tbuckley/cabot-search huggingface dataset:
Performance of stool Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis among adults living with HIV: a multicentre, prospective diagnostic study
Authors: George W Kasule, Sabine Hermans, Sozinho Acacio, Alexander Kay, Joachim Kikoyo Nsubuga, Carlos Fernández-Escobar, Nosisa Shiba, Lucia Carratalá-Castro, Derrick Semugenze, Patricia Mwachan, Shilzia Munguambe, Joanna Ehrlich, Elisa Lopez-Varela, Andrew R DiNardo, Frank Cobelens, Christoph Lange, Moses Joloba, Anna M Mandalakas, Willy Ssengooba, Alberto L García-Basteiro
Journal: The Lancet Microbe (2025)

When people living with HIV develop pulmonary tuberculosis, it often manifests without detectable acid-fast bacilli on sputum microscopy. We aimed to assess the diagnostic accuracy of stool Xpert MTB/RIF Ultra (hereafter, Ultra) for Mycobacterium tuberculosis detection among adults with HIV. This multicentre, prospective diagnostic accuracy study was done in outpatient and inpatient health centres in Eswatini, Mozambique, and Uganda. We enrolled adults aged 15 years and older with HIV with presumptive tuberculosis. We evaluated the diagnostic accuracy of stool Ultra using the simple one-step processing method against a composite microbiological reference standard (CMRS) including three WHO-recommended tuberculosis diagnostic tests (urine tuberculosis biomarker-based lateral-flow lipoarabinomannan [TB-LAM], sputum Ultra, and sputum culture), and stratified by CD4 cell count. We compared sputum versus stool Ultra performance against a composite reference standard of TB-LAM and sputum culture (CMRS2). We also calculated the diagnostic yield among all tested. This study is registered with ClinicalTrials.gov, NCT05047315. Between Dec 2, 2021, and Aug 14, 2024, 677 participants were enrolled (247 [36%] men and 430 [64%] women). Tuberculosis was microbiologically confirmed in 119 participants by the CMRS: 39 (33%) had a positive test with sputum Ultra, 30 (25%) had a positive test with culture, and 84 (71%) had a positive test with urine TB-LAM. The sensitivity of stool Ultra compared with CMRS was 23·7% (28/118 [95% CI 16·4-32·4]) and the specificity was 94·0% (504/536 [91·7-95·9]). The sensitivity of stool Ultra in participants with CD4 counts less than or equal to 200 cells per μL was 45·5% (10/22 [24·4-67·8]) compared with 21·3% (17/80 [12·9-31·8]) in those with CD4 counts greater than 200 cells per μL. Against the CMRS2, we observed no differences in sensitivity between sputum and stool Ultra on the basis of CD4 cell count. Stool Ultra resulted in additional cases detected of 23% (30/133) compared with sputum Ultra, 29% (38/133) compared with sputum culture, and 33% (44/133) compared with TB-LAM. The overall diagnostic yield for all treated for stool Ultra was 9% (60/677), for TB-LAM was 12% (84/677), for sputum Ultra was 6% (39/677), and for sputum culture was 4% (30/677). These results suggest stool Ultra could be used as an additional test for tuberculosis diagnosis among people with HIV, particularly among those with CD4 counts less than 200 cells per μL. EDCTP2 and EDCTP3 Programmes supported by the EU.
Bromination effect: A new tool to balance increased driving and repulsive forces for building “super-stable” prodrug nano-assemblies
Authors: Shuo Wang, Jun Yuan, Yaqi Li, Wenjing Wang, Hao Zhang, Qing Wang, Yuhang Zhang, Xianbao Shi, Tian Liu, Zhonggui He, Jin Sun, Bingjun Sun
Journal: Journal of Controlled Release (2025)
Use of artificial intelligence to support quality of life of people with dementia: A scoping review
Authors: Dirk Steijger, Hannah Christie, Sil Aarts, Wijnand IJselsteijn, Hilde Verbeek, Marjolein de Vugt
Journal: Ageing Research Reviews (2025)

Dementia has an impact on the quality of life (QoL) of people with dementia. Tailored services are crucial for improving their QoL. Advances in artificial intelligence (AI) offer opportunities for personalised care, potentially delaying institutionalisation and enhancing QoL. However, AI's specific role in approaches to support QoL for people with dementia remains unclear. This scoping review aims to synthesise the scientific evidence and grey literature on how AI can support the QoL of people with dementia. Following Joanna Briggs Institute guidelines, we searched PubMed, Scopus, ACM Digital Library, and Google Scholar in January 2024. Studies on AI, QoL (using Lawton's four-domain QoL definition), and people with dementia across various care settings were included. Two reviewers conducted a two-stage screening, and a narrative synthesis identified common themes arising from the individual studies to address the research question. The search yielded 5.467 studies, after screening, thirty studies were included. Three AI categories were identified: monitoring systems, social robots, and AI approaches for performing activities of daily living. Most studies were feasibility studies, with little active involvement of people with dementia during the research process. Most AI-based approaches were monitoring systems targeting Lawton's behavioural competence (capacity for independent functioning) domain. This review highlights that AI applications for enhancing QoL in people with dementia are still in early development, with research largely limited to small-scale feasibility studies rather than demonstrating clinical effectiveness. While AI holds promise, further exploration and rigorous real-world validation are needed before AI can meaningfully impact the daily lives of people with dementia.
Janus piezoelectric adhesives regulate macrophage TRPV1/Ca2+/cAMP axis to stimulate tendon-to-bone healing by multi-omics analysis
Authors: Moran Huang, Wan Li, Yaying Sun, Jize Dong, Chaojing Li, Henjie Jia, Yongjie Jiao, Lu Wang, Shanxing Zhang, Fujun Wang, Jiwu Chen
Journal: Bioactive Materials (2025)
Integration of biobank-scale genetics and plasma proteomics reveals evidence for causal processes in asthma risk and heterogeneity
Authors: Lauren J Donoghue, Christian Benner, Diana Chang, Flaviyan Jerome Irudayanathan, Rion K Pendergrass, Brian L Yaspan, Anubha Mahajan, Mark I McCarthy
Journal: Cell Genomics (2025)

Hundreds of genetic associations for asthma have been identified, yet translating these findings into mechanistic insights remains challenging. We leveraged plasma proteomics from the UK Biobank Pharma Proteomics Project (UKB-PPP) to identify biomarkers and effectors of asthma risk or heterogeneity using genetic causal inference approaches. We identified 609 proteins associated with asthma status (269 proteins after controlling for body mass index [BMI] and smoking). Analysis of genetically predicted protein levels identified 70 proteins with putative causal roles in asthma risk, including known drug targets and proteins without prior genetic evidence in asthma (e.g., GCHFR, TDRKH, and CLEC7A). The genetic architecture of causally associated proteins provided evidence for a Toll-like receptor (TLR)1-interleukin (IL)-27 asthma axis. Lastly, we identified evidence of causal relationships between proteins and heterogeneous aspects of asthma biology, including between TSPAN8 and neutrophil counts. These findings illustrate that integrating biobank-scale genetics and plasma proteomics can provide a framework to identify therapeutic targets and mechanisms underlying disease risk and heterogeneity.
Single-cell meta-analysis of T cells reveals clonal dynamics of response to checkpoint immunotherapy
Authors: Ofir Shorer, Asaf Pinhasi, Keren Yizhak
Journal: Cell Genomics (2025)

Despite the crucial role of T cell clones in anti-tumor activity, their characterization and association with clinical outcomes following immune checkpoint inhibitors are lacking. Here, we analyzed paired single-cell RNA sequencing/T cell receptor sequencing of 767,606 T cells across 460 samples spanning 6 cancer types. We found a robust signature of response based on expanded CD8+ clones that differentiates responders from non-responders. Analysis of persistent clones showed transcriptional changes that are differentially induced by therapy in the different response groups, suggesting an improved reinvigoration capacity in responding patients. Moreover, a gene trajectory analysis revealed changes in the pseudo-temporal state of de novo clones that are associated with clinical outcomes. Lastly, we found that clones shared between tumor and blood are more abundant in non-responders and execute distinct transcriptional programs. Overall, our results highlight differences in clonal transcriptional states that are linked to patient response, offering valuable insights into the mechanisms driving effective anti-tumor immunity.
Genome-wide allele-specific expression in multi-tissue samples from healthy male baboons reveals the transcriptional complexity of mammals
Authors: Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda
Journal: Cell Genomics (2025)

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could quantify ASE across 72% of the total annotated protein-coding gene set. We identified genes that exhibit ASE and affect specific tissues and genotypes. We discovered ASE SNVs that also exist in human populations with identical alleles and that are designated as pathogenic by both the PrimateAI-3D and AlphaMissense models.
MetaGP: A generative foundation model integrating electronic health records and multimodal imaging for addressing unmet clinical needs
Authors: Fei Liu, Hongyu Zhou, Kai Wang, Yunfang Yu, Yuanxu Gao, Zhuo Sun, Sian Liu, Shanshan Sun, Zixing Zou, Zhuomin Li, Bingzhou Li, Hanpei Miao, Yang Liu, Taiwa Hou, Manson Fok, Nivritti Gajanan Patil, Kanmin Xue, Ting Li, Eric Oermann, Yun Yin, Lian Duan, Jia Qu, Xiaoying Huang, Shengwei Jin, Kang Zhang
Journal: Cell Reports Medicine (2025)

Artificial intelligence makes strides in specialized diagnostics but faces challenges in complex clinical scenarios, such as rare disease diagnosis and emergency condition identification. To address these limitations, we develop Meta General Practitioner (MetaGP), a 32-billion-parameter generative foundation model trained on extensive datasets, including over 8 million electronic health records, biomedical literature, and medical textbooks. MetaGP demonstrates robust diagnostic capabilities, achieving accuracy comparable to experienced clinicians. In rare disease cases, it achieves an average diagnostic score of 1.57, surpassing GPT-4's 0.93. For emergency conditions, it improves diagnostic accuracy for junior and mid-level clinicians by 53% and 46%, respectively. MetaGP also excels in generating medical imaging reports, producing high-quality outputs for chest X-rays and computed tomography, often rated comparable to or superior to physician-authored reports. These findings highlight MetaGP's potential to transform clinical decision-making across diverse medical contexts.
Altered baseline immunological state and impaired immune response to SARS-CoV-2 mRNA vaccination in lung transplant recipients
Authors: Mengyun Hu, Ana Paula B N Oliveira, Zhuoqing Fang, Yupeng Feng, Molly Miranda, Sangeeta Kowli, Prabhu S Arunachalam, Gowri Vasudevan, Harold Sai-Yin Hui, Alba Grifoni, Alessandro Sette, Matthew Litvack, Nadine Rouphael, Mehul S Suthar, Xuhuai Ji, Holden T Maecker, Thomas Hagan, Gundeep Dhillon, Mark R Nicolls, Bali Pulendran
Journal: Cell Reports Medicine (2025)

The effectiveness of COVID-19 mRNA vaccines is diminished in organ transplant patients. Using a multi-omics approach, we investigate the immunological state of lung transplant (LTX) recipients at baseline and after SARS-CoV-2 mRNA vaccination compared to healthy controls (HCs). LTX patients exhibit a baseline immune profile resembling severe COVID-19 and sepsis, characterized by elevated pro-inflammatory cytokines (e.g., EN-RAGE [also known as S100A12], interleukin [IL]-6), reduced human leukocyte antigen (HLA)-DR expression on monocytes and dendritic cells, impaired cytokine production, and increased plasma microbial products. Single-cell RNA sequencing identifies an enriched monocyte cluster in LTX patients marked by high S100A family expression and reduced cytokine and antigen presentation genes. Post vaccination, LTX patients show diminished antibody, B cell, and T cell responses, along with blunted innate immune signatures. Integrative analysis links these altered baseline immunological features to impaired vaccine responses. These findings provide critical insights into the immunosuppressed condition of LTX recipients and their reduced vaccine-induced adaptive and innate immune responses.
CAN-Scan: A multi-omic phenotype-driven precision oncology platform identifies prognostic biomarkers of therapy response for colorectal cancer
Authors: Shumei Chia, Justine Jia Wen Seow, Rafael Peres da Silva, Chayaporn Suphavilai, Niranjan Shirgaonkar, Maki Murata-Hori, Xiaoqian Zhang, Elena Yaqing Yong, Jiajia Pan, Matan Thangavelu Thangavelu, Giridharan Periyasamy, Aixin Yap, Padmaja Anand, Daniel Muliaditan, Yun Shen Chan, Wang Siyu, Chua Wei Yong, Nguyen Hong, Gao Ran, Ngak Leng Sim, Yu Amanda Guo, Andrea Xin Yi Teh, Clarinda Chua Wei Ling, Emile Kwong Wei Tan, Fu Wan Pei Cherylin, Meihuan Chang, Shuting Han, Isaac Seow-En, Lionel Raphael Chen Hui, Anna Hwee Hsia Gan, Choon Kong Yap, Huck Hui Ng, Anders Jacobsen Skanderup, Vitoon Chinswangwatanakul, Woramin Riansuwan, Atthaphorn Trakarnsanga, Manop Pithukpakorn, Pariyada Tanjak, Amphun Chaiboonchoe, Daye Park, Dong Keon Kim, Narayanan Gopalakrishna Iyer, Petros Tsantoulis, Sabine Tejpar, Jung Eun Kim, Tae Il Kim, Somponnat Sampattavanich, Iain Beehuat Tan, Niranjan Nagarajan, Ramanuj DasGupta
Journal: Cell Reports Medicine (2025)

Application of machine learning (ML) on cancer-specific pharmacogenomic datasets shows immense promise for identifying predictive response biomarkers to enable personalized treatment. We introduce CAN-Scan, a precision oncology platform, which applies ML on next-generation pharmacogenomic datasets generated from a freeze-viable biobank of patient-derived primary cell lines (PDCs). These PDCs are screened against 84 Food and Drug Administration (FDA)-approved drugs at clinically relevant doses (Cmax), focusing on colorectal cancer (CRC) as a model system. CAN-Scan uncovers prognostic biomarkers and alternative treatment strategies, particularly for patients unresponsive to first-line chemotherapy. Specifically, it identifies gene expression signatures linked to resistance against 5-fluorouracil (5-FU)-based drugs and a focal copy-number gain on chromosome 7q, harboring critical resistance-associated genes. CAN-Scan-derived response signatures accurately predict clinical outcomes across four independent, ethnically diverse CRC cohorts. Notably, drug-specific ML models reveal regorafenib and vemurafenib as alternative treatments for BRAF-expressing, 5-FU-insensitive CRC. Altogether, this approach demonstrates significant potential in improving biomarker discovery and guiding personalized treatments.
Treatment with methotrexate plus oral prednisolone versus triple therapy (methotrexate/sulfasalazine/hydroxychloroquine) plus intra-articular glucocorticoids in early rheumatoid arthritis: a prespecified nonrandomised subgroup analysis of clinical and radiographic data at 48 weeks from the NORD-STAR trial's conventional treatment arm
Authors: Merete Lund Hetland, Marte S Heiberg, Tuulikki Sokka-Isler, Anna Rudin, Mikkel Østergaard, Espen Haavardsholm, Jarno Rutanen, Ronald van Vollenhoven, Gerdur Grondal, Lykke Midtbøll Ørnbjerg, Pernille Bøyesen, Jon Lampa, Michael Nurmohamed, Bjorn Gudbjornsson, Till Uhlig, Aulikki Kononoff, Kristina Lend, Simon Krabbe, Inge C Olsen, Joe Sexton, Kim Hørslev-Petersen
Journal: Annals of the Rheumatic Diseases (2025)

In the NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) trial, the active conventional arm had 2 nonrandomised regimens: arm 1A (oral group; Sweden, Norway, Netherlands, and Iceland) and arm 1B (injection group; Denmark and Finland). We report clinical, patient-reported, safety, and radiographic outcomes after 48 weeks. Oral group received methotrexate plus oral prednisolone (20.0 mg/d, tapered rapidly, discontinued week 36); Injection group received triple therapy (methotrexate, sulphasalazine, hydroxychloroquine) and mandatory intra-articular glucocorticoid injections. The primary end point was analysed by logistic regression with several approaches for handling missing outcomes. In total, 137 and 80 patients were included in the oral group and injection group; 78% vs. 89% completed, respectively. At 48 weeks, adjusted clinical disease activity index remission ≤2.8 rates (95% CI) were 36% (28-44) and 55% (42-68), respectively; the risk difference (primary outcome) was 19% (2-35). Similarly, key secondary clinical, patient-reported and safety outcomes showed numerically better results in the injection group vs oral group, for example, infections occurred in 53% vs 30%, respectively. Radiographic progression (Δtotal van der Heijde-modified Sharp Score) was low: oral group: adjusted mean, 0.26 (95% CI, 0.08-0.43); injection group: adjustedd mean, 0.80 (95% CI, 0.55-1.05). Cumulative dose of oral/intra-articular glucocorticoids (median) was 1905 mg prednisolone for the oral group and 165 mg for the injection group. In treatment-naïve patients with early rheumatoid arthritis, triple therapy and mandatory glucocorticoid joint injections had numerically better clinical outcomes, fewer withdrawals, fewer adverse events, and lower cumulative dose of glucocorticoids, but slightly worse radiographic outcomes than treatment with methotrexate and oral prednisolone. These findings, although nonrandomised, suggest a potential for optimising treatment strategy with conventional therapies in early rheumatoid arthritis.
Injury and obesity differentially and synergistically induce dysregulation of synovial immune cells in osteoarthritis
Authors: Natalia S Harasymowicz, Zainab Harissa, Neda Rashidi, Kristin Lenz, Ruhang Tang, Farshid Guilak
Journal: Annals of the Rheumatic Diseases (2025)

The heterogeneity and phenotype of immune cells orchestrate many physiologic and pathologic processes. Recent evidence suggests that immune cells play critical roles in the progression of osteoarthritis (OA). We hypothesised that injury and obesity, two major risk factors for OA, affect the immunophenotype of the synovium, the primary reservoir of immune cells in the joint. Using single-cell transcriptomics, immunoprofiling, transgenic mouse models, and genetic fate mapping methods, we characterised the presence and fate of multiple populations of immune cells found in the knee joint capsule. We found that joint injury and obesity differentially and synergistically alter the architectural, cellular, and molecular profiles of the synovial capsule. We observed fewer patrolling monocytes in obese animals and found a significantly higher influx of proinflammatory monocyte-derived macrophages in the first 3 days after joint injury in obese compared with that in control animals. We also showed a significant loss of barrier-forming synovial lining macrophages 3 days after destabilisation of medial meniscus surgery, with a significant restoration of their numbers in normal weight but not in obese mice in advanced stages of OA. Finally, we characterised the presence and changes of other immune cell subtypes, including T, B, and mast cells and neutrophils, as well as local synovial fluid cytokines associated with injury and obesity. Our data revealed that injury and obesity independently and synergistically contribute to the dysregulation of the synovial immune landscape, providing new insight into their role in the pathogenesis of OA.
Pathogen-targeting biomineralized bacterial outer membrane vesicles for eradicating both intracellular and extracellular Staphylococcus aureus
Authors: Xiaohong Yang, Gongming Shi, Zihua Lin, Yanfei Qiu, Feiyang Liu, Kecui Hu, Jian Guo, Haibo Peng, Yun He
Journal: Journal of Controlled Release (2025)
First ATG101-recruiting small molecule degrader for selective CDK9 degradation via autophagy–lysosome pathway
Authors: Ye Zhong, Jing Xu, Huiying Cao, Jie Gao, Shaoyue Ding, Zhaohui Ren, Huali Yang, Yili Sun, Maosheng Cheng, Jia Li, Yang Liu
Journal: Acta Pharmaceutica Sinica B (2025)
Gut microbiota shift in Ghanaian individuals along the migration axis: the RODAM-Pros cohort
Authors: Barbara J. H. Verhaar, Eva L. van der Linden, Charles F. Hayfron-Benjamin, Ellis Owusu-Dabo, Samuel N. Darko, Sampson Twumasi-Ankrah, Peter Henneman, Erik Beune, Karlijn A.C. Meeks, Max Nieuwdorp, Hilde Herrema, Bert-Jan H. van den Born, Charles Agyemang
Journal: Gut Microbes (2025)

Migration is associated with a substantial change in environmental exposures and health outcomes. We aimed to investigate the shift in gut microbiota composition and the associations with cardiometabolic outcomes in the RODAM-Pros cohort spanning multiple research sites across continents. We determined gut microbiota composition of 1,177 Ghanaian participants in rural Ghana, urban Ghana, and Amsterdam, the Netherlands, using 16S rRNA sequencing. We observed a clear gradient in gut microbiota composition and alpha and beta diversity from rural Ghana to urban Ghana, to Amsterdam. We used pairwise XGBoost machine learning classification models to identify which microbes were most distinct between locations in prevalence and abundance. The associations between these microbes and the locations could partly be explained by differences in confounders such as dietary intake. Groups of microbes that emerged or disappeared along the migration axis were associated with cardiometabolic outcomes, including higher body mass index, higher HbA1c and higher diastolic blood pressure. Concluding, we identified associations between a shift in gut microbiota composition and cardiometabolic risk along the migration axis, underscoring the relevance of gut health in the context of migration-associated adverse health outcomes.
Effect of the vaginal live biotherapeutic LACTIN-V (Lactobacillus crispatus CTV-05) on vaginal microbiota and genital tract inflammation among women at high risk of HIV acquisition in South Africa: a phase 2, randomised, placebo-controlled trial
Authors: Anke Hemmerling, Caroline M Mitchell, Suuba Demby, Musie Gebremichael, Joseph Elsherbini, Jiawu Xu, Nondumiso Xulu, Johnathan Shih, Krista Dong, Vaneshree Govender, Vanessa Pillay, Nasreen Ismail, Gardenia Casillas, Jayajothi Moodley, Agnes Bergerat, Tess Brunner, Lenine Liebenberg, Sinaye Ngcapu, Ian Mbano, Laurel Lagenaur, Thomas P Parks, Thumbi Ndung'u, Douglas S Kwon, Craig R Cohen
Journal: The Lancet Microbe (2025)
Propagation of senescent phenotypes by extracellular HMGB1 is dependent on its redox state
Authors: Ji-Won Shin, Dong-Hyun Jang, So Young Kim, Je-Jung Lee, Tae-Hwan Gil, Eunha Shim, Ji Yeon Kim, Hyeon Soo Kim, Michael J Conboy, Irina M Conboy, Christopher D Wiley, Jeon-Soo Shin, Ok Hee Jeon
Journal: Metabolism (2025)
Nasal transcriptome differences preceding recurrent wheezing in infancy
Authors: Poshmaal Dhar, Martin O'Hely, Luba Sominsky, Sarah Ashley, Sarath C Ranganathan, Peter D Sly, Fiona Collier, Mimi Lk Tang, Rachel Morgan, Toby Mansell, Richard Saffery, David Burgner, Anne-Louise Ponsonby, Peter Vuillermin
Journal: Journal of Allergy and Clinical Immunology (2025)