tbuckley/cabot-search huggingface dataset:
Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease
Authors: Kevin D Deane, V Michael Holers, Paul Emery, Kulveer Mankia, Hani El-Gabalawy, Jeffrey A Sparks, Karen H Costenbader, Georg Schett, Annette van der Helm-van Mil, Dirkjan van Schaardenburg, Ranjeny Thomas, Andrew P Cope
Journal: Annals of the Rheumatic Diseases (2024)

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials. Individuals at risk of RA can be identified through population screening, referrals to musculoskeletal programmes and by recognition of arthralgia suspicious for RA. Clinical trials in individuals at risk for future clinical RA have demonstrated that limited courses of corticosteroids, atorvastatin and hydroxychloroquine do not alter incidence rates of clinical RA; however, rituximab delays clinical RA onset, and methotrexate has transient effects in individuals who are anticitrullinated protein antibody-positive with subclinical joint inflammation identified by imaging. Abatacept delays clinical RA onset but does not fully prevent onset of RA after treatment cessation. Additionally, subclinical joint inflammation and symptoms appear responsive to interventions such as methotrexate and abatacept. To advance prevention, next steps include building networks of individuals at risk for RA, to improve risk stratification for future RA and to understand the biological mechanisms of RA development, including potential endotypes of disease, which can be targeted for prevention, thus adopting a more precision-based approach. Future trials should focus on interceptions aimed at preventing clinical RA onset and which treat existing symptoms and imaging-defined subclinical inflammation. These trials may include advanced designs (eg, adaptive) and should be combined with mechanistic studies to further define pathophysiological drivers of disease development.
Efficacy of exercise interventions on prevention of sport-related concussion and related outcomes: a systematic review and meta-analysis
Authors: Branimir Ivanic, Anna Cronström, Kajsa Johansson, Eva Ageberg
Journal: British Journal of Sports Medicine (2024)

To review the efficacy of exercise interventions on sport-related concussion (SRC) incidence, as well as on linear and rotational head accelerations, and isometric neck strength and to assess reporting completeness of exercise interventions using the Consensus on Exercise Reporting Template (CERT).
Effects of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control: a systematic review and network meta-analysis
Authors: Tong Zhao, Qize Yang, Joshua F Feuerbacher, Bizhu Yu, Christian Brinkmann, Sulin Cheng, Wilhelm Bloch, Moritz Schumann
Journal: British Journal of Sports Medicine (2024)

To compare the efficacy of exercise, metformin and their combination on glucose metabolism in individuals with abnormal glycaemic control.
Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021
Authors: Pojsakorn Danpanichkul, Kanokphong Suparan, Primrose Tothanarungroj, Disatorn Dejvajara, Krittameth Rakwong, Yanfang Pang, Romelia Barba, Jerapas Thongpiya, Michael B Fallon, Denise Harnois, Rashid N Lui, Michael B Wallace, Ju Dong Yang, Lewis R Roberts, Karn Wijarnpreecha
Journal: Gut (2024)

Gastrointestinal cancers comprise nearly one-third of global mortality from cancer, yet the comprehensive global burden of these cancers remains uninvestigated.
Erratum. Consensus Guidance for Monitoring Individuals With Islet Autoantibody–Positive Pre-Stage 3 Type 1 Diabetes. Diabetes Care 2024;47:1276–1298
Authors: Moshe Phillip, Peter Achenbach, Ananta Addala, Anastasia Albanese-O’Neill, Tadej Battelino, Kirstine J. Bell, Rachel E.J. Besser, Ezio Bonifacio, Helen M. Colhoun, Jennifer J. Couper, Maria E. Craig, Thomas Danne, Carine de Beaufort, Klemen Dovc, Kimberly A. Driscoll, Sanjoy Dutta, Osagie Ebekozien, Helena Elding Larsson, Daniel J. Feiten, Brigitte I. Frohnert, Robert A. Gabbay, Mary P. Gallagher, Carla J. Greenbaum, Kurt J. Griffin, William Hagopian, Michael J. Haller, Christel Hendrieckx, Emile Hendriks, Richard I.G. Holt, Lucille Hughes, Heba M. Ismail, Laura M. Jacobsen, Suzanne B. Johnson, Leslie E. Kolb, Olga Kordonouri, Karin Lange, Robert W. Lash, Åke Lernmark, Ingrid Libman, Markus Lundgren, David M. Maahs, M. Loredana Marcovecchio, Chantal Mathieu, Kellee M. Miller, Holly K. O’Donnell, Tal Oron, Shivajirao P. Patil, Rodica Pop-Busui, Marian J. Rewers, Stephen S. Rich, Desmond A. Schatz, Rifka Schulman-Rosenbaum, Kimber M. Simmons, Emily K. Sims, Jay S. Skyler, Laura B. Smith, Cate Speake, Andrea K. Steck, Nicholas P.B. Thomas, Ksenia N. Tonyushkina, Riitta Veijola, John M. Wentworth, Diane K. Wherrett, Jamie R. Wood, Anette-Gabriele Ziegler, Linda A. DiMeglio
Journal: Diabetes Care (2024)

In the article cited above, incorrect affiliation information was given for author Linda A. DiMeglio. The correct affiliation for Linda A. DiMeglio is Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN. The online version of the article (https://doi.org/10.2337/dci24-0042) has been updated to correct the error.
B7-H3-Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity Against Solid Tumors
Authors: Licui Jiang, Fengtao You, Hai Wu, Changsong Qi, Shufen Xiang, Ping Zhang, Huimin Meng, Min Wang, Jiequn Huang, Yafen Li, Dan Chen, Gangli An, Nan Yang, Bozhen Zhang, Lin Shen, Lin Yang
Journal: Cancer Research (2024)

Abstract Vδ1T cells, a rare subset of γδT cells, hold promise for treating solid tumors. Unlike conventional T cells, they recognize tumor antigens independently of the MHC antigen-presentation pathway, making them a potential “off-the-shelf” cell therapy product. However, isolation and activation of Vδ1T cells is challenging, which has limited their clinical investigation. Here, we developed a large-scale clinical-grade manufacturing process for Vδ1T cells and validated the therapeutic potential of B7-H3-CAR-modified Vδ1T cells in treating solid tumors. Co-expression of interleukin-2 with the B7-H3-CAR led to durable anti-tumor activity of Vδ1T cells in vitro and in vivo. In multiple subcutaneous and orthotopic mouse xenograft tumor models, a single intravenous administration of the CAR-Vδ1T cells resulted in complete tumor regression. These modified cells demonstrated significant in vivo expansion and robust homing ability to tumors, akin to natural tissue-resident immune cells. Additionally, the B7-H3-CAR-Vδ1T cells exhibited a favorable safety profile. In conclusion, B7-H3-CAR-modified Vδ1T cells represent a promising strategy for treating solid tumors.
The Pan-tumor Vasculature Under the Transcriptomic Magnifying Glass
Authors: Krish Skandha Gopalan, Gabriele Bergers
Journal: Cancer Research (2024)

Abstract In the first pan-cancer analysis of the tumor vasculature, Pan and colleagues profile nearly 200,000 endothelial and mural cells (ECs and MCs), identifying novel subclusters and cell states using consensus trajectory inference. They identify differentiation trajectories in vascular and lymphatic endothelial cells, and subtype the pericyte population. During sprouting angiogenesis, venous cells dedifferentiate and transition to capillary and, finally, arterial ECs. Capillary ECs transition via “three angiogenic stages” (SI-SIII) during which APLN+ TipS1 cells were identified as potential modulators of tumor-induced neovascularization and anti-angiogenic therapy response. In lymphatic ECs, differentiation was inversely correlated between the lymphangiogenic (T1) and antigen-presenting (T2) trajectories, with T2 associated with a better prognosis. While several pericyte clusters were identified, BASP1+ matrix-associated pericytes were associated with APLN+ TipS1 cells and had a worse prognosis. These findings present transcriptional validation of previous experimental findings and serve as a resource to examine the tumor vascular microenvironment in detail.
MYC Drives mRNA Pseudouridylation to Mitigate Proliferation-Induced Cellular Stress during Cancer Development
Authors: Jane Ding, Mohit Bansal, Yuxia Cao, Bingwei Ye, Rui Mao, Anamika Gupta, Sunil Sudarshan, Han-Fei Ding
Journal: Cancer Research (2024)

Abstract Pseudouridylation is a common RNA modification that is catalyzed by the family of pseudouridine synthases (PUS). Pseudouridylation can increase RNA stability and rigidity, thereby impacting RNA splicing, processing, and translation. Given that RNA metabolism is frequently altered in cancer, pseudouridylation may be a functionally important process in tumor biology. Here, we showed that the MYC family of oncoproteins transcriptionally upregulates PUS7 expression during cancer development. PUS7 was essential for the growth and survival of MYC-driven cancer cells and xenografts by promoting adaptive stress responses and amino acid biosynthesis and import. ATF4, a master regulator of stress responses and cellular metabolism, was identified as a key downstream mediator of PUS7 functional activity. Induction of ATF4 by MYC oncoproteins and cellular stress required PUS7, and ATF4 overexpression overcame the growth inhibition caused by PUS7 deficiency. Mechanistically, PUS7 induced pseudouridylation of MCTS1 mRNA, which enhanced its translation. MCTS1, a noncanonical translation initiation factor, drove stress-induced ATF4 protein expression. A PUS7 consensus pseudouridylation site in the 3’ untranslated region of ATF4 mRNA was crucial for the induction of ATF4 by cellular stress. These findings unveil a MYC-activated mRNA pseudouridylation program that mitigates cellular stress induced by MYC stimulation of proliferation and biomass production, suggesting that targeting PUS7 could be therapeutic strategy selectively against MYC-driven cancers.
Integrated electrophysiological and genomic profiles of single cells reveal spiking tumor cells in human glioma
Authors: Rachel N Curry, Qianqian Ma, Malcolm F McDonald, Yeunjung Ko, Snigdha Srivastava, Pey-Shyuan Chin, Peihao He, Brittney Lozzi, Prazwal Athukuri, Junzhan Jing, Su Wang, Arif O Harmanci, Benjamin Arenkiel, Xiaolong Jiang, Benjamin Deneen, Ganesh Rao, Akdes Serin Harmanci
Journal: Cancer Cell (2024)
Drug-Drug Interactions and the Clinical Tolerability of Colchicine Among Patients With COVID-19
Authors: Lama S. Alfehaid, Subrina Farah, Azza Omer, Brittany N. Weber, Omar Alkhezi, Yahya M. K. Tawfik, Amil M. Shah, Peter Libby, Leo F. Buckley
Journal: JAMA Network Open (2024)

Importance Colchicine has many drug-drug interactions with commonly prescribed medications. Only pharmacokinetic studies have provided data on colchicine drug-drug interactions. Objective To evaluate the clinical tolerability of colchicine according to the presence or absence of a drug-drug interaction. Design, Setting, and Participants A secondary analysis of the COLCORONA trial was performed. The COLCORONA trial was a randomized, double-blind, placebo-controlled trial conducted in Brazil, Canada, Greece, South Africa, Spain, and the US between March 23, 2020, and January 20, 2021. The COLCORONA trial included ambulatory patients with COVID-19 with at least 1 high-risk characteristic and compared the effects of colchicine (0.5 mg twice daily for 3 days, then 0.5 mg daily thereafter) with placebo for 27 days. Data analysis was performed from February 24, 2023, to June 20, 2024. Exposure In this secondary analysis, baseline medications that had interactions with colchicine were identified using a previously published expert classification. Main Outcomes and Measures The primary outcome for this analysis was the composite of serious and nonserious treatment-related and treatment-unrelated gastrointestinal adverse events. The secondary outcomes were other adverse events and the composite of death or hospital admission due to COVID-19 infection. Logistic regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, heart failure, and myocardial infarction were assessed for effect modification of the association between the randomization arm and the outcomes of interest by drug-drug interaction status. Results The cohort included 2205 participants in the colchicine arm and 2227 in the placebo arm (median age, 54 [IQR, 47-61] years; 2389 [54%] women). The most common colchicine drug-drug interactions were rosuvastatin (12%) and atorvastatin (10%). In fully adjusted models, the odds of any gastrointestinal adverse event were 1.80 (95% CI, 1.51-2.15) times higher in the colchicine arm than the placebo arm among people without a drug-drug interaction and 1.68 (95% CI, 1.24-2.26) times higher in the colchicine arm than the placebo arm among people with a drug-drug interaction ( P = .69 for interaction). Drug-drug interaction status did not significantly modify the effect of colchicine on the composite of COVID-19 hospitalization or death (odds ratio, 0.91; 95% CI, 0.59-1.40 for drug-drug interaction and 0.84; 95% CI, 0.60-1.19 for no drug-drug interaction; P = .80 for interaction). Conclusions and Relevance In this secondary analysis of the COLCORONA trial, operational classification of drug interactions system class 3 or 4 drug-drug interactions did not appear to significantly increase the risk of colchicine-related adverse effects. Trial Registration ClinicalTrials.gov Identifier: NCT04322682
Conservative Treatments in the Management of Acute Painful Vertebral Compression Fractures
Authors: Assil-Ramin Alimy, Athanasios D. Anastasilakis, John J. Carey, Stella D’Oronzo, Anda M. Naciu, Julien Paccou, Maria P. Yavropoulou, Willem F. Lems, Tim Rolvien
Journal: JAMA Network Open (2024)

Osteoporotic vertebral compression fractures (VCFs) frequently cause substantial pain and reduced mobility, posing a major health problem. Despite the critical need for effective pain management to restore functionality and improve patient outcomes, the value of various conservative treatments for acute VCF has not been systematically investigated.
Ethical Considerations in the Design and Conduct of Clinical Trials of Artificial Intelligence
Authors: Alaa Youssef, Ariadne A. Nichol, Nicole Martinez-Martin, David B. Larson, Michael Abramoff, Risa M. Wolf, Danton Char
Journal: JAMA Network Open (2024)

Safe integration of artificial intelligence (AI) into clinical settings often requires randomized clinical trials (RCT) to compare AI efficacy with conventional care. Diabetic retinopathy (DR) screening is at the forefront of clinical AI applications, marked by the first US Food and Drug Administration (FDA) De Novo authorization for an autonomous AI for such use.
COVID-19 and Rates of Cancer Diagnosis in the US
Authors: Todd Burus, Feitong Lei, Bin Huang, W. Jay Christian, Pamela C. Hull, Amanda R. Ellis, Svetla Slavova, Thomas C. Tucker, Krystle A. Lang Kuhs
Journal: JAMA Network Open (2024)

Importance US cancer diagnoses were substantially lower than expected during the COVID-19 pandemic in 2020. A national study on the extent to which rates recovered in 2021 has not yet been conducted. Objective To examine observed vs expected cancer rate trends for January 2020 to December 2021. Design, Setting, and Participants This cross-sectional, population-based study of cancer incidence trends used the Surveillance, Epidemiology, and End Results 22 (SEER-22) Registries Database, which covers 47.9% of the US population. Included individuals were those with an invasive cancer diagnosis reported to registries included in SEER-22 between January 1, 2000, and December 31, 2021. Exposures Age, sex, race and ethnicity, urbanicity, and stage at diagnosis. Main Outcomes and Measures Expected cancer incidence rates were measured for the COVID-19 pandemic years of 2020 and 2021 from prepandemic trends using ensemble forecasting methods. Relative difference between observed and expected cancer incidence rates and numbers of potentially missed cases were measured. Results The SEER-22 registries reported 1 578 697 cancer cases in 2020 and 2021, including 798 765 among male individuals (50.6%) and 909 654 among persons aged 65 years or older (57.6%). Observed all-sites cancer incidence rates were lower than expected by 9.4% in 2020 (95% prediction interval [PI], 8.5%-10.5%), lower than expected by 2.7% in 2021 (95% PI, 1.4%-3.9%), and lower than expected by 6.0% across both years combined (95% PI, 5.1%-7.1%), resulting in 149 577 potentially undiagnosed cancer cases (95% PI, 126 059-176 970). Of the 4 screening-detected cancers, only female breast cancer showed significant recovery in 2021, exceeding expected rates by 2.5% (95% PI, 0.1%-4.8%), while significant reductions remained for lung cancer (9.1% lower than expected; 95% PI, 6.4%-13.2%) and cervical cancer (4.5% lower than expected; 95% PI, 0.4%-8.0%), particularly for early stage at diagnosis. Rates of all-sites cancer incidence returned to prepandemic trends in 2021 among female individuals, persons aged younger than 65 years, and persons of non-Hispanic Asian and Pacific Islander race and ethnicity. Conclusions and Relevance This population-based cross-sectional study of US cancer incidence trends found that rates of diagnosis improved in 2021 but continued to be lower than expected, adding to the existing deficit of diagnosed cases from 2020. Particular attention should be directed at strategies to immediately increase cancer screenings to make up lost ground.
Safety and immunogenicity of mRNA-based seasonal influenza vaccines formulated to include multiple A/H3N2 strains with or without the B/Yamagata strain in US adults aged 50–75 years: a phase 1/2, open-label, randomised trial
Authors: Denise Hsu, Akila Jayaraman, Alicia Pucci, Riya Joshi, Kevin Mancini, Hui Ling Chen, Kindra Koslovsky, Xuezhou Mao, Angela Choi, Carole Henry, Jignesh Vakil, Daniel Stadlbauer, Patricia Jorquera, Guha Asthagiri Arunkumar, Nelia E Sanchez-Crespo, L Tyler Wadsworth, Vellore Bhupathy, Evelyn Du, Andrei Avanesov, Jintanat Ananworanich, Raffael Nachbagauer
Journal: The Lancet Infectious Diseases (2024)
The influence of education in predicting conversion from Subjective Cognitive Decline (SCD) to objective cognitive impairment: a systematic review and meta-analysis
Authors: Sonali Arora, Scott B Patten, Sabela C Mallo, Cristina Lojo-Seoane, Alba Felpete, David Facal-Mayo, Arturo X Pereiro
Journal: Ageing Research Reviews (2024)
The role of metal ions in stroke: current evidence and future perspectives
Authors: Shaoshuai Wang, Mengzhe Qin, Xiaochong Fan, Chao Jiang, Qingchuan Hou, Ziyi Ye, Xinru Zhang, Yunfan Yang, Jingyu Xiao, Kevin Wallace, Yousef Rastegar-Kashkooli, Qinfeng Peng, Dongqi Jin, Junyang Wang, Menglu Wang, Ruoqi Ding, Jin Tao, Yun Tai Kim, Ujjal K Bhawal, Junmin Wang, Xuemei Chen, Jian Wang
Journal: Ageing Research Reviews (2024)
Exposome-Wide Ranking to Uncover Environmental Chemicals Associated with Dyslipidemia: A Panel Study in Healthy Older Chinese Adults from the BAPE Study
Authors: Enmin Ding, Fuchang Deng, Jianlong Fang, Juan Liu, Wenyan Yan, Qiao Yao, Ke Miao, Yu Wang, Peijie Sun, Chenfeng Li, Yuanyuan Liu, Haoran Dong, Li Dong, Xu Zhang, Yifu Lu, Xiao Lin, Changming Ding, Tiantian Li, Yali Shi, Yaqi Cai, Xiaohui Liu, Krystal J. Godri Pollitt, John S. Ji, Shilu Tong, Song Tang, Xiaoming Shi
Journal: Environmental Health Perspectives (2024)

Environmental contaminants (ECs) are increasingly recognized as crucial drivers of dyslipidemia and cardiovascular disease (CVD), but the comprehensive impact spectrum and interlinking mechanisms remain uncertain.
Development and validation of a machine learning‐based approach to identify high‐risk diabetic cardiomyopathy phenotype
Authors: Matthew W. Segar, Muhammad Shariq Usman, Kershaw V. Patel, Muhammad Shahzeb Khan, Javed Butler, Lakshman Manjunath, Carolyn S.P. Lam, Subodh Verma, DuWayne Willett, David Kao, James L. Januzzi, Ambarish Pandey
Journal: European Journal of Heart Failure (2024)
Injury-inciting circumstances of sudden-onset hamstring injuries: video analyses of 63 match injuries in male professional football players in the Qatar Stars League (2013–2020)
Authors: Robin Vermeulen, Nicol van Dyk, Rod Whiteley, Karim Chamari, Warren Gregson, Lorenzo Lolli, Roald Bahr, Johannes L Tol, Andreas Serner
Journal: British Journal of Sports Medicine (2024)

To describe and categorise the injury-inciting circumstances of sudden-onset hamstring match injuries in professional football players using systematic video analysis.
AI-Powered Clinical Documentation and Clinicians’ Electronic Health Record Experience
Authors: Tsai-Ling Liu, Timothy C. Hetherington, Casey Stephens, Andrew McWilliams, Ajay Dharod, Tracey Carroll, Jeffrey A. Cleveland
Journal: JAMA Network Open (2024)

This nonrandomized clinical trial investigated the electronic health record (EHR) experiences of clinicians before and after implementation of an artificial intelligence (AI)–powered clinical documentation tool.
Short-Term Exposure to Ambient Air Pollution and Antimicrobial Use for Acute Respiratory Symptoms
Authors: Gabriela Abelenda-Alonso, Pau Satorra, Marc Marí-Dell’Olmo, Cristian Tebé, Ariadna Padullés, Andrea Vergara, Carlota Gudiol, Miquel Pujol, Jordi Carratalà
Journal: JAMA Network Open (2024)

Importance Ambient air pollution and antimicrobial resistance pose significant global public health challenges. It is not known whether ambient air pollution is associated with increased consumption of antimicrobials. Objective To assess whether a short-term association exists between ambient air pollution levels and antimicrobial consumption among the general population seeking primary care consultations for acute respiratory symptoms. Design, Setting, and Participants This 2-stage cross-sectional ecological time series analysis study using data on daily ambient air pollution and antimicrobial consumption was conducted in the 11 largest cities in Catalonia, Spain, from June 23, 2012, to December 31, 2019, among all inhabitants aged 12 years or older. Statistical analysis was performed from November 2022 to December 2023. Exposures Daily ambient air pollution (particulate matter of 10 μg/m 3 [PM 10 ], particulate matter of 2.5 μg/m 3 [PM 2.5 ], and nitrogen dioxide [NO 2 ]). Main Outcomes and Measures The main outcome was antimicrobial consumption associated with primary care consultations for acute respiratory symptoms in the 30 days before and after the dispensing of the antimicrobial. Antimicrobial consumption was measured as defined daily doses (DDDs) per 1000 inhabitants per day. Results Among 1 938 333 inhabitants (median age, 48 years [IQR, 34-65 years]; 55% female participants), there were 8 421 404 antimicrobial dispensations, with a median of 12.26 DDDs per 1000 inhabitants per day (IQR, 6.03-15.32 DDDs per 1000 inhabitants per day). The median adjusted morbidity score was 2.0 (IQR, 1.0-5.0). For the 1 924 814 antimicrobial dispensations associated with primary care consultations for acute respiratory symptoms, there was a significant correlation between increases of 10 μg/m 3 in the concentration of the 3 pollutants studied and heightened antimicrobial consumption at day 0 (PM 10 : relative risk [RR], 1.01 [95% CI, 1.01-1.02]; PM 2.5 : RR, 1.03 [95% CI, 1.01-1.04]; NO 2 : RR, 1.04 [95% CI, 1.03-1.05]). A delayed association emerged between increases in PM 2.5 concentration and antimicrobial consumption between day 7 (RR, 1.00 [95% CI, 1.00-1.01]) and day 10 (RR, 1.00 [95% CI, 1.00-1.01]) after exposure. Conclusions and Relevance In this 2-stage cross-sectional study using ecological time series analysis, short-term exposure to air pollution was associated with increased antimicrobial use associated with primary care consultations for acute respiratory symptoms in the general population. This finding could contribute to informing policy decisions aimed at reducing air pollution and its associated risks, thereby promoting respiratory health and reducing antimicrobial use.