tbuckley/cabot-search huggingface dataset:
Association of Residential Mobility Over the Life Course With Nonaffective Psychosis in 1.4 Million Young People in Sweden
Authors: Ceri Price, Christina Dalman, Stanley Zammit, James B. Kirkbride
Journal: JAMA Psychiatry (2018)

Residential mobility (changing residence) during childhood and early adolescence is a possible risk factor for several adverse health outcomes, including psychotic disorders. However, it is unclear whether sensitive periods to residential mobility exist over the life course, including in adulthood, or if greater moving distances, which might disrupt social networks, are associated with a greater psychosis risk.To examine the association between residential mobility over the life course and the risk of nonaffective psychosis.This prospective cohort study included all people born in Sweden between January 1, 1982, and December 31, 1995, who were alive and resided in Sweden on their 16th birthday who were followed up until up to age 29 years (ending December 2011). Participants were followed until receiving a first diagnosis of an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) nonaffective psychotic disorder (F20-29), emigration, death, or the end of 2011, whichever was sooner. National register linkage provided exposure, outcome, and covariate data (complete data were available for 1 440 383 participants [97.8%]).The exposures to distance moved and the number of residential moves were examined for participants at the following periods over the life course: 0 to 6 years, 7 to 15 years, 16 to 19 years, and 20 years and older.This study included 1 440 383 participants, of whom 4537 (0.31%) had nonaffective psychotic disorder (median age, 20.9 [interquartile range, 19.0-23.3]). More frequent moves during childhood and adolescence were associated with an increased risk of nonaffective psychosis that showed dose-response associations independent of covariates. The most sensitive period of risk occurred during late adolescence; those who moved during each year between age 16 to 19 years had an increased adjusted hazard ratio (HR) of 1.99 (95% CI, 1.30-3.05) compared with those who never moved. One move during adulthood was not associated with psychosis risk (adjusted HR, 1.04; 95% CI, 0.94-1.14), but moving 4 or more times during adulthood was associated with increased risk (adjusted hazard ratio, 1.82; 95% CI, 1.51-2.23). Independently, moving greater distances before age 16 years was associated with an increased risk (adjusted HR, 1.11; 95% CI, 1.05-1.19), with evidence of a nonlinear threshold effect for moves longer than 30 km. The distance moved after age 20 years was associated with a decreased risk (adjusted HR, 0.67; 95% CI, 0.63-0.71).Children and adolescents with less disruption in their residential environments are less likely to experience psychotic disorders in early adulthood. Moves that may necessitate changes in school and social networks were most strongly associated with future risk.
Abstract 19147: Fast, Free-breathing, Heart-rate Independent Quantitative Myocardial Oxygenation MRI at 3T for Detecting Ischemic Heart Disease Without Contrast Agents With Simultaneous 13N-Ammonia PET Validation
Authors: Hsin-Jung Yang, Damini Dey, Jane Syskes, John Butler, Xiaoming Bi, Avinash Kali, Ivan Cokic, Behzad Sharif, Sotirios Tsaftaris, Debiao Li, Piotr Slomka, Frank Prato, Rohan Dharmakumar
Journal: Circulation (2015)

Introduction: Myocardial BOLD MRI is an emerging non-contrast approach for the assessment of ischemic heart disease. Current BOLD MR methods are limited in part by poor spatial coverage, heart rate dependency and image artifacts, particularly at 3T. To address these limitations, we developed a heart-rate independent, free-breathing 3D T2 mapping technique at 3T that utilizes near perfect imaging efficiency, which can be completed within 3 minutes. We tested our approach in a canine model and validated our findings with simultaneously acquired 13N-ammonia PET perfusion data in a clinical hybrid PET-MR system. Methods: Healthy dogs (n=8) were studied with a state of the art PET-MR system (Siemens Healthcare). For validation, dynamic 13N-ammonia PET scans were simultaneously acquired with BOLD MR data. PET images were analyzed using qPET (Cedars-Sinai Medical Center). T2 values were measured from basal, mid and apical slices at rest and adenosine stress in BOLD images. Myocardial BOLD reserve (T2(stress):T2(rest)) and perfusion reserve (Q(stress):Q(rest)) were computed on a slice basis and regressed. Results: A representative set of BOLD and PET images acquired at rest and adenosine stress are shown in Fig. 2. T2 measures at stress were significantly greater than at rest (T2: 39.5±2.5 ms (rest) vs. 44.0±3.3 ms (stress), p&lt;0.05)); similar results were observed for Q (Q: 0.8±0.1 ml/mg/min (rest) vs. 2.0±0.9 ml/mg/min (stress); p&lt;0.05). Linear regression of BOLD and perfusion reserves showed high correlation (R2=0.6, p&lt;0.05). Conclusions: This is the first study to examine myocardial BOLD MRI with simultaneously acquired PET perfusion data. Our findings showed that BOLD response is highly correlated with PET perfusion suggesting that the proposed BOLD MR method is a viable non-contrast approach for imaging myocardial perfusion. Further studies are required to examine its utility in the setting of ischemic heart disease.
miRNAs in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis
Authors: Chang-Hai Liu, Javier Ampuero, Antonio Gil-Gómez, Rocío Montero-Vallejo, Ángela Rojas, Rocío Muñoz-Hernández, Rocío Gallego-Durán, Manuel Romero-Gómez
Journal: Journal of Hepatology (2018)
Evolution of Hydrogen Sulfide Therapeutics to Treat Cardiovascular Disease
Authors: Zhen Li, David J. Polhemus, David J. Lefer
Journal: Circulation Research (2018)

Hydrogen sulfide (H 2 S)—a potent gaseous signaling molecule—has emerged as a critical regulator of cardiovascular homeostasis. H 2 S is produced enzymatically by 3 constitutively active endogenous enzymes in all mammalian species. Within the past 2 decades, studies administering H 2 S-donating agents and the genetic manipulation of H 2 S-producing enzymes have revealed multiple beneficial effects of H 2 S, including vasodilation, activation of antiapoptotic and antioxidant pathways, and anti-inflammatory effects. More recently, the heightened enthusiasm in this field has shifted to the development of novel H 2 S-donating agents that exert favorable pharmacological profiles. This has led to the discovery of novel H 2 S-mediated signaling pathways. This review will discuss recently developed H 2 S therapeutics, introduce signaling pathways that are influenced by H 2 S-dependent sulfhydration, and explore the dual-protective effect of H 2 S in cardiorenal syndrome.
Ramucirumab as Second-Line Systemic Therapy in Hepatocellular Carcinoma
Authors: Masatoshi Kudo
Journal: Liver Cancer (2018)

Ramucirumab, a molecular targeted agent, is a recombinant human IgG1 monoclonal antibody directed against vascular endothelial growth factor receptor 2 (VEGFR-2) that plays an important role in vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. It inhibits VEGFR-2 activation by blocking its binding to VEGF-A, VEGF-C, and VEGF-D, thereby inhibiting endothelial growth, migration, and survival and exerting antitumor effects via inhibition of tumor angiogenesis. Ramucirumab is currently indicated for unresectable advanced/recurrent gastric cancer, colorectal cancer, and non-small-cell lung cancer and is used in routine clinical practice. A randomized phase III trial (REACH-2) investigated ramucirumab as second-line treatment following first-line sorafenib therapy for advanced hepatocellular carcinoma (HCC) in patients with an alpha-fetoprotein (AFP) level ≥400 ng/mL, and results demonstrating the superiority of ramucirumab over placebo in overall survival (OS) were reported at the American Society of Clinical Oncology (ASCO) annual meeting in June 2018. This article outlines the results of the REACH-2 trial and previous clinical trials of ramucirumab (REACH).
Peroral Endoscopic Myotomy Is Effective for Patients With Achalasia and Normal Lower-Esophageal Sphincter Relaxation Pressures
Authors: Madhusudhan R. Sanaka, Malav P. Parikh, Prashanthi N. Thota, Niyati M. Gupta, Scott Gabbard, Rocio Lopez, Sudish Murthy, Siva Raja
Journal: Clinical Gastroenterology and Hepatology (2018)
Efficacy of Resistance Exercise Training With Depressive Symptoms
Authors: Sammi R. Chekroud, Adam M. Chekroud
Journal: JAMA Psychiatry (2018)

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Abstract 12659: Hepatoma-Derived Growth Factor Related Protein-3 as a Novel Endothelial Ligand
Authors: Michelle LeBlanc, Weiwen Wang, Feiye Guo, Chen Shen, Rui Chen, Feng Wang, Wei Li
Journal: Circulation (2014)

Background: Endothelial ligands extrinsically regulate a broad spectrum of vascular functions with therapeutic potentials, but are traditionally identified on a case-by-case basis with technical challenges. We recently developed open reading frame phage display (OPD) for unbiased identification of phagocytosis ligands. In this study, we identified hepatoma-derived growth factor related protein-3 (HRP-3) as a putative endothelial ligand by OPD. We hypothesized that HRP-3 is a novel endothelial growth factor, capable of promoting endothelial cell (EC) growth and migration. Methods and Results: We performed 3 rounds of in vivo phage binding selection in mice with an OPD library, screened enriched phage clones by next generation DNA sequencing, and identified HRP-3 as one of the putative endothelial ligands. To confirm the finding, clonal phages displaying HRP-3, VEGF and GFP were generated and analyzed for their binding to human umbilical vein endothelial cells (HUVECs). The results show that HRP-3-Phage and VEGF-Phage had significantly higher binding to HUVECs than GFP-Phage. Functional analysis showed that purified recombinant HRP-3 significantly increased the proliferation of HUVECs at 24 and 48 h, whereas VEGF induced significant growth only at 48 h. Consistent with these findings, HRP-3 significantly stimulated cell proliferation by MTT assay. In vitro wound-healing assay indicated that both HRP-3 (500 ng/ml) and VEGF (50 ng/ml) significantly promoted the migration of HUVECs into the denuded area. To dissect the downstream signaling pathway, we demonstrated that HRP-3 significantly induced ERK1/2 phosphorylation in HUVECs after 10 min treatment. Similar effects of HRP-3 and VEGF on EC growth, migration, and ERK activation were also verified using human aorta endothelial cells. Conclusions: Our findings demonstrate that HRP-3 is a novel ligand, capable of promoting proliferation and migration of ECs. The pro-growth effect of HRP-3 is at least partially mediated through ERK pathway activation. These results in turn support the broad applicability of OPD for the systematic discovery of endothelial ligands.
Abstract 16326: Replication of Previously Reported Anthracycline Cardiotoxicity Risk Variants in a Large Electronic Health Record Based Cohort
Authors: Elizabeth P Held, Eric Farber-Eger, Marcia Blair, Quinn S Wells
Journal: Circulation (2016)

Introduction: Anthracyclines have well described cardiotoxic effects that limit their clinical use. Prior studies have identified putative risk alleles for anthracycline cardiotoxicity (ACT), howev...
Abstract 18019: Activation of Hepatic Hif-2a Signaling Perturbs Cholesterol Homeostasis in Mice
Authors: Sadeesh K Ramakrishnan
Journal: Circulation (2015)

Cardiovascular disease (CVD) is the leading cause of death in the United States. Therefore, identifying novel pathways involved in the pathogenesis of CVD becomes imperative. Inflammation and hypercholesterolemia are the two hallmarks of CVD. Patients with chronic intermittent hypoxia or obstructive sleep apnea are at high risk for CVD due to aberrant cholesterol levels. Evolutionarily, cholesterol synthesis is a highly oxygen and energy dependent process. Therefore, the molecular mechanism involved in the paradoxical increase in cholesterol during hypoxia remains unclear. Hypoxia signaling is mediated through a well-conserved hypoxia driven transcription factors, hypoxia-inducible factor (HIF)-1 and HIF-2. Mice with a liver-specific disruption of the Von Hippel Lindau protein ( Vhl LivKO ), a critical E3 ubiquitin ligase that degrades HIFs, exhibit increased levels of HIF-1 and HIF-2 protein and develop hepatic steatosis, systemic inflammation, hypercholesterolemia and have decreased survival. Moreover, we show that the transcription factor hypoxia-inducible factor (HIF)-2 is highly activated in the liver of rodent models of atherogenesis. Activation of HIF-2 in liver disrupts the circadian expression of cholesterol hydroxylases leading to hypercholesterolemia. Using a comprehensive metabolomic analysis, we identified an arginine metabolite, asymmetric dimethylarginine (ADMA) is highly induced in the serum and liver of C57BL/6 mice fed with high cholesterol diet. ADMA potently activates HIF-2 in human hepatoma HepG2 and colon-derived SW-480 cells. Our results demonstrate that metabolite induced HIF-2 signaling in liver perturbs cholesterol homeostasis leading to systemic inflammation and hypercholesterolemia.
Association of the Use of a Mandatory Prescription Drug Monitoring Program With Prescribing Practices for Patients Undergoing Elective Surgery
Authors: Ryland S. Stucke, Julia L. Kelly, Kristina A. Mathis, Maureen V. Hill, Richard J. Barth
Journal: JAMA Surgery (2018)

Most states have adopted the routine use of a prescription drug monitoring program (PDMP) to curb overprescribing of opioids. The American College of Surgeons promotes the use of these programs as a "guiding principle to curb the opioid epidemic." However, there is a paucity of data on the effects of the use of these programs for surgical patient populations.To determine the association of the mandatory use of a PDMP with the opioid prescribing practices for patients undergoing general surgery.A prospective observational cohort study was conducted at an academic hospital in New Hampshire among 1057 patients undergoing representative elective general surgical procedures from July 1, 2016, to June 30, 2017.New state legislation mandated the use of a PDMP and opioid risk-assessment tool for all patients receiving an outpatient opioid prescription in New Hampshire beginning January 1, 2017. The electronic medical prescribing system was modified to facilitate and support compliance with the new requirements.Change in opioid prescribing practices after January 1, 2017, and time to complete PDMP requirements.Among the 1057 patients (569 women [53.8%] and 488 men [46.2%]; mean [SD] age, 56.8 [15.4] years), the percentage of patients prescribed opioids after surgery did not decrease significantly (429 of 536 [80.0%] before the new requirements vs 401 of 521 [77.0%] after the requirements; P = .29). The mean number of opioid pills prescribed decreased from 30.8 to 24.0 (22.1%) in the 6 months prior to the mandatory PDMP requirement; the rate of decrease was actually less (from 22.8 to 21.9 pills [3.9%]) in the 6 months after the legislation. These new requirements did not identify any high-risk patients who subsequently were not prescribed opioids. The query and opioid abuse risk calculator together took a median time of 7 minutes (range, 2-17 minutes) to complete.A mandatory PDMP query requirement was not significantly associated with the overall rate of opioid prescribing or the mean number of pills prescribed for patients undergoing general surgical procedures. In no cases was a high-risk patient identified, leading to avoidance of an opioid prescription. A PDMP can be a useful adjunct in certain settings, but this study found that it did not have the intended effect in a population undergoing elective surgical procedures. Legislative efforts to mandate PDMP use should be targeted to populations in which benefit can be demonstrated.
Dual-targeted casein micelles as green nanomedicine for synergistic phytotherapy of hepatocellular carcinoma
Authors: Mona A. Abdelmoneem, Mazen Mahmoud, Amira Zaky, Maged W. Helmy, Marwa Sallam, Jia-You Fang, Kadria A. Elkhodairy, Ahmed O. Elzoghby
Journal: Journal of Controlled Release (2018)
Systemic and stratum corneum biomarkers of severity in infant atopic dermatitis include markers of innate and T helper cell‐related immunity and angiogenesis
Authors: M.A. McAleer, I. Jakasa, G. Hurault, P. Sarvari, W.H.I. McLean, R.J. Tanaka, S. Kezic, A.D. Irvine
Journal: British Journal of Dermatology (2018)

Biomarkers of atopic dermatitis (AD) are largely lacking, especially in infant AD. Those that have been examined to date have focused mostly on serum cytokines, with few on noninvasive biomarkers in the skin.We aimed to explore biomarkers obtainable from noninvasive sampling of infant skin. We compared these with plasma biomarkers and structural and functional measures of the skin barrier.We recruited 100 infants at first presentation with AD, who were treatment naive to topical or systemic anti-inflammatory therapies, and 20 healthy children. We sampled clinically unaffected skin by tape stripping the stratum corneum (SC). Multiple cytokines and chemokines and natural moisturizing factor were measured in the SC and plasma. We recorded disease severity and skin barrier function.Nineteen SC and 12 plasma biomarkers showed significant differences between healthy and AD skin. Some biomarkers were common to both the SC and plasma, and others were compartment specific. Identified biomarkers of AD severity included T helper 2-skewed markers [interleukin (IL)-13, CCL17, CCL22, IL-5]; markers of innate activation (IL-18, IL-1α, IL1β, CXCL8) and angiogenesis (Flt-1, vascular endothelial growth factor); and others (soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, IL-16, IL-17A).We identified clinically relevant biomarkers of AD, including novel markers, easily sampled and typed in infants. These markers may provide objective assessment of disease severity and suggest new therapeutic targets, or response measurement targets for AD. Future studies will be required to determine whether these biomarkers, seen in very early AD, can predict disease outcomes or comorbidities.
Abstract 19365: The Novel Biomarker Osteopontin Predicts Adverse Outcome in Patients Undergoing Treatment of Severe Aortic Stenosis by TAVI
Authors: Matthias Lutz, Nora Ingersleben, Mark Rosenberg, Sandra Freitag-Wolf, Doreen Brehm, Norbert Frey, Derk Frank
Journal: Circulation (2014)

Background: Osteopontin (OPN) is an extracellular matrix protein that plays an integral role in myocardial remodeling and was previously shown as an important emerging biomarker in risk evaluation of cardiovascular disease. However, its prognostic value in patients with pressure overload of the left ventricular, caused by symptomatic severe aortic valve stenosis, undergoing transcatheter aortic valve implantation (TAVI) remains unclear. Methods: N=217 patients undergoing TAVI (using balloon-expandable Edwards Sapien XT prostheses) were included prospectively over a continuous period from Feb. 2011 until Dec. 2013. For all patients a complete clinical data set including biomarkers (OPN and NTproBNP), basic clinical assessment and echocardiography before and 7 days after TAVI was obtained. The primary endpoint was survival time. During median follow-up of 349d (Q1, Q3: 106-659.5d), a total of 66 deaths occurred, 30d mortality was 6.9%. Mean age was 81.8 years (± 6.03 y) and 55.8 % of the patients were female. Mean log. Euroscore was 25.4% (± 17.2%) and mean STS Score was 6.2% (± 3.8%). Results: Median preprocedurale OPN values were significantly elevated in patients with severe aortic valve stenosis compared to healthy controls (675 ng/ml, Q1,Q3: 488.5-990.5 ng/ml vs. 386 ng/ml, Q1, Q3: 324.5 - 458.0, p&lt;0.001). Increased OPN levels before TAVI (upper quartile compared to lower three quartiles) revealed a HR of 2.151 (CI 1.31-3.531, p=0.002) for reduced survival. Multivariate Cox regression analysis including NTproBNP, postprocedural aortic regurgitation, atrial fibrillation, clinical risk scores and preprocedural left ventricular function (EF) demonstrates that OPN is even superior to NTproBNP and preprocedural EF in predicting adverse prognosis, showing a HR of 1.826 (CI 1.096-3.044, p=0.021). Conclusions: Elevated OPN levels predict adverse outcome in patients with severe aortic stenosis undergoing TAVI. OPN is superior to the established biomarker NTproBNP in risk stratification of patients undergoing TAVI.
Observed versus predicted mortality after MitraClip treatment in patients with symptomatic heart failure and significant functional mitral regurgitation
Authors: Cosmo Godino, Andrea Scotti, Andrea Munafò, Maurizio Taramasso, Marianna Adamo, Marco Russo, Evelina Toscano, Anna Salerno, Alberto Cappelletti, Stefano Stella, Gabriele Fragasso, Matteo Montorfano, Eustachio Agricola, Federica Ettori, Alberto Margonato, Francesco Maisano, Antonio Colombo
Journal: European Journal of Heart Failure (2018)