tbuckley/cabot-search huggingface dataset:
Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches
Authors: Lanfranco Pellesi, Mohammad Al-Mahdi Al-Karagholi, Roberto De Icco, Hande Coskun, Fatima Azzahra Elbahi, Cristina Lopez-Lopez, Josefin Snellman, Jens Hannibal, Faisal Mohammad Amin, Messoud Ashina
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) are structurally and functionally related, yet different in their migraine-inducing properties. It remains unclear whether the lack of migraine induction can be attributed to the only transient vasodilatory response after a 20-minute infusion of VIP. <h3>Objective</h3> To determine whether a 2-hour infusion of VIP would provoke migraine attacks. <h3>Design, Setting, and Participants</h3> A randomized, double-blind, placebo-controlled, crossover study was conducted between May and September 2020 at the Danish Headache Center in Copenhagen, Denmark. Patients were eligible for inclusion if they were ages 18 to 40 years, weighed between 50 and 90 kg, had a diagnosis of migraine without aura as defined by the International Classification of Headache Disorders, and had a migraine frequency of 1 to 6 attacks per month. <h3>Interventions</h3> Patients were randomly allocated to receive a 2-hour infusion of VIP or placebo on 2 different days. <h3>Main Outcomes and Measures</h3> The primary end point was the difference in incidence of experimentally induced migraine attacks during the observational period (0-12 hours) between VIP and placebo. <h3>Results</h3> Twenty-one patients (17 [81%] women and 4 [19%] men; mean [range] age, 25.9 [19-40] years) were recruited in the study. Fifteen patients (71%; 95% CI, 48%-89%) developed migraine attacks after VIP compared with 1 patient (5%; 95% CI, 0%-24%) who developed a migraine attack after placebo (<i>P</i> &lt; .001). The VIP-induced migraine attacks mimicked patients' spontaneous attacks. The area under the curve (AUC) of headache intensity scores (0-12 hours), as well as the AUC of the superficial temporal artery diameter (0-180 minute) were significantly greater after VIP compared with placebo (AUC<sub>0-12h</sub>,<i>P</i> = .003; AUC<sub>0-180min</sub>,<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> A 2-hour infusion of VIP caused migraine attacks, suggesting an important role of VIP in migraine pathophysiology. VIP and its receptors could be potential targets for novel migraine drugs. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT04260035
Characterizing the risk interplay between alcohol intake and body mass index on cirrhosis morbidity
Authors: Hamish Innes, Colin J. Crooks, Esther Aspinall, Tim R. Card, Victoria Hamill, John Dillon, Neil I. Guha, Peter C. Hayes, Sharon Hutchinson, Joe West, Joanne R. Morling
Journal: Hepatology (2021)

Abstract Background and Aims It is thought that alcohol intake and body mass index (BMI) interact supra‐additively to modulate the risk of cirrhosis, but evidence for this phenomenon is limited. We investigated the interrelationship between alcohol and BMI on the incidence of cirrhosis morbidity for participants of the United Kingdom Biobank (UKB) study. Approach and Results The primary outcome was the cumulative incidence of cirrhosis morbidity, defined as a first‐time hospital admission for cirrhosis (with noncirrhosis mortality incorporated as a competing risk). All UKB participants without a previous hospital admission for cirrhosis were included in the analysis. We determined the ratio of the 10‐year cumulative incidence in harmful drinkers versus safe drinkers according to BMI. We also calculated the excess cumulative incidence at 10 years for individuals with obesity and/or harmful alcohol compared to safe drinkers with a healthy BMI of 20–25.0 kg/m 2 . A total of 489,285 UK Biobank participants were included, with mean of 10.7 person‐years’ follow‐up. A total of 2070 participants developed the primary outcome, equating to a crude cumulative incidence of 0.36% at 10 years (95% CI:0.34–0.38). The 10‐year cumulative incidence was 8.6 times higher for harmful (1.38%) versus safe drinkers (0.16%) if BMI was healthy. Conversely, it was only 3.6 times higher for obese participants (1.99% vs. 0.56%). Excess cumulative incidence was 1.22% (95% CI:0.89–1.55) for harmful drinkers with a healthy BMI, 0.40% (95% CI:0.34–0.46) for obese individuals drinking at safe levels, and 1.83% (95% CI:1.46–2.20) for obese harmful drinkers (all compared to safe drinkers with a healthy BMI). Conclusions Alcohol intake and obesity are independent risk factors for cirrhosis morbidity, but they do not interact supra‐additively to modulate the cumulative incidence of this outcome.
Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine–Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis
Authors: John G. Rizk, Aashish Gupta, Partha Sardar, Brandon Michael Henry, John C. Lewin, Giuseppe Lippi, Carl J. Lavie
Journal: JAMA Cardiology (2021)

<h3>Importance</h3> The COVID-19 pandemic saw one of the fastest developments of vaccines in an effort to combat an out-of-control pandemic. The 2 most common COVID-19 vaccine platforms currently in use, messenger RNA (mRNA) and adenovirus vector, were developed on the basis of previous research in use of this technology. Postauthorization surveillance of COVID-19 vaccines has identified safety signals, including unusual cases of thrombocytopenia with thrombosis reported in recipients of adenoviral vector vaccines. One of the devastating manifestations of this syndrome, termed<i>vaccine-induced immune thrombotic thrombocytopenia</i>(VITT), is cerebral venous sinus thrombosis (CVST). This review summarizes the current evidence and indications regarding biology, clinical characteristics, and pharmacological management of VITT with CVST. <h3>Observations</h3> VITT appears to be similar to heparin-induced thrombocytopenia (HIT), with both disorders associated with thrombocytopenia, thrombosis, and presence of autoantibodies to platelet factor 4 (PF4). Unlike VITT, HIT is triggered by recent exposure to heparin. Owing to similarities between these 2 conditions and lack of high-quality evidence, interim recommendations suggest avoiding heparin and heparin analogues in patients with VITT. Based on initial reports, female sex and age younger than 60 years were identified as possible risk factors for VITT. Treatment consists of therapeutic anticoagulation with nonheparin anticoagulants and prevention of formation of autoantibody-PF4 complexes, the latter being achieved by administration of high-dose intravenous immunoglobin (IVIG). Steroids, which can theoretically inhibit the production of new antibodies, have been used in combination with IVIG. In severe cases, plasma exchange should be used for clearing autoantibodies. Monoclonal antibodies, such as rituximab and eculizumab, can be considered when other therapies fail. Routine platelet transfusions, aspirin, and warfarin should be avoided because of the possibility of worsening thrombosis and magnifying bleeding risk. <h3>Conclusions and Relevance</h3> Adverse events like VITT, while uncommon, have been described despite vaccination remaining the most essential component in the fight against the COVID-19 pandemic. While it seems logical to consider the use of types of vaccines (eg, mRNA-based administration) in individuals at high risk, treatment should consist of therapeutic anticoagulation mostly with nonheparin products and IVIG.
Identification and Predictors for Cardiovascular Disease Risk Equivalents Among Adults With Diabetes
Authors: Yanglu Zhao, Shaista Malik, Matthew J. Budoff, Adolfo Correa, Kellan E. Ashley, Elizabeth Selvin, Karol E. Watson, Nathan D. Wong
Journal: Diabetes Care (2021)

OBJECTIVE We examined diabetes as a cardiovascular disease (CVD) risk equivalent based on diabetes severity and other CVD risk factors. RESEARCH DESIGN AND METHODS We pooled four U.S. cohorts (Atherosclerosis Risk in Communities [ARIC], Jackson Heart Study [JHS], Multi-Ethnic Study of Atherosclerosis [MESA], and Framingham Heart Study Offspring Cohort [FHS-Offspring]) and classified subjects into groups by baseline diabetes/CVD status (positive or negative). CVD risks of the diabetes mellitus (DM)+/CVD− group versus DM−/CVD+ group were examined by diabetes severity and in subgroups of other CVD risk factors. We developed an algorithm to identify subjects with CVD risk equivalent diabetes by comparing the relative CVD risk of being DM+/CVD− versus DM−/CVD+. RESULTS The pooled cohort included 27,730 subjects (mean age 58.5 years, 44.6% male). CVD rates per 1,000 person-years were 16.5, 33.4, 43.2, and 71.4 among those DM−/CVD−, DM+/CVD−, DM−/CVD+, and DM+/CVD+, respectively. Compared with those DM−/CVD+, CVD risks were similar or higher for those with HbA1c ≥ 7%, diabetes duration ≥10 years, or diabetes medication use, while those with less severe diabetes had lower risks. Hazard ratios (95% CI) for DM+/CVD− vs. DM−/CVD+ were 0.96 (95% CI 0.86–1.07), 0.97 (0.88–1.07), 0.96 (0.82–1.13), 1.18 (0.98–1.41), 0.93 (0.85–1.02), and 1.00 (0.89–1.13) among women and those of White race, age &amp;lt;55 years, and with triglycerides ≥2.26 mmol/L, hs-CRP ≥2 mg/L, and estimated glomerular filtration rate &amp;lt;60 mL/min/1.73 m2, respectively. In the DM+/CVD− group, 19.1% had CVD risk equivalent diabetes with a lower risk score but a higher observed CVD risk. CONCLUSIONS Diabetes is a CVD risk equivalent in one-fifth of CVD-free adults living with diabetes. High HbA1c, long diabetes duration, and diabetes medication use were predictors of CVD risk equivalence. Diabetes is a CVD risk equivalent for women, white people, and those of younger age or with higher triglycerides or hs-CRP or reduced kidney function.
A Sea Glass Mind
Authors: Lynn Gao Cox
Journal: JAMA (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 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
Role of Eosinophils in Angiolymphoid Hyperplasia With Eosinophilia
Authors: Marlena Grünewald, Dora Stölzl, Ulrike Wehkamp, Michael Weichenthal, Merit Kaeding, Thomas Schwarz, Guido Heine
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
SARS-CoV-2 Infection Among Maternal-Infant Dyads in Ontario, Canada
Authors: Tiffany Fitzpatrick, Andrew S. Wilton, Hannah Chung, Astrid Guttmann
Journal: JAMA Network Open (2021)

This cohort study uses population-based health data to assess SARS-CoV-2 testing outcomes among infants born in Ontario, Canada, during 9 months of the 2020 COVID-19 pandemic to mothers with confirmed infection at delivery.
Targeting leukemia-specific dependence on the de novo purine synthesis pathway
Authors: Takuji Yamauchi, Kohta Miyawaki, Yuichiro Semba, Masatomo Takahashi, Yoshihiro Izumi, Jumpei Nogami, Fumihiko Nakao, Takeshi Sugio, Kensuke Sasaki, Luca Pinello, Daniel E. Bauer, Takeshi Bamba, Koichi Akashi, Takahiro Maeda
Journal: Leukemia (2021)
Learning From Technical Details With Effect on Postoperative Pancreatic Fistula
Authors: Javier A. Cienfuegos, Victor Valenti, Fernando Rotellar
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
P-286 Assessment of the quality of life of patients with colorectal cancer in the Tunisian Center: A report of 142 patients
Authors: C. Ben Moussa, I. Belaid, M. Limam, R. Melliti, M. Ben Mabrouk, A. Bouazzi, M. El Ghali, M. Barka, I. Chabchoub, F. Ezzairi, N. Ammar, M. Hochlef, L. Ben Fatma, S. Ben Ahmed
Journal: Annals of Oncology (2021)
Evaluation of an intervention targeted with predictive analytics to prevent readmissions in an integrated health system: observational study
Authors: Ben J Marafino, Gabriel J Escobar, Michael T Baiocchi, Vincent X Liu, Colleen C Plimier, Alejandro Schuler
Journal: BMJ (2021)

To determine the associations between a care coordination intervention (the Transitions Program) targeted to patients after hospital discharge and 30 day readmission and mortality in a large, integrated healthcare system.Observational study.21 hospitals operated by Kaiser Permanente Northern California.1 539 285 eligible index hospital admissions corresponding to 739 040 unique patients from June 2010 to December 2018. 411 507 patients were discharged post-implementation of the Transitions Program; 80 424 (19.5%) of these patients were at medium or high predicted risk and were assigned to receive the intervention after discharge.Patients admitted to hospital were automatically assigned to be followed by the Transitions Program in the 30 days post-discharge if their predicted risk of 30 day readmission or mortality was greater than 25% on the basis of electronic health record data.Non-elective hospital readmissions and all cause mortality in the 30 days after hospital discharge.Difference-in-differences estimates indicated that the intervention was associated with significantly reduced odds of 30 day non-elective readmission (adjusted odds ratio 0.91, 95% confidence interval 0.89 to 0.93; absolute risk reduction 95% confidence interval -2.5%, -3.1% to -2.0%) but not with the odds of 30 day post-discharge mortality (1.00, 0.95 to 1.04). Based on the regression discontinuity estimate, the association with readmission was of similar magnitude (absolute risk reduction -2.7%, -3.2% to -2.2%) among patients at medium risk near the risk threshold used for enrollment. However, the regression discontinuity estimate of the association with post-discharge mortality (-0.7% -1.4% to -0.0%) was significant and suggested benefit in this subgroup of patients.In an integrated health system, the implementation of a comprehensive readmissions prevention intervention was associated with a reduction in 30 day readmission rates. Moreover, there was no association with 30 day post-discharge mortality, except among medium risk patients, where some evidence for benefit was found. Altogether, the study provides evidence to suggest the effectiveness of readmission prevention interventions in community settings, but further research might be required to confirm the findings beyond this setting.
Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial
Authors: Lucas Wauters, Helena Slaets, Kim De Paepe, Matthias Ceulemans, Suzan Wetzels, Karlien Geboers, Joran Toth, Wannes Thys, Raf Dybajlo, Daan Walgraeve, Erik Biessen, Kristin Verbeke, Jan Tack, Tom Van de Wiele, Niels Hellings, Tim Vanuytsel
Journal: The Lancet. Gastroenterology & hepatology (2021)
<i>Notes from the Field:</i> Recurrence of a Multistate Outbreak of <i>Salmonella</i> Typhimurium Infections Linked to Contact with Hedgehogs — United States and Canada, 2020
Authors: Michelle A. Waltenburg, Megin Nichols, HaeNa Waechter, Jeffrey Higa, Laura Cronquist, Anne-Marie Lowe, Jennifer K. Adams, Kenai McFadden, Jennifer A. McConnell, Rebecca Blank, Colin Basler
Journal: MMWR Morbidity and Mortality Weekly Report (2021)
Multistage Cooperative Nanodrug Combined with PD‐L1 for Enhancing Antitumor Chemoimmunotherapy
Authors: Haihui Wang, Yongfei Liu, Xiaohui Zhu, Chengyun Chen, Zhangcheng Fu, Min Wang, Danying Lin, Zhaowei Chen, Chunhua Lu, Huanghao Yang
Journal: Advanced Healthcare Materials (2021)

Abstract Combinatorial CpG oligonucleotide (CPG) and chemotherapy drug represent a promising approach to reactivate immune system. However, these two agents possess different physicochemical properties, hindering the application of direct self‐assembly of these two cargos into a single nanostructure. Here, a multistage cooperative nanodrug is developed by the direct self‐assembly of cis‐platinum (CDDP, Pt), l ‐arginine ( l ‐Arg, R), and CPG (defined as PtR/CPG) for antitumor chemoimmunotherapy. First, the CDDP can induce cell apoptosis. Meanwhile, CDDP also promotes the production of H 2 O 2 , catalyzing the conversion of l ‐Arg into nitric oxide (NO). The generated NO decreases the multidrug resistance of cells toward CDDP. Thus, the synergistic effects of CDDP and NO can trigger immunogenic cell death to produce tumor‐associated antigens (TAAs). The TAAs and CPG will induce the maturation of dendritic cells (DCs) and enhance antigen presentation ability of DCs. In this way, the PtR/CPG can reverse the immunosuppressive microenvironment, sensitizing tumors to immune checkpoint inhibitors mediated by the programmed death‐ligand 1 (PD‐L1) antibody. Furthermore, the PtR/CPG combined with the PD‐L1 antibody decreases the exhaustion and dysfunction of cytotoxic T lymphocytes to elicit durable systemic immune response. As a result, the prepared PtR/CPG nanodrug in combination with PD‐L1 may be highly significant for cancer immunotherapy.
SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Authors: Lydia M. Castelli, Luisa Cutillo, Cleide Dos Santos Souza, Alvaro Sanchez-Martinez, Ilaria Granata, Ya-Hui Lin, Monika A. Myszczynska, Paul R. Heath, Matthew R. Livesey, Ke Ning, Mimoun Azzouz, Pamela J. Shaw, Mario R. Guarracino, Alexander J. Whitworth, Laura Ferraiuolo, Marta Milo, Guillaume M. Hautbergue
Journal: Molecular Neurodegeneration (2021)

Loss of motor neurons in amyotrophic lateral sclerosis (ALS) leads to progressive paralysis and death. Dysregulation of thousands of RNA molecules with roles in multiple cellular pathways hinders the identification of ALS-causing alterations over downstream changes secondary to the neurodegenerative process. How many and which of these pathological gene expression changes require therapeutic normalisation remains a fundamental question.Here, we investigated genome-wide RNA changes in C9ORF72-ALS patient-derived neurons and Drosophila, as well as upon neuroprotection taking advantage of our gene therapy approach which specifically inhibits the SRSF1-dependent nuclear export of pathological C9ORF72-repeat transcripts. This is a critical study to evaluate (i) the overall safety and efficacy of the partial depletion of SRSF1, a member of a protein family involved itself in gene expression, and (ii) a unique opportunity to identify neuroprotective RNA changes.Our study shows that manipulation of 362 transcripts out of 2257 pathological changes, in addition to inhibiting the nuclear export of repeat transcripts, is sufficient to confer neuroprotection in C9ORF72-ALS patient-derived neurons. In particular, expression of 90 disease-altered transcripts is fully reverted upon neuroprotection leading to the characterisation of a human C9ORF72-ALS disease-modifying gene expression signature. These findings were further investigated in vivo in diseased and neuroprotected Drosophila transcriptomes, highlighting a list of 21 neuroprotective changes conserved with 16 human orthologues in patient-derived neurons. We also functionally validated the high neuroprotective potential of one of these disease-modifying transcripts, demonstrating that inhibition of ALS-upregulated human KCNN1-3 (Drosophila SK) voltage-gated potassium channel orthologs mitigates degeneration of human motor neurons and Drosophila motor deficits.Strikingly, the partial depletion of SRSF1 leads to expression changes in only a small proportion of disease-altered transcripts, indicating that not all RNA alterations need normalization and that the gene therapeutic approach is safe in the above preclinical models as it does not disrupt globally gene expression. The efficacy of this intervention is also validated at genome-wide level with transcripts modulated in the vast majority of biological processes affected in C9ORF72-ALS. Finally, the identification of a characteristic signature with key RNA changes modified in both the disease state and upon neuroprotection also provides potential new therapeutic targets and biomarkers.