tbuckley/cabot-search huggingface dataset:
<i>KLF2</i>enhancer variant rs4808485 increases lupus risk by modulating inflammasome machinery and cellular homoeostasis
Authors: Manish Kumar Singh, Harikrishna Reddy Rallabandi, Xu-Jie Zhou, Yuan-Yuan Qi, Zhan-Zheng Zhao, Ting Gan, Hong Zhang, Loren L Looger, Swapan K Nath
Journal: Annals of the Rheumatic Diseases (2024)

A recent genome-wide association study linked KLF2 as a novel Asian-specific locus for systemic lupus erythematosus (SLE) susceptibility. However, the underlying causal functional variant(s), cognate target gene(s) and genetic mechanisms associated with SLE risk are unknown.
Health Equity in the Veterans Health Administration From Veterans’ Perspectives by Race and Sex
Authors: Natalie S. Lee, Shimrit Keddem, Anneliese E. Sorrentino, Kevin Ahmaad Jenkins, Judith A. Long
Journal: JAMA Network Open (2024)

Importance Advancing equitable patient-centered care in the Veterans Health Administration (VHA) requires understanding the differential experiences of unique patient groups. Objective To inform a comprehensive strategy for improving VHA health equity through the comparative qualitative analysis of care experiences at the VHA among veterans of Black and White race and male and female sex. Design, Setting, and Participants This qualitative study used a technique termed freelisting , an anthropologic technique eliciting responses in list form, at an urban academic VHA medical center from August 2, 2021, to February 9, 2022. Participants included veterans with chronic hypertension. The length of individual lists, item order in those lists, and item frequency across lists were used to calculate a salience score for each item, allowing comparison of salient words and topics within and across different groups. Participants were asked about current perceptions of VHA care, challenges in the past year, virtual care, suggestions for change, and experiences of racism. Data were analyzed from February 10 through September 30, 2022. Main Outcomes and Measures The Smith salience index, which measures the frequency and rank of each word or phrase, was calculated for each group. Results Responses from 49 veterans (12 Black men, 12 Black women, 12 White men, and 13 White women) were compared by race (24 Black and 25 White) and sex (24 men and 25 women). The mean (SD) age was 64.5 (9.2) years. Some positive items were salient across race and sex, including “good medical care” and telehealth as a “comfortable/great option,” as were some negative items, including “long waits/delays in getting care,” “transportation/traffic challenges,” and “anxiety/stress/fear.” Reporting “no impact” of racism on experiences of VHA health care was salient across race and sex; however, reports of race-related unprofessional treatment and active avoidance of race-related conflict differed by race (present among Black and not White participants). Experiences of interpersonal interactions also diverged. “Impersonal/cursory” telehealth experiences and the need for “more personal/attentive” care were salient among women and Black participants, but not men or White participants, who associated VHA care with courtesy and respect. Conclusions and Relevance In this qualitative freelist study of veteran experiences, divergent experiences of interpersonal care by race and sex provided insights for improving equitable, patient-centered VHA care. Future research and interventions could focus on identifying differences across broader categories both within and beyond race and sex and bolstering efforts to improve respect and personalized care to diverse veteran populations.
Pitfalls of Cuff Size and Blood Pressure Measurement
Authors: Marco Zuin, Gianluca Rigatelli
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
The Global Burden of Disease Epidemiology—When Big Data Impute the Nonexistent
Authors: Andres Roman-Urrestarazu, Robin van Kessel
Journal: JAMA Pediatrics (2024)

This Viewpoint discusses concerns about the data quality of the Global Burden of Disease study with respect to incidence estimates of child and adolescent mental health disorders, such as autism and attention-deficit/hyperactivity disorder, in low- and middle-income countries.
The gut microbiome regulates the clinical efficacy of sulfasalazine therapy for IBD-associated spondyloarthritis
Authors: Svetlana F. Lima, Silvia Pires, Amanda Rupert, Seun Oguntunmibi, Wen-Bing Jin, Andrew Marderstein, Gabriela Funez-dePagnier, Grace Maldarelli, Monica Viladomiu, Gregory Putzel, Wei Yang, Nancy Tran, Grace Xiang, Alex Grier, Chun-Jun Guo, Dana Lukin, Lisa A. Mandl, Ellen J. Scherl, Randy S. Longman
Journal: Cell Reports Medicine (2024)

Sulfasalazine is a prodrug known to be effective for the treatment of inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA), but the mechanistic role for the gut microbiome in regulating its clinical efficacy is not well understood. Here, treatment of 22 IBD-pSpA subjects with sulfasalazine identifies clinical responders with a gut microbiome enriched in Faecalibacterium prausnitzii and the capacity for butyrate production. Sulfapyridine promotes butyrate production and transcription of the butyrate synthesis gene but in F. prausnitzii in vitro, which is suppressed by excess folate. Sulfasalazine therapy enhances fecal butyrate production and limits colitis in wild-type and gnotobiotic mice colonized with responder, but not non-responder, microbiomes. F. prausnitzii is sufficient to restore sulfasalazine protection from colitis in gnotobiotic mice colonized with non-responder microbiomes. These findings reveal a mechanistic link between the efficacy of sulfasalazine therapy and the gut microbiome with the potential to guide diagnostic and therapeutic approaches for IBD-pSpA.
Methionine secreted by tumor-associated pericytes supports cancer stem cells in clear cell renal carcinoma
Authors: ChuanJie Zhang, ZunGuo Du, Yi Gao, Kiat Shenq Lim, WenJie Zhou, Hai Huang, HongChao He, Jun Xiao, DanFeng Xu, QingQuan Li
Journal: Cell Metabolism (2024)
Abortion Restrictions and the Child Welfare System—Reply
Authors: Savannah Adkins, Ashley L. O’Donoghue
Journal: JAMA Pediatrics (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Recent advances in polygenic scores: translation, equitability, methods and FAIR tools
Authors: Ruidong Xiang, Martin Kelemen, Yu Xu, Laura W. Harris, Helen Parkinson, Michael Inouye, Samuel A. Lambert
Journal: Genome Medicine (2024)

Abstract Polygenic scores (PGS) can be used for risk stratification by quantifying individuals’ genetic predisposition to disease, and many potentially clinically useful applications have been proposed. Here, we review the latest potential benefits of PGS in the clinic and challenges to implementation. PGS could augment risk stratification through combined use with traditional risk factors (demographics, disease-specific risk factors, family history, etc.), to support diagnostic pathways, to predict groups with therapeutic benefits, and to increase the efficiency of clinical trials. However, there exist challenges to maximizing the clinical utility of PGS, including FAIR (Findable, Accessible, Interoperable, and Reusable) use and standardized sharing of the genomic data needed to develop and recalculate PGS, the equitable performance of PGS across populations and ancestries, the generation of robust and reproducible PGS calculations, and the responsible communication and interpretation of results. We outline how these challenges may be overcome analytically and with more diverse data as well as highlight sustained community efforts to achieve equitable, impactful, and responsible use of PGS in healthcare.
Extracellular vesicles incorporating retrovirus-like capsids for the enhanced packaging and systemic delivery of mRNA into neurons
Authors: Wenchao Gu, Sijin Luozhong, Simian Cai, Ketaki Londhe, Nadine Elkasri, Robert Hawkins, Zhefan Yuan, Kai Su-Greene, Yujie Yin, Margaret Cruz, Yu-Wei Chang, Patrick McMullen, Chunyan Wu, Changwoo Seo, Akash Guru, Wenting Gao, Tara Sarmiento, Chris Schaffer, Nozomi Nishimura, Richard Cerione, Qiuming Yu, Melissa Warden, Robert Langer, Shaoyi Jiang
Journal: Nature Biomedical Engineering (2024)
Targeting Dendritic Cell Dysfunction to Circumvent Anti-PD1 Resistance in Head and Neck Cancer
Authors: Shin Saito, Michihisa Kono, Hoang C.B. Nguyen, Ann Marie Egloff, Cameron Messier, Patrick Lizotte, Cloud Paweletz, Douglas Adkins, Ravindra Uppaluri
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed. Experimental Design: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model. Results: An aPD1-resistant mouse model showed poor priming in the tumor DLN due to type 1 conventional dendritic cell (cDC1) dysfunction, which correlated with exhausted and poorly responsive antigen-specific T cells. Tumor microenvironment analysis also showed decreased cDC1 in aPD1-resistant tumors compared with sensitive tumors. Following neoadjuvant aPD1 therapy, pathologic responses in patients also positively correlated with baseline transcriptomic cDC1 signatures. In an aPD1-resistant model, intratumoral cDC1 vaccine was sufficient to restore aPD1 response by enhancing T-cell infiltration and increasing antigen-specific responses with improved tumor control. Mechanistically, CCL5 expression significantly correlated with neoadjuvant aPD1 response and enforced expression of CCL5 in an aPD1-resistant model, enhanced cDC1 tumor infiltration, restored antigen-specific responses, and recovered sensitivity to aPD1 treatment. Conclusions: These data highlight the contribution of tumor-infiltrating cDC1 in HNSCC aPD1 response and approaches to enhance cDC1 infiltration and function that may circumvent aPD1 resistance in patients with HNSCC.
Updated epithelial barrier dysfunction in chronic rhinosinusitis: Targeting pathophysiology and treatment response of tight junctions
Authors: Zhi‐Qun Huang, Jing Liu, Li‐Ying Sun, Hsiao Hui Ong, Jing Ye, Yu Xu, De‐Yun Wang
Journal: Allergy (2024)

Abstract Tight junction (TJ) proteins establish a physical barrier between epithelial cells, playing a crucial role in maintaining tissue homeostasis by safeguarding host tissues against pathogens, allergens, antigens, irritants, etc. Recently, an increasing number of studies have demonstrated that abnormal expression of TJs plays an essential role in the development and progression of inflammatory airway diseases, including chronic obstructive pulmonary disease, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS) with or without nasal polyps. Among them, CRS with nasal polyps is a prevalent chronic inflammatory disease that affects the nasal cavity and paranasal sinuses, leading to a poor prognosis and significantly impacting patients' quality of life. Its pathogenesis primarily involves dysfunction of the nasal epithelial barrier, impaired mucociliary clearance, disordered immune response, and excessive tissue remodeling. Numerous studies have elucidated the pivotal role of TJs in both the pathogenesis and response to traditional therapies in CRS. We therefore to review and discuss potential factors contributing to impair and repair of TJs in the nasal epithelium based on their structure, function, and formation process.
Clinical implications of subclinical left ventricular dysfunction in heart failure with preserved ejection fraction: The PARAGON‐HF study
Authors: Masatoshi Minamisawa, Riccardo M. Inciardi, Brian Claggett, Maja Cikes, Li Liu, Narayana Prasad, Tor Biering‐Sørensen, Carolyn S.P. Lam, Sanjiv J. Shah, Michael R. Zile, Eileen O'Meara, Margaret M. Redfield, John J.V. McMurray, Scott D. Solomon, Amil M. Shah
Journal: European Journal of Heart Failure (2024)
Age-Related Risk of Serious Fall Events and Opioid Analgesic Use
Authors: Ria E. Hopkins, Chrianna Bharat, Luke Buizen, Jacqueline Close, Rebecca Ivers, Brian Draper, Sallie-Anne Pearson, Louisa Degenhardt, Natasa Gisev
Journal: JAMA Internal Medicine (2024)

Opioid analgesics may be associated with increased risk of falls, particularly among older adults.
Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials
Authors: Sining Xie, Federica Galimberti, Elena Olmastroni, Thomas F Luscher, Stefano Carugo, Alberico L Catapano, Manuela Casula, Alberico L Catapano, Manuela Casula, Federica Galimberti, Elena Olmastroni, Sining Xie, Christoph Wanner, Salim Yusuf, Aldo Maggioni, Adrienne Kirby, Hiroshi Ogawa, Ellen K Hoogeveen, Ingebjørg Seljeflot, Francine K Welty, Michal Benderly, JoAnn E Manson, Kathy Wolski, Christopher P Cannon, Frederick J Raal, David Kallend, JoAnne Foody, Michael Louie
Journal: Cardiovascular Research (2024)

Abstract Chronic low-degree inflammation is a hallmark of atherosclerotic cardiovascular (CV) disease. To assess the effect of lipid-lowering therapies on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (i) randomized controlled trials (RCTs) in human, Phase II, III, or IV; (ii) English language; (iii) comparing the effect of lipid-lowering drugs vs. placebo; (iv) reporting the effects on CRP levels; (v) with intervention duration of more than 3 weeks; (vi) and sample size (for both intervention and control group) over than 100 subjects. The between-group (treatment-placebo) CRP absolute mean differences and 95% confidence intervals were calculated for each drug class separately. A total of 171 668 subjects from 53 RCTs were included. CRP levels (mg/L) were significantly decreased by statins [−0.65 (−0.87 to −0.43), bempedoic acid; −0.43 (−0.67 to −0.20), ezetimibe; −0.28 (−0.48 to −0.08)], and omega-3 fatty acids [omega3FAs, −0.27 (−0.52 to −0.01)]. CRP was reduced by −0.40 (−1.17 to 0.38) with fibrates, although not statistically significant. A slight increase of CRP concentration was observed for proprotein convertase subtilisin/kexin type 9 inhibitors [0.11 (0.07–0.14)] and cholesteryl-ester transfer protein inhibitors [0.10 (0.00–0.21)], the latter being not statistically significant. Meta-regression analysis did not show a significant correlation between changes in CRP and LDL cholesterol (LDL-C) or triglycerides. Statins, bempedoic acid, ezetimibe, and omega3FAs significantly reduce serum CRP concentration, independently of LDL-C reductions. The impact of this anti-inflammatory effect in terms of CV prevention needs further investigation.
Gene Expression Profiling in Pediatric Appendicitis
Authors: Bhavjinder K. Dhillon, Simone Kortbeek, Arjun Baghela, Mary Brindle, Dori-Ann Martin, Craig N. Jenne, Hans J. Vogel, Amy H. Y. Lee, Graham C. Thompson, Robert E. W. Hancock
Journal: JAMA Pediatrics (2024)

Importance Appendicitis is the most common indication for urgent surgery in the pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) and perforated appendicitis (PA) on presentation may help direct further diagnostic workup and appropriate therapy selection, including antibiotic choice and timing of surgery. Objective To provide a mechanistic understanding of the differences in disease severity of appendicitis with the objective of developing improved diagnostics and treatments, specifically for the pediatric population. Design, Setting, and Participants The Gene Expression Profiling of Pediatric Appendicitis (GEPPA) study was a single-center prospective exploratory diagnostic study with transcriptomic profiling of peripheral blood collected from a cohort of children aged 5 to 17 years with abdominal pain and suspected appendicitis between November 2016 and April 2017 at the Alberta Children’s Hospital in Calgary, Alberta, Canada, with data analysis reported in August 2023. There was no patient follow-up in this study. Exposure SA, PA, or nonappendicitis abdominal pain. Main Outcomes and Measures Blood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics. Results Seventy-one children (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) presenting to the emergency department with abdominal pain and suspected appendicitis were investigated using whole-blood transcriptomics. A central role for immune system pathways was revealed in PA, including a dampening of major innate interferon responses. Gene expression changes in patients with PA were consistent with downregulation of immune response and inflammation pathways and shared similarities with gene expression signatures derived from patients with sepsis, including the most severe sepsis endotypes. Despite the challenges in identifying early biomarkers of severe appendicitis, a 4-gene signature that was predictive of PA compared to SA, with an accuracy of 85.7% (95% CI, 72.8-94.1) was identified. Conclusions This study found that PA was complicated by a dysregulated immune response. This finding should inform improved diagnostics of severity, early management strategies, and prevention of further postsurgical complications.
Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke
Authors: Yu Fu, Anxin Wang, Renhong Tang, Shuya Li, Xue Tian, Xue Xia, Jinsheng Ren, Shibao Yang, Rong Chen, Shunwei Zhu, Xiaofei Feng, Jinliang Yao, Yan Wei, Xueshuang Dong, Yun Ling, Fei Yi, Qian Deng, Cunju Guo, Yi Sui, Shugen Han, Guoqiang Wen, Chuanling Li, Aiqin Dong, Xin Sun, Zhimin Wang, Xueying Shi, Bo Liu, Dongsheng Fan
Journal: JAMA Neurology (2024)

Sublingual edaravone dexborneol, which can rapidly diffuse and be absorbed through the oral mucosa after sublingual exposure, is a multitarget brain cytoprotection composed of antioxidant and anti-inflammatory ingredients edaravone and dexborneol.
Health Care AI and Patient Privacy—<i>Dinerstein v Google</i>
Authors: Mindy Nunez Duffourc, Sara Gerke
Journal: JAMA (2024)

This Viewpoint summarizes a recent lawsuit alleging that a hospital violated patients’ privacy by sharing electronic health record (EHR) data with Google for development of medical artificial intelligence (AI) and discusses how the federal court’s decision in the case provides key insights for hospitals planning to share EHR data with for-profit companies developing medical AI.
Lifetime Exposure to Depression and Neuroimaging Measures of Brain Structure and Function
Authors: Xinyi Wang, Felix Hoffstaedter, Jan Kasper, Simon B. Eickhoff, Kaustubh R. Patil, Juergen Dukart
Journal: JAMA Network Open (2024)

Despite decades of neuroimaging studies reporting brain structural and functional alterations in depression, discrepancies in findings across studies and limited convergence across meta-analyses have raised questions about the consistency and robustness of the observed brain phenotypes.
Ethics and Terminology for Opting In and Out—In Reply
Authors: Leah M. Marcotte, Karin M. Nelson, Ashok Reddy
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal