tbuckley/cabot-search huggingface dataset:
RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding
Authors: Elena Mitsi, Elissavet Nikolaou, Andre Goncalves, Annie Blizard, Helen Hill, Madlen Farrar, Angela Hyder-Wright, Oluwasefunmi Akeju, Josh Hamilton, Ashleigh Howard, Filora Elterish, Carla Solorzano, Ryan Robinson, Jesus Reiné, Andrea M Collins, Stephen B Gordon, Richard E Moxon, Jeffrey N Weiser, Debby Bogaert, Daniela M Ferreira
Journal: Cell Host & Microbe (2024)
Uncovering therapeutic targets for macrophage-mediated T cell suppression and PD-L1 therapy sensitization
Authors: Sushil Kumar, Dhanir Tailor, Arpit Dheeraj, Wenqi Li, Kirsten Stefan, Jee Min Lee, Dylan Nelson, Bailey F Keefe, Pepper Schedin, Shivaani Kummar, Lisa M Coussens, Sanjay V Malhotra
Journal: Cell Reports Medicine (2024)

Tumor-associated macrophages (TAMs) and other myelomonocytic cells are implicated in regulating responsiveness to immunotherapies, including immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis. We have developed an ex vivo high-throughput approach to discover modulators of macrophage-mediated T cell suppression, which can improve clinical outcomes of ICIs. We screened 1,430 Food and Drug Administration (FDA)-approved small-molecule drugs using a co-culture assay employing bone-marrow-derived macrophages (BMDMs) and splenic-derived T cells. This identified 57 compounds that disrupted macrophage-mediated T cell suppression. Seven compounds exerted prominent synergistic T cell expansion activity when combined with αPD-L1. These include four COX1/2 inhibitors and two myeloid cell signaling inhibitors. We demonstrate that the use of cyclooxygenase (COX)1/2 inhibitors in combination with αPD-L1 decreases tumor growth kinetics and enhances overall survival in triple-negative breast cancer (TNBC) tumor models in a CD8
When I use a word . . . Aphrodisiacs
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

Of all the many, mostly female, love deities that populate the polytheistic religions of the world, the most famous are the Roman goddess Venus and her Greek counterpart Aphrodite. Venus has contributed disreputably to the English vocabulary, giving us venery and venereal diseases, while Aphrodite has contributed more fancifully in the form of aphrodisiacs. The word "aphrodisiac" is first recorded in an English text from 1710, Thomas Fuller's <i>Pharmacopoeia extemporanea</i>, in his description of "An Electuary of Satyrion." If anyone can identify the plant that was called satyrion, his electuary could be recreated and put to the test in a randomised double-blind clinical trial. Until then we shall have to make do with other traditional aphrodisiacs.
Multiple sclerosis: emerging epidemiological trends and redefining the clinical course
Authors: Emilio Portaccio, Melinda Magyari, Eva Kubala Havrdova, Aurelie Ruet, Bruno Brochet, Antonio Scalfari, Massimiliano Di Filippo, Carmen Tur, Xavier Montalban, Maria Pia Amato
Journal: The Lancet Regional Health - Europe (2024)

SummaryMultiple sclerosis is a chronic, inflammatory, and neurodegenerative disease of the central nervous system and a major cause of neurological disability in young adults. Its prevalence and incidence are increasing, and it has been estimated at over 2.8 million cases worldwide, in addition to recent trends towards a shift in MS prevalence to older ages, with peak prevalence estimates in the sixth decade of life. Although historically the relapsing and progressive phases of the disease have been considered separate clinical entities, recent evidence of progression independent of relapse activity (PIRA) has led to a reconsideration of multiple sclerosis as a continuum, in which relapsing and progressive features variably coexist from the earliest stages of the disease, challenging the traditional view of the disease course. In this Series article, we provide an overview of how the traditional description of the clinical course of MS and epidemiological trends in Europe have evolved. For this purpose, we focus on the concept of PIRA, discussing its potential as the main mechanism by which patients acquire disability, how its definition varies between studies, and ongoing research in this field. We emphasise the importance of incorporating the assessment of hidden clinical manifestations into patient management to help uncover and quantify the PIRA phenomenon and the possible implications for future changes in the clinical classification of the disease. At the same time, we provide insights into overcoming the challenges of identifying and defining PIRA and adopting a new understanding of the clinical course of MS.
Treatment modalities of marginal zone lymphoma and overall survival, haematological response, and underlying Sjögren's disease activity: a multicentre, retrospective, observational study
Authors: Juliette Rocca, Maxime Beydon, Véronique Le Guern, Eric Hachulla, Marion Couderc, Sandrine Jousse-Joulin, Valérie Devauchelle-Pensec, Jacques-Eric Gottenberg, Olivier Vittecoq, Christian Lavigne, Jean Schmidt, Claire Larroche, Xavier Mariette, Raphaèle Seror, Gaetane Nocturne
Journal: The Lancet Rheumatology (2024)
STING is crucial for the survival of RUNX1::RUNX1T1 leukemia cells
Authors: Yue Sun, Yushuang Wu, Guozheng Pang, Jingru Huang, Mengyao Sheng, Jiaying Xie, Pingyue Chen, Yin Wang, Dongrui Yin, Guangjie Zhao, Stefan K. Bohlander, Jian Huang, Guo-Liang Xu, Hai Gao, Dan Zhou, Yuheng Shi
Journal: Leukemia (2024)
Disparities in time to treatment with oral antimyeloma medications
Authors: Hamlet Gasoyan, Faiz Anwer, Jeffrey D. Kovach, Nicholas J. Casacchia, Ming Wang, Jason Valent, Michael T. Halpern, Michael B. Rothberg
Journal: Blood Cancer Journal (2024)

Abstract This retrospective cohort study used Taussig Cancer Center’s Myeloma Patient Registry to identify adults with multiple myeloma diagnosed between January 2017-December 2021. Electronic health records data captured time from diagnosis to initial prescription fill for oral antimyeloma medications and initiation of facility administered or oral antimyeloma treatment. We identified 720 patients with a mean age at diagnosis of 67 years ±11; 55% were male, 77% White, 22% Black, 1% other races, covered by private insurance (36%), traditional Medicare (29%), Medicare Advantage (25%), and Medicaid (8.3%). Over a third of patients (37%) resided in an area in the most disadvantaged area deprivation index (ADI) quartile. The median available follow-up was 765 days. Seventy-five percent of the cohort filled an oral antimyeloma medication prescription (excluding corticosteroids), with a median time to fill of 28 days (IQR, 15–61). In the multivariable Cox regression model, Black race (vs. White, adjusted hazard ratio [aHR], 0.61, 95% CI, 0.42–0.87), older age at diagnosis (aHR per 1 year, 0.97, 95% CI, 0.95–0.98), diagnosis during an inpatient admission (aHR, 0.63, 95% CI, 0.43–0.92), and estimated glomerular filtration rate ≤29 ml/min/1.73 m 2 (vs. ≥60, aHR, 0.46, 95% CI, 0.29–0.73) were negatively associated with prescription fill for oral antimyeloma medication at 30 days, while insurance type and ADI were not significant predictors.
The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors in the Forthcoming 9th Edition of the TNM Classification for Pleural Mesothelioma
Authors: Hedy L Kindler, Adam Rosenthal, Dorothy J Giroux, Anna K Nowak, Andrea Billè, Ritu R Gill, Harvey Pass, David Rice, Robert T Ripley, Andrea Wolf, Kevin G Blyth, Susanna Cedres, Valerie Rusch
Journal: Journal of Thoracic Oncology (2024)
Continuum of Light Sensitivity in Atopic Dermatitis: A Retrospective Analysis of 139 Cases in Scotland
Authors: Chayada Chaiyabutr, Robert Dawe, Andrea Lesar, Sally H Ibbotson
Journal: Journal of the American Academy of Dermatology (2024)

Previous reports have characterized photosensitivity in atopic dermatitis (AD), but with differences in terminology and criteria.
Emerging role of environmental pollutants in inflammatory bowel disease risk, outcomes and underlying mechanisms
Authors: Maria Manuela Estevinho, Vishal Midya, Shirley Cohen-Mekelburg, Kristine Højgaard Allin, Mathurin Fumery, Salome S Pinho, Jean-Frederic Colombel, Manasi Agrawal
Journal: Gut (2024)

Epidemiological and translational data increasingly implicate environmental pollutants in inflammatory bowel disease (IBD). Indeed, the global incidence of IBD has been rising, particularly in developing countries, in parallel with the increased use of chemicals and synthetic materials in daily life and escalating pollution levels. Recent nationwide and ecological studies have reported associations between agricultural pesticides and IBD, particularly Crohn’s disease. Exposure to other chemical categories has also been linked with an increased risk of IBD. To synthesise available data and identify knowledge gaps, we conducted a systematic review of human studies that reported on the impact of environmental pollutants on IBD risk and outcomes. Furthermore, we summarised in vitro data and animal studies investigating mechanisms underlying these associations. The 32 included human studies corroborate that heavy and transition metals, except zinc, air pollutants, per- and polyfluorinated substances, and pesticides are associated with an increased risk of IBD, with exposure to air pollutants being associated with disease-related adverse outcomes as well. The narrative review of preclinical studies suggests several overlapping mechanisms underlying these associations, including increased intestinal permeability, systemic inflammation and dysbiosis. A consolidated understanding of the impact of environmental exposures on IBD risk and outcomes is key to the identification of potentially modifiable risk factors and to inform strategies towards prediction, prevention and mitigation of IBD.
A portable and efficient dementia screening tool using eye tracking machine learning and virtual reality
Authors: Ying Xu, Chi Zhang, Baobao Pan, Qing Yuan, Xu Zhang
Journal: npj Digital Medicine (2024)

Dementia represents a significant global health challenge, with early screening during the preclinical stage being crucial for effective management. Traditional diagnostic biomarkers for Alzheimer's Disease, the most common form of dementia, are limited by cost and invasiveness. Mild cognitive impairment (MCI), a precursor to dementia, is currently identified through neuropsychological tests like the Montreal Cognitive Assessment (MoCA), which are not suitable for large-scale screening. Eye-tracking technology, capturing and quantifying eye movements related to cognitive behavior, has emerged as a promising tool for cognitive assessment. Subtle changes in eye movements could serve as early indicators of MCI. However, the interpretation of eye-tracking data is challenging. This study introduced a dementia screening tool, VR Eye-tracking Cognitive Assessment (VECA), using eye-tracking technology, machine learning, and virtual reality (VR) to offer a non-invasive, efficient alternative capable of large-scale deployment. VECA was conducted with 201 participants from Shenzhen Baoan Chronic Hospital, utilizing eye-tracking data captured via VR headsets to predict MoCA scores and classify cognitive impairment across different educational backgrounds. The support vector regression model employed demonstrated a high correlation (0.9) with MoCA scores, significantly outperforming baseline models. Furthermore, it established optimal cut-off scores for identifying cognitive impairment with notable sensitivity (88.5%) and specificity (83%). This study underscores VECA's potential as a portable, efficient tool for early dementia screening, highlighting the benefits of integrating eye-tracking technology, machine learning, and VR in cognitive health assessments.
High-intensity interval training improves cardiovascular and physical health in patients with rheumatoid arthritis: a multicentre randomised controlled trial
Authors: Annelie Bilberg, Kaisa Mannerkorpi, Mats Borjesson, Sara Svedlund, Jenny Sivertsson, Eva Klingberg, Jan Bjersing
Journal: British Journal of Sports Medicine (2024)

Patients with rheumatoid arthritis (RA) have substantially elevated risk for cardiovascular diseases, and low cardiorespiratory fitness (VO
Epitope landscape in autoimmune neurological disease and beyond
Authors: Ivan Talucci, Hans M. Maric
Journal: Trends in Pharmacological Sciences (2024)

HighlightsEpitopes underlying autoantigen-driven neurological diseases remain largely undetermined.Powerful screening technologies now enable effective epitope identification.Such methods facilitate the direct translation of epitope-inspired blueprints for autoantibody studies.Autoantibody-mediated pathology is determined by distinct interferences involved directly in protein interaction and function as well as indirectly via complement activation.These molecular determinants enable patient stratification and have potential to reveal underlying molecular mimicry.Epitopes provide novel avenues for restoring healthy immune function.AbstractAutoantibody binding has a central role in autoimmune diseases and has also been linked to cancer, infections, and behavioral disorders. Autoimmune neurological diseases remain misclassified also due to an incomplete understanding of the underlying disease-specific epitopes. Such epitopes are crucial for both pathology and diagnosis, but have historically been overlooked. Recent technological advancements have enabled the exploration of these epitopes, potentially opening novel clinical avenues. The precise identification of novel B and T cell epitopes and their autoreactivity has led to the discovery of autoantigen-specific biomarkers for patients at high risk of autoimmune neurological diseases. In this review, we propose utilizing newly available synthetic and cellular-surface display technologies and guide epitope-focused studies to unlock the potential of disease-specific epitopes for improving diagnosis and treatments. Additionally, we offer recommendations to guide emerging epitope-focused studies to broaden the current landscape.
Unmasking the hidden impact of viruses on tuberculosis risk
Authors: Fatoumatta Darboe, Josephine F. Reijneveld, David P. Maison, Leonardo Martinez, Sara Suliman
Journal: Trends in Immunology (2024)

SignificanceFactors associated with tuberculosis (TB) risk remain poorly defined. Studies indicate that viral infections can heighten the risk of transitioning from latent Mycobacterium tuberculosis (Mtb) infection to TB. Innate antiviral responses, particularly increased type I interferon signaling, correlate with elevated TB risk and bacterial load following Mtb infection. HIV-1 illustrates how a chronic viral infection can amplify TB risk and mortality, but the relationship between viral infections and TB risk may extend beyond HIV-1. Identifying specific viral families and pathogenic mechanisms associated with heightened/persistent TB risk remains a key research area.HighlightsViral co-infections in Mycobacterium tuberculosis (Mtb)-exposed individuals are potentially a risk factor for tuberculosis (TB) pathogenesis.Some chronic viral infections, such as human immunodeficiency virus 1 (HIV-1) and cytomegalovirus (CMV), can increase TB risk. However, it is unclear whether different viruses impart unique or shared pathogenic mechanisms.Viruses modulate both systemic and local tissue environments in ways that may increase the TB risk.There is an urgent need for experimental models and approaches to help define the impact of emerging and re-emerging viral epidemics on the risk of TB incidence and mortality in TB-endemic settings.AbstractTuberculosis (TB) is a leading cause of mortality from an infectious disease. In this opinion article, we focus on accumulating scientific evidence indicating that viral infections may contribute to TB progression, possibly allowing novel preventive interventions. Viruses can remodel the mammalian immune system, potentially modulating the risk of reactivating latent microbes such as Mycobacterium tuberculosis (Mtb). Evidence is mixed regarding the impact of emergent viruses such as SARS-CoV-2 on the risk of TB. Therefore, we posit that important knowledge gaps include elucidating which viral families increase TB risk and whether these provide unique or shared immune mechanisms. We also propose potential future research to define the contribution of viruses to TB pathogenesis.
They are still children: a scoping review of conditions for positive engagement in elite youth sport
Authors: Stuart G. Wilson, Mia KurtzFavero, Haley H. Smith, Michael F Bergeron, Jean Côté
Journal: British Journal of Sports Medicine (2024)

Objective The objective of this study is to characterise the key factors that influence positive engagement and desirable developmental outcomes in sport among elite youth athletes by summarising the methods, groups and pertinent topical areas examined in the extant published research. Design Scoping review. Data sources We searched the databases SPORTDiscus, APA PsycINFO, Web of Science and Sports Medicine &amp; Education Index for peer-reviewed, published in English articles that considered the factors influencing positive developmental outcomes for athletes under 18 years competing at a national and/or international level. Results The search returned 549 articles, of which 43 met the inclusion criteria. 16 studies used a qualitative approach, 14 collected quantitative data, 2 adopted mixed methods and 11 were reviews. Seven articles involved athletes competing in absolute skill contexts (ie, against the best athletes of any age) while the majority involved athletes competing in relative skill contexts (ie, against the best in a specific age or developmental group). The studies described the characteristics of the athletes, as well as their training, relationships with others, social and physical environments, and/or their overall developmental pathways. Conclusion Existing research on positive engagement in elite youth sport aligned with and mapped onto established models of positive development in youth sport more generally. Our findings further support that, while certain youth athletes may demonstrate extraordinary performance capabilities, they are still children who benefit from positive engagement prompted and reinforced by developmentally appropriate and supportive activities, relationships and environments.
Neighborhood-Level Disparities in Hypertension Prevalence and Treatment Among Middle-Aged Adults
Authors: Madeleine M. Blazel, Adam T. Perzynski, Paul R. Gunsalus, Lyla Mourany, Douglas D. Gunzler, Robert W. Jones, Elizabeth R. Pfoh, Jarrod E. Dalton
Journal: JAMA Network Open (2024)

Hypertension in middle-aged adults (35-50 years) is associated with poorer health outcomes in late life. Understanding how hypertension varies by race and ethnicity across levels of neighborhood disadvantage may allow for better characterization of persistent disparities.
Using AI and Social Media to Understand Health Disparities for Transgender Cancer Care
Authors: Augustine Annan, Yeran Li, Jingcheng Du, Yezhou Sun, Al Asante-Facey, Xiaoyan Wang, Matthew Monberg
Journal: JAMA Network Open (2024)

This qualitative study used an artificial intelligence (AI) large language model and social media to investigate challenges encountered by transgender individuals during breast and gynecological cancer care.
Tourniquet Use and Local Tissue Concentrations of Cefazolin During Total Knee Arthroplasty
Authors: Julien Montreuil, Michael Tanzer, Yu Ling Zhang, Ewa Rajda, Daina Avizonis, Adam Hart
Journal: JAMA Network Open (2024)

Importance Prophylactic administration of antibiotics before skin incision is an important component in the prevention of periprosthetic joint infection in arthroplasty surgery. For antibiotics to be effective, the local tissue concentration (LTC) must exceed the minimum inhibitory concentration of typical infecting organisms; however, the LTC of cefazolin during arthroplasty is poorly understood. Objective To compare the systemic concentration of cefazolin in serum with the LTC in fat, synovium, and bone during primary total knee arthroplasty (TKA) while assessing the effect of tourniquet inflation. Design, Setting, and Participants This prospective randomized clinical trial was conducted from March 1, 2022, to June 30, 2023, in patients undergoing TKA at a single academic center. Intervention Total knee arthroplasty with or without a limb tourniquet. Main Outcomes and Measures Systemic blood and local tissues from the surgical site (fat, synovium, and bone) were harvested at regular intervals during the surgery. The primary outcome was the LTC of cefazolin, quantified using the liquid chromatography–tandem mass spectrometry technique. Results A total of 59 patients were included in the study, with 29 in the tourniquet group (mean [SD] age, 69.3 [9.6] years; 23 [79.3%] female) and 30 in the no tourniquet group (mean [SD] age, 69.9 [9.7] years; 21 [70.0%] female). In patients undergoing TKA without a tourniquet, the mean concentration of cefazolin in serum was 71.9 μg/mL (95% CI, 66.4-77.5 μg/mL), whereas the mean LTCs were 13.9 μg/g (95% CI, 12.1-15.7 μg/g) in fat, 27.7 μg/g (95% CI, 24.3-31.0 μg/g) in synovium, and 17.7 μg/g (95% CI, 14.8-20.5 μg/g) in bone. For patients undergoing TKA with a tourniquet, the mean concentration of cefazolin in serum was 72.0 μg/mL (95% CI, 66.3-77.7 μg/mL), and the mean LTCs were 9.9 μg/g (95% CI, 8.7-11.1 μg/g) in fat, 21.8 μg/g (95% CI, 18.7-25.0 μg/g) in synovium, and 13.0 μg/g (95% CI, 10.8-15.2 μg/g) in bone. The use of a tourniquet resulted in significantly lower mean LTCs by 60 minutes after cefazolin infusion (10.8 μg/g [95% CI, 9.1-12.4 μg/g] vs 16.9 μg/g [95% CI, 14.1-19.6 μg/g], P = .001 in fat; 18.9 μg/g [95% CI, 14.1-23.6 μg/g] vs 25.8 μg/g [95% CI, 21.4-30.3 μg/g], P = .03 in synovium; and 11.8 μg/g [95% CI, 9.3-14.2 μg/g] vs 19.4 μg/g [95% CI, 14.5-24.4 μg/g], P = .007 in bone). Conclusions and Relevance In this randomized clinical trial, the concentration of cefazolin was lower in local tissues (fat, synovium, and bone) than in systemic blood, and the use of a limb tourniquet further significantly reduced these concentrations. Although the current prophylactic dosing regimen for cefazolin provides sufficient serum concentrations, the levels in the periarticular tissue during TKA may be insufficient to prevent periprosthetic joint infection. Trial Registration ClinicalTrials.gov Identifier: NCT05604157
Targeted therapies, novel antibodies, and immunotherapies in advanced non-small cell lung cancer: clinical evidence and drug approval patterns
Authors: Marén U. Koban, Markus Hartmann, Georgios Amexis, Pedro Franco, Laura Huggins, Imran Shah, Niki Karachaliou
Journal: Clinical Cancer Research (2024)

Since 2011, the US FDA has approved 30 new drugs for use in advanced non-small cell lung cancer (NSCLC), mainly comprising tyrosine kinase inhibitors and immune checkpoint inhibitors. NSCLC with oncogene driver alterations is amenable to treatment with targeted drugs, usually small-molecule inhibitors. In these cases, the demonstration of high overall response rates, coupled with a lasting duration of response, has allowed for accelerated approval in the United States, based on single-cohort or multicohort trials. Confirmatory clinical evidence was subsequently provided through postmarketing trials. In NSCLC without such driver alterations, regulatory agencies in both the United States and the European Union set clinical evidence expectations that foster the conduct of studies primarily focused on determining survival or event-free survival, based on randomized controlled trial designs. This review analyzes the approval patterns of novel therapeutics for NSCLC with a focus on small-molecule inhibitors that target driver alterations, as well as biologics. The latter include mAbs inhibiting immune checkpoints like PD-(L)1 or cell surface receptors and antibody-drug conjugates, highly potent biologics linked to a cytotoxic compound. The differentiation of NSCLC into oncogene- and non-oncogene-addicted subtypes determines drug development strategies, the extent of the clinical development program, access to orphan drug development incentives, and regulatory approval strategies.