tbuckley/cabot-search huggingface dataset:
Evaluating the sensitivity and specificity of NEATstik technology compared to an activity-based immunoassay in sputum samples from participants with COPD
Authors: Samantha J. Thulborn, Jennifer L. Cane, Clare Connolly, Catherine Borg, Kelly L. Moffitt, David Ribeiro, Charlene Robb, Richard E.K. Russell, Mona Bafadhel
Journal: European Respiratory Journal (2020)

<b>NEATstik is a point of care test which gives a qualitative result on whether neutrophil elastase is elevated from sputum in 10 min with minimal processing and could be of benefit in clinical practice</b>http://bit.ly/2SohUhf
Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer
Authors: Jie Sun, Zicheng Zhang, Siqi Bao, Congcong Yan, Ping Hou, Nan Wu, Jianzhong Su, Liangde Xu, Meng Zhou
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Increasing evidence has demonstrated the functional relevance of long non-coding RNAs (lncRNAs) to immunity regulation and the tumor microenvironment in non-small cell lung cancer (NSCLC). However, tumor immune infiltration-associated lncRNAs and their value in improving clinical outcomes and immunotherapy remain largely unexplored. Methods We developed a computational approach to identify an lncRNA signature (TILSig) as an indicator of immune cell infiltration in patients with NSCLC through integrative analysis for lncRNA, immune and clinical profiles of 115 immune cell lines, 187 NSCLC cell lines and 1533 patients with NSCLC. Then the influence of the TILSig on the prognosis and immunotherapy in NSCLC was comprehensively investigated. Results Computational immune and lncRNA profiling analysis identified an lncRNA signature (TILSig) consisting of seven lncRNAs associated with tumor immune infiltration. The TILSig significantly stratified patients into the immune-cold group and immune-hot group in both training and validation cohorts. These immune-hot patients exhibit significantly improved survival outcome and greater immune cell infiltration compared with immune-cold patients. Multivariate analysis revealed that the TILSig is an independent predictive factor after adjusting for other clinical factors. Further analysis accounting for TILSig and immune checkpoint gene revealed that the TILSig has a discriminatory power in patients with similar expression levels of immune checkpoint genes and significantly prolonged survival was observed for patients with low TILSig and low immune checkpoint gene expression implying a better response to immune checkpoint inhibitor (ICI) immunotherapy. Conclusions Our finding demonstrated the importance and value of lncRNAs in evaluating the immune infiltrate of the tumor and highlighted the potential of lncRNA coupled with specific immune checkpoint factors as predictive biomarkers of ICI response to enable a more precise selection of patients.
Susceptibility of Rat Steatotic Liver to Ischemia–Reperfusion Is Treatable With Liver‐Selective Matrix Metalloproteinase Inhibition
Authors: Xiangdong Wang, Christopher J. Walkey, Ana C. Maretti‐Mira, Lei Wang, Deborah L. Johnson, Laurie D. DeLeve
Journal: Hepatology (2020)

Background and Aims This study examined whether enhanced susceptibility of steatotic liver to ischemia–reperfusion (I/R) injury is due to impaired recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (LSECs, also called sinusoidal endothelial cell progenitor cells [sprocs]) with diminished repair of injured LSECs and whether restoring signaling to recruit BM sprocs reduces I/R injury. Approach and Results Hepatic vessels were clamped for 1 hour in rats fed a high‐fat, high‐fructose (HFHF) diet for 5, 10, or 15 weeks. Matrix metalloproteinase 9 (MMP‐9) antisense oligonucleotides (ASO) or an MMP inhibitor were used to induce liver‐selective MMP‐9 inhibition. HFHF rats had mild, moderate, and severe steatosis, respectively, at 5, 10, and 15 weeks. I/R injury was enhanced in HFHF rats; this was accompanied by complete absence of hepatic vascular endothelial growth factor (VEGF)–stromal cell–derived factor 1 (sdf1) signaling, leading to lack of BM sproc recruitment. Liver‐selective MMP‐9 inhibition to protect against proteolytic cleavage of hepatic VEGF using either MMP‐9 ASO or intraportal MMP inhibitor in 5‐week and 10‐week HFHF rats enhanced hepatic VEGF–sdf1 signaling, increased BM sproc recruitment, and reduced alanine aminotransferase (ALT) by 92% and 77% at 5 weeks and by 80% and 64% at 10 weeks of the HFHF diet, respectively. After I/R injury in 15‐week HFHF rats, the MMP inhibitor reduced active MMP‐9 expression by 97%, ameliorated histologic evidence of injury, and reduced ALT by 58%, which is comparable to control rats sustaining I/R injury. Rescue therapy with intraportal MMP inhibitor, given after ischemia, in the 5‐week HFHF rat reduced ALT by 71% and reduced necrosis. Conclusions Lack of signaling to recruit BM sprocs that repair injured LSECs renders steatotic liver more susceptible to I/R injury. Liver‐selective MMP‐9 inhibition enhances VEGF–sdf1 signaling and recruitment of BM sprocs, which markedly protects against I/R injury, even in severely steatotic rats.
Treatment of Hepatocellular Carcinoma in the Precision Medicine Era: From Treatment Stage Migration to Therapeutic Hierarchy
Authors: Alessandro Vitale, Franco Trevisani, Fabio Farinati, Umberto Cillo
Journal: Hepatology (2020)

Treatment allocation is extremely complex in patients with hepatocellular carcinoma (HCC) because this neoplasm arises, in most cases, in patients with cirrhosis and additional comorbidities. The "stage hierarchy" approach, which involves linking each stage (or substage) of the disease to a specific treatment, has become the main proposed treatment strategy for the clinical management of HCC, particularly in the West. The Barcelona Clinic Liver Cancer (BCLC) scheme serves as the main example of the application of this strategy. In an attempt to increase the plasticity of the "stage hierarchy" approach as well as its adaptability to the requirements of real-world clinical practice, the latest versions of European and American guidelines have introduced certain relevant elements of flexibility, which were not intrinsic to the original BCLC scheme. These elements are as follows: the "treatment stage migration" strategy, which allows moving to another treatment (generally the one that is associated with the subsequent stage) if the approach linked with the current stage proves to be unfeasible, and the "treatment stage alternative" approach, which proposes further therapeutic options for each BCLC-defined stage. In regard to most of the solid cancers, another potential strategy is to consider the treatment decision to be hierarchically dictated by the efficacy of each therapy with complete or partial independence from the tumor stage. This concept of "therapeutic hierarchy" has been historically endorsed by the Asia-Pacific treatment algorithm as well as by the recent Italian multisociety guidelines. The present review provides a critical analysis of the different conceptual approaches to HCC management, highlighting their advantages and disadvantages and focusing on the remarkable differences between the stage-guided and the hierarchical strategies.
Lumen-apposing metal stent placement for drainage of pancreatic fluid collections: predictors of adverse events
Authors: Ji Young Bang, Robert H Hawes, Shyam Varadarajulu
Journal: Gut (2020)

Although rare in occurrence, adverse events such as delayed bleeding and buried stent syndrome have been reported after lumen-apposing metal stents (LAMS) placement in patients undergoing endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs). In a prospective study, we observed delayed adverse events in 6.4% of 188 patients which occurred when the PFCs were 7 cm or smaller in size and the removal of LAMS was delayed beyond 4 weeks.

LAMS are being increasingly preferred over double pigtail plastic stents for patients undergoing EUS-guided PFC drainage because their deployment is technically easy and the wide lumen facilitates quick drainage of cyst contents. However, delayed adverse events such as bleeding and buried stent syndrome have been reported after LAMS placement.1–3 In this study, we attempted to identify predictors of adverse events by examining data that were collected prospectively in all patients undergoing EUS-guided PFC drainage using LAMS. By institutional protocol, after LAMS placement, the endoprostheses were removed at outpatient follow-up in 3–4 weeks and all patients were contacted by telephone call to obtain follow-up at 6 months. The data collected included 292 demographic, laboratory, radiological, technical, clinical and treatment outcome variables, with a minimum follow-up duration of 6 months (NCT02422095).

Patient details, PFC characteristics, disease severity and clinical outcomes were summarised as means with SD and medians with IQR for continuous variables and as frequencies and proportions for categorical variables. In order to identify the factors associated with …
Association Between Sexual Orientation and Lifetime Prevalence of Skin Cancer in the United States
Authors: Sean Singer, Elizabeth Tkachenko, Rebecca I. Hartman, Arash Mostaghimi
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Sexual minority men have reported higher rates of both indoor tanning and skin cancer than heterosexual men, and sexual minority women have reported lower or equal rates of both indoor tanning and skin cancer compared with heterosexual women. Bisexual men, in particular, have reported higher rates of indoor tanning bed use than heterosexual men; however, no study has investigated skin cancer prevalence among gay, lesbian, and bisexual individuals as separate groups. <h3>Objective</h3> To evaluate the association between sexual orientation and lifetime prevalence of skin cancer. <h3>Design, Setting, and Participants</h3> This cross-sectional study analyzed data from the 2014-2018 Behavioral Risk Factor Surveillance System (BRFSS) surveys of a noninstitutionalized population in the United States that included 877 650 adult participants who self-identified as being heterosexual, gay, lesbian, or bisexual. <h3>Main Outcomes and Measures</h3> Self-reported lifetime history of skin cancer. <h3>Results</h3> The study included 877 650 participants, including 364 833 heterosexual men (mean age, 47.7; 95% CI, 47.5-47.8), 7823 gay men (mean age, 42.7; 95% CI, 41.8-43.6), 5277 bisexual men (mean age, 39.4; 95% CI, 38.4-40.5), 484 341 heterosexual women (mean age, 49.7; 95% CI, 49.6-49.8), 5609 lesbian women (mean age, 41.8; 95% CI, 40.6-43.0), and 9767 bisexual women (mean age, 32.8; 95% CI, 32.3-33.3). The adjusted odds ratios (AORs) of skin cancer prevalence were significantly higher among both gay (AOR, 1.25; 95% CI, 1.03-1.50;<i>P</i> = .02) and bisexual men (AOR, 1.46; 95% CI, 1.01-2.10;<i>P</i> = .04) compared with heterosexual men. The AORs of skin cancer were statistically significantly lower among bisexual women (AOR, 0.75; 95% CI, 0.60-0.95;<i>P</i> = .02) but not among gay or lesbian women (AOR, 1.01; 95% CI, 0.77-1.33;<i>P</i> = .95) compared with the AORs of skin cancer among heterosexual women. <h3>Conclusions and Relevance</h3> In this study, gay and bisexual men had an increased self-reported lifetime prevalence of skin cancer compared with the prevalence among heterosexual men. Patient education and community outreach initiatives focused on reducing skin cancer risk behaviors among gay and bisexual men may help reduce the lifetime development of skin cancer in this population. Continued implementation of the Behavioral Risk Factor Surveillance System's sexual orientation and gender identity module is imperative to improve understanding of the health and well-being of sexual minority populations.
Clonal tracking in gene therapy patients reveals a diversity of human hematopoietic differentiation programs
Authors: Emmanuelle Six, Agathe Guilloux, Adeline Denis, Arnaud Lecoules, Alessandra Magnani, Romain Vilette, Frances Male, Nicolas Cagnard, Marianne Delville, Elisa Magrin, Laure Caccavelli, Cécile Roudaut, Clemence Plantier, Steicy Sobrino, John Gregg, Christopher L. Nobles, John K. Everett, Salima Hacein-Bey-Abina, Anne Galy, Alain Fischer, Adrian J. Thrasher, Isabelle André, Marina Cavazzana, Frederic D. Bushman
Journal: Blood (2020)
Sudden Cardiac Arrest Survivorship: A Scientific Statement From the American Heart Association
Authors: Kelly N. Sawyer, Teresa R. Camp-Rogers, Pavitra Kotini-Shah, Marina Del Rios, Michelle R. Gossip, Vivek K. Moitra, Kirstie L. Haywood, Cynthia M. Dougherty, Steven A. Lubitz, Alejandro A. Rabinstein, Jon C. Rittenberger, Clifton W. Callaway, Benjamin S. Abella, Romergryko G. Geocadin, Michael C. Kurz
Journal: Circulation (2020)

Cardiac arrest systems of care are successfully coordinating community, emergency medical services, and hospital efforts to improve the process of care for patients who have had a cardiac arrest. As a result, the number of people surviving sudden cardiac arrest is increasing. However, physical, cognitive, and emotional effects of surviving cardiac arrest may linger for months or years. Systematic recommendations stop short of addressing partnerships needed to care for patients and caregivers after medical stabilization. This document expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac arrest survivorship.
Measuring Quality in Kidney Care: An Evaluation of Existing Quality Metrics and Approach to Facilitating Improvements in Care Delivery
Authors: Mallika L. Mendu, Sri Lekha Tummalapalli, Krista L. Lentine, Kevin F. Erickson, Susie Q. Lew, Frank Liu, Edward Gould, Michael Somers, Pranav S. Garimella, Terrence O’Neil, David L. White, Rachel Meyer, Scott D. Bieber, Daniel E. Weiner
Journal: Journal of the American Society of Nephrology (2020)

Leveraging quality metrics can be a powerful approach to identify substantial performance gaps in kidney disease care that affect patient outcomes. However, metrics must be meaningful, evidence-based, attributable, and feasible to improve care delivery. As members of the American Society of Nephrology Quality Committee, we evaluated existing kidney quality metrics and provide a framework for quality measurement to guide clinicians and policy makers.We compiled a comprehensive list of national kidney quality metrics from multiple established kidney and quality organizations. To assess the measures' validity, we conducted two rounds of structured metric evaluation, on the basis of the American College of Physicians criteria: importance, appropriate care, clinical evidence base, clarity of measure specifications, and feasibility and applicability.We included 60 quality metrics, including seven for CKD prevention, two for slowing CKD progression, two for CKD management, one for advanced CKD and kidney replacement planning, 28 for dialysis management, 18 for broad measures, and two patient-reported outcome measures. We determined that on the basis of defined criteria, 29 (49%) of the metrics have high validity, 23 (38%) have medium validity, and eight (13%) have low validity.We rated less than half of kidney disease quality metrics as highly valid; the others fell short because of unclear attribution, inadequate definitions and risk adjustment, or discordance with recent evidence. Nearly half of the metrics were related to dialysis management, compared with only one metric related to kidney replacement planning and two related to patient-reported outcomes. We advocate refining existing measures and developing new metrics that better reflect the spectrum of kidney care delivery.
Abstract 12009: Exploring Effects of Aerobic Exercise and Mindfulness Training on Cognitive Function in Older Adults at Risk of Dementia: The Active Minds Study
Authors: Elena Salmoirago-Blotcher, Dyuti Trivedi, Shira Dunsiger, Christopher Breault, Claudia Y Santos, Kristie Harris, Peter J Snyder
Journal: Circulation (2018)

Introduction: We conducted a pilot RCT to explore whether mindfulness training (MT), an intervention design to increase the moment-to-moment awareness of physical sensations, affective states and t...
Epstein–Barr Virus miRNA BART2-5p Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing RND3
Authors: Chen Jiang, Lei Li, Yan-Qun Xiang, Maria Li Lung, Tingting Zeng, Jiabin Lu, Sai Wah Tsao, Mu-Sheng Zeng, Jing-Ping Yun, Dora L.W. Kwong, Xin-Yuan Guan
Journal: Cancer Research (2020)

Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-related malignancy. Recently, we found that the EBV-encoded miRNA BART2-5p was increased in the serum of patients with preclinical nasopharyngeal carcinoma and that the copy number positively correlated with disease progression. In this study, we established its role in nasopharyngeal carcinoma progression and explored underlying mechanisms and clinical significance. BART2-5p was an independent unfavorable prognostic factor for progression-free survival and its circulating abundance positively associated with distant metastasis. Ectopic expression of BART2-5p promoted migration and invasion of EBV-negative nasopharyngeal carcinoma cells, whereas genetic downregulation of BART2-5p in EBV-positive nasopharyngeal carcinoma cells decreased aggressiveness. Mechanistically, BART2-5p targeted RND3, a negative regulator of Rho signaling. Downregulation of RND3 phenocopied the effect of BART2-5p and reconstitution of RND3 rescued the phenotype. By suppressing RND3, BART2-5p activated Rho signaling to enhance cell motility. These findings suggest a novel role for EBV miRNA BART2-5p in promoting nasopharyngeal carcinoma metastasis and its potential value as a prognostic indicator or therapeutic target. SIGNIFICANCE: This study shows that EBV-encoded BART2-5p miRNA suppresses expression of the RND3 Rho family GTPase, consequently promoting ROCK signaling, cell motility, and metastatic behavior of NPC cells.
Multiplexed monitoring of a novel autoantibody diagnostic signature of colorectal cancer using HaloTag technology-based electrochemical immunosensing platform
Authors: María Garranzo-Asensio, Ana Guzmán-Aránguez, Eloy Povedano, Víctor Ruiz-Valdepeñas Montiel, Carmen Poves, María Jesús Fernandez-Aceñero, Ana Montero-Calle, Guillermo Solís-Fernández, Servando Fernandez-Diez, Jordi Camps, Meritxell Arenas, Elisabeth Rodríguez-Tomàs, Jorge Joven, Maricruz Sanchez-Martinez, Nuria Rodriguez, Gemma Dominguez, Paloma Yáñez-Sedeño, José Manuel Pingarrón, Susana Campuzano, Rodrigo Barderas
Journal: Theranostics (2020)

Background and Purpose:The humoral immune response in cancer patients can be used for early detection of the disease.Autoantibodies raised against tumor-associated antigens (TAAs) are promising clinical biomarkers for reliable cancer diagnosis, prognosis, and therapy monitoring.In this study, an electrochemical disposable multiplexed immunosensing platform able to integrate difficult-and easy-to-express colorectal cancer (CRC) TAAs is reported for the sensitive determination of eight CRC-specific autoantibodies.Methods: The electrochemical immunosensing approach involves the use of magnetic microcarriers (MBs) as solid supports modified with covalently immobilized HaloTag fusion proteins for the selective capture of specific autoantibodies.After magnetic capture of the modified MBs onto screen-printed carbon working electrodes, the amperometric responses measured using the hydroquinone (HQ)/H2O2 system were related to the levels of autoantibodies in plasma. Results:The biosensing platform was applied to the analysis of autoantibodies against 8 TAAs described for the first time in this work in plasma samples from healthy asymptomatic individuals (n=3), and patients with high-risk of developing CRC (n=3), and from patients already diagnosed with colorectal (n=3), lung (n=2) or breast (n=2) cancer.The developed bioplatform demonstrated an improved discrimination between CRC patients and controls (asymptomatic healthy individuals and breast and lung cancer patients) compared to an ELISA-like luminescence test. Ivyspring International
Comparison of 5 Different PET Radiopharmaceuticals for the Detection of Recurrent Medullary Thyroid Carcinoma
Authors: Sang-Woo Lee, Sung Ryul Shim, Shin Young Jeong, Seong-Jang Kim
Journal: Clinical Nuclear Medicine (2020)

Purpose The aim of this study is to investigate and compare the performance of different PET radiopharmaceuticals for the detection of recurrent medullary thyroid carcinoma (MTC) by performing a network meta-analysis (NMA) using direct comparison studies with 2 or more PET radiopharmaceuticals. Methods PubMed and EMBASE were searched for the studies evaluating the performance of PET or PET/CT for the detection of recurrent MTC. The NMA was performed for different PET radiopharmaceuticals in both patient- and lesion-based analyses and with a threshold of serum calcitonin or carcinoembryonic antigen (CEA) levels and calcitonin doubling time. The consistency was evaluated by examining the agreement between direct and indirect treatment effects, and publication bias was assessed by funnel plot asymmetry tests. The surface under the cumulative ranking curve values were obtained to calculate the probability of each PET modality being the most effective diagnostic method. Results A total of 306 patients from 14 direct comparison studies using 5 different PET radiopharmaceuticals ( 18 F-FDG, 18 F-DOPA, 68 Ga-somatostatin analogs, 3-O-methyl-6-[ 18 F]fluoro-DOPA, and 11 C-methionine) for the detection of recurrent MTC was included. The detection rate of 18 F-DOPA PET was significantly higher than that of FDG PET in both patient- and lesion-based analyses (patient-based analysis: odds ratio, 2.44; 95% confidence interval, 1.4–4.31; lesion-based analysis: odds ratio, 5.74; 95% confidence interval, 1.65–23.4). Among all PET radiopharmaceuticals, 18 F-DOPA showed the highest surface under the cumulative ranking curve value in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time. Conclusions The results from this NMA indicate that 18 F-DOPA PET clearly showed a best performance for the detection of recurrent MTC in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time.