tbuckley/cabot-search huggingface dataset:
Cardioprotective GLP-1 metabolite prevents ischemic cardiac injury by inhibiting mitochondrial trifunctional protein-α
Authors: M. Ahsan Siraj, Dhanwantee Mundil, Sanja Beca, Abdul Momen, Eric A. Shikatani, Talat Afroze, Xuetao Sun, Ying Liu, Siavash Ghaffari, Warren Lee, Michael B. Wheeler, Gordon Keller, Peter Backx, Mansoor Husain
Journal: Journal of Clinical Investigation (2020)

Mechanisms mediating the cardioprotective actions of glucagon-like peptide 1 (GLP-1) were unknown. Here, we show in both ex vivo and in vivo models of ischemic injury that treatment with GLP-1(28-36), a neutral endopeptidase-generated (NEP-generated) metabolite of GLP-1, was as cardioprotective as GLP-1 and was abolished by scrambling its amino acid sequence. GLP-1(28-36) enters human coronary artery endothelial cells (caECs) through macropinocytosis and acts directly on mouse and human coronary artery smooth muscle cells (caSMCs) and caECs, resulting in soluble adenylyl cyclase Adcy10-dependent (sAC-dependent) increases in cAMP, activation of protein kinase A, and cytoprotection from oxidative injury. GLP-1(28-36) modulates sAC by increasing intracellular ATP levels, with accompanying cAMP accumulation lost in sAC-/- cells. We identify mitochondrial trifunctional protein-α (MTPα) as a binding partner of GLP-1(28-36) and demonstrate that the ability of GLP-1(28-36) to shift substrate utilization from oxygen-consuming fatty acid metabolism toward oxygen-sparing glycolysis and glucose oxidation and to increase cAMP levels is dependent on MTPα. NEP inhibition with sacubitril blunted the ability of GLP-1 to increase cAMP levels in coronary vascular cells in vitro. GLP-1(28-36) is a small peptide that targets novel molecular (MTPα and sAC) and cellular (caSMC and caEC) mechanisms in myocardial ischemic injury.
Reduction in Diabetic Ketoacidosis and Severe Hypoglycemia in Pediatric Type 1 Diabetes During the First Year of Continuous Glucose Monitoring: A Multicenter Analysis of 3,553 Subjects From the DPV Registry
Authors: Martin Tauschmann, Julia M. Hermann, Clemens Freiberg, Matthias Papsch, Angelika Thon, Bettina Heidtmann, Kerstin Placzeck, Dirk Agena, Thomas M. Kapellen, Bernd Schenk, Johannes Wolf, Thomas Danne, Birgit Rami-Merhar, Reinhard W. Holl
Journal: Diabetes Care (2020)

Use of continuous glucose monitoring (CGM) systems has become standard of care in type 1 diabetes (T1D) in many countries, particularly in children and adolescents (1,2). Results from clinical trials indicate that use of CGM leads to improved metabolic control and reduction in nonsevere hypoglycemia compared with self-monitoring of capillary blood glucose (3,4). Benefits are seen irrespective of insulin delivery method (pump or pen) (4,5) but are conditioned on near-daily sensor usage (4).

Trial participants, however, are often biased toward higher education level, greater therapy adherence, and better self-management. Small sample size and short trial duration very often preclude appropriate assessment of CGM impact on rare events such as severe hypoglycemia (SH) or diabetic ketoacidosis (DKA).

We therefore used real-world data from the German-Austrian-Swiss-Luxembourgian Diabetes Prospective Follow-up (DPV) registry to longitudinally assess HbA1c, SH, and DKA during the first year after initiation of CGM, including real-time CGM and intermittently scanned/viewed CGM. Anonymized patient registry records were analyzed. SH was defined as events requiring external assistance by another person and events resulting in coma/convulsion. DKA was defined by pH level <7.3. All HbA1c values were Diabetes Control and Complications Trial (DCCT) standardized.

Selection criteria included T1D,  1 year of diabetes duration, available registry data 6 months prior to CGM start (baseline period), and …
Assessing the impact of different distal ureter management techniques during radical nephroureterectomy for primary upper urinary tract urothelial carcinoma on oncological outcomes: A systematic review and meta-analysis
Authors: Shicong Lai, Runqi Guo, Samuel Seery, Pengjie Wu, Jianyong Liu, Yaoguang Zhang, Shengcai Zhu, Xiaoguang Li, Ming Liu, Jianye Wang
Journal: International Journal of Surgery (2020)
Prion protein glycans reduce intracerebral fibril formation and spongiosis in prion disease
Authors: Alejandro M. Sevillano, Patricia Aguilar-Calvo, Timothy D. Kurt, Jessica A. Lawrence, Katrin Soldau, Thu H. Nam, Taylor Schumann, Donald P. Pizzo, Sofie Nyström, Biswa Choudhury, Hermann Altmeppen, Jeffrey D. Esko, Markus Glatzel, K. Peter R. Nilsson, Christina J. Sigurdson
Journal: Journal of Clinical Investigation (2020)

Posttranslational modifications (PTMs) are common among proteins that aggregate in neurodegenerative disease, yet how PTMs impact the aggregate conformation and disease progression remains unclear. By engineering knockin mice expressing prion protein (PrP) lacking 2 N-linked glycans (Prnp180Q/196Q), we provide evidence that glycans reduce spongiform degeneration and hinder plaque formation in prion disease. Prnp180Q/196Q mice challenged with 2 subfibrillar, non–plaque-forming prion strains instead developed plaques highly enriched in ADAM10-cleaved PrP and heparan sulfate (HS). Intriguingly, a third strain composed of intact, glycophosphatidylinositol-anchored (GPI-anchored) PrP was relatively unchanged, forming diffuse, HS-deficient deposits in both the Prnp180Q/196Q and WT mice, underscoring the pivotal role of the GPI-anchor in driving the aggregate conformation and disease phenotype. Finally, knockin mice expressing triglycosylated PrP (Prnp187N) challenged with a plaque-forming prion strain showed a phenotype reversal, with a striking disease acceleration and switch from plaques to predominantly diffuse, subfibrillar deposits. Our findings suggest that the dominance of subfibrillar aggregates in prion disease is due to the replication of GPI-anchored prions, with fibrillar plaques forming from poorly glycosylated, GPI-anchorless prions that interact with extracellular HS. These studies provide insight into how PTMs impact PrP interactions with polyanionic cofactors, and highlight PTMs as a major force driving the prion disease phenotype.
The Hot Pleura
Authors: Pir Abdul Ahad Aziz Qureshi, Namra Asghar, Humayun Bashir, Imran Khalid Niazi, Noreen Akhtar
Journal: Clinical Nuclear Medicine (2019)

Abstract Renal cell carcinoma (RCC) is the most common solid renal malignancy that metastasizes typically to lungs, bones, liver, adrenals, and lymph nodes. Isolated pleural metastases of RCC are extremely rare, with only few cases reported in the literature. We report one such case of a 60-year-old woman, a known case of RCC of the left kidney who underwent nephrectomy, and on follow-up, PET/CT scan revealed diffuse thick nodular hypermetabolic left pleural thickening, which was later biopsied and turned out to be pleural metastases from RCC. No other site of metastases was found.
Association of <i> <scp>IRF</scp> 4 </i> single‐nucleotide polymorphism rs12203592 with melanoma‐specific survival
Authors: S.V. Ward, D.C. Gibbs, I. Orlow, N.E. Thomas, P.A. Kanetsky, L. Luo, A.E. Cust, H. Anton‐Culver, S.B. Gruber, R.P. Gallagher, S. Rosso, R. Zanetti, T. Dwyer, C.B. Begg, M. Berwick
Journal: British Journal of Dermatology (2020)
Medical Optimization of Torisel® (MOTOR): A Phase II Trial of Temsirolimus as Second-Line Treatment for Advanced RCC by the Italian Kidney Cancer Group (GIR)
Authors: M. Milella, G. Di Lorenzo, A. Felici, M. Aieta, G. Lo Re, C. Boni, E. Aitini, E. Villa, S. De Placido, F. Cognetti
Journal: Annals of Oncology (2012)
Role of Exercise in Mitigating Pediatric Nonalcoholic Fatty Liver Disease
Authors: Jennifer M. Vittorio, Joel E. Lavine
Journal: Diabetes Care (2020)

Nonalcoholic fatty liver disease (NAFLD) represents a clinical spectrum of liver abnormalities resulting from excessive fat accumulation in hepatocytes. These abnormalities extend to simple steatosis and nonalcoholic steatohepatitis (NASH), which includes lobular inflammation and evidence of cell injury. This entity may lead to fibrosis, cirrhosis, and ultimately hepatic synthetic dysfunction. This problem is more common in those who are overweight and obese and who exhibit features of metabolic syndrome including abdominal obesity, insulin resistance, dyslipidemia, and hypertension (1).

Data suggest that children with NAFLD have increased morbidity and mortality in adulthood (2). Early occurrence likely indicates deleterious environmental exposures or genetic predispositions. Given the rising prevalence in children and adults, paralleling concomitant changes in lifestyle over the past three decades, there are emerging imperatives for screening, diagnosis, and intervention.

Primary outcome measures in treating NAFLD vary. A commonly accepted goal of treatment is a decrease in hepatic steatosis and a decrease or resolution of inflammation and cell injury (i.e., NASH) and/or fibrosis, which may elude noninvasive assessment. A sustained decrease in serum alanine aminotransferase (ALT) from baseline is commonly used as a surrogate marker for histologic improvement and response to treatment (3,4). Evaluation of fibrosis requires histologic assessment obtained via liver biopsy. In children, NAFLD comorbidities (insulin resistance, dyslipidemia, and hypertension) are also important to mitigate to improve clinical outcomes.

There are currently no pharmacologics approved by the U.S. Food and Drug Administration for the treatment of NAFLD. Lifestyle modifications, including dietary interventions and a focus on increased physical activity, remain the first-line treatment options for pediatric NAFLD (5,6). There is limited evidence to …
A Synthetic Carrier of Nucleic Acids Structured as a Neutral Phospholipid Envelope Tightly Assembled on Polyplex Surface
Authors: Yonger Xue, Jia Feng, Yilei Liu, Junyi Che, Guang Bai, Xiaotao Dong, Fei Wu, Tuo Jin
Journal: Advanced Healthcare Materials (2020)

Abstract Synthetic carriers of nucleic acids remain inefficient for practical applications due to their insufficient functions as compared with viral vectors developed by evolution. Here, a synthetic carrier is designed to structurally mimic lentivirus, a widely‐used viral vector in therapeutic developments, for its neutral phospholipid membrane tightly anchored on the surface of a packed nucleic acid core. Unlike the reported lipopolyplexes of which the surface membrane around the nucleic acid core is formed from charged lipids, the stable attachment of the neutral lipids to each polyplex core in the present system is achieved through preadsorbed micelles of multicarboxyl amphiphilic molecules as lipid bilayer anchors. The adsorbed micelles are under a tension of deformation due to the electrostatic attraction of the head groups to the cationic surface and their “thermodynamic responsibility” to cover the hydrophobic tails in water. When liposomes of neutral phospholipids approach, the hydrophobic tail groups of the adsorbed micelles may insert into the lipid bilayer matrix to induce them to fuse around polyplex and relieve the thermodynamic tension. The formed neutral phospholipid membrane may encapsulate the polyplex core stably, prevent siRNA from prephagocytic leaking and degrading, and immobilize functional agents with increased capacity.
NoGrazie: an Italian initiative against commercial influence in health
Authors: Adriano Cattaneo
Journal: BMJ (2020)

I write on behalf of NoGrazie (http://www.nograzie.eu/), an Italian movement of health professionals and citizens working against the inappropriate, deceptive, or unethical marketing of health products. We have been active since 2004 and network with similar movements in other countries—for example, MEZIS (https://mezis.de/) and NoGracias (http://www.nogracias.eu/, http://www.nogracias.org/).

We agree with Moynihan and colleagues, …
Modernizing clinical practice guidelines for the American Academy of Dermatology
Authors: Esther E. Freeman, Devon E. McMahon, Matthew Fitzgerald, Sandy Robinson, Lindsy Frazer-Green, Vidhya Hariharan, Allen McMillen, Sameer Malik, Lynn Cornelius, Hon S. Pak, Terrence A. Cronin, Jeremey S. Bordeaux, Kevin D. Cooper
Journal: Journal of the American Academy of Dermatology (2020)
Trump administration moves to lower nutrition standards in schools
Authors: Owen Dyer
Journal: BMJ (2020)

Donald Trump’s administration has announced plans to roll back US school food nutrition standards introduced under the Obama administration, cutting the required levels of fruit and vegetables while allowing more hamburgers, pizza, and fries. The changes affect school programmes that feed breakfast and lunch to about 30 million children in 99 000 schools, of whom 22 million are from low income families.

Current US school food standards were set by the Healthy, Hunger-Free Kids Act of 2010, an initiative driven forward by Michelle Obama. The Trump administration began chipping away at this law within weeks of taking office, pushing back a deadline for reducing sodium content, issuing waivers …
Sepsis-associated acute respiratory distress syndrome in individuals of European ancestry: a genome-wide association study
Authors: Beatriz Guillen-Guio, Jose M Lorenzo-Salazar, Shwu-Fan Ma, Pei-Chi Hou, Tamara Hernandez-Beeftink, Almudena Corrales, M Isabel García-Laorden, Jonathan Jou, Elena Espinosa, Arturo Muriel, David Domínguez, Leonardo Lorente, María M Martín, Carlos Rodríguez-Gallego, Jordi Solé-Violán, Alfonso Ambrós, Demetrio Carriedo, Jesús Blanco, José M Añón, John P Reilly, Tiffanie K Jones, Caroline AG Ittner, Rui Feng, Franziska Schöneweck, Michael Kiehntopf, Imre Noth, Markus Scholz, Frank M Brunkhorst, André Scherag, Nuala J Meyer, Jesús Villar, Carlos Flores
Journal: The Lancet Respiratory Medicine (2020)
Full-thickness gastric plication with Overstitch endoscopic suturing device for postsurgical chronic gastroparesis
Authors: Antonino Granata, Michele Amata, Alberto Martino, Lavinia De Monte, Alessandro Bertani, Dario Ligresti, Mario Traina
Journal: Endoscopy (2020)

A 28-year-old woman with a past history of dysplastic Barrett's esophagus treated with Ivor Lewis esophagectomy presented with recurrent episodes of dysphagia. Upper gastrointestinal (UGI) series showed delayed gastric emptying with pyloric hypertrophy secondary to postsurgical denervation of the vagal nerve trunks. After multiple unsuccessful endoscopic dilations of the pylorus, the patient underwent a Roux-en-Y gastrojejunostomy with antrum and pylorus exclusion, with resolution of symptoms ([Fig. 1 a]).
Vitamin D Supplement During Pregnancy and Enamel Defects in Offspring
Authors: Xiangling Deng, Wenquan Niu
Journal: JAMA Pediatrics (2020)

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 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 Pediatrics journal
Biventricular pacemaker therapy improves exercise capacity in patients with non‐obstructive hypertrophic cardiomyopathy via augmented diastolic filling on exercise
Authors: Ibrar Ahmed, Brodie L. Loudon, Khalid Abozguia, Donnie Cameron, Ganesh N. Shivu, Thanh T. Phan, Abdul Maher, Berthold Stegemann, Anthony Chow, Howard Marshall, Peter Nightingale, Francisco Leyva, Vassilios S. Vassiliou, William J. McKenna, Perry Elliott, Michael P. Frenneaux
Journal: European Journal of Heart Failure (2020)

Aims Treatment options for patients with non‐obstructive hypertrophic cardiomyopathy (HCM) are limited. We sought to determine whether biventricular (BiV) pacing improves exercise capacity in HCM patients, and whether this is via augmented diastolic filling. Methods and results Thirty‐one patients with symptomatic non‐obstructive HCM were enrolled. Following device implantation, patients underwent detailed assessment of exercise diastolic filling using radionuclide ventriculography in BiV and sham pacing modes. Patients then entered an 8‐month crossover study of BiV and sham pacing in random order, to assess the effect on exercise capacity [peak oxygen consumption (VO 2 )]. Patients were grouped on pre‐specified analysis according to whether left ventricular end‐diastolic volume increased (+LVEDV) or was unchanged/decreased (–LVEDV) with exercise at baseline. Twenty‐nine patients (20 male, mean age 55 years) completed the study. There were 14 +LVEDV patients and 15 –LVEDV patients. Baseline peak VO 2 was lower in –LVEDV patients vs. +LVEDV patients (16.2 ± 0.9 vs. 19.9 ± 1.1 mL/kg/min, P = 0.04). BiV pacing significantly increased exercise ΔLVEDV ( P = 0.004) and Δstroke volume ( P = 0.008) in –LVEDV patients, but not in +LVEDV patients. Left ventricular ejection fraction and end‐systolic elastance did not increase with BiV pacing in either group. This translated into significantly greater improvements in exercise capacity (peak VO 2 + 1.4 mL/kg/min, P = 0.03) and quality of life scores ( P = 0.02) in –LVEDV patients during the crossover study. There was no effect on left ventricular mechanical dyssynchrony in either group. Conclusion Symptomatic patients with non‐obstructive HCM may benefit from BiV pacing via augmentation of diastolic filling on exercise rather than contractile improvement. This may be due to relief of diastolic ventricular interaction. Clinical Trial Registration: ClinicalTrials.gov NCT00504647.
The Use and Misuse of Transparency in Research
Authors: Harvey V. Fineberg, David B. Allison
Journal: JAMA (2020)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Vitamin D Supplement During Pregnancy and Enamel Defects in Offspring—Reply
Authors: Pia Elisabeth Nørrisgaard, Klaus Bønnelykke, Hans Bisgaard
Journal: JAMA Pediatrics (2020)

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 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 Pediatrics journal
An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome
Authors: Arnon Adler, Valeria Novelli, Ahmad S. Amin, Emanuela Abiusi, Melanie Care, Eline A. Nannenberg, Harriet Feilotter, Simona Amenta, Daniela Mazza, Hennie Bikker, Amy C. Sturm, John Garcia, Michael J. Ackerman, Raymond E. Hershberger, Marco V. Perez, Wojciech Zareba, James S. Ware, Arthur A.M. Wilde, Michael H. Gollob
Journal: Circulation (2020)

Background: Long QT syndrome (LQTS) is the first described and most common inherited arrhythmia. Over the last 25 years, multiple genes have been reported to cause this condition and are routinely tested in patients. Because of dramatic changes in our understanding of human genetic variation, reappraisal of reported genetic causes for LQTS is required. Methods: Utilizing an evidence-based framework, 3 gene curation teams blinded to each other’s work scored the level of evidence for 17 genes reported to cause LQTS. A Clinical Domain Channelopathy Working Group provided a final classification of these genes for causation of LQTS after assessment of the evidence scored by the independent curation teams. Results: Of 17 genes reported as being causative for LQTS, 9 ( AKAP9, ANK2, CAV3, KCNE1, KCNE2, KCNJ2, KCNJ5, SCN4B, SNTA1 ) were classified as having limited or disputed evidence as LQTS-causative genes. Only 3 genes ( KCNQ1, KCNH2, SCN5A ) were curated as definitive genes for typical LQTS. Another 4 genes ( CALM1, CALM2, CALM3, TRDN ) were found to have strong or definitive evidence for causality in LQTS with atypical features, including neonatal atrioventricular block. The remaining gene ( CACNA1C ) had moderate level evidence for causing LQTS. Conclusions: More than half of the genes reported as causing LQTS have limited or disputed evidence to support their disease causation. Genetic variants in these genes should not be used for clinical decision-making, unless accompanied by new and sufficient genetic evidence. The findings of insufficient evidence to support gene-disease associations may extend to other disciplines of medicine and warrants a contemporary evidence-based evaluation for previously reported disease-causing genes to ensure their appropriate use in precision medicine.