tbuckley/cabot-search huggingface dataset:
Norepinephrine Dysregulates the Immune Response and Compromises Host Defense during Sepsis
Authors: Roeland F. Stolk, Eva van der Pasch, Flavia Naumann, Joost Schouwstra, Steffi Bressers, Antonius E. van Herwaarden, Jelle Gerretsen, Roel Schambergen, Mike M. Ruth, Johannes G. van der Hoeven, Henk van Leeuwen, Peter Pickkers, Matthijs Kox
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Sepsis is characterized by a dysregulated immune response to infection. Norepinephrine, the cornerstone vasopressor used in septic shock, may contribute to immune dysregulation and impact host defense.Objectives: To investigate effects of norepinephrine and the alternative vasopressor vasopressin on the immune response and host defense.Methods: Leukocytes from six to nine donors were stimulated in the presence or absence of norepinephrine and vasopressin. A total of 190 C57BL/6J mice received a continuous infusion of norepinephrine or vasopressin via microosmotic pumps and were challenged with LPS or underwent cecal ligation and puncture. Thirty healthy volunteers were randomized to a 5-hour infusion of norepinephrine, vasopressin, or saline and intravenously challenged with LPS. The relationship between the norepinephrine infusion rate and the use of β-blockers and plasma cytokines was assessed in 195 patients with septic shock.Measurements and Main Results: Norepinephrine attenuated the production of proinflammatory mediators and reactive oxygen species and augmented antiinflammatory IL-10 production both in vitro and in LPS-challenged mice. Norepinephrine infusion during cecal ligation and puncture resulted in increased bacterial dissemination to the spleen, liver, and blood. In LPS-challenged volunteers, norepinephrine enhanced plasma IL-10 concentrations and attenuated the release of the proinflammatory cytokine IFN-γ-induced protein 10. Vasopressin exerted no immunomodulatory effects across these experimental setups. In patients, higher norepinephrine infusion rates were correlated with a more antiinflammatory cytokine balance, whereas β-blocker use was associated with a more proinflammatory cytokine balance.Conclusions: Norepinephrine dysregulates the immune response in mice and humans and compromises host defense. Therefore, it may significantly contribute to sepsis-induced immunoparalysis, whereas vasopressin does not have untoward immunologic effects.
Dilated cardiomyopathy-linked heat shock protein family D member 1 mutations cause up-regulation of reactive oxygen species and autophagy through mitochondrial dysfunction
Authors: Hirokazu Enomoto, Nishant Mittal, Takayuki Inomata, Takuro Arimura, Tohru Izumi, Akinori Kimura, Keiichi Fukuda, Shinji Makino
Journal: Cardiovascular Research (2020)

During heart failure, the levels of circulatory heat shock protein family D member 1 (HSP60) increase. However, its underlying mechanism is still unknown. The apical domain of heat shock protein family D member 1 (HSPD1) is conserved throughout evolution. We found a point mutation in HSPD1 in a familial dilated cardiomyopathy (DCM) patient. A similar point mutation in HSPD1 in the zebrafish mutant, nbl, led to loss of its regenerative capacity and development of pericardial oedema under heat stress condition. In this study, we aimed to determine the direct involvement of HSPD1 in the development of DCM.By Sanger method, we found a point mutation (Thr320Ala) in the apical domain of HSPD1, in one familial DCM patient, which was four amino acids away from the point mutation (Val324Glu) in the nbl mutant zebrafish. The nbl mutants showed atrio-ventricular block and sudden death at 8-month post-fertilization. Histological and microscopic analysis of the nbl mutant hearts showed decreased ventricular wall thickness, elevated level of reactive oxygen species (ROS), increased fibrosis, mitochondrial damage, and increased autophagosomes. mRNA and protein expression of autophagy-related genes significantly increased in nbl mutants. We established HEK293 stable cell lines of wild-type, nbl-type, and DCM-type HSPD1, with tetracycline-dependent expression. Compared to wild-type, both nbl- and DCM-type cells showed decreased cell growth, increased expression of ROS and autophagy-related genes, inhibition of the activity of mitochondrial electron transport chain complexes III and IV, and decreased mitochondrial fission and fusion.Mutations in HSPD1 caused mitochondrial dysfunction and induced mitophagy. Mitochondrial dysfunction caused increased ROS and cardiac atrophy.
Social Support, Social Network Size, Social Strain, Stressful Life Events, and Coronary Heart Disease in Women With Type 2 Diabetes: A Cohort Study Based on the Women’s Health Initiative
Authors: Junmei Miao Jonasson, Michael Hendryx, Aladdin H. Shadyab, Erika Kelley, Karen C. Johnson, Candyce H. Kroenke, Lorena Garcia, Sofia Lawesson, Ailiana Santosa, Shawnita Sealy-Jefferson, Xiaochen Lin, Crystal W. Cene, Simin Liu, Carolina Valdiviezo, Juhua Luo
Journal: Diabetes Care (2020)

OBJECTIVE We studied associations between social support, social network size, social strain, or stressful life events and risk of coronary heart disease (CHD) in postmenopausal women with type 2 diabetes. RESEARCH DESIGN AND METHODS From the Women’s Health Initiative, 5,262 postmenopausal women with type 2 diabetes at baseline were included. Cox proportional hazards regression models adjusted for demographics, depressive symptoms, anthropometric variables, and lifestyle factors were used to examine associations between social factors and CHD. RESULTS A total of 672 case subjects with CHD were observed during an average 12.79 (SD 6.29) years of follow-up. There was a significant linear trend toward higher risk of CHD as the number of stressful life events increased (P for trend = 0.01; hazard ratio [HR] [95% CI] for the third and fourth quartiles compared with first quartile: 1.27 [1.03–1.56] and 1.30 [1.04–1.64]). Being married or in an intimate relationship was related to decreased risk of CHD (HR 0.82 [95% CI 0.69–0.97]). CONCLUSIONS Among postmenopausal women with type 2 diabetes, higher levels of stressful life events were associated with higher risk of CHD. Experience of stressful life events might be considered as a risk factor for CHD among women with type 2 diabetes.
Advancing Research on the Complex Interrelations Between Atrial Fibrillation and Heart Failure
Authors: Sana M. Al-Khatib, Emelia J. Benjamin, Christine M. Albert, Alvaro Alonso, Cynthia Chauhan, Peng-Sheng Chen, Anne B. Curtis, Patrice Desvigne-Nickens, Jennifer E. Ho, Carolyn S.P. Lam, Mark S. Link, Kristen K. Patton, Margaret M. Redfield, Michiel Rienstra, Yves Rosenberg, Renate Schnabel, John A. Spertus, Lynne Warner Stevenson, Mellanie True Hills, Adriaan A. Voors, Lawton S. Cooper, Alan S. Go
Journal: Circulation (2020)

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.
Abstract 15444: Passive Smartphone Actigraphy Data Predicts Heart Failure Decompensation
Authors: Ayse S Cakmak, Hugh J Lanier, Erik Reinertsen, Arash Harzand, Abarmard M Zafari, Mhd Alaa Hammoud, Alaaeddin Alrohaibani, Candy Wakwe, Michael Appeadu, Gari D Clifford, Amit J Shah
Journal: Circulation (2019)

Introduction: Heart failure (HF) is a major cause of morbidity and mortality, and one of the leading causes of hospitalization. Early detection of HF symptoms and pro-active management may reduce a...
Treatment-driven selection of chemoresistant Ewing sarcoma tumors with limited drug distribution
Authors: Helena Castillo-Ecija, Carles Monterrubio, Guillem Pascual-Pasto, Soledad Gomez-Gonzalez, Daniel J. Garcia-Dominguez, Lourdes Hontecillas-Prieto, Claudia Resa-Pares, Victor Burgueño, Sonia Paco, Nagore G. Olaciregui, Monica Vila-Ubach, Camilo Restrepo-Perdomo, Maria Cuadrado-Vilanova, Leire Balaguer-Lluna, Sara Perez-Jaume, Alicia Castañeda, Vicente Santa-Maria, Monica Roldan, Mariona Suñol, Enrique de Alava, Jaume Mora, Cinzia Lavarino, Angel M. Carcaboso
Journal: Journal of Controlled Release (2020)
Landscape of RAS pathway mutations in patients with myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes: a study of 461 molecularly annotated patients
Authors: Ajinkya Buradkar, Evandro Bezerra, Giacomo Coltro, Terra L. Lasho, Christy M. Finke, Naseema Gangat, Ryan M. Carr, Moritz Binder, Abhishek A. Mangaonkar, Rhett Ketterling, Shakila Khan, Vilmarie Rodriguez, Ayalew Tefferi, Mrinal M. Patnaik
Journal: Leukemia (2020)
Expert assessment on volumetric laser endomicroscopy full scans in Barrett’s esophagus patients with or without high grade dysplasia or early cancer
Authors: Maarten Struyvenberg, Allon Kahn, David Fleischer, Anne-Fre Swager, Brett Bouma, Eric K. Ganguly, Vani Konda, Charles J. Lightdale, Douglas Pleskow, Amrita Sethi, Michael Smith, Arvind J. Trindade, Michael B. Wallace, Kenneth Wang, Herbert C. Wolfsen, G. J. Tearney, Wouter L. Curvers, Cadman L. Leggett, Jacques J. Bergman
Journal: Endoscopy (2020)

Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett's esophagus (BE). Interpretation of a 6-cm long, circumferential VLE "full scan" may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE).29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as "neoplastic" or "NDBE." If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence.VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % - 79 %) of neoplastic VLE videos. In 54 % (range 27 % - 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % - 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %).Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.
AB0943 INFECTIOUS SPONDYLODISCITIS OF THE ELDERLY: CHARACTERISTICS AND OUTCOMES
Authors: J. Mahbouba, O. Jomaa, S. Zrour, I. Bejia, M. Touzi, N. Bergaoui
Journal: Annals of the Rheumatic Diseases (2020)

Background: Spondylodiscitis still frequent. It affects both old and young patients. It makes diagnostic and therapeutic difficulties. Objectives: to identify the characteristics and outcomes of infectious spondylodiscitis (ISD) in patients over 65 years old. Methods: A monocentric retrospective study including patients hospitalized for ISD in the rheumatology department of university hospital of Monastir,TUNISIA between January 2009 and August 2019. Results: Among 70 patients with ISD, 21 (11 male, 10 female) or 30% are over 65 years old. The average age was 70.6 years (65-82 years). History of diabetes (n = 9), hypertension (n = 9), hemodialysis (n = 5), heart disease (n = 5) were the most risk factors reported, while in younger patients, spinal surgery, epidural infiltrations and long-term general corticosteroid therapy were the main risk factors. The mean time for consultation was 142.3± 73 days longer than for younger patients. Fever was present in 0,14% of cases. Assessment time found that already 5 patients had paraplegia or spinal cord compression. 19/21 patients had epiduritis on spinal cord MRI. Soft tissue abscesses were present in close rate in both younger and old patients. Biological assessment showed an inflammatory syndrome and hyperleukocytosis in 92% and 38% of patients respectively (compared to 73% and 27% in younger patients). Germs ware identified in 14 patients (47.3%). Common germs were the most involved (12 patients), while in younger patients, specific- germs were the most reported. Follow up has shown that neurological sequelae are more prevalent in elderly. Conclusion: ISD in patients over 65 years old require a careful attension in therapeutic management given that age according to this study seems to influence the prognosis. In fact, these patients are more susceptible to disability due to neurological complications. References: doi: 10.1016/j.medcli.2017.07.027. doi: 10.1016/j.jinf.2008.02.005. Acknowledgments: Rheumatology department Disclosure of Interests: None declared
IgM and IgD Differential CLL BCRs Organization and Interaction with Co-Receptors before and during Ibrutinib Therapy
Authors: Andrea Nicola Mazzarello, Marcus Dühren-von Minden, Palash Chandra Maity, Gentner Eva, Stefano Vergani, Gerardo Ferrer, Davide Bagnara, Shih-Shih Chen, Sophia Yancopoulos, Xiao J. Yan, Jacqueline C. Barrientos, Kanti Rai, Hassan Jumaa, Nicholas Chiorazzi
Journal: Blood (2017)
Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015
Authors: S. Gillessen, A. Omlin, G. Attard, J.S. de Bono, E. Efstathiou, K. Fizazi, S. Halabi, P.S. Nelson, O. Sartor, M.R. Smith, H.R. Soule, H. Akaza, T.M. Beer, H. Beltran, A.M. Chinnaiyan, G. Daugaard, I.D. Davis, M. De Santis, C.G. Drake, R.A. Eeles, S. Fanti, M.E. Gleave, A. Heidenreich, M. Hussain, N.D. James, F.E. Lecouvet, C.J. Logothetis, K. Mastris, S. Nilsson, W.K. Oh, D. Olmos, A.R. Padhani, C. Parker, M.A. Rubin, J.A. Schalken, H.I. Scher, A. Sella, N.D. Shore, E.J. Small, C.N. Sternberg, H. Suzuki, C.J. Sweeney, I.F. Tannock, B. Tombal
Journal: Annals of Oncology (2016)

Ann Oncol 2015; 26: 1589–1604 (doi: 10.1093/annonc/mdv257) The funding note for this publication was incomplete; the full funding note should read as follows: We gratefully acknowledge the financial support of the following non-profit organisations for the Advanced Prostate Cancer Consensus Conference (APCCC): Cantonal Hospital St Gallen, City and Canton of St Gallen, Swiss Cancer Research Organisation, European School of Oncology (ESO), Swiss Cancer League, the Swiss Oncology Research Network SAKK, Swiss Cancer Foundation, Prostate Cancer Foundation (PCF) and the Günter and Regine Kelm Foundation. We thank the Movember Foundation for the sponsoring of the travel grants (no grant number).
The Perils of Screening for Unhealthy Drug Use Are a Call to Action for the Mental Health Workforce
Authors: Arthur Robin Williams, Frances R. Levin
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells (vol 14, pg 1155, 2013)
Authors: Kevin Man, Maria Miasari, Wei Shi, Annie Xin, Darren C Henstridge, Simon Preston, Marc Pellegrini, Gabrielle T Belz, Gordon K Smyth, Mark A Febbraio, Stephen L Nutt, Axel Kallies
Journal: Nature Immunology (2014)
Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors: a retrospective analysis of 110 cases
Authors: Salvatore Paiella, Luca Landoni, Roberta Rota, Matteo Valenti, Giovanni Elio, Stefano Francesco Crinò, Erminia Manfrin, Alice Parisi, Sara Cingarlini, Mirko D’Onofrio, Aldo Scarpa, Rita Teresa Lawlor, Laura Bernardoni, Paola Capelli, Chiara Nessi, Marco Miotto, Armando Gabbrielli, Claudio Bassi, Roberto Salvia
Journal: Endoscopy (2020)

Abstract Background Data on the reliability of the Ki-67 index and grading calculations from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic neuroendocrine tumors (PanNETs) are controversial. We aimed to assess the accuracy of these data compared with histology. Methods Cytological analysis from EUS-FNA in patients with suspected PanNETs (n = 110) were compared with resection samples at a single institution. A minimum of 2000 cells were considered to be adequate for grading. Correlation and agreement between cytology and histology in grading and Ki-67 values, respectively, were investigated. Secondary outcomes included the diagnostic performance of EUS-FNA. Results EUS-FNA samples were adequate for PanNET diagnosis and PanNET grading in 98/110 (89.1 %) and 77/110 (70.0 %) patients, respectively; thus, 77 samples were adequate for comparing cytology vs. histology. There were 67 (62.0 %), 40 (36.4 %), and 1 (0.9 %) patients with a final diagnosis of G1, G2, and G3 tumors, respectively. EUS-FNA grading was concordant with surgical pathology in 81.8 % of patients; under- and overgrading occurred in 15.6 % and 2.6 %, respectively. The overall level of agreement for grading was moderate (Cohen’s κ = 0.59, 95 % confidence interval [CI] 0.34 – 0.78). Spearman’s rho for Ki-67 in tumors ≤ 20 mm and &gt; 20 mm was strong and moderate, respectively (rho = 0.68, 95 %CI 0.47 – 0.83; rho = 0.59, 95 %CI 0.35 – 0.75). The Bland – Altman plot showed that the Ki-67 values were comparable and reproducible between the two measurements. Conclusions Although they were not available for a significant number of patients, grading and Ki-67 values from cytology correlated with histology moderately to strongly.
ACE2: The Only Thing That Matters?
Authors: Raul Y. Sanchez-David, Olivia C. Swann, Thomas P. Peacock, Wendy S. Barclay
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

In December 2019, cases of a respiratory disease were reported in Hubei Province, China, caused by a positive-sense RNA virus from the family Coronaviridae  Subsequently, the disease was called coronavirus disease (COVID-19) and the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)  The outcome of infection with SARS-CoV-2 is highly variable;on one hand, the virus has been responsible for more than 360,000 deaths worldwide, and on the other hand, there is a diverse range of clinical outcomes in different people  For any virus, infection depends on the ability to 1) enter, 2) evade cellular defenses, 3) hijack host machineries to express viral genes, 4) replicate new genomes, 5) assemble viral particles, and 6) exit  For SARS-CoV-2 entry, the primary receptor is ACE2 (angiotensin I--converting enzyme 2), which serves as receptor for SARS-CoV and a human seasonal coronavirus, human coronavirus NL63 (HCoV-NL63)  The physiological role of ACE2 is the regulation of the reninangiotensin hormone system, regulating blood volume, systemic vascular resistance, and cardiovascular homeostasis
Novel nephronophthisis-associated variants reveal functional importance of MAPKBP1 dimerization for centriolar recruitment
Authors: Ria Schönauer, Wenjun Jin, Anastasia Ertel, Melanie Nemitz-Kliemchen, Nydia Panitz, Elena Hantmann, Anna Seidel, Daniela A. Braun, Shirlee Shril, Matthias Hansen, Khurrum Shahzad, Richard Sandford, Sophie Saunier, Alexandre Benmerah, Carsten Bergmann, Friedhelm Hildebrandt, Jan Halbritter
Journal: Kidney International (2020)
Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B
Authors: Lung-Yi Mak, Rex Wan-Hin Hui, James Fung, Fen Liu, Danny Ka-Ho Wong, Ka-Shing Cheung, Man-Fung Yuen, Wai-Kay Seto
Journal: Journal of Hepatology (2020)