tbuckley/cabot-search huggingface dataset:
New composite endpoint in early diffuse cutaneous systemic sclerosis: revisiting the provisional American College of Rheumatology Composite Response Index in Systemic Sclerosis
Authors: Dinesh Khanna, Suiyuan Huang, Celia J F Lin, Cathie Spino
Journal: Annals of the Rheumatic Diseases (2020)

American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS) is a composite endpoint to assess the likelihood of improvement in diffuse systemic sclerosis. ACR-CRISS is a weighted score and includes five core set measures: modified Rodnan skin score, FVC% predicted, health assessment questionnaire-disability index, and patient and clinician global assessments.We analysed core set measures from 354 participants who participated in three placebo-controlled trials. We generated 10 development datasets, randomly selected from 2/3 of the participants, stratified by study and treatment group. The remaining participants (1/3 of the participants) formed the validation sets. Risk differences (RDs) between active and placebo treatments were calculated by averaging over the replicate datasets; bootstrap 95% CIs for the RDs to estimate the magnitude of treatment effects.In the development sets (n=237), the proportion of participants in the active group had statistically higher improvement in >1 of 5 core set measures versus the placebo group. For example, the proportion who improved by ≥20% in ≥3 core set measures was 49.4% in the active versus338.9% in the placebo; RD: 10.5%, 95% CI4.9 % to 16.1%. In the validation sets (n=117), the proportion who improved by ≥20% in ≥3 core set measures was 50.3% in the active versus35.63% in the placebo (RD:114.8%, 95% CI 3.1% to225.7%). Similar trends were seen with larger percentage cut-offs.Revised CRISS, as assessed by the proportion of participants who improved by a certain percentage in ≥3 of 5 core set measures, is a potential new composite outcome measure.
13601 BMS-986165, an oral selective TYK2 inhibitor, in the treatment of moderate to severe psoriasis as assessed by the static Physicians Global Assessment/body surface area composite tool, a clinically useful alternative to the Psoriasis Area and Severity Index score
Authors: Alice Gottlieb, Bruce Strober, Diamant Thaci, Kenneth Gordon, Haobo Ren, Renata M. Kisa, Lan Wei, Subhashis Banerjee, Joseph F. Merola
Journal: Journal of the American Academy of Dermatology (2020)
Patient-Reported Outcomes in Patients with Classical Hodgkin Lymphoma Treated with Pembrolizumab Monotherapy, Results of a Phase 2 Study
Authors: Bastian von Tresckow, Michelle A. Fanale, Kirit M Ardeshna, Robert W. Chen, Julia Meissner, Franck Morschhauser, Craig H. Moskowitz, Pier Luigi Zinzani, Hilde Giezek, Arun Balakumaran, Monika Raut, Thao Vo, Pauline Brice
Journal: Blood (2017)
Dose Escalation Prophylactic Donor Lymphocyte Infusion (pDLI) after T-Cell Depleted (TCD) Matched Related Donor (MRD) Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) Is Feasible and Results in Higher Donor Chimerism, Faster Immune Re-Constitution and Prolonged PFS
Authors: Kothari Shawn, Andrew Artz, Sang Mee Lee, Noreen Fulton, Jae-Hyun Park, Wendy Stock, Richard A. Larson, Olatoyosi Odenike, Justin Kline, Lucy Godley, James LaBelle, Satyajit Kosuri, Peter A Riedell, Yusuke Nakamura, Michael R. Bishop, Hongtao Liu
Journal: Blood (2017)
Abstract 259: KChIP2 is a Key Transcriptional Regulator of Cardiac Excitability Under Normal and Pathogenic Conditions
Authors: Drew M Nassal, Xiaoping Wan, Haiyan Liu, Danielle Maleski, Angelina Ramirez-Navarro, Christine S Moravec, Eckhard Ficker, Kenneth R Laurita, Isabelle Deschênes
Journal: Circulation Research (2016)

Introduction: Arrhythmogenesis is the primary cause of death in patients with acquired heart disease, and is the consequence of profound dysregulation of both depolarizing and repolarizing currents. Reduction in expression of the auxiliary subunit K+ channel interacting protein 2 (KChIP2), which regulates the transient outward K+ current (Ito), is a common and early event in many cardiac pathologies. Notably, transcriptional changes observed in heart disease can be elicited through direct KChIP2 silencing without disease signaling, suggesting novel transcriptional capacity for KChIP2. Methods and Results: A miRNA microarray was conducted on neonatal rat ventricular myocytes (NRVM) following in vitro silencing of KChIP2, identifying the miR-34 family as a potential transcriptional target of KChIP2. qPCR confirmed reduction in miR-34b/c when over-expressing KChIP2 and increase following silencing. Luciferase assays conducted on the promoter for miR-34b/c reinforced KChIP2 repression on the promoter, while chromatin immunoprecipitation identified direct interaction of KChIP2 on the promoter. Previous studies show modified expression of KChIP2 can lead to changes in several ion channel subunits. Therefore, we investigated if this was the consequence of KChIP2 regulation via miR-34. Expression of miR-34b/c precursors reduced transcript levels of Nav1.5 and Navβ1, and reduced protein levels for Kv4.3, resulting in loss of INa and Ito. To determine the relevance in disease signaling, NRVMs were exposed to 100 μM phenylephrine for 48 hrs, significantly reducing KChIP2, Nav1.5, Navβ1, and Kv4.3, while elevating miR-34b/c. Maintaining KChIP2 expression by adenovirus or blocking miR-34 activity with antagomirs rescued the changes in channel expression. Consequently, miR-34 inhibition rescued the induction of sustained arrhythmias observed in a 2D culture of myocytes through the maintenance of cardiac excitability. Conclusion: Collectively, these observations identify dysregulation of the KChIP2/miR-34 axis as a nodal event in the development of electrical dysfunction that characterize cardiac pathologies, and further identifies miR-34 as a viable therapeutic target for managing arrhythmogenesis in patients with heart disease.
Combined physical and cognitive training for older adults with and without cognitive impairment: A systematic review and network meta-analysis of randomized controlled trials
Authors: Hanna Malmberg Gavelin, Christopher Dong, Ruth Minkov, Alex Bahar-Fuchs, Kathryn A Ellis, Nicola T Lautenschlager, Maddison L Mellow, Alexandra T Wade, Ashleigh E Smith, Carsten Finke, Stephan Krohn, Amit Lampit
Journal: Ageing Research Reviews (2020)
140P Preoperative and postoperative C-reactive protein levels predict recurrence and chemotherapy benefit in gastric cancer
Authors: L-L. Shen, Y-H. Tang, W-W. Qiu, J. Lu, C-H. Zheng, P. Li, J-W. Xie, J-B. Wang, J-X. Lin, Q-Y. Chen, L-L. Cao, M. Lin, R-H. Tu, Z-N. Huang, J-L. Lin, H-L. Zheng, C. Huang
Journal: Annals of Oncology (2020)
18038 Reproducibility of Myoton and durometer devices to quantify skin stiffness and hardness in sclerotic chronic graft-versus-host disease
Authors: Laura X. Wang, Fuyao Chen, Arved Vain, Yvette Ssempijja, Laura Dellalana, Kathy Zhang, Alexis Hood, Heidi Chen, Madan Jagasia, Eric Tkaczyk
Journal: Journal of the American Academy of Dermatology (2020)
Digital PCR for <i>BCR‐ABL1</i> Quantification in CML: Current Applications in Clinical Practice
Authors: Camille C.B. Kockerols, Peter J.M. Valk, Mark‐David Levin, Niels Pallisgaard, Jan J. Cornelissen, Peter E. Westerweel
Journal: HemaSphere (2020)

Abstract Molecular monitoring of the BCR‐ABL1 transcript for patients with chronic phase chronic myeloid leukemia (CML) has become increasingly demanding. Real‐time quantitative PCR (qPCR) is the routinely used method, but has limitations in quantification accuracy due to its inherent technical variation. Treatment recommendations rely on specific BCR‐ABL1 values set at timed response milestones, making precise measurement of BCR‐ABL1 a requisite. Furthermore, the sensitivity of qPCR may be insufficient to reliably quantify low levels of residual BCR‐ABL1 in patients in deep molecular response (DMR) who could qualify for an attempt to discontinue Tyrosine Kinase Inhibitor (TKI) therapy. We reviewed the current use of digital PCR (dPCR) as a promising alternative for response monitoring in CML. dPCR offers an absolute BCR‐ABL1 quantification at various disease levels with remarkable precision and a clinical sensitivity reaching down to at least MR5.0. Moreover, dPCR has been validated in multiple studies as prognostic marker for successful TKI treatment discontinuation, while this could not be achieved using classical qPCR. dPCR may thus prospectively be the preferred method to reliably identify patients achieving treatment milestones after initiation of TKI therapy as well as for the selection and timing for TKI discontinuation.
13590 Brigham Eyelash Tool for Alopecia (BELA): A reliable assessment of eyelash alopecia areata
Authors: Sara J. Li, Priya Manjaly, Justin M. Ko, Kristina J. Liu, Deborah A. Scott, Elizabeth Tkachenko, Cara Joyce, Kathie Huang, Arash Mostaghimi
Journal: Journal of the American Academy of Dermatology (2020)
Organ Acceptance and Outcomes—A Surgeon’s Perspective—Reply
Authors: Ashley Y. Choi, Hui-Jie Lee, Matthew G. Hartwig
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 44 000 middle-aged and older individuals
Authors: Ulf Ekelund, Jakob Tarp, Morten W Fagerland, Jostein Steene Johannessen, Bjørge H Hansen, Barbara J Jefferis, Peter H Whincup, Keith M Diaz, Steven Hooker, Virginia J Howard, Ariel Chernofsky, Martin G Larson, Nicole Spartano, Ramachandran S Vasan, Ing-Mari Dohrn, Maria Hagströmer, Charlotte Edwardson, Thomas Yates, Eric J Shiroma, Paddy Dempsey, Katrien Wijndaele, Sigmund A Anderssen, I-Min Lee
Journal: British Journal of Sports Medicine (2020)

To examine the joint associations of accelerometer-measured physical activity and sedentary time with all-cause mortality.We conducted a harmonised meta-analysis including nine prospective cohort studies from four countries. 44 370 men and women were followed for 4.0 to 14.5 years during which 3451 participants died (7.8% mortality rate). Associations between different combinations of moderate-to-vigorous intensity physical activity (MVPA) and sedentary time were analysed at study level using Cox proportional hazards regression analysis and summarised using random effects meta-analysis.Across cohorts, the average time spent sedentary ranged from 8.5 hours/day to 10.5 hours/day and 8 min/day to 35 min/day for MVPA. Compared with the referent group (highest physical activity/lowest sedentary time), the risk of death increased with lower levels of MVPA and greater amounts of sedentary time. Among those in the highest third of MVPA, the risk of death was not statistically different from the referent for those in the middle (16%; 95% CI 0.87% to 1.54%) and highest (40%; 95% CI 0.87% to 2.26%) thirds of sedentary time. Those in the lowest third of MVPA had a greater risk of death in all combinations with sedentary time; 65% (95% CI 1.25% to 2.19%), 65% (95% CI 1.24% to 2.21%) and 263% (95% CI 1.93% to 3.57%), respectively.Higher sedentary time is associated with higher mortality in less active individuals when measured by accelerometry. About 30-40 min of MVPA per day attenuate the association between sedentary time and risk of death, which is lower than previous estimates from self-reported data.
Test on stool samples improves the diagnosis of hospitalized patients: Detection of SARS-CoV-2 genomic and subgenomic RNA
Authors: Luiz Vinicius Leão Moreira, Luciano Kleber de Souza Luna, Gabriela Rodrigues Barbosa, Ana Helena Perosa, Ana Paula Cunha Chaves, Danielle Dias Conte, Joseane Mayara Almeida Carvalho, Nancy Bellei
Journal: Journal of Infection (2020)
Female patient with recurrent chest infections and non-resolving consolidation
Authors: Eihab O Bedawi, Thomas Moore, Gareth D Turner, Mark McCole, Fergus V Gleeson, Najib M Rahman
Journal: Thorax (2020)

A 45-year-old Caucasian woman was referred for investigation of recurrent chest infections. She had been treated over the previous 9 months for recurrent symptoms characterised by intermittent episodes of dyspnoea, cough productive of green sputum and pleuritic chest pain. Systemic enquiry was unremarkable; specifically, she had not experienced any weight loss or anorexia.

On each episode, oxygen saturations were >94% and heart rate was <100 beats/min, with a single occurrence of a low-grade fever (37.8°C). The white cell count peaked at 10.59×108 (neutrophils 8.82, eosinophils 0.18, lymphocytes 0.89), and her C reactive protein remained consistently within normal lab ranges. She was not anaemic. Liver, kidney and bone profiles were all within normal limits.

Each course of antibiotics would lead to transient improvement in cough, but the pleuritic chest pain and breathlessness remained unchanged.

Her medical history included myasthenia gravis (1991), neuromyelitis optica (2009), non-alcoholic steatosis, hypertension, obesity (body mass index 48.7 kg/m2), hypothyroidism and obstructive sleep apnoea. Surgical history included thymectomy (1993) and a gastric bypass (2010).

She worked in retail with no occupational exposures. She had never smoked and was teetotal. Her exercise tolerance had deteriorated over the preceding 12 months, from being unlimited to 50 m, due to a combination of dyspnoea and fatigue. She did not garden or tend soil, and had two cats in good health. She had no childhood respiratory illnesses. She lived with her young family in a suburban area and had no recent history of foreign travel. There was no personal or contact history of tuberculosis (TB).

Medications included prednisolone, mycophenolate, lamotrigine, topiramate, lisinopril, venlafaxine, levothyroxine, omeprazole and pregabalin.

Spirometry demonstrated an forced expiratory volume in 1 s of 1.9 litre (70% predicted) with forced vital capacity of 2.2 litre (72%predicted), similar to her results in the previous year. A contrast-enhanced CT scan of the thorax was …
Association of Adverse Childhood Experiences With Cardiovascular Disease Later in Life
Authors: Lucas C. Godoy, Claudia Frankfurter, Matthew Cooper, Christine Lay, Robert Maunder, Michael E. Farkouh
Journal: JAMA Cardiology (2020)

Adverse childhood experiences (ACEs) are potentially harmful events that occur during childhood, spanning neglect, physical or sexual abuse, parental separation, or death, among others. At least 50% of the US adult population has experienced 1 or more ACEs before the age of 18 years, but in clinical practice, ACEs remain underrecognized. Adults who have experienced ACEs are at increased risk of developing health risk behaviors and, ultimately, cardiovascular disease (CVD). This review summarizes the evidence regarding the association of ACEs with CVD and the accompanying diagnostic and therapeutic approaches in the adult population.ACEs are commonly classified into 3 domains: abuse (psychological, physical, or sexual), household dysfunction (eg, substance use by household members, mental illness, parental separation), and neglect. These experiences elicit chronic activation of the stress response system, leading to autonomic, neuroendocrine, and inflammatory dysfunction. The subsequent development of traditional risk factors, such as diabetes, hypertension, smoking, and obesity, results in the onset of CVD and premature mortality. Adults with 4 or more ACEs compared with those with none have a more than 2-fold higher risk of developing CVD and an almost 2-fold higher risk of premature mortality.Identifying methods of mitigating the health consequences of ACEs may lead to better cardiovascular outcomes. Inquiry into ACE exposure during clinical encounters and subsequent referral to psychological services when appropriate may be helpful, but strategies aimed at CVD prevention via management of ACEs in adults continue to lack adequate evidence.
Driving Under the Influence of CBD or THC—Is There a Difference?
Authors: Rita Rubin
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 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
Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment
Authors: Wenxi Zhou, Yu Zhou, Xinli Chen, Tingting Ning, Hongyi Chen, Qin Guo, Yiwen Zhang, Peixin Liu, Yujie Zhang, Chao Li, Yongchao Chu, Tao Sun, Chen Jiang
Journal: Biomaterials (2020)
Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis
Authors: Luís Almeida, Ayesha Dhillon-LaBrooy, Carla N. Castro, Nigatu Adossa, Guilhermina M. Carriche, Melanie Guderian, Saskia Lippens, Sven Dennerlein, Christina Hesse, Bart N. Lambrecht, Luciana Berod, Leif Schauser, Bruce R. Blazar, Markus Kalesse, Rolf Müller, Luís F. Moita, Tim Sparwasser
Journal: Immunity (2020)

While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressively compromised the integrity of the electron transport chain. Ultimately, this led to deficient oxidative phosphorylation, diminishing nicotinamide adenine dinucleotide concentrations and impairing cytokine production in differentiating T cells. In accordance, mice lacking mEF-G1 in T cells were protected from experimental autoimmune encephalomyelitis, demonstrating that this pathway is crucial in maintaining T cell function and pathogenicity.
Pharmaco-Invasive Therapy for Acute ST-Elevation Myocardial Infarction. - A Viable Alternative to Primary Percutaneous Coronary Intervention
Authors: Lairikyengbam SKS
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Primary percutaneous coronary intervention (pPCI) is considered as the preferred treatment for acute ST-Elevation myocardial infarction (STEMI). However, its availability is limited to less than 10% in rural and sub urban population in India (1). Therefore, Pharmaco-Invasive Therapy (PIT) (Thrombolysis first followed by planned coronary stenting) as an alternative to pPCI for acute STEMI has more recently been explored. A retrospective observational study of 60 patients with acute STEMI treated at the Dedicated Heart Attack Treatment Centre of SKY Hospital &amp; Research Centre, Imphal, India over a period of 2 years has shown that Pharmaco-Invasive Therapy improved survival of patients with acute STEMI to 100% and increased Left Ventricular Ejection Fraction (LVEF) by 5.08% at the time of discharge and may be used as a viable alternative to pPCI in the treatment of patients with acute STEMI when pPCI cannot be performed within recommended time.
Association between duodenal bile salts and gastric emptying in patients with functional dyspepsia
Authors: Lucas Wauters, Matthias Ceulemans, Maarten Lambaerts, Alison Accarie, Joran Toth, Raf Mols, Patrick Augustijns, Jan Tack, Tim Vanuytsel
Journal: Gut (2020)

We read with interest the study by Higuchi et al , which identified mechanisms of increased satiation in Cyp8b1−/− mice via slowed gastric empting.1 Following data showing that deleting Cyp8b1, which is required to produce 12α-hydroxylated bile acids, impaired intestinal lipid absorption in mice, the authors convincingly demonstrated that lowering 12α-hydroxylated bile acids slowed gastric emptying in Cyp8b1−/− mice.1 Duodenal lipid infusion affects gastric function, and duodenal hypersensitivity to lipids has been studied in GI disorders with gastric dysmotility, such as functional dyspepsia (FD).2 FD is defined by upper GI symptoms originating from the gastroduodenal region with no structural disease on routine investigation.3 Although studies showed that lipids are a major trigger of dyspeptic symptoms, the effect was only partially explained by duodenal release of cholecystokinin.4 Interestingly, the release of bile salts has been linked to the generation of dyspeptic symptoms, possibly via duodenal luminal or mucosal changes including hyperpermeability.5 6 However, duodenal alterations have not …