bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scalable and serializable networked multi-actor programming
Authors: Sang Bo , Eugster Patrick , Petri Gustavo , Ravi Srivatsan , Roman Pierre-Louis 
Published: November 2020

A major challenge in writing applications that execute across hosts, such as distributed online services, is to reconcile (a) parallelism (i.e., allowing components to execute independently on disjoint tasks), and (b)cooperation (i.e., allowing components to work together on common tasks). A good compromise between the two is vital to scalability, a core concern in distributed networked applications.
The actor model of computation is a widely promoted programming model for distributed applications, as actors can execute in individual threads (parallelism) across different hosts and interact via asynchronous message passing (collaboration). However, this makes it hard for programmers to reason about combinations of messages as opposed to individual messages, which is essential in many scenarios.
This paper presents a pragmatic variant of the actor model in which messages can be grouped into units that are executed in a serializable manner, whilst still retaining a high degree of parallelism. In short, our model is based on an orchestration of actors along a directed acyclic graph that supports efficient decentralized synchronization among actors based on their actual interaction. We present the implementation of this model, based on a dynamic DAG-inducing referencing discipline, in the actor-based programming language AEON. We argue serializability and the absence of deadlocks in our model, and demonstrate its scalability and usability through extensive evaluation and case studies of wide-ranging applications.
The Contribution of Stress and Distress to Cardiovascular Health in Adult Survivors of Childhood Cancer
Authors: Lubas Margaret M. , Wang Mingjuan , Jefferies John L. , Ness Kirsten K. , Ehrhardt Matthew J. , Krull Kevin R. , Mulrooney Daniel A. , Srivastava Deo Kumar , Howell Rebecca M. , Robison Leslie L. , Hudson Melissa M. , Armstrong Gregory T. , Brinkman Tara M. 
Published: November 2020

Abstract

Background:
Childhood cancer survivors are at risk for cardiovascular morbidity and mortality that is not fully explained by cancer-directed therapies. We examined the contribution of emotional stress and distress to cardiac health in adult survivors of childhood cancer.

Methods:
Participants included 3,267 adult survivors enrolled in the St. Jude Lifetime Cohort Study [median (range) 29.9 (18.1–64.5) years of age; 7.7 (0–24.8) years at diagnosis; 48.4% female]. Survivors completed comprehensive medical assessments and standardized measures of depression, anxiety, posttraumatic stress symptoms (PTSS), and perceived stress. Cardiovascular-related conditions included hypertension, diabetes, dyslipidemia, cardiomyopathy, dysrhythmia, myocardial infarction (severity graded 0–4), and metabolic syndrome (yes/no). Multivariable modified Poisson models examined associations between symptoms of stress/distress and cardiovascular outcomes. Longitudinal associations between stress/distress and new-onset cardiovascular outcomes, defined as a change from grade ≤1 at initial evaluation to grade ≥2 at follow-up (median 3.9 years) were examined in 1,748 participants.

Results:
In multivariable cross-sectional models, stress/distress was associated with hypertension [risk ratio (RR) = 1.24; 95% confidence interval (CI), 1.07–1.43], dyslipidemia (RR = 1.29; 95% CI, 1.03–1.61), and metabolic syndrome (RR = 1.35; 95% CI, 1.17–1.54) independent of known cardiovascular risk factors. In longitudinal models, stress/distress was associated with new-onset dysrhythmia (RR = 2.87; 95% CI, 1.21–6.78), perceived stress with hypertension (RR = 1.42; 95% CI, 1.04–1.95), and PTSS and anxiety with dyslipidemia (RR = 1.72; 95% CI, 1.13–2.62; RR = 1.54; 95% CI, 1.01–2.35, respectively).

Conclusions:
Stress/distress is independently associated with adverse cardiovascular outcomes among childhood cancer survivors.

Impact:
Improving psychological health may serve as a potential intervention target for optimizing cardiac health among childhood cancer survivors.
Critical Interaction Between Telomerase and Autophagy in Mediating Flow-Induced Human Arteriolar Vasodilation
Authors: Hughes William E. , Chabowski Dawid S. , Ait-Aissa Karima , Fetterman Jessica L. , Hockenberry Joseph , Beyer Andreas M. , Gutterman David D. 
Published: November 2020

Objective:

Coronary artery disease (CAD) is associated with a compensatory switch in mechanism of flow-mediated dilation (FMD) from nitric oxide (NO) to H
2
O
2
. The underlying mechanism responsible for the pathological shift is not well understood, and recent reports directly implicate telomerase and indirectly support a role for autophagy. We hypothesize that autophagy is critical for shear stress–induced release of NO and is a crucial component of for the pathway by which telomerase regulates FMD.

Approach and Results:

Human left ventricular, atrial, and adipose resistance arterioles were collected for videomicroscopy and immunoblotting. FMD and autophagic flux were measured in arterioles treated with autophagy modulators alone, and in tandem with telomerase-activity modulators. LC3B II/I was higher in left ventricular tissue from patients with CAD compared with non-CAD (2.8±0.2 versus 1.0±0.2-fold change;
P
<0.05), although p62 was similar between groups. Shear stress increased Lysotracker fluorescence in non-CAD arterioles, with no effect in CAD arterioles. Inhibition of autophagy in non-CAD arterioles induced a switch from NO to H
2
O
2
, while activation of autophagy restored NO-mediated vasodilation in CAD arterioles. In the presence of an autophagy activator, telomerase inhibitor prevented the expected switch (Control: 82±4%; NG-Nitro-l-arginine methyl ester: 36±5%; polyethylene glycol catalase: 80±3). Telomerase activation was unable to restore NO-mediated FMD in the presence of autophagy inhibition in CAD arterioles (control: 72±7%; NG-Nitro-l-arginine methyl ester: 79±7%; polyethylene glycol catalase: 38±9%).

Conclusions:
We provide novel evidence that autophagy is responsible for the pathological switch in dilator mechanism in CAD arterioles, demonstrating that autophagy acts downstream of telomerase as a common denominator in determining the mechanism of FMD.
Impact of Genetic Variant Reassessment on the Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy Based on the 2010 Task Force Criteria
Authors: Costa Sarah , Medeiros-Domingo Argelia , Gasperetti Alessio , Akdis Deniz , Berger Wolfgang , James Cynthia A. , Ruschitzka Frank , Brunckhorst Corinna B. , Duru Firat , Saguner Ardan M. 
Published: November 2020

Background:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy, which is associated with life-threatening ventricular arrhythmias. Approximately 60% of patients carry a putative disease-causing genetic variant, but interpretation of genetic test results can be challenging. The aims of this study were to systematically reclassify genetic variants in patients with ARVC and to assess the impact on ARVC diagnosis.

Methods:
This study included patients from the Multicenter Zurich ARVC Registry who hosted a genetic variant deemed to be associated with the disease. Reclassification of pathogenicity was performed according to the modified 2015 American College of Medical Genetics criteria. ARVC diagnosis (categories: definite, borderline, possible) based on the 2010 Task Force Criteria was reclassified after genetic readjudication.

Results:

In 79 patients bearing 80 unique genetic variants, n=47 (58.8%) genetic variants were reclassified, and reclassification was judged to be clinically relevant in n=33 (41.3%). Variants in plakophilin-2 (
PKP2
) were shown to reclassify less frequently as compared with other genes (
PKP2
, n=1, 8.3%; desmosomal non-
PKP2
, n=20, 66.7%; nondesmosomal, n=26, 68.4%;
P
=0.001for overall comparison;
PKP2
versus desmosomal non-
PKP2, P
=0.001;
PKP2
versus nondesmosomal,
P
<0.001). Genetic reclassification impacted ARVC diagnosis. Eight patients (10.1%) were downgraded from definite to borderline/possible disease at the time of initial genetic testing as well as last follow-up, respectively. Separate genetic reclassification in family members led to downgrading of n=5 (38.5%) variants.

Conclusions:
Given that approximately half of genetic variants were reclassified, with 10.1% of patients losing their definite disease status, accurate determination of variant pathogenicity is of utmost importance in the diagnosis of ARVC.
Disproportionate Impact of COVID-19 Pandemic on Racial and Ethnic Minorities
Authors: Boserup Brad , McKenney Mark , Elkbuli Adel 
Published: November 2020

Background Health disparities are prevalent in many areas of medicine. We aimed to investigate the impact of the COVID-19 pandemic on racial/ethnic groups in the United States (US) and to assess the effects of social distancing, social vulnerability metrics, and medical disparities. Methods A cross-sectional study was conducted utilizing data from the COVID-19 Tracking Project and the Centers for Disease Control and Prevention (CDC). Demographic data were obtained from the US Census Bureau, social vulnerability data were obtained from the CDC, social distancing data were obtained from Unacast, and medical disparities data from the Center for Medicare and Medicaid Services. A comparison of proportions by Fisher’s exact test was used to evaluate differences between death rates stratified by age. Negative binomial regression analysis was used to predict COVID-19 deaths based on social distancing scores, social vulnerability metrics, and medical disparities. Results COVID-19 cumulative infection and death rates were higher among minority racial/ethnic groups than whites across many states. Older age was also associated with increased cumulative death rates across all racial/ethnic groups on a national level, and many minority racial/ethnic groups experienced significantly greater cumulative death rates than whites within age groups ≥ 35 years. All studied racial/ethnic groups experienced higher hospitalization rates than whites. Older persons (≥ 65 years) also experienced more COVID-19 deaths associated with comorbidities than younger individuals. Social distancing factors, several measures of social vulnerability, and select medical disparities were identified as being predictive of county-level COVID-19 deaths. Conclusion COVID-19 has disproportionately impacted many racial/ethnic minority communities across the country, warranting further research and intervention.
Child health behaviour and parent priorities for a school-based healthy lifestyle programme
Authors: Fernández Cristina R , Lee Janet , Duroseau Nathalie , Vargas-Rodriguez Ileana , Rieder Jessica 
Published: November 2020

Objective: The purpose of this study was to characterise parents’ concerns for their children’s health behaviour and perceptions of motivators and barriers to positive child health behaviour change, and to determine associations between motivators and barriers and parents’ priorities for a school-based healthy lifestyle programme. Design: Cross-sectional study of 46 parents who had completed an un-validated survey distributed during school-wide events. Setting: School for children aged 5–14 years in The Bronx, New York City, USA. Methods: Wilcoxon Rank Sum tests compared motivators and barriers to positive child health behaviour change by heath behaviour concern; Spearman’s correlation assessed associations between motivators and barriers and programme priorities. Results: Parents concerned about child weight significantly ranked keeping up with others and decreasing clothing size as motivators, while parents concerned about child food choices significantly ranked improving food choices and decreasing body mass index (BMI) and clothing size as motivators. Food-, play-, and self-esteem-related motivators were associated with nutrition education ( rs ⩾ .41, p ⩽ .01), physical activity classes ( rs ⩾ .29, p ⩽ .04) and child involvement in programme decision-making ( rs ⩾ .43, p ⩽ .01) priorities. Consistency-, child resistance- and home rules-related barriers were associated with nutrition education ( rs ⩾ .37, p = .02), physical activity classes ( rs ⩾ .32, p = .02) and child involvement ( rs ⩾ .40, p ⩽ .02) priorities. Conclusions: Despite the study sample size, selection bias, and generalisability limitations, prioritising nutrition, physical activity and child involvement in programme decision-making may enhance parent support for school-based healthy lifestyle programmes.
Idiopathic Sudden Sensorineural Hearing Loss in Children: A Systematic Review and Meta‐analysis
Authors: Franz Leonardo , Gallo Chiara , Marioni Gino , de Filippis Cosimo , Lovato Andrea 
Published: November 2020

ObjectiveIdiopathic sudden sensorineural hearing loss (ISSNHL) is uncommon in children, and its treatment and outcome are debated. We aimed to critically review evidence in the literature about treatment options and functional outcomes of pediatric ISSNHL. Additionally, we performed a meta‐analysis of the results of combined systemic‐intratympanic steroid therapy versus solely systemic treatment.Data SourcesA search was run in the PubMed, Scopus, and Google Scholar databases.Review MethodsIncluded articles were original ISSNHL case series, written in English, with a population age ranging from 2 to 19 years. Other study types (single case reports, editorials, and reviews) and case series with known etiology of sudden hearing loss were excluded. Descriptive data of patients, treatments, outcomes, and possible prognostic factors were extracted and recorded for every included study.ResultsTwelve articles (7 cohort and 5 case‐control studies) met all the selection criteria. Based on only the studies that provided sufficient data about clinical outcome, the pooled overall recovery rate was 67.91% (95% CI, 58.34%‐77.48%). No studies showed a significant difference between systemic steroid and combined systemic‐intratympanic steroid. The pooled odds ratio for combined systemic‐intratympanic steroid versus systemic steroid alone was 0.90 (95% CI, 0.36‐2.27) based on a random effects model, ruling out any significant difference between these treatment options.ConclusionsThe results of our meta‐analysis did not support combination therapy more than systemic steroid alone. Further prospective clinical trials are necessary to establish evidence‐based therapies.
Themes of Worry Among Psychiatric Inpatients That Persist Through Acute Hospitalization
Authors: Engstrom Pia , Bolton Matthew , Bautista Cynthia , Barnes Todd 
Published: November 2020

INTRODUCTION: Problems that worry patients throughout hospitalization are complex and varied, but they fall within the scope of safe, effective, patient-centered care. To our knowledge, there is no evidence describing the problems that worry patients in inpatient psychiatric units. AIM: The purpose of this quality improvement project was to describe common themes of worry experienced by individuals in psychiatric inpatient units in order to improve patient experience. METHOD: This project took place at an urban, safety net hospital at an academic medical center in the northeastern United States between March and December 2019. All patients across five inpatient psychiatric units were offered the Combined Assessment of Psychiatric Environments (CAPE) survey as they approached the end of their stay. RESULTS: A total of 1,800 patients took the survey. Of these patients, 36% (650/1,800) patients responded never/sometimes to “During my hospitalization, I found solutions to problems that worried me,” and 46% (297/650) patients provided a response to the follow-up question “What are the problems that worry you the most?” Common themes of worry for inpatient behavioral health patients include (a) life in the hospital, (b) self, and (c) outside life. CONCLUSIONS: Each of these worry themes that emerged from this thematic analysis has implications for behavioral health staff who are preparing the psychiatric/behavioral health inpatient for discharge. These themes can also be used to focus on a variety of quality improvement initiatives to improve the patients experience while in an inpatient psychiatric/behavioral health unit.
SENP3 regulates high glucose-induced endothelial dysfunction via ROS dependent signaling
Authors: Chen Fuheng , Ma Dongdong , Li Aizhong 
Published: November 2020

Background: The current study aimed to explore the role of SENP3 in endothelial cell dysfunction in a high-glucose setting. Methods: The gene and protein expressions of SENP3 in high-glucose cultured HAECs were examined using quantitative PCR and western blotting. The effects of SENP3 on HAEC viability, apoptosis, migration, and endothelial–monocyte adhesion were evaluated in vitro by knockdown. Moreover, a mouse streptozotocin-induced type I diabetes model was established for SENP3 expression assessment. In addition, the effects of SENP3 on ROS-related signaling pathways were investigated in high-glucose cultured HAECs. Results: Significantly increased levels of SENP3 mRNA and protein were found in high-glucose cultured HAECs in a time-dependent manner. SENP3 knockdown reversed high glucose-induced HAEC viability, apoptosis, and migration reduction. SENP3 knockdown attenuated the high glucose-induced intercellular adhesion of THP-1 monocytic cells and HAECs via downregulation of ICAM-1 and VCAM-1 expression. Increased levels of SENP3, ICAM-1, and VCAM-1 expression were observed in the aorta tissue of mice with type I diabetes. Downregulation of SENP3 expression was observed in HAECs cultured with high glucose levels using the free radical scavenger N-acetyl-L-cysteine or NOX4 siRNA. Conclusions: SENP3 was involved in high glucose-induced endothelial dysfunction, and ROS-dependent signaling served as the mechanism.
Attenuated regimen of biweekly gemcitabine/nab-paclitaxel in patients aged 65 years or older with advanced pancreatic cancer
Authors: Rehman Hasan , Chi Jeffrey , Hakim Nausheen , Goyal Shreya Prasad , Olazagasti Coral , Jose Jyothi , Moriarty Linda , Saif Muhammad Wasif 
Published: November 2020

Background: Treatment with gemcitabine/nab-paclitaxel confers a survival benefit over gemcitabine monotherapy in patients with advanced pancreatic cancer (APC). However, such treatment can be associated with significant toxicities especially in older patients and carries practical disadvantages related to a weekly schedule along with financial cost. We retrospectively analyzed patients >65 years of age with APC who received a modified biweekly regimen of gemcitabine/nab-paclitaxel to evaluate efficacy and toxicity. Methods: Patients aged >65 years with chemo-naïve APC with Eastern Cooperative Oncology Group performance status ⩽2 were studied. Patients were treated with a modified regimen of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 every 2 weeks on days 1 and 15 of a 28-day cycle. Patients were evaluated for progression-free survival (PFS) and overall survival (OS) with analyses performed using the Kaplan–Meier method. Adverse events were recorded on the day of chemotherapy. Cancer antigen 19.9 was measured in every cycle and restaging scans were performed every two cycles. Results: A total of 73 patients (median age: 73 years; range: 66–93) were treated with biweekly gemcitabine/nab-paclitaxel as first-line treatment. The median OS and PFS were 9.1 months and 4.8 months, respectively. Around 66% of patients received growth-factor support based on American Society of Clinical Oncology guidelines and no patient developed neutropenic fever. The incidences of grade ⩾3 toxicity for neutropenia, anemia, thrombocytopenia, and neurotoxicity were 2%, 7%, 3%, and 5%, respectively. Dose reductions of gemcitabine/nab-paclitaxel were required in 10% and 4% patients, respectively. Conclusion: In patients older than >65 years of age with APC, a modified regimen of biweekly gemcitabine/nab-paclitaxel was found to be effective when compared with the historical control from the MPACT study. This regimen allowed for fewer dose reductions, reduced healthcare costs from additional appointments, travel-related cost, as well as a favorable side-effect profile while maintaining efficacy. Though retrospective in nature, this study underlines the need for further investigation, particularly in elderly patients with poor performance status, such as those with pancreatic cancer, and in order to combine with a third agent, such as a targeted treatment or immunotherapy.
Diagnostic utility of whole spine and thoracic spine MRI corner inflammatory lesions in axial spondyloarthritis
Authors: Chan Shirley Chiu Wai , Li Philip Hei , Lee Kam Ho , Tsang Helen Hoi Lun , Lau Chak Sing , Chung Ho Yin 
Published: November 2020

Background: The presence of ⩾3 corner inflammatory lesions has been proposed as the definition of a positive spinal magnetic resonance imaging (MRI) for axial spondyloarthritis (axSpA), but subsequent studies showed inconclusive findings. Our objective was to evaluate whether locations of corner inflammatory lesions (CILs) would affect the diagnostic utility of MRI in axSpA. Method: Two groups were consecutively recruited from eight rheumatology centers in Hong Kong. The ‘axSpA’ group included 369 participants with a known diagnosis of axSpA. The ‘non-specific back pain’ (NSBP) control group consisted of 117 participants. Clinical, biochemical, and radiological parameters were collected and all patients underwent MRI of the spine and sacroiliac joints. CILs were assessed based on their locations (cervical, thoracic or lumbar) to determine the optimal cutoff for diagnosis. Results: The cutoff of ⩾5 whole spine CILs (W-CILs) and ⩾3 thoracic spine CILs (T-CILs) had comparable specificity to MRI sacroiliitis. Of 85/369 axSpA patients without sacroiliitis on conventional radiograph or MRI, 7 had ⩾5 W-CILs and 11 had ⩾3 T-CILs. Incorporating the proposed cutoffs into Assessment of SpondyloArthritis international Society axSpA criteria, ⩾5 W-CILs and ⩾3 T-CILs had similar performance when added to the imaging criteria for sacroiliitis (sensitivity 0.79 versus 0.80, specificity 0.92 versus 0.91). Conclusion: Spinal MRI provided little incremental diagnostic value in unselected axSpA patients. However, in patients without sacroiliitis on MRI or radiographs, 8–13% might be diagnosed by spinal MRI. Thoracic and whole spine MRI had similar diagnostic performance using the proposed cutoff of ⩾5 W-CILs and ⩾3 T-CILs.