tbuckley/cabot-search huggingface dataset:
New insights into the role and mechanism of c‐Jun‐N‐terminal kinase signaling in the pathobiology of liver diseases
Authors: Sanda Win, Tin Aung Than, Jun Zhang, Christina Oo, Robert Win Maw Min, Neil Kaplowitz
Journal: Hepatology (2017)

The c‐Jun‐N‐terminal‐kinase (JNK) family is highly conserved across species such as Drosophila, C. elegans , zebrafish and mammals, and plays a central role in hepatic physiologic and pathophysiologic responses. These responses range from cell death to cell proliferation and carcinogenesis, as well as metabolism and survival, depending on the specific context and duration of activation of the JNK signaling pathway. Recently, several investigators identified the key molecules in the JNK activation loop which include apoptosis signal‐regulating kinase (ASK1) and SH3‐domain binding protein 5 (Sab) and their involvement in acute or chronic liver disease models. Thus, regulating JNK activation through modulating the JNK activation loop may represent an important new strategy in the prevention and treatment of acute and chronic liver diseases. In this review, we will discuss the molecular pathophysiology of the JNK activation loop and its role in the pathogenesis of liver diseases. (H epatology 2018;67:2013‐2024).
Abstract B33: The role of WWOX in HNSCC through Wnt/beta-catenin pathway
Authors: Ayse Nur Buyru, Asuman Celebi, Betul Seyhan
Journal: Cancer Research (2017)

Abstract The second most common fragile site in the human genome is the FRA16D region where the WWOX gene is localized which codes for a 414 amino acid protein. WWOX is a member of the WW-domain containing protein family consisting of 2000 members. It is a partner of several transcription factors and therefore functions in multiple physiological and pathological processes such as cell growth, differentiation and tumor suppression. Genomic alterations within the WWOX gene and its differential expression have been found in a variety of human tumors. Although some transcription factor partners of the WWOX protein have been identified its exact mechanism of action is not known. A recent study indicated that WWOX inhibits the Wnt/β-catenin pathway by preventing the nuclear import of the Dishvelled (Dvl) proteins. Dvl proteins are the main down-stream target of Wnt receptors (Frizzled- FRZ). Following binding of Wnt to its receptor alterations of β-catenin degradation lead to β-catenin accumulation in the cytoplasm. Accumulated β-catenin translocates into the nucleus and activates expression of target genes. Therefore dysregulation of the Wnt signaling pathway is a key oncogenic mechanism in many different cancers. Although Wnt and its receptor FRZ have been analyzed in head and neck squamous cell carcinoma (HNSCC) the intracellular components of the pathway have not been investigated. This is the first study in the literature reporting a role for β-catenin and Dvl mRNA level alterations in HNSCC. In our previous study we have identified that the WWOX gene is inactivated in HNSCC as a result of genetic and epigenetic alterations. To identify the mechanism of action of WWOX in HNSCC in this study we investigated its expression in association with Dvl-1, Dvl-2, Dvl-3 and β-catenin expression in 98 HNSCC samples. We observed down-regulation of the WWOX mRNA in 73.5% of the HNSCC tumor samples compared to their non-cancerous counterparts. Up-regulation of the Dvl-1, Dvl-2, Dvl-3 and β-catenin mRNAs were detected in 32.7%, 36%, 38.8% and 24.5% of the same tumor samples, respectively. We also detected a statistically significant correlation between the WWOX gene expression and mRNA levels of the intracellular components of the Wnt pathway genes. Our results indicate that WWOX acts as a tumor suppressor in the HNSCC development and progression by inhibiting the expression of the Dvl proteins. Citation Format: Ayse Nur Buyru, Asuman Celebi, Betul Seyhan. The role of WWOX in HNSCC through Wnt/beta-catenin pathway [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B33.
Abstract 19495: Compensatory Strategies Improve Medication Adherence in Heart Failure Patients With Mild Global Cognitive Impairment
Authors: Anton M Vehovec, Mary A Dolansky, Rich Josephson, Joel W Hughes
Journal: Circulation (2015)

Introduction: Mild cognitive impairment is common in patients with HF and is linked to poor medication adherence. Poor medication adherence is associated with higher mortality and hospitalizations. Medication adherence strategies to compensate for cognitive impairment are not well understood. The purpose of this secondary analysis is to identify the type and frequency of compensatory strategies used by patients with HF and mild cognitive impairment and to determine if compensatory strategy use is associated with medication adherence. Methods and Results: The parent study was a longitudinal descriptive study (N=379) to determine the relationships among cognitive impairment and self-management. The Modified Mental Status (3MS), a global measure of cognition and an electronic pill box (Medsignals) were used. A subsample of 156 patients with mild to moderate global cognitive impairment was selected based on a 3MS of less than 90. The frequencies of four compensatory strategies use were: pillbox (n=85, 57%), family reminders (n=17, 11%), reminders including calendars and alarms (n=17, 11%), and combining administration with other tasks (n=51, 33%). An independent samples t-test was performed to test the difference in medication adherence between persons that did and did not use each compensatory strategy. Pillbox use was associated with medication adherence (p&lt;.05). The group that used a pillbox (n=80) had a mean medication adherence of 82.5%, while no pillbox use (n=90) had a mean of 74.8% No other compensatory strategies were related to better medication adherence. Conclusion: In clinical practice, global cognition screening and education on pillbox use to improve medication adherence is recommended. Although other compensatory strategies did not have a significant impact on medication adherence, more research is need to understand compensatory strategies to help patients with mild cognitive impairment improve medication adherence.
Abstract 18496: Trends in Healthcare Expenditures and Cardiovascular Risk Profile Among Individuals Without ASCVD: Analysis of the Medical Expenditure Panel Survey 2002-2013
Authors: Javier Valero-Elizondo, Joseph A Salami, Haider J Warraich, Oluseye Ogunmoroti, Erica S Spatz, Nihar Desai, Jamal S Rana, Salim S Virani, Ron Blankstein, Michael J Blaha, Khurram Nasir
Journal: Circulation (2016)

Introduction:  American Heart Association 2020 Strategic Goals emphasize the importance of optimizing cardiovascular modifiable risk factor (CRF) profile to diminish burden of CV disease. In this study we aimed to quantify the trends in expenditures and expenditures by CRF profiles among individuals without ASCVD.   Methods:  Data were obtained annually from 2002-2013 using publicly available household component file of Medical Expenditure Panel Survey (MEPS) database. ASCVD risk factors (hypertension, diabetes mellitus, hypercholesterolemia, smoking, physical activity & obesity) were ascertained by ICD-9-CM codes and self-report. CRF profile was then categorized as “Optimal”, “Average” and “Poor” (0-1, 2-3 & ≥ 4 CRF, respectively). Individuals with established ASCVD,  2  were excluded. Full-year consolidated data files were used to generate estimates of annual healthcare expenditures. All analyses took into account MEPS complex design; costs were adjusted to 2013 USD using Gross Domestic Product Index.   Results:  Optimal profile prevalence decreased from 48% in 2002-2003 to 41% in 2012-2013. During the same period, average and poor profiles increased (42% to 45% and 11% to 14%, respectively). Mean adjusted per capita healthcare expenditures among those with poor CRF profile was $6192 [95% CI 5747-6638] in 2002-2003 vs. $6886 [95% CI 6183-7588] in 2012-2013). In pooled data over 12 years, after adjusting for confounding variables, as compared to those with poor CRF profile, costs for average and optimal profiles were significantly lower by $2,412 & $3,744, respectively.   Conclusions:  Favorable CRF profile is associated with lower per capita expenditures among individuals without established ASCVD. Our findings support AHA strategic emphasis on optimizing CRF profile not only to reduce future risk of clinical ASCVD but also to favorably impact economic burden of managing with these risk factors.
Abstract 18439: Improved Physical Capacity but Unaltered Left Ventricular Mass and Function at Rest Following a 12-Week Indoor Cycling Intervention in Previously Sedentary Women
Authors: Kristofer Hedman, Niclas Bjarnegård, Toste Länne
Journal: Circulation (2016)

Introduction: The amount of physical training needed to elicit effects on cardiac dimensions and function in previously sedentary subjects has not been well established, depending on i.a. that long...
Abstract 12706: Novel Correlates of Depressive Symptoms in Family Caregivers of Heart Failure Patients
Authors: Sandra B Dunbar, Elizabeth Corwin, Rebecca A Gary, Melinda K HIggins, Alicia Smith, Javed Butler
Journal: Circulation (2016)

Introduction: Family Caregivers (FCGs) of persons with heart failure (HF) often experience depressive symptoms. Greater understanding of associated factors is essential to direct HF FCG interventions. Purpose: This study examined correlates of depressive symptoms in FCGs of HF patients including individual factors, caregiving demands, family context, and genotype (serotonin transporter-linked polymorphic region [5-HTTLPR]) associated with a predisposition to depression. Methods: HF FCGs (n=127; mean age 55.3 ± 11.5 years, 92% women, 58% African American) were recruited. Measures were: demographics, family functioning (FAD), caregiving demands (Oberst Caregiving Demands, caregiver strain [CS], caring for others), sleep quality (PSQI) and depressive symptoms (CES-D). In a subsample (n= 82), 5-HTTLPR genotype was determined. Analyses included correlations and regression models for the full sample and the 5-HTTLPR genotype allele groups (XL/L, any S) separately. Results: Mean CES-D scores were 15.2 ± 10.4; 41.7% scored &gt; 16 indicating depressive symptoms. Bivariate correlations (p&lt;.05) were found between CES-D scores and caring for others, FAD, mental and physical CS, and Oberst and PSQI scores. Regression models accounted for 42.7% (F 5,106 =17.55, p&lt;.001) of the variability in CES-D scores with PSQI (p&lt;.001), Oberst (p=.006), FAD (p=.005), caring for others (p=.003), and race (p=.01) retained as predictors. In the 5-HTTLPR analyses of the XL/L group, only FAD and PSQI were associated with CESD (n=42; adjR 2 =.339, F( 2,39 )=11.527, p&lt;.001). For the any S allele group, caring for others, and strain were associated with depressive symptoms (n=40; adjR 2 =.54, F ( 3,46 )=20.160, p&lt;.001). Conclusions: Greater depressive symptoms in HF FCGs were predicted by worse sleep, greater burden, worse family functioning, and white race. Caregiver demand/strain had less effect on depressive symptoms in the XL/L allele group whereas these factors affected the any S-type group. Allele variants of the 5-HTTLPR may interact with caregiving burden to affect depressive symptoms differentially and may help identify caregivers at greater risk for depressive symptoms. Improving sleep and reducing caregiving demand may be important targets for intervention.
Treatment of post-herpetic pain with scrambler therapy, a patient-specific neuro-cutaneous electrical stimulation device.
Authors: Thomas J. Smith, Giuseppe Marineo
Journal: Journal of Clinical Oncology (2012)

e19564^ Background: Post herpetic neuropathy (PHN) is common in cancer and hematologic malignancy patients. It can be debilitating and difficulty to treat effectively. Scrambler therapy, a patient-specific neurocutaneous stimulation device, can be effective in treating chemotherapy induced neuropathy (JPSM 2010) and other neuropathic pain (JPSM 2012). Methods: We treated ten patients, 2 with cancer as their primary diagnosis, with refractory PHN Scrambler therapy at two institutions. Scrambler therapy was given as 30 minute sessions daily for 10 days. Pain was recorded before and after treatment. Results: The patient mean age was 54 ± SD 13 years, 6 men and 4 women, with a mean duration of PHN for 15.6 months (range 2.5 to 48 months) without satisfactory relief despite conventional drugs. The average pain score rapidly diminished from 7.64 ± 1.46 at baseline to 0.42 ± 0.89 at one month, a 95% reduction, with continued relief at 2 and 3 months. Patients achieved maximum pain relief with less than 5 treatments. Conclusions: Scrambler therapy appears to have a promising effect on PHN, with prompt and continued relief and no side effects. Further research is warranted. [Table: see text]
Flowcytometric expression of LAIR-1 inhibitory immune-receptor in pediatric acute lymphoblastic leukemia cases does not correlate with standard risk factors and minimal residual disease
Authors: P. Bhatia, M. Singh, J. Shandilya, N. Varma, M.S. Sachdeva, A. Trehan, D. Bansal, R. Jain, S. Totadri
Journal: Annals of Oncology (2017)
Abstract 298: Pluripotent Stem Cell Microrna-294 as a Mediator of Cardiac Proliferative Response After Myocardial Injury
Authors: Mohsin Khan, Brandon Booth, Constantine D Troupes, Sadia Mohsin, Emily Nickoloff, Cynthia Benedict, Steven R Houser, Walter J Koch, Raj Kishore
Journal: Circulation Research (2016)

Rationale: Embryonic heart is characteristic of rapidly dividing cardiomyocytes required to build a working myocardium. In contrast, cardiomyocytes retain some proliferative capacity in the neonates but lose most of it in adulthood. Embryonic stem cell cycle (ESCC) miRs are a class of microRNAs regulating the unique cell cycle of ESCs and their characteristic pluripotency. Nevertheless, expression of miR-294, a member of the ESCC miRs is lost during developmental transitions from the ESCs to mature cells. Effect of miR-294 to induce cardiac proliferation and heart function has not been previously studied. Objective: To determine whether miR-294 drives cardiac proliferative response leading to augmentation of cardiac function after myocardial infarction. Methods and Results: miR expression analysis in the heart during development revealed elevated levels of miR-294 in the prenatal stages while the expression was lost in the neonates and adults as confirmed by qRT-PCR. Neonatal ventricular cardiomyocytes (NRVMs) treated with miR-294 mimic to showed elevated mRNA levels of cell cycle markers ( E2F family and cyclins ) concurrent with increased expression of p-histone 3, Ki67 and Aurora B kinase (G2/M) as confirmed by immunocytochemistry compared to control cells. Cardiac progenitor cells (CPCs) engineered with miR-294 lentivirus led to increased proliferation and metabolic activity. An inducible cardiac specific AAV-9 carrying miR-294 was administered in mice subjected to myocardial infarction. Increased cardiac function in mice receiving AAV-miR-294 was observed 8 weeks after injury. Increase myocyte proliferation was observed in the heart after miR-294 treatment as analyzed by BrdU uptake, p-Histone 3 and Aurora B expression by immunostaining. Concurrently, a decrease in infarct size along with decreased apoptosis was observed in the miR-294 hearts compared to the control. Furthermore, increased c-kit+ CPCs activation and proliferation was observed in the miR-294 receiving hearts. Conclusion: Ectopic expression of miR-294 recapitulates embryonic signaling and enhances cardiomyocyte ability to proliferate together with CPC activation and expansion leading to augmented cardiac function in mice after myocardial infarction.
PTH-118 Cyclic vomiting syndrome: a prevalent and under-recognised condition
Authors: R Sagar, R Sood, D Gracie, M Gold, N To, A Ford
Journal: Gut (2017)

Introduction  Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder (FGID) whose aetiology is poorly understood. It is characterised by acute episodes of vomiting and nausea followed by asymptomatic periods. Average age of symptom onset in adults is 22 years but average age of diagnosis is 31 years. This delay is probably because, until recently, CVS was considered to be a paediatric condition. Few studies have reported the prevalence in adults or risk factors for CVS. We examined this issue in patients attending gastroenterology clinics in a single secondary care centre.  Method  1002 consecutive adult patients seen in gastroenterology clinics completed the Rome III questionnaire and provided demographic data. Symptoms compatible with CVS were classified according to the Rome III criteria. All patients were investigated to a level deemed appropriate by the responsible physician. We recorded if vomiting symptoms were documented at the initial consultation and if a diagnosis of CVS was considered after negative investigations in those who met Rome III criteria and who were deemed to have “true” CVS. We compared demographics of those who did and did not have “true” CVS.  Results  Of the 1002 patients, 920 provided complete questionnaire data. 112 (12.2%) had symptoms that met Rome III criteria for CVS. However, after investigation, 51 had an organic diagnosis, which included gastro-oesophageal reflux in 16 (31.4%), confirmed dysmotility in six (11.8%), coeliac disease in four (7.8%), hiatus hernia in three (5.9%), oesophageal adenocarcinoma in one, and peritoneal metastases in one. The remaining 61 (6.6%) were deemed to have “true” CVS (mean age 43.6 years, 80.3% female). Of these, only 21 (34.4%) had documentation of whether vomiting was present or absent at their initial consultation. After investigation, a diagnosis of CVS was considered in only four (6.6%) of these 61 patients. “True” CVS was associated with younger age, female gender, tobacco smoking, and presence of symptoms compatible with other FGIDs including irritable bowel syndrome, chronic proctalgia, proctalgia fugax, post-prandial distress syndrome, functional belching and functional chest pain (p  Conclusion  Prevalence of “true” CVS in this adult secondary care outpatient population was 6.6%. Younger age, female gender, tobacco smoking and presence of symptoms compatible with other FGIDs were associated with “true” CVS. Presence of vomiting was poorly documented by consulting physicians and the diagnosis was considered in   Disclosure of Interest  None Declared
Prediction of Posthepatectomy Liver Failure Proposed by the International Study Group of Liver Surgery
Authors: Yoichi Mizutani, Toshinori Hirai, Shigeki Nagamachi, Atsushi Nanashima, Koichi Yano, Kazuhiro Kondo, Masahide Hiyoshi, Naoya Imamura, Tamasa Terada
Journal: Clinical Nuclear Medicine (2017)

The International Study Group of Liver Surgery (ISGLS) proposed a definition and grading system for posthepatectomy liver failure (PHLF). We evaluated the usefulness of residual liver function estimation using Tc-galactosyl human serum albumin (Tc-GSA) for the prediction of PHLF.Patients with liver tumors (n = 136) and scheduled for hepatectomy underwent Tc-GSA scintigraphy. Based on their imaging data, the maximal GSA removal rate (GSA-Rmax)was calculated using multicompartment analysis. We also calculated GSA-Rmax in the predicted residual liver (GSA-RL) whose volume was determined on computed tomography (CT) scans. We compared the age, sex, 15-minute indocyanine green retention rate; albumin, bilirubin, hyaluronic acid, and type 4 collagen levels; the Child-Pugh classification; residual liver volume; residual liver percentage; GSA-Rmax; and GSA-RL in patients with and without PHLF. Univariate and multivariate logistic analyses were used for statistical assessments.Of 136 patients, 17 (12.5%) met the ISGLS criteria for PHLF (ISGLS-PHLF). There was a statistically significant difference in the age, albumin level, Child-Pugh classification, residual liver volume, residual liver percentage, GSA-Rmax, and GSA-RL between patients with and without PHLF. Based on multivariate analysis, GSA-RL and the residual liver volume were significant independent predictors of ISGLS-PHLF (P = 0.004 and P = 0.038, respectively). The odds ratio was 149423 for GSA-RL and 1.003 for the residual liver volume.GSA-RL calculated using Tc-GSA scintigraphy was the most useful independent predictor for ISGLS-PHLF.
Risk Trajectories of Readmission and Death in the First Year after Hospitalization for Chronic Obstructive Pulmonary Disease
Authors: Peter K. Lindenauer, Kumar Dharmarajan, Li Qin, Zhenqiu Lin, Andrea S. Gershon, Harlan M. Krumholz
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Characterization of the dynamic nature of posthospital risk in chronic obstructive pulmonary disease (COPD) is needed to provide counseling and plan clinical services.Objectives: To analyze risk of readmission and death after discharge for COPD among Medicare beneficiaries aged 65 years and older and to determine the association between ventilator support and risk trajectory.Methods: We computed daily absolute risks of hospital readmission and death for 1 year after discharge for COPD, stratified by ventilator support. We determined the time required for risks to decline by 50% from maximum daily values after discharge and for daily risks to plateau. We compared risks with those found in the general elderly population.Measurements and Main Results: Among 2,340,637 hospitalizations, the readmission rate at 1 year was 64.2%, including 63.5%, 66.0%, and 64.1% among those receiving invasive, noninvasive, and no ventilation, respectively. Among 1,283,069 hospitalizations, mortality at 1 year was 26.2%, including 45.7%, 41.8%, and 24.4% among those same respective groups. Daily risk of readmission declined by 50% within 28, 39, and 43 days and plateaued at 46, 54, and 61 days among those receiving invasive, noninvasive, and no ventilation, respectively. Risk of death declined by 50% by 3, 4, and 17 days and plateaued by 21, 18, and 24 days in the same respective groups. Risks of hospitalization and death were significantly higher after discharge for COPD than among the general Medicare population.Conclusions: Discharge from the hospital is associated with prolonged risks of readmission and death that vary with need for ventilator support. Interventions limited to the first month after discharge may be insufficient to improve longitudinal outcomes.