tbuckley/cabot-search huggingface dataset:
Powerful and accurate detection of temporal gene expression patterns from multi-sample multi-stage single-cell transcriptomics data with TDEseq
Authors: Yue Fan, Lei Li, Shiquan Sun
Journal: Genome biology (2024)

Abstract We present a non-parametric statistical method called TDEseq that takes full advantage of smoothing splines basis functions to account for the dependence of multiple time points in scRNA-seq studies, and uses hierarchical structure linear additive mixed models to model the correlated cells within an individual. As a result, TDEseq demonstrates powerful performance in identifying four potential temporal expression patterns within a specific cell type. Extensive simulation studies and the analysis of four published scRNA-seq datasets show that TDEseq can produce well-calibrated p -values and up to 20% power gain over the existing methods for detecting temporal gene expression patterns.
Household Air Pollution Interventions to Improve Health in Low- and Middle-Income Countries: An Official American Thoracic Society Research Statement
Authors: Peggy S. Lai, Nicholas L. Lam, Bill Gallery, Alison G. Lee, Heather Adair-Rohani, Donee Alexander, Kalpana Balakrishnan, Iwona Bisaga, Zoe A. Chafe, Thomas Clasen, Anaité Díaz-Artiga, Andrew Grieshop, Kat Harrison, Stella M. Hartinger, Darby Jack, Seyram Kaali, Melissa Lydston, Kevin M. Mortimer, Laura Nicolaou, Esther Obonyo, Gabriel Okello, Christopher Olopade, Ajay Pillarisetti, Alisha Noella Pinto, Joshua P. Rosenthal, Neil Schluger, Xiaoming Shi, Claudia Thompson, Lisa M. Thompson, John Volckens, Kendra N. Williams, John Balmes, William Checkley, Obianuju B. Ozoh
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Section:ChooseTop of pageAbstract <<OverviewIntroductionMethodsTopic 1: Do HAP Intervent...Topic 2: What Are Importa...Topic 3: Does Academic Re...Topic 4: What Are the Nex...ConclusionsReferences
Important lessons on healthcare from rare diseases
Authors: None The Lancet Neurology
Journal: The Lancet Neurology (2024)

Promoting the wellbeing of its citizens, fighting discrimination, and supporting scientific progress are among core values of the European Union (EU), where the rare diseases community must be commended for translating these values into actions. After two decades of intense efforts by patients' organisations, healthcare providers, and research institutions, on March 8, 2024, the European Commission launched the JARDIN Joint Action. If successful, JARDIN—in coordination with other ongoing initiatives—can make rare diseases healthcare and research in the EU a model for the rest of the world.
Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial
Authors: Rabi Tawil, Kathryn R Wagner, Johanna I Hamel, Doris G Leung, Jeffrey M Statland, Leo H Wang, Angela Genge, Sabrina Sacconi, Hanns Lochmüller, David Reyes-Leiva, Jordi Diaz-Manera, Jorge Alonso-Perez, Nuria Muelas, Juan J Vilchez, Alan Pestronk, Summer Gibson, Namita A Goyal, Lawrence J Hayward, Nicholas Johnson, Samantha LoRusso, Miriam Freimer, Perry B Shieh, S H Subramony, Baziel van Engelen, Joost Kools, Olof Dahlqvist Leinhard, Per Widholm, Christopher Morabito, Christopher M Moxham, Diego Cadavid, Michelle L Mellion, Adefowope Odueyungbo, William G Tracewell, Anthony Accorsi, Lucienne Ronco, Robert J Gould, Jennifer Shoskes, Luis Alejandro Rojas, John G Jiang
Journal: The Lancet Neurology (2024)
Pyridine‐2,6‐Dicarboxamide Proligands and their Cu(II)/Zn(II) Complexes Targeting <i>Staphylococcus Aureus</i> for the Attenuation of In Vivo Dental Biofilm
Authors: Kajal Chaudhary, Bhumika Agrahari, Bhumika Biswas, Niranjan Chatterjee, Ayushi Chaudhary, Ashwini Kumar, Himanshu Sonker, Sayari Dewan, Deepanshi Saxena, Abdul Akhir, Nidhi Malhotra, Sidharth Chopra, Santosh Misra, Saravanan Matheswaran, Ritika Gautam Singh
Journal: Advanced Healthcare Materials (2024)

In the pursuit to combat stubborn bacterial infections, particularly those stemming from gram-positive bacteria, this study is an attempt to craft a precision-driven platform characterized by unparalleled selectivity, specificity, and synergistic antimicrobial mechanisms. Leveraging remarkable potential of metalloantibiotics in antimicrobial applications, herein, this work rationally designs, synthesizes, and characterizes a new library of Pyridine-2,6-dicarboxamide ligands and their corresponding transition metal Cu(II)/Zn(II) complexes. The lead compound L
Infectious Diseases: What You May Have Missed in 2023
Authors: Amena Alhammadi, Rasha Alshawaf, Swati Chavda, Sonya Ramondino, Mindy Schuster
Journal: Annals of Internal Medicine (2024)

In 2023, published research on COVID-19 remains prominent. The aim of this article is to highlight important developments in infectious disease evidence unrelated to COVID-19 that were published in 2023. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The highlighted publications relate to various organisms and patient populations. One article provides insight into the updated guidelines for the diagnosis and management of infective endocarditis. Several articles address the management of sepsis and bacteremia: comparison of cefepime versus piperacillin-tazobactam, ceftobiprole for the treatment of complicated
Pulmonology: What You May Have Missed in 2023
Authors: Aram Karkar, Sana Khan, Rebecca O'Leary, Albina Tyker, Michael Unger
Journal: Annals of Internal Medicine (2024)

The field of pulmonology saw significant advances in 2023. The publications highlighted in this article address advances and changes in practice related to asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease, pleural disorders, and sleep-disordered breathing. One article reviews data examining the efficacy of vaccination against respiratory syncytial virus, a respiratory viral illness that has had devastating effects globally. Four studies evaluate the role of various therapies in COPD, including dupilumab, ensifentrine, pulmonary rehabilitation programs, and lung volume reduction versus endobronchial valves. Another study explores the effect on vascular events of positive-pressure ventilation in patients with sleep-disordered breathing and recent stroke. The use of combination therapy with rituximab and mycophenolate mofetil on progression-free survival in patients with nonspecific interstitial pneumonia is the topic of another study. We also highlight an update of clinical recommendations for the evaluation of patients with pleural disorders and a systematic review analyzing the effectiveness of inhaled corticosteroids as a supplement to dual therapy for COPD.
Cardiology: What You May Have Missed in 2023
Authors: Abdulrahman Alfraih, Achieng Tago, Michael Lacombe, William G. Kussmaul
Journal: Annals of Internal Medicine (2024)

Cardiology and all its subspecialties continue to push the envelope in developing new treatment strategies for a wide variety of diseases. After screening more than 1300 articles, we highlight a selection of important cardiology articles published in 2023. Starting with prevention, we note articles that look at the effect of semaglutide in patients with obesity as well as a first-in-class drug, bempedoic acid, on cardiovascular outcomes. We have also examined new evidence comparing conservative management with invasive management of frail, older patients with non-ST-segment elevation myocardial infarction (NSTEMI). In patients with cardiac arrest secondary to NSTEMI, another article examines the rationale for expedited transfer to a cardiac arrest center. The STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) trial builds on looking at half-dose thrombolysis in older populations with STEMI. Emphasis is placed on guideline-directed medical therapy before hospital discharge in those with heart failure. In addition, in patients with stable symptomatic coronary artery disease, initial noninvasive testing using coronary computed tomography angiography may be a viable option compared with invasive strategies. More details have emerged on anticoagulation strategies in those with device-detected atrial fibrillation. Finally, transcatheter approaches to treat both mitral and tricuspid regurgitation have also been included.
Nephrology: What You May Have Missed in 2023
Authors: Ali A.M. AlHabobi, Ashwaq M.S. Almutairi, Danah A.S.Y. Bohemid, Ashwini R. Sehgal
Journal: Annals of Internal Medicine (2024)

This article highlights a selection of important nephrology studies published in 2023 that have relevance for nonnephrologist physicians. Four studies examined progression of chronic kidney disease or cardiovascular disease with respect to finerenone use, magnesium supplementation, iron markers, and COVID-19. Two studies examined treatments to improve specific aspects of chronic kidney disease management, including daprodustat to address anemia and patiromer to address hyperphosphatemia. One study showed that acetazolamide added to loop diuretics increased diuresis in acute decompensated heart failure across a wide range of renal function. Another study found that once-daily hydrochlorothiazide did not prevent kidney stone recurrence. Finally, an antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infection in frail older adults.
Gastroenterology/Hepatology: What You May Have Missed in 2023
Authors: Sama Anvari, Kayla Dadgar, Ciarán Galts, Michael Bretthauer
Journal: Annals of Internal Medicine (2024)

This article summarizes clinically important gastroenterology developments from 2023 for internal medicine specialists. In colorectal cancer screening, a new RNA fecal screening test is on the horizon, as well as a new analysis on the benefits of using artificial intelligence in screening colonoscopy to detect more polyps. There is new evidence for management of gastrointestinal bleeding, a new drug for treatment of recurrent small-intestinal angiodysplasia, and a new endoscopic treatment method in patients with gastrointestinal tumor bleeding. The authors feature a randomized trial about amitriptyline as treatment for patients with irritable bowel syndrome by primary care providers and bring you news about new biologic agents for inflammatory bowel disease and eosinophilic esophagitis. Finally, they review 2 important articles on new terminology and management of metabolic dysfunction-associated fatty liver disease.
Critical Care: What You May Have Missed in 2023
Authors: Henry Ajzenberg, Mansor Abdalaziz N. Binhashr, Mark Keith Hewitt, Michael Unger
Journal: Annals of Internal Medicine (2024)

Critical care medicine is a specialty that brings together a truly wide spectrum of patient populations, disease states, and treatment methods. This article highlights 10 important pieces of research from 2023 (and 1 from 2022) in critical care. The literature was screened for new evidence relevant to internal medicine physicians and hospitalists whose focus of practice is not critical care but who may be taking care of seriously ill patients. The articles highlight the diverse spectrum of pathology and interplay of various specialties that go into critical care. Topics include transfusion medicine, fluid resuscitation, safe intubation practices and respiratory failure, and the management of acute ischemic stroke. Several trials are groundbreaking, forcing clinicians to reconsider preexisting dogma and likely adopt new treatment strategies.
Cell Type– and Age-Specific Expression of lncRNAs across Kidney Cell Types
Authors: Gyeong Dae Kim, So-I Shin, Su Woong Jung, Hyunsu An, Sin Young Choi, Minho Eun, Chang-Duk Jun, Sangho Lee, Jihwan Park
Journal: Journal of the American Society of Nephrology (2024)

Key Points We constructed a single-cell long noncoding RNA atlas of various tissues, including normal and aged kidneys. We identified age- and cell type–specific expression changes of long noncoding RNAs in kidney cells. Background Accumulated evidence demonstrates that long noncoding RNAs (lncRNAs) regulate cell differentiation and homeostasis, influencing kidney aging and disease. Despite their versatility, the function of lncRNA remains poorly understood because of the lack of a reference map of lncRNA transcriptome in various cell types. Methods In this study, we used a targeted single-cell RNA sequencing method to enrich and characterize lncRNAs in individual cells. We applied this method to various mouse tissues, including normal and aged kidneys. Results Through tissue-specific clustering analysis, we identified cell type–specific lncRNAs that showed a high correlation with known cell-type marker genes. Furthermore, we constructed gene regulatory networks to explore the functional roles of differentially expressed lncRNAs in each cell type. In the kidney, we observed dynamic expression changes of lncRNAs during aging, with specific changes in glomerular cells. These cell type– and age-specific expression patterns of lncRNAs suggest that lncRNAs may have a potential role in regulating cellular processes, such as immune response and energy metabolism, during kidney aging. Conclusions Our study sheds light on the comprehensive landscape of lncRNA expression and function and provides a valuable resource for future analysis of lncRNAs (https://gist-fgl.github.io/sc-lncrna-atlas/).
Oncology: What You May Have Missed in 2023
Authors: Courtney H. Coschi, Lorin Dodbiba, DuPont Guerry
Journal: Annals of Internal Medicine (2024)

Advances in oncology treatment methods have improved outcomes and quality of life for patients with cancer. However, care of these patients can be complex, and the contribution of physicians from different specialties is crucial. This article highlights important publications from 2023 on topics across a wide spectrum relating to the management of oncology patients. The literature was screened for significant new evidence that is relevant to internal medicine specialists and subspecialists whose focus is not oncology. Two articles address the importance of social interventions targeting end-of-life care for low-income and minority patients and the well-being of caregivers. Two additional articles address screening considerations in patients at risk for colorectal and lung cancer. Two more articles address safe use of hormone-related therapies to treat symptoms of menopause and prevent disease recurrence or progression in patients diagnosed with noninvasive breast neoplasia. Finally, several articles were included on topics related to COVID-19 vaccination in patients with cancer, use of cannabinoids for cancer pain control, chronic autoimmune adverse effects related to use of immune checkpoint inhibitors, and the incidence of second primary neoplasms.
Measurement and Application of Incidentally Detected Coronary Calcium
Authors: Shyon Parsa, Adam Saleh, Viraj Raygor, Natalie Hoeting, Anjali Rao, Ann Marie Navar, Anand Rohatgi, Fernando Kay, Suhny Abbara, Amit Khera, Parag H. Joshi
Journal: Journal of the American College of Cardiology (2024)
Precision Medicine in Rheumatic Diseases: Unlocking the Potential of Antibody-Drug Conjugates
Authors: Zhiwen Huang, Zachary Braunstein, Jun Chen, Yingying Wei, Xiaoquan Rao, Lingli Dong, Jixin Zhong
Journal: Pharmacological Reviews (2024)

In the era of precision medicine, Antibody-Drug Conjugates (ADCs) have emerged as a cutting-edge therapeutic strategy. These innovative compounds combine the precision of monoclonal antibodies with the potent cell-killing or immune-modulating abilities of attached drug payloads. This unique strategy not only reduces off-target toxicity but also enhances the therapeutic effectiveness of drugs. Beyond their well-established role in oncology, ADCs are now showing promising potential in addressing the unmet needs in the therapeutics of rheumatic diseases. Rheumatic diseases, a diverse group of chronic autoimmune diseases with varying etiologies, clinical presentations, and prognoses, often demand prolonged pharmacological interventions, creating a pressing need for novel, efficient and low-risk treatment options. ADCs, with their ability to precisely target the immune components, have emerged as a novel therapeutic strategy in this context. This review will provide an overview of the core components and mechanisms behind ADCs, a summary of the latest clinical trials of ADCs for the treatment if rheumatic diseases, as well as a discussion on the challenges and future prospects faced by the development of next-generation ADCs. <b>Significance Statement</b> There is a lack of efficient and low-risk targeted therapeutics for rheumatic diseases. Antibody-drug conjugates, a class of cutting-edge therapeutic drugs, have emerged as a promising targeted therapeutic strategy for rheumatic disease. While there is limited literature summarizing the progress of antibody-drug conjugates in the field of rheumatic disease, updating the advancements in this area provides novel insights into the development of novel anti-rheumatic drugs.
A Path to Persistence after EGFR Inhibition
Authors: Purva H. Rumde, Timothy F. Burns
Journal: Cancer Research (2024)

Abstract Residual cancer cells persist even after targeted therapies, serving as a reservoir for the subsequent acquisition of genetic alterations that lead to acquired drug resistance and tumor relapse. These initial drug-tolerant persisters (DTP) are phenotypically heterogenous with transient phenotypes attributed to epigenetic, metabolic, and cell-cycle changes. DTPs are responsible for the inevitable relapse seen in EGFR-mutant non–small cell lung cancer (NSCLC) despite high initial response to tyrosine kinase inhibitor (TKI) treatment. While past in vitro studies identified diverse drivers of drug-tolerant persistence to EGFR TKIs in NSCLC, the resultant phenotypic plasticity is not well understood and in vivo models of persistence are lacking. In this issue of Cancer Research, Hu and colleagues used patient-derived xenograft models of EGFR-mutant lung cancer treated with the third-generation TKI osimertinib to investigate mechanisms of persistence at the time of maximal response. Using bulk and single-cell RNA sequencing, the authors identified a DTP transcriptional cluster mediated by the key neuroendocrine lineage transcription factor ASCL1, which triggers an epithelial-to-mesenchymal transition transcriptional program. ASCL1 overexpression increased osimertinib tolerance in vitro as well, apparently independent of its role in neuroendocrine differentiation. Interestingly, the ability of ASCL1 to induce persistence was context dependent as this occurred only in epigenetically permissive cells. Overall, these findings contribute to our understanding of DTP heterogeneity seen after osimertinib treatment and provide insights into potential therapeutic targets. See related article by Hu et al., p. 1303
SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features
Authors: Marta Sureda-Gómez, Ingram Iaccarino, Anna De Bolòs, Mieke Meyer, Patricia Balsas, Julia Richter, Marta-Leonor Rodríguez, Cristina López, Maria Carreras-Caballé, Selina Glaser, Ferran Nadeu, Pedro Jares, Guillem Clot, Maria Chiara Siciliano, Cristiana Bellan, Salvatore Tornambè, Roberto Boccacci, Lorenzo Leoncini, Elias Campo, Reiner Siebert, Virginia Amador, Wolfram Klapper
Journal: Blood (2024)

SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and SOX11 expression were mutually exclusive in BL. SOX11 expression in EBV-negative (EVB-) BL was associated with an IG∷MYC translocation generated by aberrant class switch recombination, whereas in EBV-negative (EBV-)/SOX11-negative (SOX11-) tumors the IG∷MYC translocation was mediated by mistaken somatic hypermutations. Interestingly, EBV- SOX11-expressing BL showed higher frequency of SMARCA4 and ID3 mutations than EBV-/SOX11- cases. By RNA sequencing, we identified a SOX11-associated gene expression profile, with functional annotations showing partial overlap with the SOX11 transcriptional program of MCL. Contrary to MCL, no differences on cell migration or B-cell receptor signaling were found between SOX11- and SOX11-positive (SOX11+) BL cells. However, SOX11+ BL showed higher adhesion to vascular cell adhesion molecule 1 (VCAM-1) than SOX11- BL cell lines. Here, we demonstrate that EBV- BL comprises 2 subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.
Visual interpretable MRI fine grading of meniscus injury for intelligent assisted diagnosis and treatment
Authors: Anlin Luo, Shuiping Gou, Nuo Tong, Bo Liu, Licheng Jiao, Hu Xu, Yingchun Wang, Tan Ding
Journal: npj Digital Medicine (2024)

Abstract Meniscal injury represents a common type of knee injury, accounting for over 50% of all knee injuries. The clinical diagnosis and treatment of meniscal injury heavily rely on magnetic resonance imaging (MRI). However, accurately diagnosing the meniscus from a comprehensive knee MRI is challenging due to its limited and weak signal, significantly impeding the precise grading of meniscal injuries. In this study, a visual interpretable fine grading (VIFG) diagnosis model has been developed to facilitate intelligent and quantified grading of meniscal injuries. Leveraging a multilevel transfer learning framework, it extracts comprehensive features and incorporates an attributional attention module to precisely locate the injured positions. Moreover, the attention-enhancing feedback module effectively concentrates on and distinguishes regions with similar grades of injury. The proposed method underwent validation on FastMRI_Knee and Xijing_Knee dataset, achieving mean grading accuracies of 0.8631 and 0.8502, surpassing the state-of-the-art grading methods notably in error-prone Grade 1 and Grade 2 cases. Additionally, the visually interpretable heatmaps generated by VIFG provide accurate depictions of actual or potential meniscus injury areas beyond human visual capability. Building upon this, a novel fine grading criterion was introduced for subtypes of meniscal injury, further classifying Grade 2 into 2a, 2b, and 2c, aligning with the anatomical knowledge of meniscal blood supply. It can provide enhanced injury-specific details, facilitating the development of more precise surgical strategies. The efficacy of this subtype classification was evidenced in 20 arthroscopic cases, underscoring the potential enhancement brought by intelligent-assisted diagnosis and treatment for meniscal injuries.
Nanopore Detection of METTL3-Dependent m6A-Modified mRNA Reveals a New Mechanism Regulating Cardiomyocyte Mitochondrial Metabolism
Authors: Charles P. Rabolli, Isabel S. Naarmann-de Vries, Catherine A. Makarewich, Kedryn K. Baskin, Christoph Dieterich, Federica Accornero
Journal: Circulation (2024)
Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients
Authors: Christina S Thornton, Barbara J Waddell, Stephen E Congly, Julianna Svishchuk, Ranjani Somayaji, Linda Fatovich, Debra Isaac, Karen Doucette, Kevin Fonseca, Steven J Drews, Jamie Borlang, Carla Osiowy, Michael D Parkins
Journal: Gut (2024)

In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers.