bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA07: Hippo signaling in liver regeneration and liver tumors
Authors: Halder Georg 
Published: September 2020

Abstract
The Hippo pathway is required for normal tissue growth during development, and it is also involved in regeneration in flies and mammals. Hyperactivation of the Hippo pathway effector YAP drives cell proliferation and malignancy of tumor cells, and YAP is frequently hyperactivated in a broad range of different human carcinomas. Thus, targeting the activity of YAP may inhibit cancer cells. However, how the Hippo pathway is regulated during development and what role it plays during normal growth, regeneration, and in cancer cells is poorly understood. My group uses genetic approaches in Drosophila and mice to unravel the function of the Hippo pathway in the growth and regeneration of imaginal discs and liver and in liver cancer. I will present our recent efforts towards these aims and discuss our findings in light of different growth control models.
Citation Format: Georg Halder. Hippo signaling in liver regeneration and liver tumors [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr IA07.
Abstract IA23: The role of hepatocyte TAZ in NASH and NASH-HCC
Authors: Wang Xiaobo , Schwabe Robert , Tabas Ira 
Published: September 2020

Abstract
NASH has emerged as the leading cause of chronic liver disease and hepatocellular carcinoma (HCC) worldwide. However, there is a dearth of treatment options, which is due in large part to a poor understanding of NASH pathophysiology, particularly in the conversion of the relatively benign steatosis to clinically important fibrosis and HCC. We hypothesized that the transcription factor TAZ (WWTR1) in hepatocytes (HCs) promotes the progression of steatosis to fibrotic NASH and HCC. We studied liver tissue from humans with NASH and NASH-HCC and used several mouse models, including a dietary model of obesity, insulin resistance, NASH fibrosis, and HCC. NASH mice were treated with various AAV8-H1-shRNAs to silence genes specifically in HCs. The data show that TAZ is markedly increased in HCs in both human and murine NASH liver compared with normal or steatotic liver. In murine models of NASH, silencing of HC TAZ prevents or reverses hepatic inflammation, HC death, and fibrosis. Moreover, HC-targeted expression of TAZ in a mouse model of steatosis promoted NASH features, including fibrosis. Mechanistic studies using cultured cells and molecular-genetic causation studies in mice revealed that a key mechanism linking is TAZ-mediated induction of Indian hedgehog (Ihh), an HC secretory factor that activates fibrogenic genes in hepatic stellate cells (Wang et al., Cell Metabolism). The mechanism of TAZ upregulation in NASH involves a pathway in which excess cholesterol in HCs disrupts the normal proteasomal degradation of TAZ. Prolonged feeding of mice with the NASH diet leads to HCC, with both the tumors and surrounding tissues expressing high levels of TAZ. Silencing TAZ in HCs after advanced NASH has developed eliminates the progression to HCC, and silencing HC TAZ in mice with NASH-HCC shrinks the tumors. The mechanisms of linking TAZ to NASH-HCC likely both niche (surrounding tissue) and oncogenic effects. In conclusion, HC TAZ, whose levels markedly increase during NASH progression via a pathway involving cholesterol enrichment of HCs, plays an essential role in the progression of steatosis to fibrotic NASH and in the progression of NASH to HCC. As such, silencing TAZ in hepatocytes in the setting of early NASH is a potentially powerful new strategy to prevent the progression of NASH to cirrhosis and HCC.
Citation Format: Xiaobo Wang, Robert Schwabe, Ira Tabas. The role of hepatocyte TAZ in NASH and NASH-HCC [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr IA23.
Loss of RNA-Binding Protein RBMS1 Promotes a Metastatic Transcriptional Program in Colorectal Cancer
Authors: Carter Hannah 
Published: September 2020

Abstract

Summary:
Yu and colleagues combined computational and experimental techniques to identify a new post-transcriptional regulator of metastatic potential in colon cancer. This study reveals that the RNA-binding protein RBMS1 is a positive regulator of mRNA stability for multiple genes, including the tumor suppressor AKAP12 and a WNT pathway interacting protein, SDCBP, and its loss is a common event associated with poor prognosis.
See related article by Yu et al., p. 1410.
Survival Following Implantable Cardioverter‐Defibrillator Implantation in Patients With Amyloid Cardiomyopathy
Authors: Higgins Angela Y. , Annapureddy Amarnath R. , Wang Yongfei , Minges Karl E. , Lampert Rachel , Rosenfeld Lynda E. , Jacoby Daniel L. , Curtis Jeptha P. , Miller Edward J. , Freeman James V. 
Published: September 2020

Background
Outcomes data in patients with cardiac amyloidosis after implantable cardioverter‐defibrillator (ICD) implantation are limited. We compared outcomes of patients with ICDs implanted for cardiac amyloidosis versus nonischemic cardiomyopathies (NICMs) and evaluated factors associated with mortality among patients with cardiac amyloidosis.

Methods and Results

Using National Cardiovascular Data Registry’s ICD Registry data between April 1, 2010 and December 31, 2015, we created a 1:5 propensity‐matched cohort of patients implanted with ICDs with cardiac amyloidosis and NICM. We compared mortality between those with cardiac amyloidosis and matched patients with NICM using Kaplan‐Meier survival curves and Cox proportional hazards models. We also evaluated risk factors associated with 1‐year mortality in patients with cardiac amyloidosis using multivariable Cox proportional hazards regression models. Among 472 patients with cardiac amyloidosis and 2360 patients with propensity‐matched NICMs, 1‐year mortality was significantly higher in patients with cardiac amyloidosis compared with patients with NICMs (26.9% versus 11.3%,
P
<0.001). After adjustment for covariates, cardiac amyloidosis was associated with a significantly higher risk of all‐cause mortality (hazard ratio [HR], 1.80; 95% CI, 1.56–2.08). In a multivariable analysis of patients with cardiac amyloidosis, several factors were significantly associated with mortality: syncope (HR, 1.78; 95% CI, 1.22–2.59), ventricular tachycardia (HR, 1.65; 95% CI, 1.15–2.38), cerebrovascular disease (HR, 2.03; 95% CI, 1.28–3.23), diabetes mellitus (HR, 1.55; 95% CI, 1.05–2.27), creatinine = 1.6 to 2.5 g/dL (HR, 1.99; 95% CI, 1.32–3.02), and creatinine >2.5 (HR, 4.34; 95% CI, 2.72–6.93).

Conclusions
Mortality after ICD implantation is significantly higher in patients with cardiac amyloidosis than in patients with propensity‐matched NICMs. Factors associated with death among patients with cardiac amyloidosis include prior syncope, ventricular tachycardia, cerebrovascular disease, diabetes mellitus, and impaired renal function.
Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage in Patients With a History of Migraine
Authors: van Os Hendrikus J.A. , Ruigrok Ynte M. , Verbaan Dagmar , Dennesen Paul , Müller Marcella C.A. , Coert Bert A. , Algra Ale , Vergouwen Mervyn D.I. , Wermer Marieke J.H. 
Published: September 2020

Background and Purpose:
Delayed cerebral ischemia (DCI) is a major contributor to the high morbidity in patients with aneurysmal subarachnoid hemorrhage (aSAH). Spreading depolarizations may play a role in DCI pathophysiology. Because patients with migraine are probably more susceptible to spreading depolarizations, we investigated whether patients with aneurysmal subarachnoid hemorrhage with migraine are at increased risk for DCI.

Methods:
We included patients with aneurysmal subarachnoid hemorrhage from 3 hospitals in the Netherlands. We assessed lifetime migraine history with a short screener. DCI was defined as neurological deterioration lasting >1 hour not attributable to other causes by diagnostic work-up. Adjustments were made for possible confounders in multivariable Cox regression analyses and adjusted hazard ratios (aHR) were calculated. We assessed the interaction effects of age and sex.

Results:

We included 582 patients (mean age 57 years, 71% women) mostly with mild to moderate aneurysmal subarachnoid hemorrhage of whom 108 (19%) had a history of migraine (57 with aura). Patients with migraine were not at increased risk of developing DCI compared with patients without migraine (22% versus 24%, aHR, 0.89 [95% CI, 0.56–1.43]). Additionally, no increased risk was found in patients with migraine with possible aura (aHR, 0.74 [95% CI, 0.39–1.43]), in women (aHR, 0.88 [95% CI, 0.53–1.45],
P
interaction
=0.859), or in young patients aged <50 years (aHR, 1.59 [95% CI, 0.72–3.49]), although numbers in these subgroups were limited. We found an interaction between migraine and age with an increased risk of DCI among young patients with migraine (
P
interaction
=0.075).

Conclusions:
Patients with migraine are in general not at increased risk of DCI. Future studies should focus in particular on young SAH patients, in whom there might be an association between migraine history and development of DCI.
Establishing an Office‐Based Framework for Resuming Otolaryngology Care in Academic Practice During the COVID‐19 Pandemic
Authors: Pearlman Aaron N. , Tabaee Abtin , Sclafani Anthony P. , Sulica Lucian , Selesnick Samuel H. , Kutler David I. , Montano Joseph J. , Levinger Joshua I. , Suurna Maria V. , Modi Vikash K. , Stewart Michael G. 
Published: September 2020

ObjectiveThe COVID‐19 health crisis abruptly disrupted the practice of otolaryngology. This article aims to define the changes needed to operate an academic otolaryngology practice safely and efficiently from within the epicenter of the pandemic. We define the areas of normal patient workflow that have been affected by COVID‐19, and we offer mitigation strategies with attention paid to the specific needs of subspecialties.Data SourcesThe article includes data specific to the office practice metrics of the Weill Cornell Medicine Department of Otolaryngology–Head and Neck Surgery, as well as publically available data from New York Presbyterian Hospital system and the New York Times.Review MethodsExpert opinion.ConclusionsThrough careful planning and execution, it is possible to reestablish safe otolaryngologic patient care during the COVID‐19 pandemic. It will require a significant change from prior practice models for successful implementation. Additionally, telemedicine can be positively integrated into the treatment of otolaryngology diseases for new and established patients.Implications for PracticeThe information conveyed in this review can be used as a guide by large and small otolaryngology groups to identify aspects of the patient visit that are “at risk” due to COVID‐19, and it suggests sensible responses that can be made without a significant disruption to normal practice. The methods used to identify vulnerabilities with the patient visit process can be applied to future unforeseen crises, such as a resurgence of COVID‐19 or a novel pandemic.
Major dietary patterns and predicted cardiovascular disease risk in an Iranian adult population
Authors: Shahavandi Mahshid , Amini Mohammad Reza , Shahinfar Hossein , Shab-Bidar Sakineh 
Published: September 2020

Background: Limited data are available on the association of major dietary patterns and predicted risk of cardiovascular disease (CVD) using the Framingham Risk Score (FRS). Aim: To investigate the association between major dietary patterns and the predicted 10-year CVD risk in an Iranian population Methods: This cross-sectional study was conducted on 522 apparently healthy adults referred to health centers in Tehran. Usual dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. The association between dietary patterns and the predicted risk of development of CVD was evaluated using linear multiple regression. Principal component analysis was used to identify major dietary patterns. Results: In total, 41% of the men ( n = 95) and 46% of women ( n = 134) were in the low risk (<10%) and 6% of men ( n = 14) and 1% of women ( n = 3) were in the high risk (> 20%) category of the FRS. A significant decrease was found for body mass index ( p < 0.001), systolic blood pressure (SBP) ( p = 0.003), diastolic blood pressure ( p = 0.005), and triglyceride ( p = 0.02) in the higher tertile of healthy dietary pattern. Adherence to an unhealthy dietary pattern was associated with a significant increase in body weight ( p = 0.03) and a significant decrease in high-density lipoprotein cholesterol ( p < 0.001). The healthy dietary pattern score was negatively associated with SBP ( p = 0.04) and FRS ( p < 0.001). Conclusion: Although we observed improvements in CVD risk factors with greater adherence to healthy dietary patterns, there was no association between identified dietary patterns and the predicted risk of 10-year CVD.
Predicting the outcome of the greater occipital nerve block – an observational study on migraine patients with and without musculoskeletal cervical impairment
Authors: Schwarz Annika , Ziegeler Christian , Daneshkhah Sima , May Arne , Luedtke Kerstin 
Published: September 2020

Background and objective The importance of neck pain and the trigeminocervical complex in migraine is of high pathophysiological interest since a block to the greater occipital nerve is more effective for some primary headaches than others. This observational study hypothesised that the response to manual palpation of the upper cervical spine predicts the efficacy of the greater occipital nerve-block. Methods We divided patients, scheduled by a neurologist to receive a greater occipital nerve-block to reduce their migraine symptoms, into three groups: Patients with no pain response to manual palpation of the neck, patients with local pain, and those with referred pain to the head. Primary outcome was the percentage change in headache frequency. Additionally, items from the quantitative sensory testing protocol were included. Results Eighty-seven chronic migraine patients were recruited consecutively from a specialised outpatient clinic and 71 were included for analyses and stratified into the three groups: No pain (n = 11), local pain (n = 28), and referred pain to the head (n = 32). Overall, patients experienced a reduction of 1.9 headache days per month (SD 3.4, p < 0,0001). The groups differed significantly in the percentage change of headache frequency ( p = 0.041) with the “no pain” group showing the largest reduction. The pressure-pain-threshold over C2 and headache on the day of the intervention influenced the outcome significantly (R2 0,27, p = 0,00078). No serious adverse events occurred. Sixty-five percent of the patients had headaches during the examination. The groups did not differ regarding the distribution of patients with neck-pain in absence of migraine at baseline ( p = 0.618). Conclusion Patients that were less sensitive to palpation in the cervical region and headache-free on the day of the intervention improved more after the greater occipital nerve-block. Registration: Registered a priori at the German Clinical Trials Register (DRKS00015995).
Erenumab does not alter cerebral hemodynamics and endothelial function in migraine without aura
Authors: Altamura Claudia , Viticchi Giovanna , Fallacara Adriana , Costa Carmelina Maria , Brunelli Nicoletta , Fiori Chiara , Silvestrini Mauro , Vernieri Fabrizio 
Published: September 2020

Objective To assess whether erenumab influences cerebral vasomotor reactivity and flow-mediated dilation in migraine patients. Methods Consecutive migraineurs prescribed erenumab at our Headache Centre and age and sex-matching controls were invited to participate in this observational longitudinal study. Patients were evaluated for cerebral vasomotor reactivity to hypercapnia (breath-holding index) in middle and posterior cerebral arteries and for brachial corrected flow mediated dilation at baseline (T0), after 2 weeks from the first erenumab injection (T2) and after 2 weeks from the fourth Erenumab injection (T18). Patients displaying a reduction of at least 50% in monthly migraine days after completing the fourth month of therapy were classified as responders. Results Sixty patients and 25 controls agreed to participate. Middle and posterior cerebral artery mean flow velocities, breath-holding index and flow-mediated dilation did not differ at T0 and from T0 to T2 in patients and controls. In patients, we neither observed a variation of the explored variables from T0 to T18 nor an interaction between evaluation times (T0–T2 or T0–T18) and chronic condition at T0, responder state or erenumab fourth dose. Conclusions Our findings demonstrate that erenumab preserves cerebral vasomotor reactivity and flow-mediated dilation in migraineurs without aura.
Interleukin-17 and Interleukin-10 Association with Disease Progression in Schizophrenia
Authors: Chenniappan Raghavi , Nandeesha Hanumanthappa , Kattimani Shivanand , Nanjaiah Nandakumar Dalavaikodihalli 
Published: September 2020

Background: Alteration in cytokine levels are known to be involved in the pathogenesis of schizophrenia. Objectives: To estimate the serum levels of interleukin-17 (IL-17) and interleukin-10 (IL-10) and their association with disease progression in schizophrenia. Methods: A total of 67 schizophrenia cases were enrolled in the present study. IL-17 and IL-10 were estimated by enzyme-linked immunosorbent assay. Positive and Negative Syndrome Scale (PANSS) was used to evaluate disease severity. Results: IL-17 was positively correlated with positive symptom score ( r = 0.256, p = .036), general psychopathology score ( r = 0.255, p = .038) and total score ( r = 0.273, p = .025) in schizophrenia. IL-17 and IL-10 were significantly increased in schizophrenia cases with PANSS more than 85 compared to those with 71–85. Conclusion: IL-17 and IL-10 are associated with disease severity in schizophrenia but are not good markers for predicting the disease progression.
A Survey-Based Study of Patient-Centered Costs Associated With Indwelling Pleural Catheters
Authors: Aboudara Matthew , Roller Lance , Lentz Rob , Rickman Otis B. , Gillaspie Erin A. , Maldonado Fabien 
Published: September 2020

Introduction: Indwelling pleural catheters (IPC) are effective at palliating benign and malignant pleural effusions (MPE). They have also been found to be cost effective from a third-party payor perspective. Little is known of the impact IPCs have on patient-centered quality of life outcomes such as financial burden and patient and caregiver burden. We performed a cross-sectional survey study evaluating the impact of IPCs on multiple patient and caregiver quality of life metrics. Methods: Patients ≥ 18 years old with an IPC in place for 2 months were eligible. Twenty patients were recruited over a 10-month period. Patients completed the CDC-Health Related Quality of Life (HRQOL)-4 and a HRQOL-financial questionnaire. The primary objective was to describe the socio-economic impact of IPCs. Demographic and IPC specific data were collected. Descriptive statistics were used. Results: The mean (SD) age was 64.3 (0.70). The indication was MPE in 19/20. All patients had medical insurance. Medicare or Medicaid (CMS) comprised 10/20 of payors. The median (IQR) copay for private insurers was $238.45 (72-875); 11/20 had additional costs related to the IPC; 4/20 had significant life changes after the IPC; 17/20 received assistance from a non-paid caregiver; 6/20 patients could not do activities because of the IPC and this negatively impacted QOL in 3/6 of those patients. Conclusion: Patients with IPCs may experience negative life consequences, incur additional medical expenses, and require assistance from a non-paid caregiver. Activities may be negatively impacted by IPC. Discussion of alternative means of symptom palliation and pleurodesis would be beneficial.
Titrating the Amount of Bony Correction in Progressive Collapsing Foot Deformity
Authors: Ellis Scott J. , Johnson Jeffrey E. , Day Jonathan , de Cesar Netto Cesar , Deland Jonathan T. , Hintermann Beat , Myerson Mark S. , Schon Lew C. , Thordarson David B. , Sangeorzan Bruce J. 
Published: September 2020

Recommendation: There is evidence indicating that the amount of bony correction performed in the setting of progressive collapsing foot deformity reconstructive surgery can be titrated within a recommended range for a variety of procedures. The typical range when performing a medial displacement calcaneal osteotomy should be 7 to 15 mm of medialization of the tuberosity. The typical range when performing an Evans lateral column lengthening should be 5 to 10 mm of a laterally based wedge in the anterior calcaneus. The typical range when performing a plantarflexion opening wedge osteotomy of the medial cuneiform (Cotton) osteotomy should be 5 to 10 mm of a dorsal wedge. Level of Evidence: Level V, consensus, expert opinion.
Acute cardiomyopathy following a single dose of doxorubicin in a patient with adult T-Cell leukemia/lymphoma
Authors: Farina Kyle , Kalac Matko , Kim Sara 
Published: September 2020

Introduction Anthracycline-based chemotherapy regimens are associated with decreased cardiac function with cumulative dosing, yet there is limited information regarding the acute cardiotoxic potential of these medications and appropriate medical management strategies. Herein, we report a case of cardiomyopathy following a single dose of doxorubicin and describe our pharmacologic management approach. Case report A 37 year old Jamaican male presented for work-up and treatment of HTLV-1 associated T-cell leukemia/lymphoma. Upon diagnosis, the patient received one cycle of CHOEP, which was complicated by tumor lysis syndrome. Subsequently, the treatment was changed to DA-EPOCH, however, immediately after the initiation of DA-EPOCH on day 1, the patient was found to have t-wave inversions on EKG and an ejection fraction (EF) of 20% with new mitral regurgitation. EPOCH infusion was discontinued within 3 hours of initiation. Management and outcome: The chemotherapy regimen was modified to DA-EPOC with the removal of doxorubicin. The patient was started on metoprolol succinate 12.5 mg once daily for 2 days and subsequently switched to carvedilol 3.125 mg twice daily and lisinopril 5 mg once daily; the patient’s ejection fraction improved to baseline after 2.5 months of therapy. Discussion Though anthracyclines are associated with cardiotoxicity at high cumulative doses, this case highlights the cardiotoxic potential of these medications in the acute setting. Management of anthracycline cardiotoxicity is similar to heart failure management, with data suggesting benefit of using carvedilol and lisinopril. It is unclear if our patient would have benefited from prophylactic angiotensin converting enzymes inhibitors (ACEi) and/or beta-blocker therapy, as he had no known cardiac disease. Acute anthracycline-induced cardiac toxicity is an adverse drug reaction with which providers should be familiar and know how to appropriately manage.