bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epicardial Surface Area of Infarction
Authors: Smulders Martijn W. , Van Assche Lowie M.R. , Bekkers Sebastiaan C.A.M. , Nijveldt Robin , Beijnink Casper W.H. , Kim Han W. , Hayes Brenda , Parker Michele A. , Kaolawanich Yodying , Judd Robert M. , Kim Raymond J. 
Published: February 2021

Background:
Microvascular obstruction (MO) is a pathophysiologic complication of acute myocardial infarction that portends poor prognosis; however, it is transient and disappears with infarct healing. Much remains unknown regarding its pathophysiology and whether there are predictors of MO that could function as stable surrogates. We tested for clinical and cardiovascular magnetic resonance predictors of MO to gain insight into its pathophysiology and to find a stable surrogate.

Methods:
Three hundred two consecutive patients from 2 centers underwent cardiovascular magnetic resonance within 2 weeks of first acute myocardial infarction. Three measures of infarct morphology: infarct size, transmurality, and a new index—the epicardial surface area (EpiSA) of full-thickness infarction—were quantified on delayed-enhancement cardiovascular magnetic resonance.

Results:

Considering all clinical characteristics, only measures of infarct morphology were independent predictors of MO. EpiSA was the strongest predictor of MO and provided incremental predictive value beyond that of infarct size and transmurality (
P
<0.0001). In patients with 3-month follow-up cardiovascular magnetic resonance (n=81), EpiSA extent remained stable while MO disappeared, and EpiSA was a predictor of adverse ventricular remodeling. After 20 months of follow-up, 11 died and 1 had heart transplantation. Patients with an EpiSA larger than the median value (≥6%) had worse outcome than those with less than the median value (adverse events: 6.4% versus 1.9%,
P
=0.045).

Conclusions:
The EpiSA of infarction is a novel index of infarct morphology which accurately predicts MO during the first 2 weeks of MI, but unlike MO, does not disappear with infarct healing. This index has potential as a stable surrogate of the presence of acute MO and may be useful as a predictor of adverse remodeling and outcome which is less dependent on the time window of patient assessment.
Titin Circular RNAs Create a Back-Splice Motif Essential for SRSF10 Splicing
Authors: Tijsen Anke J. , Cócera Ortega Lucía , Reckman Yolan J. , Zhang Xiaolei , van der Made Ingeborg , Aufiero Simona , Li Jiuru , Kamps Selina C. , van den Bout Anouk , Devalla Harsha D. , van Spaendonck-Zwarts Karin Y. , Engelhardt Stefan , Gepstein Lior , Ware James S. , Pinto Yigal M. 
Published: February 2021

Background:

TTN (Titin), the largest protein in humans, forms the molecular spring that spans half of the sarcomere to provide passive elasticity to the cardiomyocyte. Mutations that disrupt the
TTN
transcript are the most frequent cause of hereditary heart failure. We showed before that
TTN
produces a class of circular RNAs (circRNAs) that depend on RBM20 to be formed. In this study, we show that the back-splice junction formed by this class of circRNAs creates a unique motif that binds SRSF10 to enable it to regulate splicing. Furthermore, we show that one of these circRNAs (cTTN1) distorts both localization of and splicing by RBM20.

Methods:
We calculated genetic constraint of the identified motif in 125 748 exomes collected from the gnomAD database. Furthermore, we focused on the highest expressed RBM20-dependent circRNA in the human heart, which we named cTTN1. We used shRNAs directed to the back-splice junction to induce selective loss of cTTN1 in human induced pluripotent stem cell–derived cardiomyocytes.

Results:

Human genetics suggests reduced genetic tolerance of the generated motif, indicating that mutations in this motif might lead to disease. RNA immunoprecipitation confirmed binding of circRNAs with this motif to SRSF10. Selective loss of cTTN1 in human induced pluripotent stem cell–derived cardiomyocytes induced structural abnormalities, apoptosis, and reduced contractile force in engineered heart tissue. In line with its SRSF10 binding, loss of cTTN1 caused abnormal splicing of important cardiomyocyte SRSF10 targets such as
MEF2A
and
CASQ2
. Strikingly, loss of cTTN1 also caused abnormal splicing of
TTN
itself. Mechanistically, we show that loss of cTTN1 distorts both localization of and splicing by RBM20.

Conclusions:

We demonstrate that circRNAs formed from the
TTN
transcript are essential for normal splicing of key muscle genes by enabling splice regulators RBM20 and SRSF10. This shows that the
TTN
transcript also has regulatory roles, besides its well-known signaling and structural function. In addition, we demonstrate that the specific sequence created by the back-splice junction of these circRNAs has important functions. This highlights the existence of functionally important sequences that cannot be recognized as such in the human genome but provides an as-yet unrecognized source for functional sequence variation.
Cardiac Remodeling During Pregnancy With Metabolic Syndrome
Authors: Yang Yijun , Kurian Justin , Schena Giana , Johnson Jaslyn , Kubo Hajime , Travers Joshua G. , Kang Chunya , Lucchese Anna Maria , Eaton Deborah M. , Lv Maoting , Li Na , Leynes Lorianna G. , Yu Daohai , Yang Fengzhen , McKinsey Timothy A. , Kishore Raj , Khan Mohsin , Mohsin Sadia , Houser Steven R. 
Published: February 2021

Background:
The heart undergoes physiological hypertrophy during pregnancy in healthy individuals. Metabolic syndrome (MetS) is now prevalent in women of child-bearing age and might add risks of adverse cardiovascular events during pregnancy. The present study asks if cardiac remodeling during pregnancy in obese individuals with MetS is abnormal and whether this predisposes them to a higher risk for cardiovascular disorders.

Methods:
The idea that MetS induces pathological cardiac remodeling during pregnancy was studied in a long-term (15 weeks) Western diet–feeding animal model that recapitulated features of human MetS. Pregnant female mice with Western diet (45% kcal fat)–induced MetS were compared with pregnant and nonpregnant females fed a control diet (10% kcal fat).

Results:
Pregnant mice fed a Western diet had increased heart mass and exhibited key features of pathological hypertrophy, including fibrosis and upregulation of fetal genes associated with pathological hypertrophy. Hearts from pregnant animals with WD-induced MetS had a distinct gene expression profile that could underlie their pathological remodeling. Concurrently, pregnant female mice with MetS showed more severe cardiac hypertrophy and exacerbated cardiac dysfunction when challenged with angiotensin II/phenylephrine infusion after delivery.

Conclusions:
These results suggest that preexisting MetS could disrupt physiological hypertrophy during pregnancy to produce pathological cardiac remodeling that could predispose the heart to chronic disorders.
Association Between Hospital Resuscitation Champion and Survival for In‐Hospital Cardiac Arrest
Authors: Chan Jesse L. , Lehrich Jessica , Nallamothu Brahmajee K. , Tang Yuanyuan , Kennedy Mary , Trumpower Brad , Chan Paul S. ,   for the American Heart Association's Get With the Guidelines‐Resuscitation Investigators
Published: February 2021

Background
Although many hospitals have resuscitation champions, it is unknown if hospitals with very active physician or nonphysician champions have higher survival rates for in‐hospital cardiac arrest (IHCA).

Methods and Results
We surveyed adult hospitals in Get With The Guidelines‐Resuscitation about resuscitation practices, including about their resuscitation champion. Hospitals were categorized as having a very active physician champion, a very active nonphysician champion, or other (no champion or not very active champion). For each hospital, we calculated risk‐standardized survival rates for IHCA during the period of 2016 to 2018 and categorized them into quintiles of risk‐standardized survival rates. The association between a hospital's resuscitation champion type and their quintile of survival was evaluated using multivariable hierarchical proportional odds logistic regression. Overall, 192 hospitals (total of 44 477 IHCAs) comprised the study cohort. Risk‐standardized survival rates for IHCA varied widely between hospitals (median: 24.7%; range: 9.2%–37.5%). Very active physician champions were present in 29 (15.1%) hospitals, 64 (33.3%) had very active nonphysician champions, and 99 (51.6%) did not have a very active champion. Compared with sites without a very active resuscitation champion, hospitals with a very active physician champion were 4 times more likely to be in a higher survival quintile, even after adjusting for resuscitation practices across hospital groups (adjusted odds ratio [OR], 3.90; 95% CI, 1.39–10.95). In contrast, there was no difference in survival between sites without very active champions and those with very active non‐physician champions (adjusted OR, 1.28; 95% CI, 0.62–2.65).

Conclusions
The background and engagement level of a resuscitation champion is a critical factor in a hospital's survival outcomes for IHCA.
Meta‐Analysis of Intensive Lipid‐Lowering Therapy in Patients With Polyvascular Disease
Authors: Alkhalil Mohammad , Kuzemczak Michał , Whitehead Nicholas , Kavvouras Charalampos , Džavík Vladimír 
Published: February 2021

Background
Polyvascular atherosclerotic disease is associated with an increased risk of future cardiovascular events. Intensive lipid‐lowering therapy (ILT) may mitigate this risk. The aims of this study‐level meta‐analysis were to examine the effects of ILT in patients with polyvascular disease and whether baseline low‐density lipoprotein cholesterol (LDL‐C) may determine the level of benefit.

Methods and Results

Electronic databases were searched through January 2020 to identify randomized controlled trials of treatments targeting upregulation of LDL‐C receptors (ie, statins, ezetimibe, and PCSK9 [proprotein convertase subtilisin–kexin type 9] inhibitors). The primary end point was major adverse vascular events as defined by the included studies. A total of 94 362 patients (14 821 [18.6%] with polyvascular disease) from 7 studies were included. In patients with monovascular disease, ILT was associated with a 13% reduction in the primary end point (rate ratio [RR] 0.87; 95% CI, 0.81–0.93 [
P
=0.0002]) (absolute RR, 1.8%) compared with less ILT, while patients with polyvascular disease had 15% relative RR (0.85; 95% CI, 0.80–0.90 [
P
<0.00001]) (absolute RR, 6.5%) (
P
=0.66 for interaction). When factoring LDL‐C, unlike patients with monovascular disease, the relative benefits of ILT, compared with less ILT, in patients with polyvascular disease were comparable with LDL‐C >100 mg/dL (RR, 0.85; 95% CI, 0.80–0.90 [
P
<0.00001]) and LDL‐C <100 mg/dL (RR, 0.88; 95% CI, 0.81–0.96 [
P
=0.003]) (
P
=0.23 for interaction).

Conclusions
Patients with polyvascular disease experienced comparable benefits to those with monovascular disease in response to ILT. The benefits of ILT in patients with polyvascular disease were not dependent on baseline LDL‐C, challenging the approach of using LDL‐C as a prerequisite to commence ILT for this high‐risk subgroup.
Sirtuin 3 Alleviates Diabetic Cardiomyopathy by Regulating TIGAR and Cardiomyocyte Metabolism
Authors: Li Lanfang , Zeng Heng , He Xiaochen , Chen Jian‐Xiong 
Published: February 2021

Background
Impairment of glycolytic metabolism is suggested to contribute to diabetic cardiomyopathy. In this study, we explored the roles of SIRT3 (Sirtuin 3) on cardiomyocyte glucose metabolism and cardiac function.

Methods and Results
Exposure of H9c2 cardiomyocyte cell lines to high glucose (HG) (30 mmol/L) resulted in a gradual decrease in SIRT3 and 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase isoform 3 (PFKFB3) expression together with increases in p53 acetylation and TP53‐induced glycolysis and apoptosis regulator (TIGAR) expression. Glycolysis was significantly reduced in the cardiomyocyte exposed to HG. Transfection with adenovirus‐SIRT3 significantly increased PFKFB3 expression and reduced HG‐induced p53 acetylation and TIGAR expression. Overexpression of SIRT3 rescued impaired glycolysis and attenuated HG–induced reactive oxygen species formation and apoptosis. Knockdown of TIGAR in cardiomyocytes by using siRNA significantly increased PFKFB3 expression and glycolysis under hyperglycemic conditions. This was accompanied by a significant suppression of HG–induced reactive oxygen species formation and apoptosis. In vivo, overexpression of SIRT3 by an intravenous jugular vein injection of adenovirus‐SIRT3 resulted in a significant reduction of p53 acetylation and TIGAR expression together with upregulation of PFKFB3 expression in the heart of diabetic db/db mice at day 14. Overexpression of SIRT3 further reduced reactive oxygen species formation and blunted microvascular rarefaction in the diabetic db/db mouse hearts. Overexpression of SIRT3 significantly blunted cardiac fibrosis and hypertrophy and improved cardiac function at day 14.

Conclusions
Our study demonstrated that SIRT3 attenuated diabetic cardiomyopathy via regulating p53 acetylation and TIGAR expression. Therefore, SIRT3 may be a novel target for abnormal energy metabolism in diabetes mellitus.
Marijuana Legalization and Rates of Crashing Under the Influence of Tetrahydrocannabinol and Alcohol
Authors: Kruse Michelle , Perez Martin , Blatt Melissa , Zielonka Tania , Dolich Mathew , Keric Natasha , Schreiber Martin , Bini John , Hofmann Luke , Cohn Stephen M. 
Published: February 2021

Objective To determine if statewide marijuana laws impact upon the detection of drugs and alcohol in victims of motor vehicle collisions (MVC). Methods A retrospective analysis of data collected at trauma centers in Arizona, California, Ohio, Oregon, New Jersey, and Texas between 2006 and 2018 was performed. The percentage of patients testing positive for marijuana tetrahydrocannabinol (THC) was compared to the percentage of patients driving under the influence of alcohol (blood alcohol level >0.08 g/dL) that were involved in an MVC. Results The data were analyzed to evaluate the trends in THC and alcohol use in victims of MVC, related to marijuana legalization. The change in incidence of THC detection (percentage) over the time period where data were available are as follows: Arizona 9.5% (0.4 to 9.9), California 5.4% (20.8 to 26.2), Ohio 5.9% (6.7 to 12.6), Oregon 3% (3.0 to 6.0), New Jersey 2.3% (2.7 to 5.0), and Texas 15.3% (3.0 to 18.3). Alcohol use did not change over time in most states. There did not appear to be a relationship between the legalization of marijuana and the likelihood of finding THC in patients admitted after MVC. In fact, in Texas, where marijuana remains illegal, there was the largest change in detection of THC. Conclusions There was no apparent increase in the incidence of driving under the influence of marijuana after legalization. In addition, the changes in marijuana legislation did not appear to impact alcohol use.
An Eight-Week Mindful Eating Program Applied in a Mediterranean Population With Overweight or Obesity: The EATT Intervention Study
Authors: Zervos Konstantinos , Koletsi Marsha , Mantzios Michael , Skopeliti Niki , Tsitsas Georgios , Naska Androniki 
Published: February 2021

Background Overweight and obesity are important public health priorities. Mindful eating can contribute in preventing automatic eating behavior and emotional dysregulation, both being primary causes of overeating and negative body image. This research outlines an eight-week mindful eating intervention (i.e., project EATT) focusing on people with overweight or obesity in assisting positive behavioral, psychological and physiological change. Methods Fifty-seven people residing in Athens were recruited to participate in this research, where participants were allocated to either an experimental or a waitlist condition. Changes in body weight, and eating attitude, mindfulness, self-compassion, anxiety questionnaires were administered at baseline and post-intervention, and at a 14-month follow-up. Results Results indicated that mindfulness and self-compassion increased significantly, while anxiety symptoms decreased. Significance was also observed in reduction of overeating symptoms and oral control. While a negative relationship was observed between anxiety and mindfulness, and anxiety and self-compassion, self-compassion was negatively associated with overeating episodes. Conclusions The intervention improved participants’ relationship with food and enabled changes towards successful weight regulation.
The COVID-19 Pandemic, the Courts and Online Hearings: Maintaining Open Justice, Procedural Fairness and Impartiality
Authors: Legg Michael 
Published: February 2021

AbstractThe COVID-19 pandemic and the ensuing mandated health protections saw courts turn to communications technology as a means to be able to continue to function. However, courts are unique institutions that exercise judicial power in accordance with the rule of law. Even in a pandemic, courts need to function in a manner consistent with their institutional role and their essential characteristics. This article uses the unique circumstances brought about by the pandemic to consider how courts can embrace technology but maintain the core or essential requirements of a court. This article identifies three essential features of courts—open justice, procedural fairness and impartiality—and examines how this recent adoption of technology has maintained or challenged those essential features. This examination allows for an assessment of how the courts operated during the pandemic and also provides guidance for making design decisions about a technology-enabled future court.
Description of content, structure and theoretical model of a group-based pain management programme in the treatment of patients with persistent non-specific low back pain and psychological risk factors in a secondary sector setting
Authors: Skovbo Mette Høj , Agerbo Karina , Jakobsen Anna , Clausen Stine Aalkjær , Langagergaard Vivian , Rolving Nanna 
Published: February 2021

Objective: To present the theoretical foundation and methodological considerations for a group-based pain management programme for patients with persistent non-specific low back pain and psychosocial risk factors. Method: The Template for Intervention Description and Replication (TIDieR) checklist was used as a framework for describing the content, structure and context of the program. The theoretical rationale underlying the pain management programme was described using the first three steps of the Intervention Mapping framework. The Fear-avoidance model and the Self-efficacy Theory were identified as the two main theories. These were used to establish specific factors addressed by the pain management programme as well as expected outcomes. Intervention description: A multidisciplinary, group-based programme using a cognitive-behavioural approach was developed. The programme consisting of six sessions of two hours duration, took place at a spine clinic at a regional hospital in Denmark. Psychoeducation and cognitive restructuring were specific strategies hypothesised to induce changes in outcome measures. The outcomes expected to change as a result of the intervention were disability, quality of life, sick leave and physical activity. A pilot study was performed, subsequent adjustments made and the final content and educational materials completed by January 2017. Conclusion: The theoretical foundation and underlying evidence for the hypothesised change mechanisms in the use of a cognitive-behavioural approach was presented. A theoretically sound and practically feasible intervention has been developed and its effectiveness is being determined in a randomised controlled trial, including 130 low back pain patients, which is currently underway.
Effects of omega-3 polyunsaturated fatty acids supplements on psychopathology and metabolic parameters in schizophrenia: A meta-analysis of randomized controlled trials
Authors: Goh Kah K , Chen Cynthia Yi-An , Chen Chun-Hsin , Lu Mong-Liang 
Published: February 2021

Background: Several monotherapy and augmentation strategies have been introduced to improve the treatment of schizophrenia. The benefits of omega-3 polyunsaturated fatty acids in patients with mental disorders is becoming increasingly acknowledged. However, its role in the treatment of schizophrenia raises complex considerations about which there has been little consensus. The aim of this study was to synthesize the findings of randomized controlled trials that were conducted to determine the efficacy and safety of omega-3 polyunsaturated fatty acids in patients with schizophrenia. Methods: The MEDLINE, Embase, Cochrane, Scopus, and Web of Science databases were searched for relevant literature. The primary outcome was changes in psychopathology and the secondary outcomes were changes in metabolic parameters and safety profiles. Results: Twenty double-blind randomized controlled trials in 1494 patients were included. Omega-3 polyunsaturated fatty acids augmentation was associated with significantly improved psychopathology in patients with schizophrenia, particularly general psychopathology and positive symptoms but not negative symptoms. Patients who were severely ill and received omega-3 polyunsaturated fatty acids containing eicosapentaenoic acid >1 g/d showed significant improvement. A favorable effect of omega-3 polyunsaturated fatty acids supplements on serum triglycerides was also demonstrated. Omega-3 polyunsaturated fatty acids are well-tolerated and safe in patients with schizophrenia. Conclusions: These findings tentatively support the use of omega-3 polyunsaturated fatty acids as a potential augmentation strategy in schizophrenia. Further research in larger samples is warranted to clarify the optimal dosage and the correct proportions of omega-3 polyunsaturated fatty acids to administer, together with elucidation of the underlying mechanisms.
Clinical characteristics and prognosis of postpartum acute kidney injury
Authors: Shu Hong , Nie Fang 
Published: February 2021

Objective To investigate the clinical characteristics and prognoses of patients with postpartum acute kidney injury (PPAKI). Methods We retrospectively reviewed the clinical presentations, laboratory examinations, treatments, and outcomes of patients with PPAKI admitted to our hospital from January 2013 to December 2017. We then analyzed the clinical characteristics and prognoses of the mothers and their infants. Results Of 37 patients diagnosed with PPAKI, 26 (70.3%) received treatment in the intensive care unit, mainly for hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome (28/37, 75.7%), pre-eclampsia (26/37, 70.3%), and postpartum hemorrhage (22/37, 59.5%). Twenty patients required renal replacement treatment (RRT), but renal recovery times were similar in the RRT and non-RRT groups. Renal function recovered completely in 30 patients (81.1%) and partially in one patient (2.7%), and was not re-examined in two patients (5.4%). Three patients (8.1%) were lost to follow-up. Only one patient (2.7%) remained dialysis-dependent, and no maternal deaths occurred. The preterm birth, low birth weight, and infant survival rates were 70.7% (29/41), 68.3% (28/41), and 78.0% (32/41), respectively. Conclusion RRT does not reduce renal recovery time compared with non-RRT. Overall, the prognoses of both mothers and their fetuses are good following treatment for PPAKI.