tbuckley/cabot-search huggingface dataset:
Health-Related Quality of Life and Health Utility After Metabolic/Bariatric Surgery Versus Medical/Lifestyle Intervention in Individuals With Type 2 Diabetes and Obesity: The ARMMS-T2D Study
Authors: Donald C. Simonson, William F. Gourash, David E. Arterburn, Bo Hu, Sangeeta R. Kashyap, David E. Cummings, Mary-Elizabeth Patti, Anita P. Courcoulas, Ashley H. Vernon, John M. Jakicic, Sarah Kirschling, Ali Aminian, Philip R. Schauer, John P. Kirwan
Journal: Diabetes Care (2025)

OBJECTIVE Type 2 diabetes and obesity are associated with reduced health-related quality of life (HRQoL) and health utility (HU), but long-term effects of metabolic/bariatric surgery (MBS) compared with those of medical/lifestyle intervention (MLI) on these outcomes are unclear. RESEARCH DESIGN AND METHODS We studied 228 individuals with type 2 diabetes and obesity randomly assigned to MBS (Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band; n = 152) or MLI (n = 76) in the ARMMS-T2D study. HRQoL (36-Item Short-Form Health Survey [SF-36], including Physical Component Score [PCS] and Mental Component Score [MCS]) and HU (Short Form 6 Dimensions [SF-6D]) were measured annually up to 12 years. RESULTS At baseline, participants’ mean ± SD age was 49.2 ± 8.0 years, 68.4% were female, BMI was 36.3 ± 3.4 kg/m2, and HbA1c was 8.7 ± 1.6%. PCS improved significantly more in the MBS versus MLI group over 12 years (+2.37 ± 0.53 vs. −0.95 ± 0.73; difference 3.32 ± 0.85; P &amp;lt; 0.001). MBS was associated with better general health (P &amp;lt; 0.001), physical functioning (P = 0.001), and vitality (P = 0.003). Reduction in BMI was greater after MBS versus MLI (P &amp;lt; 0.001) and correlated with improved PCS (r = −0.43; P &amp;lt; 0.001). Change in PCS was not associated with change in HbA1c. MCS changed minimally from baseline and was similar between MBS and MLI groups during follow-up (−0.21 ± 0.61 vs. −0.89 ± 0.84; difference 0.68 ± 0.97; P = 0.48). Improvements in HU were greater in the MBS versus MLI group over 12 years (+0.02 ± 0.01 vs. −0.01 ± 0.01; difference 0.03 ± 0.01; P = 0.003). CONCLUSIONS Metabolic surgery produces sustained weight loss and improves PCS, general health, physical functioning, vitality, and HU in individuals with type 2 diabetes and obesity compared with medical therapy up to 12 years after intervention.
The Mode of Action and Clinical Outcomes of Sacituzumab Govitecan in Solid Tumors
Authors: Sara M. Tolaney, Thomas M. Cardillo, Chih-Chien Chou, Carrie Dornan, Mary Faris
Journal: Clinical Cancer Research (2025)

Abstract Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is currently approved to treat metastatic triple-negative breast cancer and HR+/HER2– breast cancer, and is under clinical investigation for a range of other tumor types. This review describes its mode of action, development, and clinical outcomes. SG is composed of SN-38 (a topoisomerase I inhibitor derived from irinotecan) covalently linked to an anti-Trop-2 monoclonal antibody (sacituzumab; hRS7) via a hydrolysable CL2A linker. SN-38 was chosen due to its potent antitumor activity; CL2A occupies the most effective position on SN-38 for maintaining stability during transport, with pH-sensitive payload release in the tumor, and the antigen target (Trop-2) is highly expressed on many solid tumors. SG has an ~8:1 drug-to-antibody ratio and delivers therapeutic SN-38 concentration to Trop-2+ expressing tumor cells via rapid internalization and efficient payload release. Free SN-38 can subsequently enter the tumor microenvironment and kill adjacent tumor cells with or without Trop-2 expression (bystander effect). SN-38 induces DNA breakage and inhibits nucleic acid synthesis via a drug-induced topoisomerase 1:DNA complex that interferes with cell proliferation, causing apoptosis. Dose-finding studies support SG 10 mg/kg on days 1 and 8 of a 21-day cycle as the monotherapy dose for clinical use; this was determined by therapeutic index improvement based on efficacy and safety. Payload-linker dynamics and SG potency ensure continued tissue penetration. Neutropenia and diarrhea are the most common grade ≥ 3 treatment-emergent adverse events with SG, but they are manageable. Efficacy of SG has been demonstrated across a broad spectrum of solid tumors.
Beyond Amyloid Plaque, Targeting α-Synuclein in Alzheimer Disease: The Battle Continues
Authors: Hayder M Al-Kuraishy, Ghassan M Sulaiman, Hamdoon A Mohammed, Ali I Al-Gareeb, Ali K Albuhadily, Amer Al Ali, Mohammed H Abu-Alghayth
Journal: Ageing Research Reviews (2025)
The Freiburg Index of Post-TIPS Survival (FIPS) identifies patients at risk for further decompensation and ACLF after TIPS
Authors: Lukas Sturm, Michael Schultheiss, Fabian Stöhr, Christian Labenz, Benjamin Maasoumy, Anja Tiede, Michael Praktiknjo, Leon Louis Seifert, Timo Alexander Auer, Uli Fehrenbach, Felix Piecha, Aenne Harberts, Johannes Kluwe, Tony Bruns, Maike Rebecca Pollmanns, Johannes Chang, Jakub Grobelski, Christian Jansen, Carsten Meyer, Marlene Reincke, Charlotte Rohrer, Sina Rastin Philipp Arbabi, Markus Kimmann, Cristina Ripoll, Alexander Zipprich, Jan Hinrichs, Michael Koehler, Jonel Trebicka, Roman Kloeckner, Robert Thimme, Dominik Bettinger
Journal: Journal of Hepatology (2025)

The Freiburg Index of Post-TIPS Survival (FIPS) defines a high-risk group of patients with significantly reduced survival following transjugular intrahepatic portosystemic shunt (TIPS) implantation. However, the clinical hallmarks responsible for these patients' unfavorable outcome remain to be identified. Therefore, the present study aimed to characterize the clinical course after TIPS implantation according to the FIPS. A total of 1359 patients with cirrhosis allocated to TIPS implantation for treatment of recurrent or refractory ascites or secondary prophylaxis of variceal bleeding from eight tertiary centers were retrospectively included. The patients' clinical course following TIPS placement was analyzed, stratified according to the FIPS. Primary study outcome was further decompensation of cirrhosis within 90 days after TIPS, secondary outcomes were acute-on-chronic liver failure (ACLF) within 90 days and one-year transplant-free survival. Further decompensation after TIPS implantation was significantly more frequent in FIPS high-risk patients compared to low-risk patients (cumulative incidence function 0.58 vs. 0.38, p < 0.001). Moreover, FIPS high-risk patients developed ACLF significantly more often (0.18 vs. 0.08; p = 0.008). Uni- and multivariable competing risk regression analyses confirmed that the FIPS high-risk group independently predicted further decompensation (sHR 1.974, 95 % CI 1.531 - 2.544, p < 0.001) and ACLF after TIPS (sHR 2.586, 95 % CI 1.449 - 4.616, p = 0.001). Importantly, further decompensation and ACLF after TIPS were associated with significantly reduced transplant-free survival. The present study reveals that the FIPS predicts development of further decompensation and ACLF after TIPS implantation. These events are responsible for impaired transplant-free survival in FIPS high-risk patients. These results pave the way for the development of tailored clinical management strategies.
A human gut bacterium antagonizes neighboring bacteria by altering their protein-folding ability
Authors: Bentley Lim, Jinghua Xu, Igor H Wierzbicki, Carlos G Gonzalez, Zhe Chen, David J Gonzalez, Xiang Gao, Andrew L Goodman
Journal: Cell Host & Microbe (2025)

Antagonistic interactions play a key role in determining microbial community dynamics. Here, we report that one of the most widespread contact-dependent effectors in human gut microbiomes, Bte1, directly targets the PpiD-YfgM periplasmic chaperone complex in related microbes. Structural, biochemical, and genetic characterization of this interaction reveals that Bte1 reverses the activity of the chaperone complex, promoting substrate aggregation and toxicity. Using Bacteroides, we show that Bte1 is active in the mammalian gut, conferring a fitness advantage to expressing strains. Recipient cells targeted by Bte1 exhibit sensitivity to membrane-compromising conditions, and human gut microbes can use this effector to exploit pathogen-induced inflammation in the gut. Further, Bte1 allelic variation in gut metagenomes provides evidence for an arms race between Bte1-encoding and immunity-encoding strains in humans. Together, these studies demonstrate that human gut microbes alter the protein-folding capacity of neighboring cells and suggest strategies for manipulating community dynamics.
Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses
Authors: Xiaoqiang Zhu, Muni Hu, Xiaowen Huang, Lingxi Li, Xiaolin Lin, Xiaoyan Shao, Jiantao Li, Xiaoyue Du, Xinjia Zhang, Rongrong Sun, Tianying Tong, Yanru Ma, Lijun Ning, Yi Jiang, Yue Zhang, Yuqi Shao, Zhenyu Wang, Yilu Zhou, Jinmei Ding, Ying Zhao, Baoqin Xuan, Hongyang Zhang, Youwei Zhang, Jie Hong, Jing-Yuan Fang, Xiuying Xiao, Bo Shen, Songbing He, Haoyan Chen
Journal: Cell Metabolism (2025)
Spatially resolved transcriptomics reveal the determinants of primary resistance to immunotherapy in NSCLC with mature tertiary lymphoid structures
Authors: Florent Peyraud, Jean-Philippe Guégan, Christophe Rey, Oren Lara, Ophélie Odin, Marie Del Castillo, Lucile Vanhersecke, Jean-Michel Coindre, Emma Clot, Maxime Brunet, Thomas Grellety, Angélique Tasseel, Sylvestre Le Moulec, Robert J. Johnston, Alban Bessede, Antoine Italiano
Journal: Cell Reports Medicine (2025)

Highlights•mTLSs are predictive of response to ICIs in NSCLC•Two CAF subsets within the TME are key determinants of primary resistance to ICIs•FAP+αSMA+ CAFs correlate with the inflammatory response and exhaustion of CD8+ T cells•MYH11+αSMA+ CAFs favor an immunosuppressive TME with CD4+ Treg cell infiltrationSummaryEffectiveness of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) has been linked to the presence of mature tertiary lymphoid structures (mTLSs) within the tumor microenvironment (TME). However, only a subset of mTLS-positive NSCLC derives benefit, thus highlighting the need to unravel ICI response determinants. The comprehensive analysis of ICI-treated patients with NSCLC (n = 509) from the Bergonié Institute Profiling (BIP) study (NCT02534649) reveals that the presence of mTLSs correlates with improved clinical outcomes, independently of programmed death ligand 1 (PD-L1) expression and genomic features. Employing spatial transcriptomics alongside multiplex immunofluorescence (mIF), we show that two distinct subsets of cancer-associated fibroblasts (CAFs) are essential factors in mediating primary resistance to ICIs in mTLS-positive NSCLC. These CAFs are associated with immune exclusion, CD8+ T cell exhaustion, and increased regulatory CD4+ T cell infiltration, underscoring an immunosuppressive TME. Our study highlights the pivotal role of specific CAF subsets in thwarting ICIs, proposing new therapeutic targets to enhance immunotherapy efficacy.Graphical abstract
The Marriage of Computable Phenotypes With Machine Learning—A Pathway to Evidence-Based Care for Critically Ill Children
Authors: Anita K. Patel
Journal: JAMA Network Open (2025)

Christopher M. Horvat, MD, MHA; Amie J. Barda, PhD; Eddie Perez Claudio, BS; Alicia K. Au, MD, MS; Andrew Bauman, PhD; Qingyang Li, MS; Ruoting Li, PhD; Neil Munjal, MD, MS; Mark S. Wainwright, MD, PhD; Tanupat Boonchalermvichien, MD; Harry Hochheiser, PhD; Robert S. B. Clark, MD
Large Language Models for Chatbot Health Advice Studies
Authors: Bright Huo, Amy Boyle, Nana Marfo, Wimonchat Tangamornsuksan, Jeremy P. Steen, Tyler McKechnie, Yung Lee, Julio Mayol, Stavros A. Antoniou, Arun James Thirunavukarasu, Stephanie Sanger, Karim Ramji, Gordon Guyatt
Journal: JAMA Network Open (2025)

Importance There is much interest in the clinical integration of large language models (LLMs) in health care. Many studies have assessed the ability of LLMs to provide health advice, but the quality of their reporting is uncertain. Objective To perform a systematic review to examine the reporting variability among peer-reviewed studies evaluating the performance of generative artificial intelligence (AI)–driven chatbots for summarizing evidence and providing health advice to inform the development of the Chatbot Assessment Reporting Tool (CHART). Evidence Review A search of MEDLINE via Ovid, Embase via Elsevier, and Web of Science from inception to October 27, 2023, was conducted with the help of a health sciences librarian to yield 7752 articles. Two reviewers screened articles by title and abstract followed by full-text review to identify primary studies evaluating the clinical accuracy of generative AI-driven chatbots in providing health advice (chatbot health advice studies). Two reviewers then performed data extraction for 137 eligible studies. Findings A total of 137 studies were included. Studies examined topics in surgery (55 [40.1%]), medicine (51 [37.2%]), and primary care (13 [9.5%]). Many studies focused on treatment (91 [66.4%]), diagnosis (60 [43.8%]), or disease prevention (29 [21.2%]). Most studies (136 [99.3%]) evaluated inaccessible, closed-source LLMs and did not provide enough information to identify the version of the LLM under evaluation. All studies lacked a sufficient description of LLM characteristics, including temperature, token length, fine-tuning availability, layers, and other details. Most studies (136 [99.3%]) did not describe a prompt engineering phase in their study. The date of LLM querying was reported in 54 (39.4%) studies. Most studies (89 [65.0%]) used subjective means to define the successful performance of the chatbot, while less than one-third addressed the ethical, regulatory, and patient safety implications of the clinical integration of LLMs. Conclusions and Relevance In this systematic review of 137 chatbot health advice studies, the reporting quality was heterogeneous and may inform the development of the CHART reporting standards. Ethical, regulatory, and patient safety considerations are crucial as interest grows in the clinical integration of LLMs.
Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development
Authors: Maria C Hesselman, Marius Zeeb, Peter Rusert, Chloé Pasin, Jennifer Mamrosh, Samuel Kariuki, Ian Pichler, Michèle Sickmann, Masako M Kaufmann, Daniel Schmidt, Nikolas Friedrich, Karin J Metzner, Audrey Rindler, Herbert Kuster, Craig Adams, Ruwayhida Thebus, Michael Huber, Sabine Yerly, Karoline Leuzinger, Matthieu Perreau, Roger Koller, Günter Dollenmaier, Simona Frigerio, Dylan H Westfall, Wenjie Deng, Allan C deCamp, Michal Juraska, Srilatha Edupuganti, Nyaradzo Mgodi, Hugh Murrell, Nigel Garrett, Kshitij Wagh, James I Mullins, Carolyn Williamson, Penny L Moore, Huldrych F Günthard, Roger D Kouyos, Alexandra Trkola
Journal: Cell Host & Microbe (2025)

Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cysteine (Cys) residues in V1 that are enriched in individuals with elite neutralization breadth. Analyzing over 65,000 V1 sequences from the CATNAP database, AMP trials, and longitudinal HIV-1 cohorts (SHCS, ZPHI, and CAPRISA), we found that Env variants with extra V1 Cys are present at low levels and fluctuate over time. Extra V1 Cys associate with elite plasma neutralization, and two additional Cys are preferred, suggesting stabilization through disulfide bonds. Among 34 broadly neutralizing antibody (bnAb)-inducer Envs, 17.6% had elongated V1 regions with extra Cys. These extra Cys moderately increased neutralization resistance and altered bnAb epitope accessibility. Collectively, altering epitope exposure alongside Env stabilization renders the V1 twin Cys motif a promising feature for HIV-1 bnAb immunogens.
Exercise Interventions for Depression, Anxiety, and Quality of Life in Older Adults With Cancer
Authors: Rou Yi Soong, Chen Ee Low, Vanessa Ong, Isaac Sim, Charmaine Lee, Fattah Lee, Lucas Chew, Chun En Yau, Ainsley Ryan Yan Bin Lee, Matthew Zhixuan Chen
Journal: JAMA Network Open (2025)

Importance Cancer and its treatment negatively impact the mental health of older adults. The potential of exercise interventions as a complementary treatment to alleviate the psychological impacts of cancer is promising, but there are gaps in the current literature. Objective To determine if exercise interventions are associated with improvements in psychological outcomes among older adults with cancer. Data Sources PubMed, Embase, PsycINFO, and Cochrane databases were searched from database inception to November 5, 2024. Search terms used were geriatrics , cancer , depression , anxiety , quality of life , and exercise interventions . Study Selection English-language randomized clinical trials (RCTs) that analyzed the association of various exercise interventions with at least 1 of 3 psychological outcomes (depression, anxiety, or health-related quality-of-life [HRQOL]) were included. The control groups were given usual care. Studies were included if the mean age of participants was older than 60 years and had participants with a diagnosis of any cancer regardless of comorbidities. Data Extraction and Synthesis Studies were screened, and data were extracted by 2 independent authors. Random-effects meta-analyses and meta-regressions were used for analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. Main Outcomes and Measures The primary outcomes were depression, anxiety, and HRQOL. Standardized mean difference (SMD) was used to quantify the association of exercise interventions with outcomes. Results A total of 27 RCTs with 1929 participants were included. Meta-analyses observed an association of exercise with a significant reduction in levels of depression (SMD = −0.53; 95% CI, −0.79 to −0.28) and anxiety (SMD = −0.39; 95% CI, −0.66 to −0.12) and improvements in overall HRQOL (SMD = 0.63; 95% CI, 0.10 to 1.17). Subgroup analyses revealed that mind-body exercise interventions were significantly associated with improved depression (SMD = −0.89; 95% CI, −1.51 to −0.27) and anxiety levels (SMD = −0.77; 95% CI, −1.54 to −0.01) compared with conventional exercise interventions. Conclusion In this systematic review and meta-analysis of 27 RCTs, exercise interventions were found to be associated with significantly reduced levels of depression and anxiety and significantly improved HRQOL in older adults with cancer. These findings suggest that health care professionals and policymakers should focus more on implementing exercise interventions to improve mental health outcomes in this vulnerable population.
Guidance for protocol content and reporting of factorial randomised trials: explanation and elaboration of the CONSORT 2010 and SPIRIT 2013 extensions
Authors: Brennan C Kahan, Edmund Juszczak, Elaine Beller, Megan Birchenall, An-Wen Chan, Sophie Hall, Paul Little, John Fletcher, Robert M Golub, Beatriz Goulao, Sally Hopewell, Nazrul Islam, Merrick Zwarenstein, Diana Elbourne, Alan Montgomery
Journal: BMJ (2025)

This report presents the explanation and elaboration paper for the CONSORT (Consolidated Standards of Reporting Trials) 2010 and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 extensions for factorial trials. Factorial trials involve randomising participants to more than one intervention, often with the aim of evaluating multiple interventions in one study or assessing whether treatments interact. The CONSORT and SPIRIT statements have been extended to allow for the unique features of the factorial design. Reporting items along with detailed explanations and examples of good practice are provided, as well as a glossary of key terms and an overview of the methodological features of factorial trials.
In vivo engineering of murine T cells using the evolved adeno-associated virus variant Ark313
Authors: William A Nyberg, Charlotte H Wang, Jonathan Ark, Chang Liu, Sylvanie Clouden, Anita Qualls, Sofia Caryotakis, Elina Wells, Katherine Simon, Celeste Garza, Pierre-Louis Bernard, Maya Lopez-Ichikawa, Zhongmei Li, Jin Seo, Gabriella R Kimmerly, Joseph J Muldoon, Peixin Amy Chen, Mingcheng Li, Hong-Erh Liang, Kelly Kersten, Alan Rosales, Nicholas Kuhn, Chun Jimmie Ye, James M Gardner, Ari Molofsky, Roberto R Ricardo-Gonzalez, Aravind Asokan, Justin Eyquem
Journal: Immunity (2025)
Structural basis for complement receptor engagement and virus neutralization through Epstein-Barr virus gp350
Authors: M Gordon Joyce, Wei Bu, Wei-Hung Chen, Rebecca A Gillespie, Sarah F Andrews, Adam K Wheatley, Yaroslav Tsybovsky, Jaime L Jensen, Tyler Stephens, Madhu Prabhakaran, Brian E Fisher, Sandeep R Narpala, Meghna Bagchi, Adrian B McDermott, Gary J Nabel, Peter D Kwong, John R Mascola, Jeffrey I Cohen, Masaru Kanekiyo
Journal: Immunity (2025)

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with malignancies in humans. Viral infection of B cells is initiated by the viral glycoprotein 350 (gp350) binding to complement receptor 2 (CR2). Despite decades of effort, no vaccines or curative agents have been developed, partly due to lack of atomic-level understanding of the virus-host interface. Here, we determined the 1.7 Å structure of gp350 in complex with CR2. CR2 binding of gp350 utilized the same set of Arg residues required for recognition of its natural ligand, complement C3d. We further determined the structures of gp350 in complex with three potently neutralizing antibodies (nAbs) obtained from vaccinated macaques and EBV-infected individuals. Like the CR2 interaction, these nAbs targeted the acidic pocket within the CR2-binding site on gp350 using Arg residues. Our results illustrate two axes of molecular mimicry-gp350 versus C3d and CR2 versus EBV nAbs-offering insights for EBV vaccines and therapeutics development.
Deciphering the Foundations of Mitochondrial Mutational Spectra: Replication-Driven and Damage-Induced Signatures Across Chordate Classes
Authors: Dmitrii Iliushchenko, Bogdan Efimenko, Alina G Mikhailova, Victor Shamanskiy, Murat K Saparbaev, Bakhyt T Matkarimov, Ilya Mazunin, Alexandr Voronka, Dmitry Knorre, Wolfram S Kunz, Philipp Kapranov, Stepan Denisov, Jacques Fellay, Konstantin Khrapko, Konstantin Gunbin, Konstantin Popadin
Journal: Molecular Biology and Evolution (2025)

Mitochondrial DNA (mtDNA) mutagenesis remains poorly understood despite its crucial role in disease, aging, and evolutionary tracing. In this study, we reconstructed a comprehensive 192-component mtDNA mutational spectrum for chordates by analyzing 118,397 synonymous mutations in the CytB gene across 1,697 species and five classes. This analysis revealed three primary forces shaping mtDNA mutagenesis: (i) symmetrical, replication-driven errors by mitochondrial polymerase (POLG), resulting in C > T and A > G mutations that are highly conserved across classes; (ii) asymmetrical, damage-driven C > T mutations on the single-stranded heavy strand with clock-like dynamics; and (iii) asymmetrical A > G mutations on the heavy strand, with dynamics suggesting sensitivity to oxidative damage. The third component, sensitive to oxidative damage, positions mtDNA mutagenesis as a promising marker for metabolic and physiological processes across various classes, species, organisms, tissues, and cells. The deconvolution of the mutational spectra into mutational signatures uncovered deficiencies in both base excision repair (BER) and mismatch repair (MMR) pathways. Further analysis of mutation hotspots, abasic sites, and mutational asymmetries underscores the critical role of single-stranded DNA damage (components ii and iii), which, uncorrected due to BER and MMR deficiencies, contributes roughly as many mutations as POLG-induced errors (component i).