tbuckley/cabot-search huggingface dataset:
A Nonviable Probiotic in Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study
Authors: Isabelle Mack, Juliane Schwille-Kiuntke, Nazar Mazurak, Beate Niesler, Kurt Zimmermann, Hubert Mönnikes, Paul Enck
Journal: Clinical Gastroenterology and Hepatology (2021)

The aim of this study was to investigate the effectiveness of oral treatment with a nonviable probiotic lysate (BL) of Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) in patients with irritable bowel syndrome (IBS).A phase IV, randomized, double-blind, placebo-controlled, multicenter (30 study sites), parallel group study was conducted in 389 patients of both sexes with IBS according to Rome III criteria. The treatment period was 26 weeks. The participants were allocated to either placebo or BL after a 2-week baseline period. The primary outcome was based on the European Medicines Agency IBS guideline: improvement in global assessment (GAI) and improvement in abdominal pain.Patients (BL, n = 191; placebo, n = 198) had similar baseline values and dropout rates. Overall, the response was similar between BL and placebo for IBS-GAI (17.4% and 14.4%, respectively; P = ·4787) and abdominal pain (42.0% and 35.4%, respectively; P = ·1419). Some secondary outcome measures and sensitivity analyses pointed toward potentially higher sensitivity of the abdominal pain measures in diarrhea-predominant IBS (IBS-D) but not the other subtypes. For the GAI, no subgroup differences were detected. For IBS-D, post hoc analyses for abdominal pain response over time and stool consistency showed potentially promising effects of BL. Finally, the treatment with BL was well-tolerated.BL is not effective across all IBS subtypes. However, BL may offer a treatment option for IBS-D that needs verification by an adequately powered drug trial; EudraCT-No.: 2012-002741-38.
Neutrophils initiate and exacerbate Stevens-Johnson syndrome and toxic epidermal necrolysis
Authors: Manao Kinoshita, Youichi Ogawa, Natsumi Hama, Inkin Ujiie, Akito Hasegawa, Saeko Nakajima, Takashi Nomura, Jun Adachi, Takuya Sato, Schuichi Koizumi, Shinji Shimada, Yasuyuki Fujita, Hayato Takahashi, Yoshiko Mizukawa, Takeshi Tomonaga, Keisuke Nagao, Riichiro Abe, Tatsuyoshi Kawamura
Journal: Science Translational Medicine (2021)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous adverse drug reactions characterized by massive epidermal detachment. Cytotoxic T cells and associated effector molecules are known to drive SJS/TEN pathophysiology, but the contribution of innate immune responses is not well understood. We describe a mechanism by which neutrophils triggered inflammation during early phases of SJS/TEN. Skin-infiltrating CD8+ T cells produced lipocalin-2 in a drug-specific manner, which triggered the formation of neutrophil extracellular traps (NETs) in early lesional skin. Neutrophils undergoing NETosis released LL-37, an antimicrobial peptide, which induced formyl peptide receptor 1 (FPR1) expression by keratinocytes. FPR1 expression caused keratinocytes to be vulnerable to necroptosis that caused further release of LL-37 by necroptotic keratinocytes and induced FPR1 expression on surrounding keratinocytes, which likely amplified the necroptotic response. The NETs-necroptosis axis was not observed in less severe cutaneous adverse drug reactions, autoimmune diseases, or neutrophil-associated disorders, suggesting that this was a process specific to SJS/TEN. Initiation and progression of SJS/TEN keratinocyte necroptosis appear to involve a cascade of events mediated by innate and adaptive immune responses, and understanding these responses may contribute to the identification of diagnostic markers or therapeutic targets for these adverse drug reactions.
Prevention and Mitigation of Heart Failure in the Treatment of Calcific Aortic Stenosis
Authors: Brian R. Lindman, JoAnn Lindenfeld
Journal: JAMA Cardiology (2021)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 2023 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 Cardiology journal
Covid-19: Millions could be offered booster vaccinations from September
Authors: Shaun Griffin
Journal: BMJ (2021)

Millions could be offered booster vaccinations from September Shaun GriffinCovid-19 booster vaccinations should be offered in England from September 2021, the Joint Committee on Vaccination and Immunisation has advised.But some experts have questioned the necessity and the practicalities of the plan.JCVI's interim advice, 1 which will be updated by September after further data analysis, could lead to millions of the people who are most vulnerable to covid-19 being offered the booster vaccination in a two stage approach alongside the annual flu vaccination programme.JCVI advised that in the first stage a third dose of covid-19 booster and annual flu vaccine should be offered as soon as possible from September 2021 to immunosuppressed adults aged 16 or over, people living in residential care homes for older adults, all adults aged 70 years or over, clinically extremely vulnerable adults aged 16 or over; and frontline health and social care workers. 2 World first COVID-19 vaccine booster study launches in UK. 20 May 2021.
Association of the Extension for Community Healthcare Outcomes Project With Use of Direct-Acting Antiviral Treatment Among US Adults With Hepatitis C
Authors: Linh Tran, Roger Feldman, Thomas Riley, Jeah Jung
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Direct-acting antiviral (DAA) medications are highly effective in treating hepatitis C virus (HCV) infection. However, use of DAAs in rural and underserved areas is low owing to limited access to specialist physicians with experience in care of HCV infection. Project ECHO (Extension for Community Healthcare Outcomes) is a distance education model that trains primary care physicians to improve access to care for underserved populations with complex diseases such as HCV infection. Evidence on whether Project ECHO is associated with increased DAA use is limited. <h3>Objective</h3> To examine the association between Project ECHO and use of DAA treatment in patients with HCV infection. <h3>Design, Setting, and Participants</h3> This cohort study used data from Medicare beneficiaries who newly sought care for HCV infection between January 1, 2014, and December 31, 2017. Data were analyzed between September and December 2020. <h3>Exposures</h3> Project ECHO. <h3>Main Outcomes and Measures</h3> Use of DAA treatment. Discrete-time hazard models with state and year fixed effects were used to examine the association between Project ECHO and DAA use in rural areas and areas with low specialist density. <h3>Results</h3> A total of 267 908 patients (mean [SD] age, 60.7 [11.5] years; 57.9% male; 66.6% White patients) were included in the analysis. For every 100 clinicians attending a Project ECHO training, the odds of DAA treatment initiation among patients with HCV infection increased by 9% (adjusted odds ratio [OR], 1.09; 95% CI, 1.07-1.11;<i>P</i> &lt; .001) in nonrural areas with specialist density equaling 0. The association between DAA use and Project ECHO was stronger in areas with lower vs higher specialist density. For every additional 100 Project ECHO participants, the odds of DAA use decreased by 1% as specialist density in the area increased (adjusted OR, 0.99; 95% CI, 0.98-1.00;<i>P</i> = .03). There was no association between Project ECHO and the odds of receiving DAAs among patients in rural vs urban areas (adjusted OR, 1.01; 95% CI, 0.99-1.02;<i>P</i> = .49). <h3>Conclusions and Relevance</h3> In this cohort study, implementation of Project ECHO was associated with increased DAA use in areas with few specialist physicians, suggesting that Project ECHO may enhance access to DAA treatment through expanding the capacity of primary care physicians to treat HCV infection, especially in underserved areas.
Respiratory disease, and treatment / thematic poster session inhaled corticosteroid was not associated with poor prognosis in COVID-19
Authors: C. Rhee, T. An, Y. Kim, K. Yoo
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

RATIONALE: Coronavirus disease 2019 (COVID-19) is a worldwide pandemic. The effects of inhaled corticosteroid (ICS) on COVID-19 are controversial. We aimed to examine clinical outcomes according to premorbid ICS in COVID-19. METHODS: COVID-19 patients at least 18 years old were assessed using nationwide health insurance data. Comorbidities were evaluated using the Charlson Comorbidity Index (CCI). Baseline characteristics including inhaler use and comorbidity were obtained. Outcomes ofCOVID-19 were assessed, such as hospital length of stay (LOS), intensive care unit (ICU) admission, and mortality. RESULTS: ICS was used by 2.8% of COVID-19 patients before they were confirmed to be infected with COVID-19. ICS users were older (53.7 vs. 47.7, p < 0.001) and had higher CCI scores (2.1 vs. 0.9, p < 0.001). The ICU admission rate and hospital LOS did not significantlydiffer between the two groups. Mortality was higher in ICS users than nonusers (9.7% vs. 3.1%). In the adjusted analyses, ICS was not associated with mortality in COVID-19. Factors contributing to COVID-19 mortality were older age (odds ratio [OR] 1.12;95% confidenceinterval [CI] 1.11-1.14;p < 0.001), male sex (OR 2.31;95% CI 1.69-3.16;p < 0.001), higher CCI score (OR 1.30;95% CI 1.20-1.41;p < 0.001), and medical aid insurance (OR 1.54;95% CI 1.03-2.31;p = 0.037). CONCLUSION: Mortality was significantly associated with age, male sex, CCI score, and socioeconomic status. ICS was not associated with poor outcomes in COVID-19.
micro-RNA-486-5p protects against kidney ischemic injury and modifies the apoptotic transcriptome in proximal tubules
Authors: Jose L. Viñas, Matthew Spence, Christopher J. Porter, Adrianna Douvris, Alex Gutsol, Joseph A. Zimpelmann, Pearl A. Campbell, Kevin D. Burns
Journal: Kidney International (2021)

Acute kidney injury (AKI) carries high morbidity and mortality, and effective treatments are lacking. Preclinical models support involvement of micro-RNAs (miRs) in AKI pathogenesis, although effects on the kidney transcriptome are unclear. We previously showed that injection of cord blood endothelial colony forming cell-derived exosomes, enriched in miR-486-5p, prevented ischemic AKI in mice. To further define this, we studied direct effects of miR-486-5p in mice with kidney ischemia-reperfusion injury. RNA-Seq was used to compare the impact of miR-486-5p and exosomes on the transcriptome of proximal tubules and kidney endothelial cells 24 hours after ischemia-reperfusion. In mice with AKI, injection of miR-486-5p mimic increased its levels in proximal tubules and endothelial cells, and improved plasma creatinine, histological injury, neutrophil infiltration, and apoptosis. Additionally, miR-486-5p inhibited expression of its target phosphatase and tensin homolog, and activated protein kinase B. In proximal tubules, miR-486-5p or exosomes reduced expression of genes associated with ischemic injury and the tumor necrosis factor (TNF) pathway, and altered distinct apoptotic genes. In endothelial cells, genes associated with metabolic processes were altered by miR-486-5p or exosomes, although TNF pathway genes were not affected. Thus, our results suggest that miR-486-5p may have therapeutic potential in AKI.
Predicting Mortality Rates After Esophagectomy for Cancer
Authors: Marco G. Patti, Fernando A. Herbella
Journal: JAMA Surgery (2021)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 2023 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 Surgery journal
3,3′,5-Triiodothyroacetic acid (TRIAC) induces embryonic ζ-globin expression via thyroid hormone receptor α
Authors: Huiqiao Chen, Zixuan Wang, Shanhe Yu, Xiao Han, Yun Deng, Fuhui Wang, Yi Chen, Xiaohui Liu, Jun Zhou, Jun Zhu, Hao Yuan
Journal: Journal of Hematology & Oncology (2021)

Abstract The human ζ-globin gene ( HBZ ) is transcribed in primitive erythroid cells only during the embryonic stages of development. Reactivation of this embryonic globin synthesis would likely alleviate symptoms both in α-thalassemia and sickle-cell disease. However, the molecular mechanisms controlling ζ-globin expression have remained largely undefined. Moreover, the pharmacologic agent capable of inducing ζ-globin production is currently unavailable. Here, we show that TRIAC, a bioactive thyroid hormone metabolite, significantly induced ζ-globin gene expression during zebrafish embryogenesis. The induction of ζ-globin expression by TRIAC was also observed in human K562 erythroleukemia cell line and primary erythroid cells. Thyroid hormone receptor α (THRA) deficiency abolished the ζ-globin-inducing effect of TRIAC. Furthermore, THRA could directly bind to the distal enhancer regulatory element to regulate ζ-globin expression. Our study provides the first evidence that TRIAC acts as a potent inducer of ζ-globin expression, which might serve as a new potential therapeutic option for patients with severe α-thalassemia or sickle-cell disease.
B- and T-cell immune responses elicited by the Comirnaty® COVID-19 vaccine in nursing-home residents
Authors: Ignacio Torres, Eliseo Albert, Estela Giménez, María Jesús Alcaraz, Pilar Botija, Paula Amat, María José Remigia, María José Beltrán, Celia Rodado, Dixie Huntley, Beatriz Olea, David Navarro
Journal: Clinical Microbiology and Infection (2021)
Combination of radiation therapy, bempegaldesleukin, and checkpoint blockade eradicates advanced solid tumors and metastases in mice
Authors: Alexander A Pieper, Alexander L Rakhmilevich, Daniel V Spiegelman, Ravi B Patel, Jen Birstler, Won Jong Jin, Peter M Carlson, Deborah H Charych, Jacquelyn A Hank, Amy K Erbe, Willem W Overwijk, Zachary S Morris, Paul M Sondel
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Current clinical trials are using radiation therapy (RT) to enhance an antitumor response elicited by high-dose interleukin (IL)-2 therapy or immune checkpoint blockade (ICB). Bempegaldesleukin (BEMPEG) is an investigational CD122-preferential IL-2 pathway agonist with prolonged in vivo half-life and preferential intratumoral expansion of T effector cells over T regulatory cells. BEMPEG has shown encouraging safety and efficacy in clinical trials when used in combination with PD-1 checkpoint blockade. In this study, we investigated the antitumor effect of local RT combined with BEMPEG in multiple immunologically ‘cold’ tumor models. Additionally, we asked if ICB could further enhance the local and distant antitumor effect of RT+BEMPEG in the setting of advanced solid tumors or metastatic disease. Methods Mice bearing flank tumors (B78 melanoma, 4T1 breast cancer, or MOC2 head and neck squamous cell carcinoma) were treated with combinations of RT and immunotherapy (including BEMPEG, high-dose IL-2, anti(α)-CTLA-4, and α-PD-L1). Mice bearing B78 flank tumors were injected intravenously with B16 melanoma cells to mimic metastatic disease and were subsequently treated with RT and/or immunotherapy. Tumor growth and survival were monitored. Peripheral T cells and tumor-infiltrating lymphocytes were assessed via flow cytometry. Results A cooperative antitumor effect was observed in all models when RT was combined with BEMPEG, and RT increased IL-2 receptor expression on peripheral T cells. This cooperative interaction was associated with increased IL-2 receptor expression on peripheral T cells following RT. In the B78 melanoma model, RT+BEMPEG resulted in complete tumor regression in the majority of mice with a single ~400 mm 3 tumor. This antitumor response was T-cell dependent and supported by long-lasting immune memory. Adding ICB to RT+BEMPEG strengthened the antitumor response and cured the majority of mice with a single ~1000 mm 3 B78 tumor. In models with disseminated metastasis (B78 primary with B16 metastasis, 4T1, and MOC2), the triple combination of RT, BEMPEG, and ICB significantly improved primary tumor response and survival. Conclusion The combination of local RT, BEMPEG, and ICB cured mice with advanced, immunologically cold tumors and distant metastasis in a T cell-dependent manner, suggesting this triple combination warrants clinical testing.
Do Additional Testing Locations Improve the Detection of Macular Perimetric Defects in Glaucoma?
Authors: Giovanni Montesano, Allison M. McKendrick, Andrew Turpin, Paolo Brusini, Francesco Oddone, Paolo Fogagnolo, Andrea Perdicchi, Chris A. Johnson, Paolo Lanzetta, Luca M. Rossetti, David F. Garway-Heath, David P. Crabb
Journal: Ophthalmology (2021)
PROLIFERATION AND APOPTOSIS BIOMARKER MODULATION IN A PHASE II COLORECTAL (CRC) CHEMOPREVENTION TRIAL OF ATORVASTATIN, SULINDAC, OR OLIGOFRUCTOSE-ENRICHED INLULIN: A CANCER PREVENTION NETWORK (CPN) TRIAL
Authors: Mahoney M, Smyrk T, Allen Ziegler K, Heigh R, Schoen R, Levine J, Stoffel E, Chiorean M, Benya R, Sontag S, Weinberg D, Lawson M, Gostout C, Rodriguez Lm, Limburg P
Journal: Annals of Oncology (2010)
The Genesis and Dissolution of the Faculty of Speech. A Clinical and Psychological Study of Aphasia.
Journal: JAMA (1898)

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 HomeNew OnlineCurrent IssueFor Authors Publications 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 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 journal
Islet Autoimmunity and HLA Markers of Presymptomatic and Clinical Type 1 Diabetes: Joint Analyses of Prospective Cohort Studies in Finland, Germany, Sweden, and the U.S.
Authors: Vibha Anand, Ying Li, Bin Liu, Mohamed Ghalwash, Eileen Koski, Kenney Ng, Jessica L. Dunne, Josefine Jönsson, Christiane Winkler, Mikael Knip, Jorma Toppari, Jorma Ilonen, Michael B. Killian, Brigitte I. Frohnert, Markus Lundgren, Anette-Gabriele Ziegler, William Hagopian, Riitta Veijola, Marian Rewers
Journal: Diabetes Care (2021)

OBJECTIVE To combine prospective cohort studies, by including HLA harmonization, and estimate risk of islet autoimmunity and progression to clinical diabetes. RESEARCH DESIGN AND METHODS For prospective cohorts in Finland, Germany, Sweden, and the U.S., 24,662 children at increased genetic risk for development of islet autoantibodies and type 1 diabetes have been followed. Following harmonization, the outcomes were analyzed in 16,709 infants-toddlers enrolled by age 2.5 years. RESULTS In the infant-toddler cohort, 1,413 (8.5%) developed at least one autoantibody confirmed at two or more consecutive visits (seroconversion), 865 (5%) developed multiple autoantibodies, and 655 (4%) progressed to diabetes. The 15-year cumulative incidence of diabetes varied in children with one, two, or three autoantibodies at seroconversion: 45% (95% CI 40–52), 85% (78–90), and 92% (85–97), respectively. Among those with a single autoantibody, status 2 years after seroconversion predicted diabetes risk: 12% (10–25) if reverting to autoantibody negative, 30% (20–40) if retaining a single autoantibody, and 82% (80–95) if developing multiple autoantibodies. HLA-DR-DQ affected the risk of confirmed seroconversion and progression to diabetes in children with stable single-autoantibody status. Their 15-year diabetes incidence for higher- versus lower-risk genotypes was 40% (28–50) vs. 12% (5–38). The rate of progression to diabetes was inversely related to age at development of multiple autoantibodies, ranging from 20% per year to 6% per year in children developing multipositivity in ≤2 years or &amp;gt;7.4 years, respectively. CONCLUSIONS The number of islet autoantibodies at seroconversion reliably predicts 15-year type 1 diabetes risk. In children retaining a single autoantibody, HLA-DR-DQ genotypes can further refine risk of progression.