tbuckley/cabot-search huggingface dataset:
Occupational rhinitis
Authors: G. Moscato, O. Vandenplas, R. Gerth Van Wijk, J. L. Malo, S. Quirce, J. Walusiak, R. Castano, H. De Groot, I. Folletti, D. Gautrin, M. R. Yacoub, L. Perfetti, A. Siracusa
Journal: Allergy (2008)

The present document is the result of a consensus reached by a panel of experts from European and nonEuropean countries on Occupational Rhinitis (OR), a disease of emerging relevance, which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio‐economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored to that of occupational asthma, as well as a diagnostic algorithm based on steps allowing different levels of diagnostic evidence, are proposed. The needs for future research are pointed out. Key messages are issued for each item.
Lectures on Appendicitis and Notes on Other Subjects.
Journal: JAMA (1899)

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
Genomic Autopsy of Sudden Deaths in Young Individuals
Authors: Gregory Webster, Megan J. Puckelwartz, Lorenzo L. Pesce, Lisa M. Dellefave-Castillo, Carlos G. Vanoye, Franck Potet, Patrick Page, Samuel D. Kearns, Tess Pottinger, Steven White, Ponni Arunkumar, Rachael Olson, Amber Kofman, Nora Ibrahim, Alexander Ing, Casey Brew, Kai Lee Yap, Sabah Kadri, Alfred L. George, Elizabeth M. McNally
Journal: JAMA Cardiology (2021)

Postmortem genetic testing of young individuals with sudden death has previously identified pathogenic gene variants. However, prior studies primarily considered highly penetrant monogenic variants, often without detailed decedent and family clinical information.To assess genotype and phenotype risk in a diverse cohort of young decedents with sudden death and their families.Pathological and whole-genome sequence analysis was conducted in a cohort referred from a national network of medical examiners. Cases were accrued prospectively from May 2015 to March 2019 across 24 US states. Analysis began September 2016 and ended November 2020.Evaluation of autopsy and clinical data integrated with whole-genome sequence data and family member evaluation.A total of 103 decedents (mean [SD] age at death, 23.7 [11.9] years; age range, 1-44 years), their surviving family members, and 140 sex- and genetic ancestry-matched controls were analyzed. Among 103 decedents, autopsy and clinical data review categorized 36 decedents with postmortem diagnoses, 23 decedents with findings of uncertain significance, and 44 with sudden unexplained death. Pathogenic/likely pathogenic (P/LP) genetic variants in arrhythmia or cardiomyopathy genes were identified in 13 decedents (12.6%). A multivariable analysis including decedent phenotype, ancestry, and sex demonstrated that younger decedents had a higher burden of P/LP variants and select variants of uncertain significance (effect size, -1.64; P = .001). These select, curated variants of uncertain significance in cardiac genes were more common in decedents than controls (83 of 103 decedents [86%] vs 100 of 140 controls [71%]; P = .005), and decedents harbored more rare cardiac variants than controls (2.3 variants per individual vs 1.8 in controls; P = .006). Genetic testing of 31 parent-decedent trios and 14 parent-decedent dyads revealed 8 transmitted P/LP variants and 1 de novo P/LP variant. Incomplete penetrance was present in 6 of 8 parents who transmitted a P/LP variant.Whole-genome sequencing effectively identified P/LP variants in cases of sudden death in young individuals, implicating both arrhythmia and cardiomyopathy genes. Genomic analyses and familial phenotype association suggest potentially additive, oligogenic risk mechanisms for sudden death in this cohort.
Purnell W Choppin: led the Howard Hughes Medical Institute from hope to prominence
Authors: Bob Roehr
Journal: BMJ (2021)

Photo credit: Paul Fetters

Howard Hughes was one of the most flamboyant billionaires of the mid-20th century. Think Elon Musk or Richard Branson, then add another healthy dollop of ego and media showmanship. As a young man, Hughes built and flew record breaking fast aeroplanes, created a company to build them, and gained control of Trans World Airlines, one of the few globe spanning carriers. As a sideline he ran a Hollywood motion picture studio and squired a bevy of starlets with names such as Joan Crawford, Bette Davis, and Ava Gardner. He made a lot of money too.

He had a lifelong interest in medicine and established the namesake institute in 1953. Initially it was little more than a tax dodge. Hughes would donate stock to the institute and write off the charitable contribution against tax. But he maintained voting control of the stock and of his company. Congress investigated, changed the law, and slowly the institute began to spend more money supporting research. …
Abstract 12673: Fitbit-derived Physical Activity in Atrial Fibrillation Patients
Authors: Sarah Semaan, Geoffrey H Tison, Gregory Nah, Eric Vittinghoff, Mark J Pletcher, Jeffrey Olgin, Gregory M Marcus
Journal: Circulation (2019)

Introduction: Regular physical activity is critical to reduce morbidity and mortality. The impact of atrial fibrillation (AF) on regular exercise has relied on self-report and has not been well-cha...
Bone morphogenetic proteins (BMPs) in the central regulation of energy balance and adult neural plasticity
Authors: Gabriel S. Jensen, Noelle E. Leon-Palmer, Kristy L. Townsend
Journal: Metabolism (2021)

The current worldwide obesity pandemic highlights a need to better understand the regulation of energy balance and metabolism, including the role of the nervous system in controlling energy intake and energy expenditure. Neural plasticity in the hypothalamus of the adult brain has been implicated in full-body metabolic health, however, the mechanisms surrounding hypothalamic plasticity are incompletely understood. Bone morphogenetic proteins (BMPs) control metabolic health through actions in the brain as well as in peripheral tissues such as adipose, together regulating both energy intake and energy expenditure. BMP ligands, receptors, and inhibitors are found throughout plastic adult brain regions and have been demonstrated to modulate neurogenesis and gliogenesis, as well as synaptic and dendritic plasticity. This role for BMPs in adult neural plasticity is distinct from their roles in brain development. Existing evidence suggests that BMPs induce weight loss through hypothalamic pathways, and part of the mechanism of action may be through inducing neural plasticity. In this review, we summarize the data regarding how BMPs affect neural plasticity in the adult mammalian brain, as well as the relationship between central BMP signaling and metabolic health.
Worsening Cardiomyopathy Despite Biventricular Pacing
Authors: Gustavo S. Guandalini, Matthew C. Hyman
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 Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 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
Phase II Open-Label, Single-Arm Trial to Investigate the Efficacy and Safety of Topical Remetinostat Gel in Patients with Basal Cell Carcinoma
Authors: James M. Kilgour, Aatman Shah, Nicole M. Urman, Shaundra Eichstadt, Hanh N. Do, Irene Bailey, Amar Mirza, Shufeng Li, Anthony E. Oro, Sumaira Z. Aasi, Kavita Y. Sarin
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The mainstay of treatment for basal cell carcinoma (BCC) is surgical excision, which can result in significant associated morbidity, particularly for patients with recurrent tumors. We previously conducted a drug repositioning screen using molecular data from human BCCs and identified histone deacetylase (HDAC) inhibitors as a potential treatment for BCC. Here we conduct the first proof-of-principle study of a topical pan-HDAC inhibitor, remetinostat, in human BCC. Patients and Methods: We conducted a phase II, open-label, single-arm, single-institution trial of a topical HDAC inhibitor. Participants with at least one BCC were recruited. All participants applied 1% remetinostat gel three times daily for 6 weeks, with measurements of tumor diameter conducted at baseline and week 8. Surgical excision of the remaining tumor was conducted at the end of the study and microscopic evaluation was performed. Results: Thirty-three per-protocol tumors from 25 participants were included in the analysis. The overall response rate, defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8, was 69.7% [90% confidence interval (CI), 54%–82.5%]. On pathologic examination, 54.8% of tumors demonstrated complete resolution. Pharmacodynamic analysis demonstrated similar levels of acetylated histone H3 in skin tissue before and after treatment, however, phosphorylation was increased. No systemic adverse events were reported. Conclusions: The HDAC inhibitor remetinostat is a well-tolerated and effective topical treatment for reducing BCC disease burden in a clinically significant manner. This provides in-human validation of HDAC inhibitors as a therapy for BCC.
Genetic effects of single-nucleotide polymorphisms in the PPARGC1B gene on airway hyperreactivity in asthmatic patients
Authors: P. Jong-Sook, L. Shin-Hwa, J. An-Soo, Sung P. Woo, Yang K. Ki, U. Soo-Taek, Yong K. Hoon, Il C. Yup, P. Byung-Lae, Hyung S. Doo, P. Choon-Sik
Journal: Allergy (2011)
Facile Polyphenol–Europium Assembly Enabled Functional Poly(<scp>l</scp>‐Lactic Acid) Nanofiber Mats with Enhanced Antioxidation and Angiogenesis for Accelerated Wound Healing
Authors: Keke Wu, Xiaoxian Wu, Jinshan Guo, Yanpeng Jiao, Changren Zhou
Journal: Advanced Healthcare Materials (2021)

Burns, trauma, surgery and chronic diabetic ulcers are the most common reasons causing skin wounds in clinic. Thus, developing a functional wound dressing has been an imperative issue. Herein, functional wound dressing (poly(l-lactic acid) PLLA-((tanic acid (TA)/europium (Eu))n ) is fabricated through a facile polyphenol-europium ion assembly to ameliorate wound microenvironment via scavenging excessive reactive oxygen species (ROS) and promoting angiogenesis. The physicochemical characterization indicates that the multicycle assembled TA/Eu is uniformly deposited on PLLA-(TA/Eu)n nanofiber mats surface. In vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant tests display good antioxidant ability by scavenging more than 75% ROS, and significantly increasing the antioxidant enzyme levels in vivo. Cytocompatibility experiments illustrate that PLLA-(TA/Eu)n nanofiber mats can promote the adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) and L929 cells. Meanwhile, real-time quantitative polymerase chain reaction (PCR) (RT-qPCR) and western blot assays illustrate that it can stimulate proangiogenesis by elevating the expression of angiogenesis-related genes and proteins. In vivo Sprague-Dawley (SD) rats experiments indicate that PLLA-(TA/Eu)n nanofiber mats can significantly promote wound healing by improving both angiogenesis and antioxidant activity. Taken together, the functional PLLA-(TA/Eu)n nanofiber mats can offer significant promise as wound dressing for accelerated wound healing.
COVID-19 and Diabetes
Authors: Awadhesh Kumar Singh, Kamlesh Khunti
Journal: Annual Review of Medicine (2021)

The prevalence of diabetes in people with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has varied worldwide. Most of the available evidence suggests a significant increase in severity and mortality of COVID-19 in people with either type 1 (T1DM) or type 2 diabetes mellitus (T2DM), especially in association with poor glycemic control. While new-onset hyperglycemia and new-onset diabetes (both T1DM and T2DM) have been increasingly recognized in the context of COVID-19 and have been associated with worse outcome, no conclusive evidence yet suggests direct tropism of SARS-CoV-2 on the β cells of pancreatic islets. While all approved oral antidiabetic agents appear to be safe in people with T2DM having COVID-19, no conclusive data are yet available to indicate a mortality benefit with any class of these drugs, in the absence of large randomized controlled trials.
Modulating effects of RAMPs on signaling profiles of the glucagon receptor family
Authors: Lijun Shao, Yan Chen, Shikai Zhang, Zhihui Zhang, Yongbing Cao, Dehua Yang, Ming-Wei Wang
Journal: Acta Pharmaceutica Sinica B (2021)

Receptor activity-modulating proteins (RAMPs) are accessory molecules that form complexes with specific G protein-coupled receptors (GPCRs) and modulate their functions. It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood. In this study, we used a bioluminescence resonance energy transfer (BRET) approach to comprehensively investigate such interactions. In conjunction with cAMP accumulation, Gαq activation and β-arrestin1/2 recruitment assays, we not only verified the GPCR-RAMP pairs previously reported, but also identified new patterns of GPCR-RAMP interaction. While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), and RAMP2 mainly affected β-arrestin1/2 recruitment by GCGR, GLP-1R and glucagon-like peptide-2 receptor, RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways. Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner. Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.
Variations in end-of-life practices in intensive care units worldwide (Ethicus-2): a prospective observational study
Authors: Alexander Avidan, Charles L Sprung, Joerg C Schefold, Bara Ricou, Christiane S Hartog, Joseph L Nates, Ulrich Jaschinski, Suzana M Lobo, Gavin M Joynt, Olivier Lesieur, Manfred Weiss, Massimo Antonelli, Hans-Henrik Bülow, Maria G Bocci, Annette Robertsen, Matthew H Anstey, Belén Estébanez-Montiel, Alexandre Lautrette, Anastasiia Gruber, Angel Estella, Sudakshina Mullick, Roshni Sreedharan, Andrej Michalsen, Charles Feldman, Kai Tisljar, Martin Posch, Steven Ovu, Barbara Tamowicz, Alexandre Demoule, Freda DeKeyser Ganz, Hans Pargger, Alberto Noto, Philipp Metnitz, Laszlo Zubek, Veronica de la Guardia, Christopher M Danbury, Orsolya Szűcs, Alessandro Protti, Mario Filipe, Steven Q Simpson, Cameron Green, Alberto M Giannini, Ivo W Soliman, Claudio Piras, Eliana B Caser, Manuel Hache-Marliere, Spyros D Mentzelopoulos
Journal: The Lancet Respiratory Medicine (2021)
A tumor-penetrable drug nanococktail made from human histones for interventional nucleus-targeted chemophotothermal therapy of drug-resistant tumors
Authors: Jianquan Guo, Dongsheng Tan, Chenmei Lou, Shiying Guo, Xing Jin, Haijing Qu, Lijia Jing, Sijin Li
Journal: Bioactive Materials (2021)

Nanoparticle-based chemophotothermal therapy (CPT) is a promising treatment for multidrug resistant tumors. In this study, a drug nanococktail of DIR825@histone was developed by employing doxorubicin (DOX), NIR dye IR825 and human histones for interventional nucleus-targeted CPT of multidrug resistant tumors with an interventional laser. After localized intervention, DIR825@histone penetrated tumor tissues by transcytosis, efficiently entered tumor cells and targeted the cell nuclei. DIR825@histone also exhibited good photothermal performance and thermal-triggered drug release. Efficient multidrug resistant tumor inhibition was achieved by enhanced CPT sensitization and MDR reversion via nuclear targeting. Moreover, an interventional laser assisted DIR825@histone in inhibiting multidrug resistant tumors by promoting the sufficient delivery of laser energy inside the tumor while reducing skin injury. Therefore, DIR825@histone together with this interventional nucleus-targeted CPT strategy holds great promise for treating multidrug resistant tumors.
Abstract 16005: Correlation Between Spatial Differences in Action Potential Duration and Diastolic Dysfunction in Transgenic LQT2 Rabbits
Authors: Katja E Odening, Bernd A Jung, David Ziupa, Gerlind Franke, Stefanie Perez Feliz, Michael Brunner, Gideon Koren, Manfred Zehender, Christoph Bode, Michael Markl, Daniela Foell
Journal: Circulation (2011)

Introduction: Enhanced dispersion of action potential duration (APD) due to heterogeneous prolongation of cardiac repolarization is a major contributor to Long-QT syndrome (LQTS)-related arrhythmia...
P-281 Low proliferation indexes in colorectal cancer in Tunisian patients: Association with rectal localization, mucinous histological type and stage
Authors: D. Wider, H. Guettiti Tounsi, F. Letaief-ksontini, S. Ben Nasr, A. Jaballah, I. Ben Ayed, H. Yaïche, A. Haddauoi, S. Boubaker
Journal: Annals of Oncology (2021)
New Insights on the Interactions Between Insulin Clearance and the Main Glucose Homeostasis Mechanisms
Authors: Roberto Bizzotto, Domenico Tricò, Andrea Natali, Amalia Gastaldelli, Elza Muscelli, Ralph A. De Fronzo, Silva Arslanian, Ele Ferrannini, Andrea Mari
Journal: Diabetes Care (2021)

Endogenous insulin clearance (EIC) is physiologically reduced at increasing insulin secretion rate (ISR). Computing EIC at the prevailing ISR does not distinguish the effects of hypersecretion from those of other mechanisms of glucose homeostasis. We aimed to measure EIC in standardized ISR conditions (i.e., at fixed ISR levels) and to analyze its associations with relevant physiologic factors.We estimated standardized EIC (EICISR) by mathematical modeling in nine different studies with insulin and glucose infusions (N = 2,067). EICISR association with various traits was analyzed by stepwise multivariable regression in studies with both euglycemic clamp and oral glucose tolerance test (OGTT) (N = 1,410). We also tested whether oral glucose ingestion, as opposed to intravenous infusion, has an independent effect on EIC (N = 1,555).Insulin sensitivity (as M/I from the euglycemic clamp) is the strongest determinant of EICISR, approximately four times more influential than insulin resistance-related hypersecretion. EICISR independently associates positively with M/I, fasting and mean OGTT glucose or type 2 diabetes, and β-cell glucose sensitivity and negatively with African American or Hispanic race, female sex, and female age. With oral glucose ingestion, an ISR-independent ∼10% EIC reduction is necessary to explain the observed insulin concentration profiles.Based on EICISR, we posit the existence of two adaptive processes involving insulin clearance: the first reduces EICISR with insulin resistance (not with higher BMI per se) and is more relevant than the concomitant hypersecretion; the second reduces EICISR with β-cell dysfunction. These processes are dysregulated in type 2 diabetes. Finally, oral glucose ingestion per se reduces insulin clearance.
Profiling genomic characteristics related to immunotherapy for gastric cancer with amplified <i>MET</i>.
Authors: Yiyi Yu, Wei Li, Shan Yu, Yan Wang, Mengxuan Zhu, Zhao Yi, Tianshu Liu
Journal: Journal of Clinical Oncology (2021)

e16066 Background: Gastric cancer (GCA) is one of the most deadly cancers all over the world, with an estimate of 26,560 new cases and 11,180 deaths in United States according to the cancer statistics of 2021. As immunotherapy has become available for GCA, it is necessary to distinguish patients who might be resistant to it. Methods: We identified 41 patients with amplified MET from a large Chinese cohort including 934 GCA (4.4% out of them) according to the ratio of purity adjusted copy number of MET and chromosome 7. Then, we comprehensively profiled genomic characteristics related to immunotherapy for GCA with amplified MET and compared them with other GCA. Results: First, mutated RNF43 and AXIN1 were much more prevalent in GCA with amplified MET. These two genes are components of Wnt pathway, whose aberrance is associated with resistance to immunotherapy. Second, carrier ratios of amplified CDK6 and CCND1 were much higher in GCA with amplified MET. These two genes play important roles in cell cycle pathway, while amplification of CCND1 has been recognized as a negatively predictive biomarker for immunotherapy. Third, we calculated mutational load of immunotherapy-related positively (mutated ATM, BRCA1, BRCA2, CHEK2, ERCC2, ERCC4, FANCA, KRAS, MLH1, MSH2, MSH6, NRAS, PALB2, PBRM1, PMS2, POLD1, POLE, RAD50 and TP53; deleted POLE) and negatively (mutated B2M, CTNNB1, DNMT3A, EGFR, JAK1, JAK2 and STK11; amplified CCND1, EGFR, FGF19, FGF3, FGF4, MDM2 and MDM4; deleted B2M, JAK2, PTEN and STK11) predictive biomarkers for GCA with amplified MET. We defined the mutational load as mean carrier ratio of point mutations or copy number variations (CNVs) appeared in a gene set. As is expected, the mutational load of point mutations in 19 positively predictive biomarkers in GCA with amplified MET was much lower than that in other GCA, whereas the mutational load of CNV in 11 negatively predictive biomarkers in GCA with amplified MET was much higher than that in other GCA. Finally, we found GCA with amplified MET possessed lower tumor mutational burden (TMB) and microsatellite instability (MSI), depleted somatic signature of defective DNA mismatch repair and higher copy number instability (CNI). Conclusions: Genomic characteristics of GCA with amplified MET are associated with adverse response to immunotherapy and thus it should be carefully evaluated when these patients are treated with immunotherapy.