bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of differentially expressed circRNAs and ceRNA regulatory network in porcine skeletal muscle
Authors: Li Meng , Zhang Na , Zhang Wanfeng , Hei Wei , Cai Chunbo , Yang Yang , Lu Chang , Gao Pengfei , Guo Xiaohong , Cao Guoqing , Li Bugao 
Published: May 2021

Abstract
Background
Circular RNA (circRNA), a novel class of non-coding RNA, has a closed-loop structure with important functions in skeletal muscle growth. The purpose of this study was to investigate the role of differentially expressed circRNAs (DEcircRNAs), as well as the DEcircRNA-miRNA-mRNA regulatory network, at different stages of porcine skeletal muscle development. Here, we present a panoramic view of circRNA expression in porcine skeletal muscle from Large White and Mashen pigs at 1, 90, and 180 days of age.

Results
We identified a total of 5819 circRNAs. DEcircRNA analysis at different stages showed 327 DEcircRNAs present in both breeds. DEcircRNA host genes were concentrated predominately in TGF-β, MAPK, FoxO, and other signaling pathways related to skeletal muscle growth and fat deposition. Further prediction showed that 128 DEcircRNAs could bind to 253 miRNAs, while miRNAs could target 945 mRNAs. The constructed ceRNA network plays a vital role in skeletal muscle growth and development, and fat deposition. Circ_0015885/miR-23b/SESN3 in the ceRNA network attracted our attention. miR-23b and SESN3 were found to participate in skeletal muscle growth regulation, also playing an important role in fat deposition. Using convergent and divergent primer amplification, RNase R digestion, and qRT-PCR, circ_0015885, an exonic circRNA derived from Homer Scaffold Protein 1 (HOMER1), was confirmed to be differentially expressed during skeletal muscle growth. In summary, circ_0015885 may further regulate SESN3 expression by interacting with miR-23b to function in skeletal muscle.

Conclusions
This study not only enriched the circRNA library in pigs, but also laid a solid foundation for the screening of key circRNAs during skeletal muscle growth and intramural fat deposition. In addition, circ_0015885/miR-23b/SESN3, a new network regulating skeletal muscle growth and fat deposition, was identified as important for increasing the growth rate of pigs and improving meat quality.
Comparative analysis of spreading depolarizations in brain slices exposed to osmotic or metabolic stress
Authors: Frank Rita , Bari Ferenc , Menyhárt Ákos , Farkas Eszter 
Published: May 2021

AbstractBackgroundRecurrent spreading depolarizations (SDs) occur in stroke and traumatic brain injury and are considered as a hallmark of injury progression. The complexity of conditions associated with SD in the living brain encouraged researchers to study SD in live brain slice preparations, yet methodological differences among laboratories complicate integrative data interpretation. Here we provide a comparative evaluation of SD evolution in live brain slices, in response to selected SD triggers and in various media, under otherwise standardized experimental conditions.MethodsRat live coronal brain slices (350 μm) were prepared (n = 51). Hypo-osmotic medium (Na+content reduced from 130 to 60 mM, HM) or oxygen-glucose deprivation (OGD) were applied to cause osmotic or ischemic challenge. Brain slices superfused with artificial cerebrospinal fluid (aCSF) served as control. SDs were evoked in the control condition with pressure injection of KCl or electric stimulation. Local field potential (LFP) was recorded via an intracortical glass capillary electrode, or intrinsic optical signal imaging was conducted at white light illumination to characterize SDs. TTC and hematoxylin-eosin staining were used to assess tissue damage.ResultsSevere osmotic stress or OGD provoked a spontaneous SD. In contrast with SDs triggered in aCSF, these spontaneous depolarizations were characterized by incomplete repolarization and prolonged duration. Further, cortical SDs under HM or OGD propagated over the entire cortex and occassionally invaded the striatum, while SDs in aCSF covered a significantly smaller cortical area before coming to a halt, and never spread to the striatum. SDs in HM displayed the greatest amplitude and the most rapid propagation velocity. Finally, spontaneous SD in HM and especially under OGD was followed by tissue injury.ConclusionsWhile the failure of Na+/K+ATP-ase is thought to impair tissue recovery from OGD-related SD, the tissue swelling-related hyper excitability and the exhaustion of astrocyte buffering capacity are suggested to promote SD evolution under osmotic stress. In contrast with OGD, SD propagating under hypo-osmotic condition is not terminal, yet it is associated with irreversible tissue injury. Further investigation is required to understand the mechanistic similarities or differences between the evolution of SDs spontaneously occurring in HM and under OGD.
Atrial fibrillation evolution and rhythm control strategy following left appendage closure: new insights from the prospective FLAAC registry
Authors: Lellouche Nicolas , Arrouasse Raphaele , Ternacle Julien , Gallet Romain , Hermida Jean-Sylvain , Hamon David , Juliard Jean-Michel , Pasquie Jean-Luc , Dhanjal Tarvinder , Teiger Emmanuel , Le Corvoisier Philippe 
Published: May 2021

Abstract
Background
Percutaneous left atrial appendage (LAA) closure is an alternative to oral anticoagulation (OAC) for atrial fibrillation (AF) patients with high thromboembolism risk, particularly with contraindications to OAC. The LAA itself could possess proarrhythmogenic properties. As patients undergoing LAA closure could be candidates for cardioversion or ablation, we aimed to evaluate AF disease progression following LAA closure and the outcome of patients undergoing a rhythm control strategy after the procedure.

Methods
The prospective multicenter French Nationwide Observational LAA Closure Registry (FLAAC) comprises 33 French interventional cardiology departments. Patients were included if they fulfilled the following criteria: history of non-valvular AF, successful LAA closure and long-term ECG follow-up.

Results
A total of 331 patients with successful LAA closure were enrolled in the study. Patients mean age was 75.4 ± 0.5 years. The study population was characterized by a high thromboembolic risk (CHA2DS2-VASc score: 4.5 ± 0.1) and frequent comorbidities. The median follow-up was 11.9 months. One hundred and nineteen (36.0%) patients were in sinus rhythm (SR) at baseline. Among SR patients, documented AF was observed in 16 (13.4%) patients whereas 15 (7.1%) patients in AF at baseline restored SR, at the end of follow up. Finally, only 13 patients (4%) underwent procedures to restore SR without complications during the follow-up.

Conclusions
The vast majority of patients undergoing LAA closure have the same AF status at baseline and one year after the index procedure. During the follow-up, a very small proportion (4%) of our population underwent procedures to restore SR without complications whatever the post-procedural antithrombotic strategy was.
Hsa_circ_0004831 downregulation is partially responsible for atorvastatinalleviated human umbilical vein endothelial cell injuries induced by ox-LDL through targeting the miR-182-5p/CXCL12 axis
Authors: Su Gang , Sun Guangli , Lv Jian , Zhang Weiwei , Liu Hai , Tang Yajing , Su Haoang 
Published: May 2021

Abstract
Background
The dysfunction and injury of human umbilical vein endothelial cells (HUVECs) are key events of atherosclerosis (AS). Atorvastatin (ATV) has been shown to play a protective role on endothelial cells. However, the associated molecular mechanisms remain not fully illustrated.

Methods
HUVECs were treated with oxidized low-density lipoprotein (ox-LDL) to mimic the pathological conditions of endothelial cell injury in AS. Cell injuries were assessed according to cell viability, cell apoptosis, cycle progression, oxidative stress and inflammatory responses using CCK-8 assay, flow cytometry assay or commercial kits. The expression of hsa_circ_0004831, miR-182-5p, and C-X-C motif chemokine 12 (CXCL12) mRNA was examined using quantitative real-time PCR (qPCR). The expression of CXCL12 protein was quantitated by western blot. The predicted target relationship between miR-182-5p and hsa_circ_0004831 or CXCL12 was verified by pull-down assay, dual-luciferase reporter assay or RIP assay.

Results
The expression of hsa_circ_0004831 was upregulated by ox-LDL but downregulated by ATV in HUVECs. ATV promoted cell viability and cell cycle progression but inhibited apoptosis, oxidative stress and inflammation in ox-LDL-treated HUVECs, while the role of ATV was partially reversed by hsa_circ_0004831 overexpression. MiR-182-5p was targeted by hsa_circ_0004831, and hsa_circ_0004831 overexpression-restored apoptosis, oxidative stress and inflammation were blocked by miR-182-5p restoration. Further, CXCL12 was targeted by miR-182-5p, and miR-182-5p inhibition-stimulated apoptosis, oxidative stress and inflammation were lessened by CXCL12 knockdown.

Conclusion
Hsa_circ_0004831-targeted miR-182-5p/CXCL12 regulatory network is one of the pathways by which ATV protects against ox-LDL-induced endothelial injuries.
An Aboriginal and Torres Strait Islander Cardiac Rehabilitation program delivered in a non-Indigenous health service (Yeddung Gauar): a mixed methods feasibility study
Authors: Freene Nicole , Brown Roslyn , Collis Paul , Bourke Chris , Silk Katharine , Jackson Alicia , Davey Rachel , Northam Holly L. 
Published: May 2021

Abstract
Background
There is limited evidence of Aboriginal and Torres Strait Islander people attending cardiac rehabilitation (CR) programs despite high levels of heart disease. One key enabler for CR attendance is a culturally safe program. This study evaluates improving access for Aboriginal and Torres Strait Islander women to attend a CR program in a non-Indigenous health service, alongside improving health workforce cultural safety.

Methods
An 18-week mixed-methods feasibility study was conducted, with weekly flexible CR sessions delivered by a multidisciplinary team and an Aboriginal and/or Torres Strait Islander Health Worker (AHW) at a university health centre. Aboriginal and Torres Strait Islander women who were at risk of, or had experienced, a cardiac event were recruited. Data was collected from participants at baseline, and at every sixth-session attended, including measures of disease risk, quality-of-life, exercise capacity and anxiety and depression. Cultural awareness training was provided for health professionals before the program commenced. Assessment of health professionals’ cultural awareness pre- and post-program was evaluated using a questionnaire (n = 18). Qualitative data from participants (n = 3), the AHW, health professionals (n = 4) and referrers (n = 4) was collected at the end of the program using yarning methodology and analysed thematically using Charmaz’s constant comparative approach.

Results
Eight referrals were received for the CR program and four Aboriginal women attended the program, aged from 24 to 68 years. Adherence to the weekly sessions ranged from 65 to 100%. At the program’s conclusion, there was a significant change in health professionals’ perception of social policies implemented to ‘improve’ Aboriginal people, and self-reported changes in health professionals’ behaviours and skills. Themes were identified for recruitment, participants, health professionals and program delivery, with cultural safety enveloping all areas. Trust was a major theme for recruitment and adherence of participants. The AHW was a key enabler of cultural authenticity, and the flexibility of the program contributed greatly to participant perceptions of cultural safety. Barriers for attendance were not unique to this population.

Conclusion
The flexible CR program in a non-Indigenous service provided a culturally safe environment for Aboriginal women but referrals were low. Importantly, the combination of cultural awareness training and participation in the program delivery improved health professionals’ confidence in working with Aboriginal people. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) 12618000581268, http://www.ANZCTR.org.au/ACTRN12618000581268.aspx, registered 16 April 2018.
Massive pulmonary embolism presenting with hemoptysis and S1Q3T3 ECG findings
Authors: Islamoglu Mehmet Sami , Dokur Mehmet , Ozdemir Emrah , Unal Omer Faruk 
Published: May 2021

AbstractBackgroundVenous thromboembolism clinically presenting with a deep vein thrombosis or pulmonary embolism is among the most commonly seen cardiovascular syndromes. The aim of this case presentation is to emphasise the typical electrocardiographic findings that are detected with massive pulmonary embolism along with the electrocardiographic S1Q3 and S1Q3T3 accompanied by T negativity at the D3 derivation based on prevalent T negativity.Case presentationWe present the case of an adult male who presented with a massive pulmonary embolism that was associated with tachycardia, haemoptysis and typical S1Q3T3 electrocardiographic findings. Tomographic findings showed filling defects in the two main pulmonary artery lumens, which were found to be compatible with a massive embolism. Intravenous heparin was injected (5000 IU), and low molecule weight heparin (LMWH) treatment was initiated. After two days of observation and treatment in the coronary intensive care unit, the patient was discharged for outpatient care.DiscussionMassive pulmonary embolism is an urgent life-threatening clinical situation that is frequently confused with acute ST elevation myocardial infarction. The definitive diagnosis of massive pulmonary embolism was made with a computed tomography pulmonary angiogram. Electrocardiographic findings and hypoxic hypercarbia in the blood gas analysis are typical. Early diagnosis with laboratory and imaging investigations is vital in the treatment and prognosis of pulmonary embolism.ConclusionsVentricular overload signs accompanied by ST segment elevation in electrocardiography and S1Q3 and prevalent T negativity are crucial features in terms of distinguishing between pulmonary embolism and myocardial infarction and selecting effective treatments for patients admitted to the emergency department.
Stakeholder-engaged process for refining the design of a clinical trial in home hospice
Authors: Tjia Jennifer , Clayton Margaret , Chiriboga Germán , Staples Brooke , Puerto Geraldine , Rappaport Lynley , DeSanto-Madeya Susan 
Published: May 2021

Abstract
Background
Clinical trials in home hospice settings are important to build the evidence base for practice, but balancing the burden and benefit of clinical trial conduct for clinicians, patients, and family caregivers is challenging. A stakeholder-engaged process can help inform and refine key aspects of home hospice clinical trials. The aim of this study was to describe a stakeholder-engaged process to refine, design, and implement aspects of an educational intervention trial in home hospice, including recommendations for refining intervention content and delivery, recruitment and enrollment strategies, and content and frequency of outcome measurement.

Methods
A panel of interprofessional (1 hospice administrator, 3 nurses, 2 physicians, 2 pharmacists) and 2 former family caregiver stakeholders was systematically selected and invited to participate based on expertise, representing 2 geographically distinct hospices who were participating in the clinical trial. Teleconferences followed a predetermined procedural sequence: 1. pre-meeting materials distribution and review; 2. pre-meeting email solicitation of concerns in response to materials; 3. teleconference with structured and guided discussion; and 4. documentation and distribution of minutes for accuracy review and future meeting guidance. Discussion topics were distinct for each panel meeting. Written reflections on the stakeholder engagement process were collected from panel members to further refine our process.

Results
Five initial biweekly teleconferences resulted in recommendations for recruitment strategy, enrollment process, measurement frequency, patient inclusion, and primary care physician notification of the patient’s trial involvement. The panel continues to participate in quarterly teleconferences to review progress and unexpected questions and concerns. Panelist reflections reveal personal and professional benefit from participation.

Conclusions
An interprofessional stakeholder process is feasible and invaluable for developing home hospice intervention studies, contributing to better science, successful trial implementation, and relevant, valid outcomes.

Trial registration
Clinicaltrials.gov, NCT03972163, Registered June 3, 2019.
Gene expression profiling of inflammatory cytokines in esophageal biopsies of different phenotypes of gastroesophageal reflux disease: a cross-sectional study
Authors: Zavala-Solares Mónica R. , Fonseca-Camarillo Gabriela , Valdovinos Miguel , Granados Julio , Grajales-Figueroa Guido , Zamora-Nava Luis , Aguilar-Olivos Nancy , Valdovinos-García Luis R. , Yamamoto-Furusho Jesús K. 
Published: May 2021

Abstract
Background
The clinical endoscopic phenotypes of gastroesophageal reflux disease (GERD) are classified as Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD is subclassified as abnormal acid exposure (AAE) and normal acid exposure (NAE) based on pH monitoring study results. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD.

Methods
This is an observational and cross-sectional study. All patients with BE, EE, AAE, and NAE and a control group were subjected to superior endoscopy (with biopsies of esophageal mucosa). Relative mRNA quantification of cytokine and target genes was conducted by quantitative Polymerase Chain Reaction (RT-qPCR). Changes in the expression of genes associated with inflammation were assessed for each disease phenotype. Statistical analysis of differential gene expression was performed using the Mann–Whitney U non-parametric test. A p value < 0.05 was considered significant.

Results
A total of 82 patients were included and were divided into the following groups: Group BE, 16 (19.51%); Group EE, 23 (28.04%); Group AAE, 13 (15.86%); NAE 13 (15.86%); and Control Group, 17 (20.73%). Compared with the control group, patients with BE exhibited increased IL-8 expression (p < 0.05) and increased levels of IL-10, MMP-3, and MMP-9. Patients with EE exhibited increased levels of IL-1B, IL-6 and IL-10 (p < 0.05), and patients with AAE exhibited increased expression of IL-1B, IL-6, IFN-γ and TNF-α (p < 0.05). AAE exhibited increased IL-1B and TNF-α expression compared with NAE (p < 0.05).

Conclusion
This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients with different GERD endoscopic phenotypes. IL-1B and TNF-α could be useful to differentially diagnose AAE and NAE in the non-erosive phenotype using endoscopic biopsies.
Projecting COVID-19 disease severity in cancer patients using purposefully-designed machine learning
Authors: Navlakha Saket , Morjaria Sejal , Perez-Johnston Rocio , Zhang Allen , Taur Ying 
Published: May 2021

Abstract
Background
Accurately predicting outcomes for cancer patients with COVID-19 has been clinically challenging. Numerous clinical variables have been retrospectively associated with disease severity, but the predictive value of these variables, and how multiple variables interact to increase risk, remains unclear.

Methods
We used machine learning algorithms to predict COVID-19 severity in 348 cancer patients at Memorial Sloan Kettering Cancer Center in New York City. Using only clinical variables collected on or before a patient’s COVID-19 positive date (time zero), we sought to classify patients into one of three possible future outcomes: Severe-early (the patient required high levels of oxygen support within 3 days of being tested positive for COVID-19), Severe-late (the patient required high levels of oxygen after 3 days), and Non-severe (the patient never required oxygen support).

Results
Our algorithm classified patients into these classes with an area under the receiver operating characteristic curve (AUROC) ranging from 70 to 85%, significantly outperforming prior methods and univariate analyses. Critically, classification accuracy is highest when using a potpourri of clinical variables — including basic patient information, pre-existing diagnoses, laboratory and radiological work, and underlying cancer type — suggesting that COVID-19 in cancer patients comes with numerous, combinatorial risk factors.

Conclusions
Overall, we provide a computational tool that can identify high-risk patients early in their disease progression, which could aid in clinical decision-making and selecting treatment options.
The healthcare costs of antimicrobial resistance in Lebanon: a multi-centre prospective cohort study from the payer perspective
Authors: Iskandar Katia , Roques Christine , Hallit Souheil , Husni-Samaha Rola , Dirani Natalia , Rizk Rana , Abdo Rachel , Yared Yasmina , Matta Matta , Mostafa Inas , Matta Roula , Salameh Pascale , Molinier Laurent 
Published: May 2021

Abstract
Background
Our aim was to examine whether the length of stay, hospital charges and in-hospital mortality attributable to healthcare- and community-associated infections due to antimicrobial-resistant bacteria were higher compared with those due to susceptible bacteria in the Lebanese healthcare settings using different methodology of analysis from the payer perspective .

Methods
We performed a multi-centre prospective cohort study in ten hospitals across Lebanon. The sample size consisted of 1289 patients with documented healthcare-associated infection (HAI) or community-associated infection (CAI). We conducted three separate analysis to adjust for confounders and time-dependent bias: (1) Post-HAIs in which we included the excess LOS and hospital charges incurred after infection and (2) Matched cohort, in which we matched the patients based on propensity score estimates (3) The conventional method, in which we considered the entire hospital stay and allocated charges attributable to CAI. The linear regression models accounted for multiple confounders.

Results
HAIs and CAIs with resistant versus susceptible bacteria were associated with a significant excess length of hospital stay (2.69 days [95% CI,1.5–3.9]; p < 0.001) and (2.2 days [95% CI,1.2–3.3]; p < 0.001) and resulted in additional hospital charges ($1807 [95% CI, 1046–2569]; p < 0.001) and ($889 [95% CI, 378–1400]; p = 0.001) respectively. Compared with the post-HAIs analysis, the matched cohort method showed a reduction by 26 and 13% in hospital charges and LOS estimates respectively. Infections with resistant bacteria did not decrease the time to in-hospital mortality, for both healthcare- or community-associated infections. Resistant cases in the post-HAIs analysis showed a significantly higher risk of in-hospital mortality (odds ratio, 0.517 [95% CI, 0.327–0.820]; p = 0.05).

Conclusion
This is the first nationwide study that quantifies the healthcare costs of antimicrobial resistance in Lebanon. For cases with HAIs, matched cohort analysis showed more conservative estimates compared with post-HAIs method. The differences in estimates highlight the need for a unified methodology to estimate the burden of antimicrobial resistance in order to accurately advise health policy makers and prioritize resources expenditure.