tbuckley/cabot-search huggingface dataset:
Dyspnoea and respiratory muscle ultrasound to predict extubation failure
Authors: Martin Dres, Thomas Similowski, Ewan C. Goligher, Tai Pham, Liliya Sergenyuk, Irene Telias, Domenico Luca Grieco, Wissale Ouechani, Detajin Junhasavasdikul, Michael C. Sklar, L. Felipe Damiani, Luana Melo, Cesar Santis, Lauriane Degravi, Maxens Decavèle, Laurent Brochard, Alexandre Demoule
Journal: European Respiratory Journal (2021)

Background This study investigated dyspnoea intensity and respiratory muscle ultrasound early after extubation to predict extubation failure. Methods The study was conducted prospectively in two intensive care units in France and Canada. Patients intubated for at least 48 h were studied within 2 h after an extubation following a successful spontaneous breathing trial. Dyspnoea was evaluated by a dyspnoea visual analogue scale (Dyspnoea-VAS) ranging from 0 to 10 and the Intensive Care Respiratory Distress Observational Scale (IC-RDOS). The ultrasound thickening fraction of the parasternal intercostal and the diaphragm was measured; limb muscle strength was evaluated using the Medical Research Council (MRC) score (range 0–60). Results Extubation failure occurred in 21 out of 122 enrolled patients (17%). The median (interquartile range (IQR)) Dyspnoea-VAS and IC-RDOS were higher in patients with extubation failure versus success: 7 (4–9) versus 3 (1–5) (p&lt;0.001) and 3.7 (1.8–5.8) versus 1.7 (1.5–2.1) (p&lt;0.001), respectively. The median (IQR) ratio of parasternal intercostal muscle to diaphragm thickening fraction was significantly higher and MRC was lower in patients with extubation failure compared with extubation success: 0.9 (0.4–2.1) versus 0.3 (0.2–0.5) (p&lt;0.001) and 45 (36–50) versus 52 (44–60) (p=0.012), respectively. The thickening fraction of the parasternal intercostal and its ratio to diaphragm thickening showed the highest area under the receiver operating characteristic curve (AUC) for an early prediction of extubation failure (0.81). AUCs of Dyspnoea-VAS and IC-RDOS reached 0.78 and 0.74, respectively. Conclusions Respiratory muscle ultrasound and dyspnoea measured within 2 h after extubation predict subsequent extubation failure.
COVID-19 Mortality and Stress to the Hospital System from High Patient Load—Reply
Authors: David A. Asch
Journal: JAMA Internal Medicine (2021)

David A. Asch, MD, MBA; Natalie E. Sheils, PhD; Md Nazmul Islam, PhD, MBA; Yong Chen, PhD; Rachel M. Werner, MD, PhD; John Buresh, BS; Jalpa A. Doshi, PhD
Bosutinib Vs Imatinib for Newly Diagnosed Chronic Myeloid Leukemia in the BFORE Trial: Results By 3-Month BCR-ABL1 Transcript Level
Authors: Andreas Hochhaus, Carlo Gambacorti-Passerini, Michael W. Deininger, Michael J. Mauro, Charles Chuah, Dong-Wook Kim, Iryna Dyagil, Nataliia Glushko, Dragana Milojkovic, Philipp D. le Coutre, Valentín García Gutiérrez, Laurence Reilly, Allison Jeynes-Ellis, Rocco J. Crescenzo, Eric Leip, Nathalie Bardy-Bouxin, Timothy H. Brümmendorf, Jorge E. Cortes
Journal: Blood (2017)
HDAC1 and 2 regulate endothelial VCAM-1 expression and atherogenesis by suppressing methylation of the <i>GATA6</i> promoter
Authors: Chengxiu Hu, Kai Peng, Qianqian Wu, Yiying Wang, Xing Fan, Dai-Min Zhang, Anthony G Passerini, ChongXiu Sun
Journal: Theranostics (2021)

Increased expression of vascular cell adhesion molecule (VCAM)-1 on the activated arterial endothelial cell (EC) surface critically contributes to atherosclerosis which may in part be regulated by epigenetic mechanisms. This study investigated whether and how the clinically available histone deacetylases 1 and 2 (HDAC1/2) inhibitor drug Romidepsin epigenetically modulates VCAM-1 expression to suppress atherosclerosis. Methods: VCAM-1 expression was analyzed in primary human aortic EC (HAEC) treated with Romidepsin or transfected with HDAC1/2-targeting siRNA. Methylation of GATA6 promoter region was examined with methylation-specific PCR assay. Enrichment of STAT3 to GATA6 promoter was detected with chromatin immunoprecipitation. Lys685Arg mutation was constructed to block STAT3 acetylation. The potential therapeutic effect of Romidepsin on atherosclerosis was evaluated in Apoe-/- mice fed with a high-fat diet. Results: Romidepsin significantly attenuated TNFα-induced VCAM-1 expression on HAEC surface and monocyte adhesion through simultaneous inhibition of HDAC1/2. This downregulation of VCAM-1 was attributable to reduced expression of transcription factor GATA6. Romidepsin enhanced STAT3 acetylation and its binding to DNA methyltransferase 1 (DNMT1), leading to hypermethylation of the GATA6 promoter CpG-rich region at +140/+255. Blocking STAT3 acetylation at Lys685 disrupted DNMT1-STAT3 interaction, decreased GATA6 promoter methylation, and reversed the suppressive effects of HDAC1/2 inhibition on GATA6 and VCAM-1 expression. Finally, intraperitoneal administration of Romidepsin reduced diet-induced atherosclerotic lesion development in Apoe-/- mice, accompanied by a reduction in GATA6/VCAM-1 expression in the aorta. Conclusions: HDAC1/2 contributes to VCAM-1 expression and atherosclerosis by suppressing STAT3 acetylation-dependent GATA6 promoter methylation. These findings may provide a rationale for HDAC1/2-targeting therapy in atherosclerotic heart disease.
Exploratory Assessment of K-means Clustering to Classify 18F-Flutemetamol Brain PET as Positive or Negative
Authors: Katherine Zukotynski, Sandra E. Black, Phillip H. Kuo, Aparna Bhan, Sabrina Adamo, Christopher J.M. Scott, Benjamin Lam, Mario Masellis, Sanjeev Kumar, Corinne E. Fischer, Maria Carmela Tartaglia, Anthony E. Lang, David F. Tang-Wai, Morris Freedman, Neil Vasdev, Vincent Gaudet
Journal: Clinical Nuclear Medicine (2021)

We evaluated K-means clustering to classify amyloid brain PETs as positive or negative.Sixty-six participants (31 men, 35 women; age range, 52-81 years) were recruited through a multicenter observational study: 19 cognitively normal, 25 mild cognitive impairment, and 22 dementia (11 Alzheimer disease, 3 subcortical vascular cognitive impairment, and 8 Parkinson-Lewy Body spectrum disorder). As part of the neurocognitive and imaging evaluation, each participant had an 18F-flutemetamol (Vizamyl, GE Healthcare) brain PET. All studies were processed using Cortex ID software (General Electric Company, Boston, MA) to calculate SUV ratios in 19 regions of interest and clinically interpreted by 2 dual-certified radiologists/nuclear medicine physicians, using MIM software (MIM Software Inc, Cleveland, OH), blinded to the quantitative analysis, with final interpretation based on consensus. K-means clustering was retrospectively used to classify the studies from the quantitative data.Based on clinical interpretation, 46 brain PETs were negative and 20 were positive for amyloid deposition. Of 19 cognitively normal participants, 1 (5%) had a positive 18F-flutemetamol brain PET. Of 25 participants with mild cognitive impairment, 9 (36%) had a positive 18F-flutemetamol brain PET. Of 22 participants with dementia, 10 (45%) had a positive 18F-flutemetamol brain PET; 7 of 11 participants with Alzheimer disease (64%), 1 of 3 participants with vascular cognitive impairment (33%), and 2 of 8 participants with Parkinson-Lewy Body spectrum disorder (25%) had a positive 18F-flutemetamol brain PET. Using clinical interpretation as the criterion standard, K-means clustering (K = 2) gave sensitivity of 95%, specificity of 98%, and accuracy of 97%.K-means clustering may be a powerful algorithm for classifying amyloid brain PET.
Congestive Heart Failure–associated Chronic Diffuse Alveolar Hemorrhage
Authors: Akihito Okazaki, Yoshihiro Takeda, Masaru Kiyama, Kazuyasu Okeie, Kazuhiko Shibata
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Congestive Heart Failure–associated Chronic Diffuse Alveolar Hemorrhage." American Journal of Respiratory and Critical Care Medicine, 204(6), pp. 723–724
Abstract 16981: Proteomic Profiles of Diabetic Heart Failure Report on Myocardial Metabolism, Ventricular Hypertrophy, and Endothelial Dysfunction
Authors: Lauren K Truby, Lydia Kwee, Jessica A Regan, Dawn E Bowles, Carmelo A Milano, Elizabeth Grass, Michael R Bristow, Robert W McGarrah, Christopher L Holley, Svati H Shah
Journal: Circulation (2020)

Introduction: There is a complex epidemiologic relationship between type two diabetes mellitus (DM) and heart failure (HF), and it is unclear whether the biochemical basis of HF differs in patients with and without DM. Hypothesis: Proteomic profiling of myocardial tissue from patients with and without DM will identify unique signatures of diabetic HF. Methods: Using the Olink aptamer-based platform, we performed proteomic profiling of 552 proteins on 37 myocardial tissue samples: 9 controls, 10 with HF, 7 with DM, and 11 with HF+DM. One-way ANOVA was first used to identify proteins that differed across the four groups. Associated proteins were then tested for differences between HF+DM and each other group independently; we retained proteins with the same direction of effect for each comparison. Each analysis was controlled for false discovery rate (q&lt;0.1). Results: We identified 12 proteins that differed significantly between HF+DM and all three other groups. Among these, six proteins were significant after FDR adjusted ANOVA and had the same direction of effect. These included 5’-NT (q=5.35E-07), a regulator of intracellular energy utilization, and carboxypeptidase A2, a metalloprotease that cleaves peptides during digestion (q=0.0003). Expression of myocardial leptin receptors (q=0.001), complement factor H related protein (q=0.003), and carbonic anhydrase (q=0.006) were also upregulated in diabetic HF, and have previously been linked to myocyte hypertrophy. Markers of endothelial dysfunction - ESM-1 (q=5.62E-06) and VEGFR-3 (q=0.024) - were also increased in HF+DM myocardium as compared to other groups (Figure 1). Conclusions: Proteomic profiling of HF, DM, and HF+DM myocardial tissue suggest alterations in intracellular energy substrate utilization as well as increased expression of tissue biomarkers previously associated with ventricular hypertrophy and myocardial remodeling.
Prospective assessment of breast cancer risk from multimodal multiview ultrasound images via clinically applicable deep learning
Authors: Xuejun Qian, Jing Pei, Hui Zheng, Xinxin Xie, Lin Yan, Hao Zhang, Chunguang Han, Xiang Gao, Hanqi Zhang, Weiwei Zheng, Qiang Sun, Lu Lu, K. Kirk Shung
Journal: Nature Biomedical Engineering (2021)
CD122-directed interleukin-2 treatment mechanisms in bladder cancer differ from αPD-L1 and include tissue-selective γδ T cell activation
Authors: Ryan Michael Reyes, Yilun Deng, Deyi Zhang, Niannian Ji, Neelam Mukherjee, Karen Wheeler, Harshita B Gupta, Alvaro S Padron, Aravind Kancharla, Chenghao Zhang, Myrna Garcia, Anand V R Kornepati, Onur Boyman, Jose R Conejo-Garcia, Robert S Svatek, Tyler J Curiel
Journal: Journal for ImmunoTherapy of Cancer (2021)

Anti-programmed death-ligand 1 (αPD-L1) immunotherapy is approved to treat bladder cancer (BC) but is effective in <30% of patients. Interleukin (IL)-2/αIL-2 complexes (IL-2c) that preferentially target IL-2 receptor β (CD122) augment CD8
THE STRUCTURE OF THE CELL
Journal: JAMA (1935)

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
Overdiagnosis of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents
Authors: Luise Kazda, Katy Bell, Rae Thomas, Kevin McGeechan, Rebecca Sims, Alexandra Barratt
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Reported increases in attention-deficit/hyperactivity disorder (ADHD) diagnoses are accompanied by growing debate about the underlying factors. Although overdiagnosis is often suggested, no comprehensive evaluation of evidence for or against overdiagnosis has ever been undertaken and is urgently needed to enable evidence-based, patient-centered diagnosis and treatment of ADHD in contemporary health services. <h3>Objective</h3> To systematically identify, appraise, and synthesize the evidence on overdiagnosis of ADHD in children and adolescents using a published 5-question framework for detecting overdiagnosis in noncancer conditions. <h3>Evidence Review</h3> This systematic scoping review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Extension for Scoping Reviews and Joanna Briggs Methodology, including the PRISMA-ScR Checklist. MEDLINE, Embase, PsychINFO, and the Cochrane Library databases were searched for studies published in English between January 1, 1979, and August 21, 2020. Studies of children and adolescents (aged ≤18 years) with ADHD that focused on overdiagnosis plus studies that could be mapped to 1 or more framework question were included. Two researchers independently reviewed all abstracts and full-text articles, and all included studies were assessed for quality. <h3>Findings</h3> Of the 12 267 potentially relevant studies retrieved, 334 (2.7%) were included. Of the 334 studies, 61 (18.3%) were secondary and 273 (81.7%) were primary research articles. Substantial evidence of a reservoir of ADHD was found in 104 studies, providing a potential for diagnoses to increase (question 1). Evidence that actual ADHD diagnosis had increased was found in 45 studies (question 2). Twenty-five studies showed that these additional cases may be on the milder end of the ADHD spectrum (question 3), and 83 studies showed that pharmacological treatment of ADHD was increasing (question 4). A total of 151 studies reported on outcomes of diagnosis and pharmacological treatment (question 5). However, only 5 studies evaluated the critical issue of benefits and harms among the additional, milder cases. These studies supported a hypothesis of diminishing returns in which the harms may outweigh the benefits for youths with milder symptoms. <h3>Conclusions and Relevance</h3> This review found evidence of ADHD overdiagnosis and overtreatment in children and adolescents. Evidence gaps remain and future research is needed, in particular research on the long-term benefits and harms of diagnosing and treating ADHD in youths with milder symptoms; therefore, practitioners should be mindful of these knowledge gaps, especially when identifying these individuals and to ensure safe and equitable practice and policy.
Racial disparities in the survival of patients with indolent <scp>non‐Hodgkin</scp> lymphomas in the United States
Authors: John L. Vaughn, Daniela Spies, Ana C. Xavier, Narendranath Epperla
Journal: American Journal of Hematology (2021)

There is a paucity of data regarding racial disparities in the survival of patients with indolent non-Hodgkin lymphomas (iNHL) in the contemporary time-period. Hence, we sought to determine whether racial disparities exist in the survival of patients with iNHLs in the US. We included 68 059 adult patients with follicular lymphoma (FL, n = 41 943), marginal zone lymphoma (MZL, n = 22 485), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM, n = 3631) who were diagnosed in the US between 2000 and 2017. Race was categorized as White, Black, Asian/Pacific Islander, or American Indian/Alaska Native (API/AI). The primary outcome was relative survival (RS), which was estimated using flexible parametric survival models. The RS estimates varied according to race and disease histology but were consistently lower for racial minorities, including those diagnosed during the most recent 5-year time-period of 2012-2017. On multivariable analysis for RS, Black patients with FL had a 32% higher excess mortality rate compared to White patients [adjusted excess hazard ratio (aEHR), 1.32; 95% CI, 1.15-1.51; p < .001], corresponding to a difference of 55 (95% CI, 24-86) excess deaths per 10 000 person-years. For MZL, Black patients had a 40% higher excess mortality rate compared to White patients (aEHR 1.40; 95% CI, 1.18-1.66; p < .001), corresponding to a difference of 62 (95% CI, 26-98) excess deaths per 10 000 person-years. No significant racial differences were detected for patients with WM. The greatest disparity was seen for younger Black patients with FL. Our findings highlight the need for interventions to improve the outcomes of Black patients with iNHLs, particularly younger Black patients with FL.
The cause of obesity is multifactorial but GPs can do more
Authors: Saud A Jukaku, Simon R P Williams
Journal: BMJ (2021)

Though the causes and ways to treat obesity are many,1 the medical profession in general, and GPs in particular, can do more to tackle the problem. Adiposity now accounts for more deaths in England and Scotland than smoking among people in middle and old age.2

Studies have shown that only 52% of adult patients have had their body mass index (BMI) documented …
EXPEDITED MITRAL VALVE REPAIR USING ONE-STOP TEE DURING THE COVID-19 PANDEMIC
Authors: Alexis K. Okoh, Amy Suhotliv, Fady Ibrahim, Abdul Hakeem, Ankur Sethi, James Coromilas, Antonio Chiricolo, Leonard Lee, Mark Russo, Chunguang Chen
Journal: Journal of the American College of Cardiology (2021)
Integration of Genomic and Transcriptomic Markers Improves the Prognosis Prediction of Acute Promyelocytic Leukemia
Authors: Xiaojing Lin, Niu Qiao, Yang Shen, Hai Fang, Qing Xue, Bowen Cui, Li Chen, Hongming Zhu, Sujiang Zhang, Yu Chen, Lu Jiang, Shengyue Wang, Junmin Li, Bingshun Wang, Bing Chen, Zhu Chen, Saijuan Chen
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The current stratification system for acute promyelocytic leukemia (APL) is based on the white blood cell (WBC) and the platelet counts (i.e., Sanz score) over the past two decades. However, the borderlines among different risk groups are sometimes ambiguous, and for some patients, early death and relapse remained challenges. Besides, with the evolving of the treatment strategy from all-trans-retinoic acid (ATRA) and chemotherapy to ATRA–arsenic trioxide-based synergistic targeted therapy, the precise risk stratification with molecular markers is needed. Experimental Design: This study performed a systematic analysis of APL genomics and transcriptomics to identify genetic abnormalities in 348 patients mainly from the APL2012 trial (NCT01987297) to illustrate the potential molecular background of Sanz score and further optimize it. The least absolute shrinkage and selection operator algorithm was used to analyze the gene expression in 323 cases to establish a scoring system (i.e., APL9 score). Results: Through combining NRAS mutations, APL9 score, and WBC, 321 cases can be stratified into two groups with significantly different outcomes. The estimated 5-year overall (P = 0.00031), event-free (P &amp;lt; 0.0001), and disease-free (P = 0.001) survival rates in the revised standard-risk group (95.6%, 93.8%, and 98.1%, respectively) were significantly better than those in the revised high-risk group (82.9%, 77.4%, and 88.4%, respectively), which could be validated using The Cancer Genome Atlas dataset. Conclusions: We have proposed a two-category system for improving prognosis in patients with APL. Molecular markers identified in this study may also provide genomic insights into the disease mechanism for improved therapy.
Endoscopic ultrasound-guided gastrojejunostomy does not prevent pancreaticoduodenectomy after long-term symptom-free neoadjuvant treatment
Authors: Giuseppe Vanella, Domenico Tamburrino, Giuseppe Dell’Anna, Maria Chiara Petrone, Stefano Crippa, Massimo Falconi, Paolo Giorgio Arcidiacono
Journal: Endoscopy (2021)

A 55-year-old woman was diagnosed with pancreatic head adenocarcinoma with hepatic artery and mesenteric vein contact. Due to cholangitis and papillary infiltration, an endoscopic ultrasound-guided choledochoduodenostomy (EUS-CD) was performed with an 8 × 8-mm electrocautery-enhanced lumen-apposing metal stent (LAMS; Hot Axios; Boston Scientific, Marlborough, Massachusetts, USA). One month later, she experienced gastric outlet obstruction (GOO) secondary to duodenal infiltration ([Fig. 1]).
Cancer-speciﬁc calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy
Authors: Dan Li, Yingli Wang, Chang Li, Qiu Wang, Bingjun Sun, Haotian Zhang, Zhonggui He, Jin Sun
Journal: Acta Pharmaceutica Sinica B (2021)

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-speciﬁc calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca2+ by inhibiting Na+/K+-ATPase, which help restrain cell-cell junctions to disaggregate CTC clusters. Meanwhile, CPDDs suppress the epithelial-mesenchymal transition (EMT) process, resulting in inhibiting tumor cells escape from the primary site. Moreover, the combination of DOX and DIG at a mass ratio of 5:1 synergistically induces the apoptosis of tumor cells. In vitro and in vivo results demonstrate that CPDDs not only effectively inhibit the generation and circulation of CTC clusters, but also precisely target and eliminate primary tumors. Our findings present a novel approach for anti-metastasis combinational chemotherapy.