tbuckley/cabot-search huggingface dataset:
Effect of mesenteric sparing or extended resection in primary ileocolic resection for Crohn's disease on postoperative endoscopic recurrence (SPICY): an international, randomised controlled trial
Authors: Eline M L van der Does de Willebois, Vittoria Bellato, Marjolijn Duijvestein, Jarmila D W van der Bilt, Koen van Dongen, Antonino Spinelli, Geert R D'Haens, Marco W Mundt, Federica Furfaro, Silvio Danese, Andrea Vignali, Willem A Bemelman, Christianne J Buskens
Journal: The Lancet. Gastroenterology & hepatology (2024)
Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study
Authors: Ming Hong Choi, Eric Yuk Fai Wan, Ian Chi Kei Wong, Esther Wai Yin Chan, Wing Ming Chu, Anthony Raymond Tam, Kwok Yung Yuen, Ivan Fan Ngai Hung
Journal: The Lancet Infectious Diseases (2024)
Cluster analysis of blood biomarkers to identify molecular patterns in pulmonary fibrosis: assessment of a multicentre, prospective, observational cohort with independent validation
Authors: Hernan P Fainberg, Yuben Moodley, Isaac Triguero, Tamera J Corte, Jannie M B Sand, Diana J Leeming, Morten A Karsdal, Athol U Wells, Elisabetta Renzoni, John Mackintosh, Dino B A Tan, Roger Li, Joanne Porte, Rebecca Braybrooke, Gauri Saini, Simon R Johnson, Louise V Wain, Philip L Molyneaux, Toby M Maher, Iain D Stewart, R Gisli Jenkins
Journal: The Lancet Respiratory Medicine (2024)

Pulmonary fibrosis results from alveolar injury, leading to extracellular matrix remodelling and impaired lung function. This study aimed to classify patients with pulmonary fibrosis according to blood biomarkers to differentiate distinct disease patterns, known as endotypes.
Influenza-associated and COVID-19-associated pulmonary aspergillosis in critically ill patients
Authors: Simon Feys, Agostinho Carvalho, Cornelius J Clancy, Jean-Pierre Gangneux, Martin Hoenigl, Katrien Lagrou, Bart J A Rijnders, Laura Seldeslachts, Lore Vanderbeke, Frank L van de Veerdonk, Paul E Verweij, Joost Wauters
Journal: The Lancet Respiratory Medicine (2024)
Time from injury to hip-fracture surgery in low-income and middle-income regions: a secondary analysis of data from the International Orthopaedic Multicentre Study in Fracture Care (INORMUS)
Authors: Elizabeth Armstrong, Kris Rogers, Chuan Silvia Li, Jagnoor Jagnoor, Paul Moroz, Gerald Chukwuemeka Oguzie, Samuel Hailu, Theodore Miclau, Fernando de la Huerta, Jose de Jesus Martinez-Ruiz, Fernando Bidolegui, Junlin Zhou, Xinlong Ma, Bo Wu, Parag Sancheti, La Ngoc Quang, Vali Baigi, Mashyaneh Haddadi, Maoyi Tian, Sheila Sprague, P J Devereaux, Mohit Bhandari, Rebecca Ivers
Journal: The Lancet Healthy Longevity (2024)

Globally, fall-related injuries are a substantial problem, and 80% of fatal falls occur in low-income and middle-income countries. We aimed to measure time from injury to hip-fracture surgery in people aged 50 years or older living in low-income and middle-income regions, as well as to measure the proportion of patients with surgical stabilisation of their hip fracture within 72 h of admission to hospital and to identify risk factors associated with surgical delay.
Drug-Drug Interactions and Synergy: From Pharmacological Models to Clinical Application
Authors: Luigino Calzetta, Clive Page, Maria Gabriella Matera, Mario Cazzola, Paola Rogliani
Journal: Pharmacological Reviews (2024)

This review explores the concept of synergy in pharmacology, emphasizing its importance in optimizing treatment outcomes through the combination of drugs with different mechanisms of action. Synergy, defined as an effect greater than the expected additive effect elicited by individual agents according to specific predictive models, offers a promising approach to enhance therapeutic efficacy while minimizing adverse events. The historical evolution of synergy research, from ancient civilizations to modern pharmacology, highlights the ongoing quest to understand and harness synergistic interactions. Key concepts, such as concentration-response curves, additive effects, and predictive models, are discussed in detail, emphasizing the need for accurate assessment methods throughout translational drug development. Although various mathematical models exist for synergy analysis, selecting the appropriate model and software tools remains a challenge, necessitating careful consideration of experimental design and data interpretation. Furthermore, this review addresses practical considerations in synergy assessment, including preclinical and clinical approaches, mechanism of action, and statistical analysis. Optimizing synergy requires attention to concentration/dose ratios, target site localization, and timing of drug administration, ensuring that the benefits of combination therapy detected bench-side are translatable into clinical practice. Overall, the review advocates for a systematic approach to synergy assessment, incorporating robust statistical analysis, effective and simplified predictive models, and collaborative efforts across pivotal sectors, such as academic institutions, pharmaceutical companies, and regulatory agencies. By overcoming critical challenges and maximizing therapeutic potential, effective synergy assessment in drug development holds promise for advancing patient care. SIGNIFICANCE STATEMENT: Combining drugs with different mechanisms of action for synergistic interactions optimizes treatment efficacy and safety. Accurate interpretation of synergy requires the identification of the expected additive effect. Despite innovative models to predict the additive effect, consensus in drug-drug interactions research is lacking, hindering the bench-to-bedside development of combination therapies. Collaboration among science, industry, and regulation is crucial for advancing combination therapy development, ensuring rigorous application of predictive models in clinical settings.
Glucagon-Like Peptide-1 Receptor Agonists and Risk for Suicidal Ideation and Behaviors in U.S. Older Adults With Type 2 Diabetes
Authors: Huilin Tang, Ying Lu, William T. Donahoo, Hui Shao, Lizheng Shi, Vivian A. Fonseca, Yi Guo, Jiang Bian, Jingchuan Guo
Journal: Annals of Internal Medicine (2024)

A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes.
Mammography Screening Preferences Among Screening-Eligible Women in Their 40s
Authors: Laura D. Scherer, Carmen L. Lewis, Kirsten McCaffery, Jolyn Hersch, Joseph N. Cappella, Channing Tate, Brad Morse, Kelly Arnett, Bridget Mosley, Heather L. Smyth, Marilyn M. Schapira
Journal: Annals of Internal Medicine (2024)

The U.S. Preventive Services Task Force (USPSTF) recently changed its recommendation for mammography screening from informed decision making to biennial screening for women aged 40 to 49 years. Although many women welcome this change, some may prefer not to be screened at age 40 years.
Development and Evaluation of a Framework for Identifying and Addressing Spin for Harms in Systematic Reviews of Interventions
Authors: Riaz Qureshi, Kevin Naaman, Nicolas G. Quan, Evan Mayo-Wilson, Matthew J. Page, Victoria Cornelius, Roger Chou, Isabelle Boutron, Su Golder, Lisa Bero, Peter Doshi, Matt Vassar, Reint Meursinge Reynders, Tianjing Li
Journal: Annals of Internal Medicine (2024)

"Spin" refers to misleading reporting, interpretation, and extrapolation of findings in primary and secondary research (such as in systematic reviews). The study of spin primarily focuses on beneficial outcomes. The objectives of this research were threefold: first, to develop a framework for identifying spin associated with harms in systematic reviews of interventions; second, to apply the framework to a set of reviews, thereby pinpointing instances where spin may be present; and finally, to revise the spin examples, offering guidance on how spin can be rectified.
Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians (Version 1, Update Alert 2)
Authors: Amir Qaseem, Douglas K. Owens, Itziar Etxeandia-Ikobaltzeta, Janice E. Tufte, J. Thomas Cross, Timothy J. Wilt, Carolyn J. Crandall, Carolyn J. Crandall, Lauri A. Hicks, Lauri A. Hicks, Timothy J. Wilt, Ethan M. Balk, Ethan M. Balk, Thomas G. Cooney, Thomas G. Cooney, J. Thomas Cross, Nick Fitterman, Nick Fitterman, Jennifer S. Lin, Jennifer S. Lin, Michael Maroto, Michael Maroto, Matthew C. Miller, Matthew C. Miller, Adam J. Obley, Adam J. Obley, Douglas K. Owens, Paul G. Shekelle, Paul G. Shekelle, Jeffrey A. Tice, Jeffrey A. Tice, Janice E. Tufte, Itziar Etxeandia-Ikobaltzeta, Curtis S. Harrod, Curtis S. Harrod, Amir Qaseem, Jennifer Yost, Jennifer Yost
Journal: Annals of Internal Medicine (2024)
Morbidity and Mortality of Hospital-Onset SARS-CoV-2 Infections Due to Omicron Versus Prior Variants
Authors: Michael Klompas, Caroline S. McKenna, Sanjat Kanjilal, Theodore Pak, Chanu Rhee, Tom Chen
Journal: Annals of Internal Medicine (2024)

Many hospitals have scaled back measures to prevent nosocomial SARS-CoV-2 infection given large decreases in the morbidity and mortality of SARS-CoV-2 infections for most people. Little is known, however, about the morbidity and mortality of nosocomial SARS-CoV-2 infections for hospitalized patients in the Omicron era.
Innovating cancer drug discovery with refined phenotypic screens
Authors: Zhenyi Wang, Alzbeta Hulikova, Pawel Swietach
Journal: Trends in Pharmacological Sciences (2024)

Before molecular pathways in cancer were known to a depth that could predict targets, drug development relied on phenotypic screening, where the effectiveness of candidate chemicals is judged from functional readouts without considering the mechanisms of action. The unraveling of tumor-specific pathways has brought targets for molecularly driven drug discovery, but precedents in the field have shown that awareness of pathways does not necessarily predict therapeutic efficacy, and many cancers still lack druggable targets. Phenotypic screening therefore retains a niche in drug development where a targeted approach is not informative. We analyze the unique advantages of phenotypic screens, and how technological advances have improved their discovery power. Notable advances include the use of larger biological panels and refined protocols that address the disease-relevance and increase data content with imaging and omic approaches.
Genetic Counseling, Testing, and Family Communication Into Survivorship After Diagnosis of Breast Cancer
Authors: Steven J. Katz, Paul Abrahamse, Allison Furgal, Rachel Hodan, Rachel S. Tocco, Kevin C. Ward, Ann S. Hamilton, Lauren P. Wallner, Allison W. Kurian
Journal: Journal of Clinical Oncology (2024)

PURPOSE To examine receipt of genetic testing and communication with relatives about results into survivorship after diagnosis of breast cancer. METHODS Women age 20-79 years diagnosed with early-stage breast cancer in 2014-2015 and reported to the Georgia and Los Angeles County SEER registries were surveyed approximately 7 months and 6 years after diagnosis (n = 1,412). We asked about genetic counseling, testing, and communication with relatives about results. We categorized women into indications for testing on the basis of clinical guidelines at the time of diagnosis and at the time of the follow-up survey (FUPs). RESULTS A total of 47.4% had indications for genetic testing at any time: 28.0% at baseline and an additional 19.4% at the time of the FUPs (only); 71.9% (95% CI, 67.4 to 76.4) of those with a baseline indication reported genetic testing versus 53.3% (95% CI, 47.3 to 59.2) with an indication at FUPs only and 35.0% (95% CI, 31.6 to 38.4) with no indication ( P &lt; .001). There were no significant racial or ethnic differences in receipt of testing, controlling for age and clinical indications ( P = .239); results for genetic counseling were similar. Only 3.4% of survivors had direct-to-consumer genetic testing (DTCt) for cancer. Testers who reported a pathogenic variant (n = 62) were much more likely to have talked to most or all their first-degree adult relatives about genetic testing than those with a variant of unknown significance (n = 49) or a negative finding (n = 419): 62.7% versus 38.8% and 38.0%, respectively ( P &lt; .001). CONCLUSION Many women with indications for genetic counseling and testing into survivorship do not receive it. But those tested reach out to family members on the basis of the clinical relevance of their results. Very few patients obtained DTCt, which suggests that these tests do not substitute for clinical testing in breast cancer survivors.
Novel insights into paclitaxel’s role on tumor-associated macrophages in enhancing PD-1 blockade in breast cancer treatment
Authors: Yoonjeong Choi, Seong A Kim, Hanul Jung, Eunhae Kim, Yoon Kyoung Kim, Seohyun Kim, Jaehyun Kim, Yeji Lee, Min Kyoung Jo, Jiwan Woo, Yakdol Cho, Dongjoo Lee, Hongyoon Choi, Cherlhyun Jeong, Gi-Hoon Nam, Minsu Kwon, In-San Kim
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Triple-negative breast cancer (TNBC) poses unique challenges due to its complex nature and the need for more effective treatments. Recent studies showed encouraging outcomes from combining paclitaxel (PTX) with programmed cell death protein-1 (PD-1) blockade in treating TNBC, although the exact mechanisms behind the improved results are unclear. Methods We employed an integrated approach, analyzing spatial transcriptomics and single-cell RNA sequencing data from TNBC patients to understand why the combination of PTX and PD-1 blockade showed better response in TNBC patients. We focused on toll-like receptor 4 (TLR4), a receptor of PTX, and its role in modulating the cross-presentation signaling pathways in tumor-associated macrophages (TAMs) within the tumor microenvironment. Leveraging insights obtained from patient-derived data, we conducted in vitro experiments using immunosuppressive bone marrow-derived macrophages (iBMDMs) to validate if PTX could augment the cross-presentation and phagocytosis activities. Subsequently, we extended our study to an in vivo murine model of TNBC to ascertain the effects of PTX on the cross-presentation capabilities of TAMs and its downstream impact on CD8+ T cell-mediated immune responses. Results Data analysis from TNBC patients revealed that the activation of TLR4 and cross-presentation signaling pathways are crucial for the antitumor efficacy of PTX. In vitro studies showed that PTX treatment enhances the cross-presentation ability of iBMDMs. In vivo experiments demonstrated that PTX activates TLR4-dependent cross-presentation in TAMs, improving CD8+ T cell-mediated antitumor responses. The efficacy of PTX in promoting antitumor immunity was elicited when combined with PD-1 blockade, suggesting a complementary interaction. Conclusions This study reveals how PTX boosts the effectiveness of PD-1 inhibitors in treating TNBC. We found that PTX activates TLR4 signaling in TAMs. This activation enhances their ability to present antigens, thereby boosting CD8+ T cell antitumor responses. These findings not only shed light on PTX’s immunomodulatory role in TNBC but also underscore the potential of targeting TAMs’ antigen presentation capabilities in immunotherapy approaches.
Racial Differences in the Burden of Atherosclerotic Cardiovascular Disease Related to Elevated Lipoprotein(a) Levels: The ARIC Study
Authors: Jelani K. Grant, Seth S. Martin, Sui Zhang, Kunihiro Matsushita, Salim S. Virani, Roger S. Blumenthal, Ron C. Hoogeveen, Eric Boerwinkle, Christie M. Ballantyne, Josef Coresh, Chiadi E. Ndumele
Journal: Circulation (2024)
Implications of microbe-derived ɣ-aminobutyric acid (GABA) in gut and brain barrier integrity and GABAergic signaling in Alzheimer’s disease
Authors: Kathryn A. Conn, Emily M. Borsom, Emily K. Cope
Journal: Gut Microbes (2024)

The gut microbial ecosystem communicates bidirectionally with the brain in what is known as the gut-microbiome-brain axis. Bidirectional signaling occurs through several pathways including signaling via the vagus nerve, circulation of microbial metabolites, and immune activation. Alterations in the gut microbiota are implicated in Alzheimer's disease (AD), a progressive neurodegenerative disease. Perturbations in gut microbial communities may affect pathways within the gut-microbiome-brain axis through altered production of microbial metabolites including ɣ-aminobutyric acid (GABA), the primary inhibitory mammalian neurotransmitter. GABA has been shown to act on gut integrity through modulation of gut mucins and tight junction proteins and may be involved in vagus nerve signal inhibition. The GABAergic signaling pathway has been shown to be dysregulated in AD, and may be responsive to interventions. Gut microbial production of GABA is of recent interest in neurological disorders, including AD. Bacteroides and Lactic Acid Bacteria (LAB), including Lactobacillus, are predominant producers of GABA. This review highlights how temporal alterations in gut microbial communities associated with AD may affect the GABAergic signaling pathway, intestinal barrier integrity, and AD-associated inflammation.
Digital Footprints of Obesity Treatment: GLP-1 Receptor Agonists and the Health Equity Divide
Authors: Zahra Azizi, Fatima Rodriguez, Themistocles L. Assimes
Journal: Circulation (2024)

Our research investigates the societal implications of access to glucagon-like peptide-1 (GLP-1) agonists, particularly in light of recent clinical trials demonstrating the efficacy of semaglutide in reducing cardiovascular mortality. A decade-long analysis of Google Trends indicates a significant increase in searches for GLP-1 agonists, primarily in North America. This trend contrasts with the global prevalence of obesity. Given the high cost of GLP-1 agonists, a critical question arises: Will this disparity in medication accessibility exacerbate the global health equity gap in obesity treatment? This viewpoint explores strategies to address the health equity gap exacerbated by this emerging medication. Because GLP-1 agonists hold the potential to become a cornerstone in obesity treatment, ensuring equitable access is a pressing public health concern.
Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective – a SENTICOL ancillary study
Authors: Gaurav Thareja, Anna Salvioni, Françoise Lauzeral-Vizcaino, Najeeb Halabi, Eliane Mery-Lamarche, Noemie Thebault, Clara-Maria Scarlata, Marie Michelas, Anne-Sophie Navarro, Gwenaël Ferron, Fabrice Lecuru, Patrice Mathevet, Jonathan Khalifa, Maha Ayyoub, Arash Rafii, Alejandra Martinez
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Cervical cancer’s lymphatic spread primarily begins from the sentinel lymph nodes (SLNs), underlining their pivotal role in disease metastasis. However, these nodes’ immune gene expression profiles and immunoregulation mechanisms have yet to be explored. Methods Our study aimed to elucidate the immune cell populations and their roles in the immune gene expression profile of negative SLNs compared with positive SLNs and non-SLNs using Nanostring RNA seq analysis. We performed a principal component analysis on the log2 normalized expression of 685 endogenous genes in the nCounter PanCancer Immune Profiling Panel, followed by an assessment of the differential expression of genes and immune cell type abundance. Results We found significant variations in gene expression among the groups, with negative SLNs displaying overexpression of genes related to tumor-infiltrating immune cells, specifically innate cell populations. They also demonstrated the upregulation of genes involved in antigen presentation and T-cell priming. In contrast, positive SLNs were enriched in regulatory networks, suggesting their potential role in immune evasion. A comparison of negative SLNs and non-SLNs revealed increased innate and adaptive immune cell types, underscoring the ongoing T cell response to tumor antigens. Conclusion Our findings underscore a specific immunogenetic phenotype profile in negative SLNs, emphasizing their crucial role in the initial anticancer response, immunosurveillance, and the propagation of immune tolerance from the primary cervical tumor. These results highlight the potential of SLNs as a novel target for immunotherapy strategies and underscore the importance of new imaging methods for accurately identifying SLN status without removal. Future investigations are needed to understand further the immunological interplay within SLNs and their influence on cervical cancer progression.
Influence of Sex, Race and Ethnicity, and Deprivation on Survival and Completion of the Fontan Pathway for Children With Functionally Single Ventricle Heart Disease
Authors: Rachel L. Knowles, Deborah Ridout, Qi Huang, Rodney C. Franklin, Anna N. Seale, Hannah Bellsham-Revell, Ferran Espuny-Pujol, Katherine L. Brown
Journal: Circulation (2024)
Equitable Care for Hypertension: Blood Pressure and Patient-Reported Outcomes of the RICH LIFE Cluster Randomized Trial
Authors: Lisa A. Cooper, Jill A. Marsteller, Kathryn A. Carson, Katherine B. Dietz, Romsai T. Boonyasai, Carmen Alvarez, Deidra C. Crews, Cheryl R. Dennison Himmelfarb, Chidinma A. Ibe, Lisa Lubomski, Edgar R. Miller, Nae-Yuh Wang, Gideon D. Avornu, Deven Brown, Debra Hickman, Michelle Simmons, Ariella Apfel Stein, Hsin-Chieh Yeh, Rexford Ahima, Denis G. Antoine, Jagriti Bhattarai, Lee Bone, Jeanne Charleston, Suna Chung, Marcia Cort, Gail L. Daumit, Teresa Eyer, Demetrius Frazier, Raquel Greer, Felicia Hill-Briggs, Anika Hines, Tammie Hull, Lawrence Johnson, Susan Johnson, Mary Kargbo, Mary Kelleher, Mariana Lazo, Lena M. Mathews, Chiadi E. Ndumele, Ruth-Alma Turkson-Ocran, Randy Parker, Cassandra Peterson, Tanjala S. Purnell, Natalie Spicyn, DeNotta Teagle, Marcee White, Joan Young, Kimberly L. Zeren
Journal: Circulation (2024)

Disparities in hypertension control are well documented but underaddressed.
Bidirectional Associations Between Mental Health Disorders and Chronic Diabetic Complications in Individuals With Type 1 or Type 2 Diabetes
Authors: Maya Watanabe, Evan L. Reynolds, Mousumi Banerjee, Morten Charles, Kara Mizokami-Stout, Dana Albright, Lynn Ang, Joyce M. Lee, Rodica Pop-Busui, Eva L. Feldman, Brian C. Callaghan
Journal: Diabetes Care (2024)

To determine bidirectional associations between the timing of chronic diabetes complications (CDCs) and mental health disorders (MHDs) in individuals with type 1 or type 2 diabetes.
The safety of antivirals and neutralising monoclonal antibodies used in prehospital treatment of Covid-19
Authors: Katie Bechman, Amelia Ca Green, Mark D Russell, Zijing Yang, Bang Zheng, Sam Norton, Rebecca M Smith, Amir Mehrkar, Sebastian C J Bacon, Ben Goldacre, Brian MacKenna, James B Galloway
Journal: Journal of Infection (2024)
Estrogen receptor-α signaling in tanycytes lies at the crossroads of fertility and metabolism
Authors: Daniela Fernandois, Mariam Rusidzé, Helge Mueller-Fielitz, Florent Sauve, Eleonora Deligia, Mauro S.B. Silva, Florence Evrard, Aurelio Franco-García, Daniele Mazur, Ines Martinez-Corral, Nathalie Jouy, S. Rasika, Claude-Alain Maurage, Paolo Giacobini, Ruben Nogueiras, Benedicte Dehouck, Markus Schwaninger, Francoise Lenfant, Vincent Prevot
Journal: Metabolism (2024)
Effect of Pemafibrate on Diabetic Foot Ulceration and Gangrene
Authors: Lucas L Marinho, Brendan M Everett, Aaron W Aday, Frank L J Visseren, Jean G MacFadyen, Elaine Zaharris, Jorge Plutzky, Raul D Santos, Peter Libby, Jean-Charles Fruchart, Paul M Ridker, Aruna Das Pradhan
Journal: Journal of the American College of Cardiology (2024)