meaning and measure of the attachment system: this theory excludes cultural diversity in social-emotional constructs focused on communal orientations (e.g., interdependence, attachment networks) found in many people of the Global South, and neglects culture-specific adaptive behavior patterns. Acknowledging the lack of inclusivity at the level of theory is necessary. We urge researchers to take a more WILD approach: obtain W orldwide samples, study development I n situ, focus on L ocal cultural practices and ethnotheories, and consider development as D iverse. Being WILD entails attending to inclusivity during the entire research process, from framing the research questions to interpreting the data (e.g., respecting all adaptive behaviors in development). Five Steps for Increasing Inclusivity can be used as a practical guide to decenter psychological theories from their current WEIRD mindset.
Comprehensive single-cell RNA atlas of human laryngeal normal, preneoplastic and tumorigenic states
Authors: Zi-Ming Fu, Yang-Yang Bao, Li-Bo Dai, Jiang-Tao Zhong, Heng-Chao Chen, Zhe Chen, Shui-Hong Zhou
Journal: Clinical Cancer Research (2025)

Abstract Purpose: The mechanisms driving the progression of vocal cord leukoplakia (VCL) to laryngeal squamous cell carcinoma (LSCC) remain unclear, posing a significant barrier to the effective prevention, early diagnosis, and targeted treatment of LSCC. Therefore, it is essential to characterize the cellular microenvironmental differences between VCL and LSCC at the single-cell resolution. Experimental Design: In the study, we conducted single-cell RNA sequencing and spatial transcriptomics on surgical tissue specimens obtained from 36 patients diagnosed with vocal cord polyps (VCP), VCL and LSCC. Results: Our study generated the first single-cell atlas of VCP and VCL, while expanding the cancer cell atlas of LSCC. This dataset comprises 318,907 cells and 12,679 spatial transcriptomic spots, allowing the identification of distinct cellular subclusters. We observed that VCL, as a transitional lesion between benign and malignant states, exhibits a hybrid microenvironment that mirrors VCP and LSCC, with early signs of immunosuppressive activity. Immunoregulatory cell populations demonstrate significant gene expression and functional pathway differences between VCL and LSCC. Conclusions: Our scRNA-seq and spatial transcriptomics analyses revealed the cellular heterogeneity underlying benign, precancerous, and malignant laryngeal lesions. We identified epithelial subclusters in VCL with malignant potential and observed shared immunosuppressive features with LSCC, suggesting their role in disease progression. These findings provide valuable insights into the molecular transition from VCL to LSCC and emphasize potential targets for early diagnosis and therapeutic intervention.
Real world outcomes with elotuzumab-based therapies for patients with relapsed refractory multiple myeloma: a Mayo Clinic experience
Authors: Ricardo D Parrondo, Saurav Das, Hanna Sledge, Leif Bergsagel, Rafael Fonseca, Nelson Leung, Prashant Kapoor, Morie Gertz, Francis Buadi, Angela Dispenzieri, Jamie Elliott, Andre Fernandez, Caitlin Flott, Asher A Chanan-Khan, Vivek Roy, Sikander Ailawadhi
Journal: Blood Cancer Journal (2025)
MSFusion: A Multi-source hybrid feature fusion network for accurate grading of invasive breast cancer using H&amp;E-stained histopathological images
Authors: Yuli Chen, Jiayang Bai, Jinjie Wang, Guoping Chen, Xinxin Zhang, Duan-Bo Shi, Xiujuan Lei, Peng Gao, Cheng Lu
Journal: Medical Image Analysis (2025)
Iterative refinement and goal articulation to optimize large language models for clinical information extraction
Authors: David Hein, Alana Christie, Michael Holcomb, Bingqing Xie, A J Jain, Joseph Vento, Neil Rakheja, Ameer Hamza Shakur, Scott Christley, Lindsay G Cowell, James Brugarolas, Andrew R Jamieson, Payal Kapur
Journal: npj Digital Medicine (2025)
Remote monitoring or patient-initiated care in axial spondyloarthritis: a 3-armed randomised controlled noninferiority trial
Authors: Inger Jorid Berg, Eirik K Kristianslund, Anne Therese Tveter, Joseph Sexton, Gunnstein Bakland, Laure Gossec, Sarah Hakim, Gary J Macfarlane, Ellen Moholt, Sella Aarrestad Provan, Emil E Kvernberg Thomassen, Annette de Thurah, Espen A Haavardsholm, Siri Lillegraven, Nina Osteras
Journal: Annals of the Rheumatic Diseases (2025)

This study aimed to determine whether novel follow-up regimen, remote monitoring, or patient-initiated care is noninferior to usual care in maintaining low disease activity, in patients with axial spondyloarthritis (axSpA). This is a randomised, controlled, 3-armed, parallel-group, open-label, noninferiority trial. Patients with axSpA in low disease activity on stable treatment with tumour necrosis factor inhibitor were recruited from a Norwegian outpatient clinic. Patients were randomly allocated 1:1:1 to remote monitoring, patient-initiated care, or usual care (control group), with 18 months of follow-up. Primary outcome was mean probability of axSpA Disease Activity Score (ASDAS) of <2.1, compared between groups at 6, 12, and 18 months, with 15% noninferiority margin. Secondary outcomes included other measures of disease activity, physical function, patient satisfaction, change of medication, resource use, and adverse events. Of 243 patients enrolled patients, 235 completed the study (remote monitoring = 75, patient-initiated care = 79, usual care = 81). At the 6-month, 12-month, and 18-month assessments, 90% or more patients in all 3 groups had ASDAS of <2.1. The estimated difference of probability of ASDAS < 2.1 was as follows: usual care vs remote monitoring, -4.1% (97.5% CI, -9.9% to 1.8%); usual care vs patient-initiated care, -1.1% (97.5% CI, -7.2% to 4.9%); and remote monitoring vs patient-initiated care, 2.9% (95% CI, -1.5% to 7.4%). Health providers' resource use was lowest in patient-initiated care; other secondary outcomes were comparable. In patients with axSpA in low disease activity and on stable treatment with tumour necrosis factor inhibitor, follow-up with remote monitoring or patient-initiated care was noninferior to usual care in maintaining low disease activity, supporting the implementation of novel follow-up strategies.
Metaproteomics reveals age-specific alterations of gut microbiome in hamsters with SARS-CoV-2 infection
Authors: Marybeth Creskey, Fabiola Silva Angulo, Qing Wu, Levi Tamming, Emily E. F. Fekete, Kai Cheng, Zhibin Ning, Angela Wang, Patrícia Brito Rodrigues, Vinícius de Rezende Rodovalho, Marco Aurélio Ramirez Vinolo, Daniel Figeys, Xuguang Li, Francois Trottein, Xu Zhang
Journal: Gut Microbes (2025)

The gut microbiome's pivotal role in health and disease is well established. SARS-CoV-2 infection often causes gastrointestinal symptoms and is associated with changes of the microbiome in both human and animal studies. While hamsters serve as important animal models for coronavirus research, there exists a notable void in the functional characterization of their microbiomes with metaproteomics. In this study, we present a workflow for analyzing the hamster gut microbiome, including a metagenomics-derived hamster gut microbial protein database and a data-independent acquisition metaproteomics method. Using this workflow, we identified 32,419 protein groups from the fecal microbiomes of young and old hamsters infected with SARS-CoV-2. We showed age-specific changes in the expressions of microbiome functions and host proteins associated with microbiomes, providing further functional insight into the interactions between the microbiome and host in SARS-CoV-2 infection. Altogether, this study established and demonstrated the capability of metaproteomics for the study of hamster microbiomes.
Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages
Authors: Adrián Cortés-Martín, Colin Buttimer, Jessie L. Maier, Ciara A. Tobin, Lorraine A. Draper, R. Paul Ross, Manuel Kleiner, Colin Hill, Andrey N. Shkoporov
Journal: Gut Microbes (2025)

Bacteriophages (phages) and bacteria within the gut microbiome persist in long-term stable coexistence. These interactions are driven by eco-evolutionary dynamics, where bacteria employ a variety of mechanisms to evade phage infection, while phages rely on counterstrategies to overcome these defenses. Among the most abundant phages in the gut are the crAss-like phages that infect members of the order Bacteroidales, in particular, genus Bacteroides. In this study, we explored some of the mechanisms enabling the co-existence of four phage-Bacteroidales host pairs in vitro using a multi-omics approach (transcriptomics, proteomics and metabolomics). These included three Bacteroides species paired with three crAss-like phages (Bacteroides intestinalis and фcrAss001, Bacteroides xylanisolvens and фcrAss002, and an acapsular mutant of Bacteroides thetaiotaomicron with DAC15), and Parabacteroides distasonis paired with the siphovirus фPDS1. We show that phase variation of individual capsular polysaccharides (CPSs) is the primary mechanism promoting phage co-existence in Bacteroidales, but this is not the only strategy. Alternative resistance mechanisms, while potentially less efficient than CPS phase variation, can be activated to support bacterial survival by regulating gene expression and resulting in metabolic adaptations, particularly in amino acid degradation pathways. These mechanisms, also likely regulated by phase variation, enable bacterial populations to persist in the presence of phages, and vice versa. An acapsular variant of B. thetaiotaomicron demonstrated broader transcriptomic, proteomic, and metabolomic changes, supporting the involvement of additional resistance mechanisms beyond CPS variation. This study advances our understanding of long-term phage-host interaction, offering insights into the long-term persistence of crAss-like phages and extending these observations to other phages, such as фPDS1. Knowledge of the complexities of phage-bacteria interactions is essential for designing effective phage therapies and improving human health through targeted microbiome interventions.
Evaluation of European severe acute respiratory infection (SARI) surveillance, 27 European countries, 2022/23
Authors: Diogo FP Marques, Dory Kovacs, Miguel-Angel Sanchez-Ruiz, Ana Paula Rodrigues, Ausenda Machado, Clara Mazagatos, Susana Monge, Lisa Domegan, Joan O’Donnell, Mariette Hooiveld, Hanne-Dorthe Emborg, Baltazar Nunes, Carlos Carvalho, Angela MC Rose
Journal: Eurosurveillance (2025)

Background Between 2020 and 2023, ECDC has supported 21 of 30 EU/EEA and six Western Balkan countries by enhancing severe acute respiratory infection (SARI) surveillance to monitor trends, detect unexpected events, evaluate public health interventions, identify risk factors and support vaccine effectiveness studies. Using diverse strategies, countries have implemented SARI surveillance and reported data at national/European levels. Aim We evaluated European-level SARI surveillance and provided recommendations to achieve objectives and improve key attribute performance. Methods We analysed 2022/23 surveillance data for completeness. We administered a questionnaire, targeting country-level representatives, to evaluate surveillance attributes (meeting objectives, usefulness, acceptability, timeliness, representativeness) and identify strengths, weaknesses, opportunities and threats. Results Thirteen countries (13/27) reported data at European level. Data showed good overall completeness but varied across countries and some variables need improvement (vaccination, sequencing). The questionnaire was completed by all 27 countries. Most countries (23/27) reported that the system effectively monitored trends and considered it useful and acceptable (25/27), but only 16 found it timely and 14 representative. Challenges included insufficient case-based data, data linkage issues and insufficient data completeness. Slow/inefficient manual data extraction affected timeliness, while insufficient geographical coverage affected representativeness. Multi-pathogen surveillance was identified as the main strength, heterogeneity of systems the main weakness, improvements of hospital information systems the main opportunity, and lack of sustainable funding the main threat. Conclusions SARI surveillance was perceived as effective in monitoring trends, useful and acceptable. To achieve additional objectives and enhance timeliness and representativeness, we recommend improving data completeness, digitalisation/automation and geographical coverage.