tbuckley/cabot-search huggingface dataset:
Atherosclerosis and Microvascular Complications: Results From the Canadian Study of Longevity in Type 1 Diabetes
Authors: Julie A. Lovshin, Petter Bjornstad, Leif E. Lovblom, Johnny-Wei Bai, Yuliya Lytvyn, Geneviève Boulet, Mohammed A. Farooqi, Sam Santiago, Andrej Orszag, Daniel Scarr, Alanna Weisman, Hillary A. Keenan, Michael H. Brent, Narinder Paul, Vera Bril, Bruce A. Perkins, David Z.I. Cherney
Journal: Diabetes Care (2018)

OBJECTIVE Type 1 diabetes carries a significant risk for cardiovascular mortality, but it is unclear how atherosclerosis associates with microvascular complications. We aimed to determine the relationships between atherosclerotic burden and neuropathy, retinopathy, and diabetic kidney disease (DKD) in adults with a ≥50-year history of type 1 diabetes. RESEARCH DESIGN AND METHODS Adults with type 1 diabetes (n = 69) underwent coronary artery calcification (CAC) volume scoring by wide-volume computerized tomography. Microvascular complications were graded as follows: neuropathy by clinical assessment, electrophysiology, vibration and cooling detection thresholds, heart rate variability, and corneal confocal microscopy; retinopathy by ultra–wide-field retinal imaging; and DKD by renal hemodynamic function measured by inulin and para-aminohippurate clearance at baseline and after intravenous infusion of angiotensin II. The cohort was dichotomized to high (≥300 Agatston units [AU]) or low (&amp;lt;300 AU) CAC and was stratified by diabetes status. A comparator group without diabetes (n = 73) matched for age and sex also underwent all study procedures except for retinal imaging. RESULTS CAC scores were higher in participants with type 1 diabetes (median Agatston score 1,000 [interquartile range = 222, 2,373] AU vs. 1 [0.75] AU in comparators, P &amp;lt; 0.001). In participants with type 1 diabetes, high CAC scores associated with markers of neuropathy and retinopathy, but not with DKD, or renal hemodynamic function at baseline or in response to angiotensin II. CONCLUSIONS The presence of high CAC in adults with longstanding type 1 diabetes was associated with large nerve fiber neuropathy and retinopathy but not with renal hemodynamic function, suggesting that neuropathy, retinopathy, and macrovascular calcification share common risk factors.
Neurodegeneration-associated FUS is a novel regulator of circadian gene expression
Authors: Xin Jiang, Tao Zhang, Haifang Wang, Tao Wang, Meiling Qin, Puhua Bao, Ruiqi Wang, Yuwei Liu, Hung-Chun Chang, Jun Yan, Jin Xu
Journal: Translational Neurodegeneration (2018)

Circadian rhythms are oscillating physiological and behavioral changes governed by an internal molecular clock, and dysfunctions in circadian rhythms have been associated with ageing and various neurodegenerative diseases. However, the evidence directly connecting the neurodegeneration-associated proteins to circadian control at the molecular level remains sparse. Using meta-analysis, synchronized animals and cell lines, cells and tissues from FUS R521C knock-in rats, we examined the role of FUS in circadian gene expression regulation. We found that FUS, an oscillating expressed nuclear protein implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), exerted a novel feedback route to regulate circadian gene expression. Nr1d1-encoded core circadian protein REV-ERBα bound the Fus promoter and regulated the expression of Fus. Meanwhile, FUS was in the same complex as PER/CRY, and repressed the expression of E box-containing core circadian genes, such as Per2, by mediating the promoter occupancy of PSF-HDAC1. Remarkably, a common pathogenic mutant FUS (R521C) showed increased binding to PSF, and caused decreased expression of Per2. Therefore, we have demonstrated FUS as a modulator of circadian gene expression, and provided novel mechanistic insights into the mutual influence between circadian control and neurodegeneration-associated proteins.
Association of Increased Attending Physician Supervision With Patient Safety and Educational Outcomes—Reply
Authors: Kathleen M. Finn, Joshua P. Metlay, Christiana Iyasere
Journal: JAMA Internal Medicine (2018)

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 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 Internal Medicine journal
Altered Cervical Spinal Cord Resting‐State Activity in Fibromyalgia
Authors: Katherine T. Martucci, Kenneth A. Weber, Sean C. Mackey
Journal: Arthritis & Rheumatology (2018)

Objective Altered afferent input and central neural modulation are thought to contribute to fibromyalgia symptoms, and these processes converge within the spinal cord. We undertook this study to investigate the hypothesis that, using resting‐state functional magnetic resonance imaging (rs‐fMRI) of the cervical spinal cord, we would observe altered frequency‐dependent activity in fibromyalgia. Methods Cervical spinal cord rs‐fMRI was conducted in fibromyalgia patients (n = 16) and healthy controls (n = 17). We analyzed the amplitude of low‐frequency fluctuations (ALFF), a measure of low‐frequency oscillatory power, for frequencies of 0.01–0.198 Hz and frequency sub‐bands to determine regional and frequency‐specific alterations in fibromyalgia. Functional connectivity and graph metrics were also analyzed. Results As compared to healthy controls (n = 14), greater ventral and lesser dorsal mean ALFF of the cervical spinal cord was observed in fibromyalgia patients ( n = 15) (uncorrected P &lt; 0.05) for frequencies of 0.01–0.198 Hz and all sub‐bands. Additionally, lesser mean ALFF within the right dorsal quadrant (corrected P &lt; 0.05) for frequencies of 0.01–0.198 Hz and sub‐band frequencies of 0.073–0.198 Hz was observed in fibromyalgia. Regional mean ALFF was not correlated with pain; however, regional lesser mean ALFF was correlated with fatigue in patients (r = 0.763, P = 0.001). Functional connectivity and graph metrics were similar between groups. Conclusion Our results indicate unbalanced activity between the ventral and dorsal cervical spinal cord in fibromyalgia. Increased ventral neural processes and decreased dorsal neural processes may reflect the presence of central sensitization and contribute to fatigue and other bodily symptoms in fibromyalgia.
Genomic analyses of human European diversity at the southwestern edge: isolation, African influence and disease associations in the Canary Islands
Authors: Beatriz Guillen-Guio, Jose M Lorenzo-Salazar, Rafaela González-Montelongo, Ana Díaz-de Usera, Itahisa Marcelino-Rodríguez, Almudena Corrales, Antonio Cabrera de León, Santos Alonso, Carlos Flores
Journal: Molecular Biology and Evolution (2018)

Despite the genetic resemblance of Canary Islanders to other southern European populations, their geographical isolation and the historical admixture of aborigines (from North Africa) with sub-Saharan Africans and Europeans have shaped a distinctive genetic makeup that likely affects disease susceptibility and health disparities. Based on single nucleotide polymorphism array data and whole genome sequencing (30×), we inferred that the last African admixture took place ∼14 generations ago and estimated that up to 34% of the Canary Islander genome is of recent African descent. The length of regions in homozygosis and the ancestry-related mosaic organization of the Canary Islander genome support the view that isolation has been strongest on the two smallest islands. Furthermore, several genomic regions showed significant and large deviations in African or European ancestry and were significantly enriched in genes involved in prevalent diseases in this community, such as diabetes, asthma, and allergy. The most prominent of these regions were located near LCT and the HLA, two well-known targets of selection, at which 40‒50% of the Canarian genome is of recent African descent according to our estimates. Putative selective signals were also identified in these regions near the SLC6A11-SLC6A1, KCNMB2, and PCDH20-PCDH9 genes. Taken together, our findings provide solid evidence of a significant recent African admixture, population isolation, and adaptation in this part of Europe, with the favoring of African alleles in some chromosome regions. These findings may have medical implications for populations of recent African ancestry.
Macrophage migration inhibitory factor mediates metabolic dysfunction induced by atypical antipsychotic therapy
Authors: Donghong Cui, Yanmin Peng, Chengfang Zhang, Zezhi Li, Yousong Su, Yadan Qi, Mengjuan Xing, Jia Li, Grace E. Kim, Kevin N. Su, Jinjie Xu, Meiti Wang, Wenhua Ding, Marta Piecychna, Lin Leng, Michiru Hirasawa, Kaida Jiang, Lawrence Young, Yifeng Xu, Dake Qi, Richard Bucala
Journal: Journal of Clinical Investigation (2018)

Atypical antipsychotics are highly effective antischizophrenic medications but their clinical utility is limited by adverse metabolic sequelae. We investigated whether upregulation of macrophage migration inhibitory factor (MIF) underlies the insulin resistance that develops during treatment with the most commonly prescribed atypical antipsychotic, olanzapine. Olanzapine monotherapy increased BMI and circulating insulin, triglyceride, and MIF concentrations in drug-naive schizophrenic patients with normal MIF expression, but not in genotypic low MIF expressers. Olanzapine administration to mice increased their food intake and hypothalamic MIF expression, which led to activation of the appetite-related AMP-activated protein kinase and Agouti-related protein pathway. Olanzapine also upregulated MIF expression in adipose tissue, which reduced lipolysis and increased lipogenic pathways. Increased plasma lipid concentrations were associated with abnormal fat deposition in liver and skeletal muscle, which are important determinants of insulin resistance. Global MIF-gene deletion protected mice from olanzapine-induced insulin resistance, as did intracerebroventricular injection of neutralizing anti–MIF antibody, supporting the role of increased hypothalamic MIF expression in metabolic dysfunction. These findings uphold the potential pharmacogenomic value of MIF genotype determination and suggest that MIF may be a tractable target for reducing the metabolic side effects of atypical antipsychotic therapy.
Electronic Cigarette Sales in the United States, 2013-2017
Authors: Brian A. King, Doris G. Gammon, Kristy L. Marynak, Todd Rogers
Journal: JAMA (2018)

Karen A. Cullen, PhD; Andrea S. Gentzke, PhD; Michael D. Sawdey, PhD; Joanne T. Chang, PhD; Gabriella M. Anic, PhD; Teresa W. Wang, PhD; MeLisa R. Creamer, PhD; Ahmed Jamal, MBBS; Bridget K. Ambrose, PhD; Brian A. King, PhD
Patient outcomes from time of listing for lung transplantation in the UK: are there disease-specific differences?
Authors: Antonios Kourliouros, Rachel Hogg, Jenny Mehew, Mohamed Al-Aloul, Martin Carby, James Laurence Lordan, Richard Damian Thompson, Steven Tsui, Jasvir Parmar
Journal: Thorax (2018)

The demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high waiting list mortality. We set out to examine factors influencing patient outcomes from the time of listing for lung transplantation in the UK, examining for differences by patient characteristics, lung disease category and transplant centre.Data were obtained from the UK Transplant Registry held by NHS Blood and Transplant for adult lung-only registrations between 1January 2004 and 31 March 2014. Pretransplant and post-transplant outcomes were evaluated against lung disease category, blood group and height.Of the 2213 patient registrations, COPD comprised 28.4%, pulmonary fibrosis (PF) 26.2%, cystic fibrosis (CF) 25.4% and other lung pathologies 20.1%. The chance of transplantation after listing differed by the combined effect of disease category and centre (p<0.001). At 3 years postregistration, 78% of patients with COPD were transplanted followed by 61% of patients with CF, 59% of other lung pathology patients and 48% of patients with PF, who also had the highest waiting list mortality (37%). The chance of transplantation also differed by height with taller patients having a greater chance of transplant (HR: 1.03, 95% CI: 1.02 to 1.04, p<0.001). Patients with blood group O had the highest waiting mortality at 3 years postregistration compared with all other blood groups (27% vs 20%, p<0.001).The way donor lungs were allocated in the UK resulted in discrepancies between the risk profile and probability of lung transplantation. A new donor lung allocation scheme was introduced in 2017 to try to address these shortcomings.
The regenerating family member 3 β instigates IL-17A-mediated neutrophil recruitment downstream of NOD1/2 signalling for controlling colonisation resistance independently of microbiota community structure
Authors: Nadine Waldschmitt, Sho Kitamoto, Thomas Secher, Vassiliki Zacharioudaki, Olivier Boulard, Emilie Floquet, Myriam Delacre, Bruno Lamas, Hang-Phuong Pham, Adrien Six, Mathias L. Richard, Jean-Charles Dagorn, Gérard Eberl, Philippe Langella, Jean-Marc Chatel, Bernhard Ryffel, Juan Lucio Iovanna, Lionel F Poulin, Harry Sokol, Nobuhiko Kamada, Mathias Chamaillard
Journal: Gut (2018)

Objective Loss of the Crohn’s disease predisposing NOD2 gene results in an intestinal microenvironment conducive for colonisation by attaching-and-effacing enteropathogens. However, it remains elusive whether it relies on the intracellular recruitment of the serine-threonine kinase RIPK2 by NOD2, a step that is required for its activation of the transcription factor NF-κB. Design Colonisation resistance was evaluated in wild type and mutant mice, as well as in ex-germ-free (ex-GF) mice which were colonised either with faeces from Ripk2 -deficient mice or with bacteria with similar preferences for carbohydrates to those acquired by the pathogen. The severity of the mucosal pathology was quantified at several time points postinfection by using a previously established scoring. The community resilience in response to infection was evaluated by 16S ribosomal RNA gene sequence analysis. The control of pathogen virulence was evaluated by monitoring the secretion of Citrobacter -specific antibody response in the faeces. Results Primary infection was similarly outcompeted in ex-GF Ripk2 -deficient and control mice, demonstrating that the susceptibility to infection resulting from RIPK2 deficiency cannot be solely attributed to specific microbiota community structures. In contrast, delayed clearance of Citrobacter rodentium and exacerbated histopathology were preceded by a weakened propensity of intestinal macrophages to afford innate lymphoid cell activation. This tissue protection unexpectedly required the regenerating family member 3β by instigating interleukin (IL) 17A-mediated neutrophil recruitment to the intestine and subsequent phosphorylation of signal transducer and activator of transcription 3. Conclusions These results unveil a previously unrecognised mechanism that efficiently protects from colonisation by diarrhoeagenic bacteria early in infection.
Abstract 20733: Cytochrome B5 Reductase 3 Is Essential for Cardiomyocyte Function
Authors: Nolan T Carew, Helene M Altmann, Joseph C Galley, Scott Hahn, Megan P Miller, Sruti Shiva, Dennis McNamara, Adam C Straub
Journal: Circulation (2017)

Cardiomyocyte redox dysregulation contributes to oxidative and metabolic stress during heart failure. We previously showed in endothelial and vascular smooth muscle cells, cytochrome b5 reductase 3...
Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus
Authors: Max Renner, Aleksandra Flanagan, Wanwisa Dejnirattisai, Chunya Puttikhunt, Watchara Kasinrerk, Piyada Supasa, Wiyada Wongwiwat, Kriangkrai Chawansuntati, Thaneeya Duangchinda, Alison Cowper, Claire M. Midgley, Prida Malasit, Juha T. Huiskonen, Juthathip Mongkolsapaya, Gavin R. Screaton, Jonathan M. Grimes
Journal: Nature Immunology (2018)
Abstract 12742: Positive Cardiac Positron Emission Tomography Correlates with the Appearance of Advanced Heart Block in Patients with Cardiac Sarcoidosis
Authors: Mohamed A Abdel-Shafee, Koji Fukuda, Yuji Wakayama, Makoto Nakano, Masateru Kondo, Yuhi Hasebe, Akiko Kawana, Hiroaki Shimokawa
Journal: Circulation (2012)

Background: Although the long-term prognosis of patients with sarcoidosis is generally well, that of patients with cardiac sarcoidosis (CS) is poor as it causes fatal arrhythmias including advanced heart block (AHB) and heart failure. In this study, we thus aimed to identify the predictors of occurrence of AHB in patients. Methods: We examined 61 consecutive patients with CS who were admitted to our Hospital from April 2002 until March 2012. The diagnosis of CS was made based on the guidelines by the Japanese Ministry of Health and Welfare. We analyzed various demographic, clinical, and imaging data and examined their association with AHB as a primary presentation of CS. Results: The CS patients were characterized by middle-age (57±12 years), more females (70%) and normal heart structure in half of them and septal thinning and a dilated cardiomyopathy-like phenotype in the remaining half. AHB was the most commonly encountered electrical abnormality (39%). Of the parameters studied, no significant associat...
Abstract 19508: Thirty-Day Hospital Spending and Acute Myocardial Infarction Outcomes Among Medicare Beneficiaries
Authors: Rishi K Wadhera, Karen E Joynt, Yun Wang, Changyu Shen, Deepak L Bhatt, Robert W Yeh
Journal: Circulation (2017)

Introduction: There is increasing policy focus on reducing costs of care for acute myocardial infarction (AMI). However, the degree to which hospital-level variation in 30-day spending during and i...
Rheumatic Syndromes Associated With Immune Checkpoint Inhibitors: A Single‐Center Cohort of Sixty‐One Patients
Authors: Michael D. Richter, Cynthia Crowson, Lisa A. Kottschade, Heidi D. Finnes, Svetomir N. Markovic, Uma Thanarajasingam
Journal: Arthritis & Rheumatology (2018)

Objective To describe the prevalence, clinical presentation, and management of rheumatic immune‐related adverse effects (Rh‐ir AE s) from immune checkpoint inhibitor ( ICI ) therapy. Methods From a database of all patients who received any ICI at the Mayo Clinic Rochester, Minnesota campus between January 1, 2011 and March 1, 2018, we retrospectively identified those with Rh‐ir AE s, using diagnostic codes, search terms, and manual chart review. Results Of the 1,293 patients who received any ICI , Rh‐ir AE s were clinically diagnosed in 43. Eighteen patients with Rh‐ir AE s who received ICI therapy elsewhere were also analyzed. Clinical syndromes included inflammatory arthritis (n = 34 [prevalence 2%]), myopathy (n = 10), and other rheumatic syndromes (n = 17). Inflammatory arthritis was most commonly polyarticular, and glucocorticoid treatment was required in 26 patients (76%). The mean ± SD duration of treatment was 18 ± 18 weeks. Five patients (15%) also received disease‐modifying antirheumatic drugs, and ICI therapy had to be discontinued in 3 patients (9%). Myopathy was treated with glucocorticoids in all cases (mean ± SD treatment duration 15 ± 17 weeks) and led to 2 deaths and permanent ICI discontinuation in 9 patients (90%). Other syndromes included connective tissue diseases, vasculitis, polymyalgia rheumatica–like syndrome, and flare of preexisting rheumatic disease. Most (71%) were treated with immunosuppression, with 12% requiring ICI discontinuation. Conclusion This study represents the largest cohort of patients with Rh‐ir AE s reported to date. Most patients received long courses of immunosuppressive treatment, although discontinuation of ICI therapy was required in only a minority.
A Population-Based Analysis of the Relationship Between Substance Use and Adolescent Cognitive Development
Authors: Jean-François G. Morin, Mohammad H. Afzali, Josiane Bourque, Sherry H. Stewart, Jean R. Séguin, Maeve O’Leary-Barrett, Patricia J. Conrod
Journal: American Journal of Psychiatry (2018)

Alcohol and cannabis misuse are related to impaired cognition. When inferring causality, four nonexclusive theoretical models can account for this association: 1) a common underlying vulnerability model; 2) a neuroplasticity model in which impairment is concurrent with changes in substance use but temporary because of neuroplastic brain processes that restore function; 3) a neurotoxicity model of long-term impairment consequential to substance use; and 4) a developmental sensitivity hypothesis of age-specific effects. Using a developmentally sensitive design, the authors investigated relationships between year-to-year changes in substance use and cognitive development.A population-based sample of 3,826 seventh-grade students from 31 schools consisting of 5% of all students entering high school in 2012 and 2013 in the Greater Montreal region were assessed annually for 4 years on alcohol and cannabis use, recall memory, perceptual reasoning, inhibition, and working memory, using school-based computerized assessments. Multilevel regression models, performed separately for each substance, were used to simultaneously test vulnerability (between-subject) and concurrent and lagged within-subject effects on each cognitive domain.Common vulnerability effects were detected for cannabis and alcohol on all domains. Cannabis use, but not alcohol consumption, showed lagged (neurotoxic) effects on inhibitory control and working memory and concurrent effects on delayed memory recall and perceptual reasoning (with some evidence of developmental sensitivity). Cannabis effects were independent of any alcohol effects.Beyond the role of cognition in vulnerability to substance use, the concurrent and lasting effects of adolescent cannabis use can be observed on important cognitive functions and appear to be more pronounced than those observed for alcohol.