bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo Dominant-Negative Effect of an SCN5A Brugada Syndrome Variant
Authors: Doisne Nicolas , Grauso Marta , Mougenot Nathalie , Clergue Michel , Souil Charlotte , Coulombe Alain , Guicheney Pascale , Neyroud Nathalie 
Published: May 2021

Loss-of-function mutations in the cardiac Na+ channel α-subunit Nav1.5, encoded by SCN5A, cause Brugada syndrome (BrS), a hereditary disease characterized by sudden cardiac death due to ventricular fibrillation. We previously evidenced in vitro the dominant-negative effect of the BrS Nav1.5-R104W variant, inducing retention of wild-type (WT) channels and leading to a drastic reduction of the resulting Na+ current (INa). To explore this dominant-negative effect in vivo, we created a murine model using adeno-associated viruses (AAVs).MethodsDue to the large size of SCN5A, a dual AAV vector strategy was used combining viral DNA recombination and trans-splicing. Mice were injected with two AAV serotypes capsid 9: one packaging the cardiac specific troponin-T promoter, the 5′ half of hSCN5A cDNA, a splicing donor site and a recombinogenic sequence; and another packaging the complementary recombinogenic sequence, a splicing acceptor site, the 3′ half of hSCN5A cDNA fused to the gfp gene sequence, and the SV40 polyA signal. Eight weeks after AAV systemic injection in wild-type (WT) mice, echocardiography and ECG were recorded and mice were sacrificed. The full-length hSCN5A-gfp expression was assessed by western blot and immunohistochemistry in transduced heart tissues and the Na+ current was recorded by the patch-clamp technique in isolated adult GFP-expressing heart cells.ResultsAlmost 75% of the cardiomyocytes were transduced in hearts of mice injected with hNav1.5 and ∼30% in hNav1.5-R104W overexpressing tissues. In ventricular mice cardiomyocytes expressing R104W mutant channels, the endogenous INa was significantly decreased. Moreover, overexpression of R104W channels in normal hearts led to a decrease of total Nav1.5 expression. The R104W mutant also induced a slight dilatation of mice left ventricles and a prolongation of RR interval and P-wave duration in transduced mice. Altogether, our results demonstrated an in vivo dominant-negative effect of defective R104W channels on endogenous ones.ConclusionUsing a trans-splicing and viral DNA recombination strategy to overexpress the Na+ channel in mouse hearts allowed us to demonstrate in vivo the dominant-negative effect of a BrS variant identified in the N-terminus of Nav1.5.
Epidemiology of Sleep Disturbances and Their Effect on Psychological Distress During the COVID-19 Outbreak: A Large National Study in China
Authors: Cui Xilong , He Yuqiong , Gong Jingbo , Luo Xuerong , Liu Jianbo 
Published: May 2021

Background: The purpose of the current study was to assess the prevalence of sleep disturbances among Chinese people during the COVID-19 pandemic in a large national survey, analyze the relationship between sleep disturbances and mental health status, and explore the influencing factors of the relationship between sleep disturbances and mental health status.Methods: An online survey was accessed by 19,740 people throughout China from February 14 to 21, 2020. The survey included the Depression Anxiety Stress Scale-21 (DASS-21) to measure psychological distress and two questions about sleep disturbances. Logistic regression analyses and moderation analysis were performed.Results: (1) Among the 14,505 respondents included in analyses, 3,783 (26.08%) reported sleep disturbances at least 3 days during the past week. (2) Sleep disturbances increased the risk of depression, anxiety, and stress (p &lt; 0.05). (3) Gender, age, education, occupation, frequency of attending to epidemic information, nervousness about supplies, receiving provisions of living necessities from the service department during the outbreak, number of correct responses to questions about the epidemic, and isolation/quarantine affected the risk of mental health problems among participants experiencing sleep disturbances (p &lt; 0.05). (4) A moderation analysis found that sleep problems were more likely to affect depression, anxiety, and stress scores in men than women during the COVID-19 outbreak.Conclusion: During the COVID-19 outbreak, 26.08% people surveyed experienced sleep disturbances, and the presence of sleep disturbances was positively related to depression, anxiety, and stress, especially among front-line anti-epidemic workers, younger people, people living in isolation/quarantine, people with a college or greater education, and males.
Immediate Psychosocial Impact on Healthcare Workers During COVID-19 Pandemic in China: A Systematic Review and Meta-Analysis
Authors: Dong Fei , Liu Hong-liang , Yang Ming , Lu Chun-li , Dai Ning , Zhang Ying , Robinson Nicola , Liu Jian-ping 
Published: May 2021

Objectives: The corona virus disease-2019 (COVID-19) pandemic spread globally, and we aimed to investigate the psychosocial impact on healthcare workers (HWs) in China during the pandemic.Methods: In this systematic review and meta-analysis, we searched seven electronic databases for cross-sectional studies on psychosocial impact on HWs in relation to COVID-19 from January 1, 2020 to October 7, 2020. We included primary studies involving Chinese HWs during the pandemic, and data were extracted from the published articles. Our primary outcome was prevalence of anxiety, depression, and stress disorders. We pooled prevalence value with their 95% confidence interval using random effect models and assessed study quality on the basis of an 11-item checklist recommended by the Agency for Healthcare Research and Quality. The study protocol was registered in PROSPERO (CRD42020195843).Results: We identified 25 articles comprising a total of 30,841 completed questionnaires and 22 studies for meta-analysis. The prevalence of anxiety, depression, and stress disorders was 34.4% (29.5–39.4%), 31.1% (24.5–37.7%), and 29.1% (24.3–33.8%) for HWs. The pooled prevalence of anxiety disorders for HWs from late January to early February was 46.4% (42.9–49.9%), significantly higher than those in mid-term February (28.0%, 23.9–32.1%) and after late February (27.6%, 16.0–39.2%). The pooled prevalence of depression disorders for HWs from late January to early February was 46.5% (38.8–54.2%), significantly higher than those in mid-term February (27.1%, 19.8–34.5%) and after late February (32.9%, 16.2–49.5%). HWs working in Hubei Province had a higher prevalence of anxiety (37.9 vs. 30.8%) and a lower prevalence of depression (27.5 vs. 34.7%) than those working in other regions. Nurses had a higher prevalence of anxiety (44.1 vs. 29.0%) and depression (34.1 vs. 29.2%) than other HWs.Conclusions: About one-third of HWs in China suffered anxiety, depression, and stress at the early epidemic of COVID-19. HWs in Hubei Province, especially nurses, had a higher prevalence of psychological disorders. During the pandemic, a negative psychological state may persist in a proportion of Chinese HWs, fluctuating with the control of the pandemic. The long-term impact should continue to be observed. Attention should be paid to HWs for their psychological impact due to the pandemic.Systematic Review Registration: The study protocol was registered with PROSPERO (CRD42020195843).
Social Isolation During COVID-19 Pandemic. Perceived Stress and Containment Measures Compliance Among Polish and Italian Residents
Authors: Grabowski Jakub , Stepien Joanna , Waszak Przemyslaw , Michalski Tomasz , Meloni Roberta , Grabkowska Maja , Macul Aleksandra , Rojek Jakub , Lorettu Liliana , Sagan Iwona , Bidzan Leszek 
Published: May 2021

BackgroundIn this study, we analyze the association of social isolation in the first phase of the pandemic with perceived stress among residents of Poland and Italy with a look at how these populations adjust to and comply with implemented regulations, guidelines, and restrictions.Materials and MethodsInternet survey with Perceived Stress Scale (PSS-10) and questions regarding mobility patterns, attitude, and propensity to adjust toward the implemented measures and current health condition was made among Polish and Italian residents (Cronbach’s alpha 0.86 and 0.79, respectively). The sample size was 7,108 (6,169 completed questionnaires in Poland and 939 in Italy).ResultsThe Polish group had a higher stress level than the Italian group (mean PSS-10 total score 22,14 vs 17,01, respectively;p&lt; 0.01). There was a greater prevalence of chronic diseases among Polish respondents. Italian subjects expressed more concern about their health, as well as about their future employment. Italian subjects did not comply with suggested restrictions as much as Polish subjects and were less eager to restrain from their usual activities (social, physical, and religious), which were more often perceived as “most needed matters” in Italian than in Polish residents.ConclusionHigher activity level was found to be correlated with lower perceived stress, but the causality is unclear. Difference in adherence to restrictions between Polish and Italian residents suggests that introducing similar lockdown policies worldwide may not be as beneficial as expected. However, due to the applied method of convenience sampling and uneven study groups, one should be careful with generalizing these results.
Sinisan Protects Primary Hippocampal Neurons Against Corticosterone by Inhibiting Autophagy via the PI3K/Akt/mTOR Pathway
Authors: Zhang Mingjia , Zhang Yi , Sun Haitao , Ni Hui , Sun Jialing , Yang Xuemei , Chen Weicong , Zhao Wenting , Zhong Xiaodan , He Chunyu , Ao Haiqing , He Songqi 
Published: May 2021

Objective: Corticosterone causes significant neurotoxicity in primary hippocampal neurons which is associated with depression. Dysfunctional autophagy is implicated in cognitive impairment and depressive-like behavior. The traditional Chinese medicine Sinisan (SNS) is highly effective in clinical treatment of depression. However, the molecular mechanisms underlying therapeutic effects of SNS are unknown.Purpose: The aim of this study was to elucidate the protective effect of SNS and the underlying mechanisms against corticosterone-induced neuronal damage.Study Design: The effects of serum derived from rats containing SNS (or untreated controls) on the expression of autophagy-related molecules in primary rat hippocampal neurons exposed to different concentrations of corticosterone for different intervals were explored.Methods: CCK-8 assay, LDH assay were used to analyze cell viability and LDH activity. Western blot, qRT-PCR, and immunofluorescence assays were used to determine protein and mRNA expression levels of molecules such as LC3, p62, Beclin1, ULK1, PI3K, p-PI3K, Akt p-Akt, mTOR, p-mTOR, p70S6, p-p70S6, 4ebp1 and p-4ebp1.Results: Corticosterone induced a dose- and time-dependent reduction in cellular viability. Moreover, corticosterone (100–400 μM) treatment for 24 h increased LC3-II/LC3-I protein ratio, increased Beclin1 and ULK1 protein expression levels, and decreased p62, PI3K, p-PI3K, p-Akt, p-mTOR, p-p70S6, and p-4ebp1 protein expression levels. Notably, SNS-containing serum reversed corticosterone-induced reduction of neuronal viability, and increased p62, PI3K, p-Akt, p-mTOR, p-p70S6, and p-4ebp1 protein and mRNA expression levels. In addition, SNS-containing serum decreased LC3-II/LC3-I protein ratio, and downregulated Beclin1, and ULK1 protein and mRNA expression in primary hippocampal neurons.Conclusion: SNS protects primary hippocampal neurons against corticosterone-induced neurotoxicity by preventing excessive autophagy through activation of PI3K/AKT/mTOR pathway.
Improvements on Clinical Status of Adolescents With Anorexia Nervosa in Inpatient and Day Hospital Treatment: A Retrospective Pilot Study
Authors: Zanna Valeria , Cinelli Giulia , Criscuolo Michela , Caramadre Anna Maria , Castiglioni Maria Chiara , Chianello Ilenia , Marchili Maria Rosaria , Casamento Tumeo Chiara , Guolo Stefano , Tozzi Alberto Eugenio , Vicari Stefano 
Published: May 2021

Introduction: Medical and psychiatric complications and treatment compliance are important considerations in determining the treatment program for patients with severe anorexia nervosa (AN). Clinical practice guidelines agree that an outpatient program is the first choice for the treatment of most eating disorders, but vary in supporting these programs for AN. However, inpatient care is known to be costly and the risk of relapse and readmission is high. This pilot study aimed to describe the first data on an Italian partial hospitalization care program for AN adolescents [high-level care treatment (HLCT)], evaluating its impact on patients' clinical status, average hospitalization time, and the hospital costs compared to inpatient treatment (IP).Methods: For this retrospective pilot study, we have selected a group of 34 females with AN aged 11–18 years, divided between those who followed inpatient treatment and those who received HLCT treatment; they were matched for age and severity. We investigated the differences in treatment and outcomes between the two groups in terms of heart rate, length of treatment, weight gain, psychological characteristics, and hospital costs. Statistics for non-parametric distributions were used to compare the two groups.Results: No differences between the two groups were found at admission. At discharge, patients in the HLCT group presented a lower number of in-hospital treatment days, a higher increase of weight, and a significant improvement in outcomes compared to the inpatient group. No significant differences were found in heart rate and hospital costs.Conclusions: This study represents a first comparison between inpatient care and the HLCT treatment program, which suggests that day hospital treatment could represent a meeting point between inpatient and outpatient treatment, combining the merits of both forms of treatment. Further studies are needed in order to better investigate the different treatment programs for severe AN in adolescence.
Mental Health Outcomes of Healthcare Providers During COVID-19 Pandemic in Saudi Arabia: A Cross-Sectional Study
Authors: Alhurishi Sultana A. , Almutairi Khalid M. , Vinluan Jason M. , Aboshaiqah Ahmad E. , Marie Mohammed A. 
Published: May 2021

Objective: In this descriptive cross-sectional study we aimed, to assess the level of depression, anxiety, insomnia and distress symptoms experienced by healthcare providers during the COVID-19 pandemic in Saudi Arabia.Methods: All healthcare providers currently working in different hospitals were invited to participate in this study. Data gathering started in March 2020 to May 2020. The participants answered a five-part questionnaire which includes demographic data, a 9-item Patient Health Questionnaire, a 7-item Generalized Anxiety Disorder, a 7-item Insomnia Severity Index, and a 22-item Impact of Event Scale-Revised, which assess the level of depression, anxiety, insomnia, and distress.Results: Out of 200 healthcare providers, 40% were males. 52% were aged 31–40 years old, 61% were married. The majority of the participants were Saudi nationals (84%), 74% were nurses, 11% were physicians and 15% were other healthcare providers. More than half of the participants worked as front-liners (57%). Overall, 73, 69, 62, and 83% of all healthcare providers reported symptoms of depression, anxiety, insomnia, and distress, respectively. The analysis showed severe symptoms level of depression for physicians and nurses was 35% and 20% (p &lt; 0.05), respectively. Only three of the independent variables made a unique contribution to the model (gender, profession, and working position) (p &lt; 0.05).Conclusion: COVID-19 pandemic has a significant impact on the mental health of healthcare providers in Saudi Arabia. Female nurses and healthcare providers working in the frontline who were directly treating patients with COVID-19 are at increased risk of severe depression, anxiety and distress.
IMPAACT 2016: Operationalizing HIV Intervention Adaptations to Inform the Science and Outcomes of Implementation
Authors: Libous Jennifer L. , Montañez Nicole A. , Dow Dorothy E. , Kapetanovic Suad , Buckley Janice , Kakhu Tebogo Jacqueline , Kamthunzi Portia , Maliwichi Limbika A. , Vhembo Tichaona , Chawana Tariro Dianah , Nematadzira Teacler , Donenberg Geri R. 
Published: May 2021

Introduction: Uptake of evidence-based interventions for adolescents and young adults living with HIV (AYA-LWH) in sub-Saharan Africa (SSA) is complex, and cultural differences necessitate local adaptations to enhance effective implementation. Few models exist to guide intervention tailoring, yet operationalizing strategies is critical to inform science and implementation outcomes, namely acceptability, appropriateness, feasibility, fidelity, and sustainability. This paper describes operationalizing the ADAPT-ITT framework applied to a manualized trauma-informed cognitive behavioral therapy (TI-CBT) intervention addressing mental and sexual health for AYA-LWH in SSA in preparation for a randomized controlled trial (RCT).Methods: Phase 1 of the RCT focused on operationalizing ADAPT-ITT steps 3–7 to tailor the intervention for use in eight sites across Botswana, Malawi, South Africa, and Zimbabwe. Well-defined processes were developed to supplement the general guidelines for each step to provide clear, consistent direction on how to prepare and conduct each step, including documenting, assessing, and determining adaptations, while maintaining intervention fidelity. The processes provided efficient standardized step-by-step progression designed for future replication. All sites participated in Phase 1 using the created tools and strategies to translate and present the TI-CBT to community stakeholders for feedback informing local adaptations.Results: The research team developed and operationalized materials guiding adaptation. A translation review process verified local adaptability, maintained core concepts, and revealed differing interpretations of words, idioms, and culturally acceptable activities. Strategically designed tools comprised of feedback and translation verification forms resulted in meticulous management of adaptations. Robust collaborations between investigators, research managers, site personnel, and topical experts maximized multidisciplinary expertise, resulting in ~10–15 personnel per site facilitating, collecting, assessing, and integrating local feedback. Processes and tools operationalized in steps 3–7 effectively addressed implementation outcomes during community engagements (n = 108), focus groups (n = 5–8 AYA-LWH and caregivers per group), and strategic training of youth leaders.Discussion: This paper offers a novel generalizable approach using well-defined processes to guide intervention adaptation building on the ADAPT-ITT framework. The processes strengthen the science of implementation and provide much-needed specificity in adaptation steps to optimize and sustain real-world impact and help researchers and community stakeholders maximize existing infrastructure, culture, and resources to inform implementation strategies.
Validation of airborne and satellite altimetry data by Arctic Truck citizen science
Authors: Stokholm Andreas , Hvidegaard Sine M. , Forsberg Rene , Simonsen Sebastian B. 
Published: May 2021

The elevation of ice sheets changes due to climate change, and satellite altimetry is the preferred tool for measuring ice sheet-wide height changes. In situ validation is needed to ensure the quality of the observed elevation changes, but the cost often limits the amount of in situ data which can be collected. As more tourists are accessing the ice sheets, citizen science might provide in situ data in an environmentally friendly and cost-efficient way. Here, we investigate the opportunistic kinematic global positioning system (GPS) profiles across the Greenland ice sheet, collected by the American-Icelandic expedition on the Greenlandic icecap 2018. The collected GPS data are in good agreement with the widely used NASA’s Operation IceBridge Airborne LiDAR data measured within ± 10 days, with an average difference of 10.7 cm ± 11.7 cm. The main difference is attributed to changes in the compaction of the snow while driving and changes in the tires’ pressure. The kinematic GPS data are then compared with data from the European Space Agency’s CryoSat-2 mission. Here, an average bias of 92.3 cm ± 65.7 cm in the two records is observed between the spring CryoSat-2 and the truck GPS data obtained largely in the dry-snow zone. This suggests that the surface penetration of Ku-band radar on the Greenland ice sheet and the observed magnitude are consistent with the literature. Finally, we compared the 2018 GPS data to a profile obtained in 2005 near Kangerlussuaq, West Greenland. Here, the records show an average ice-elevation decrease of 9 m, with peaks at 26 m. These results show that the citizen science kinematic GPS data can provide high-resolution data necessary for the validation of satellite altimetry, with the added benefit of potential direct sampling properties of the surface and firn. Linking up with citizen-science expeditions is a beneficial way of providing cost-effective satellite validations and may also have a societal impact by involving more people in the climate monitoring of ice sheets.
IMPACTS OF INNOVATION AND SKILLS FOR THE DEVELOPMENT OF LATVIAN FOOD SMES
Authors:   Turiba University, Latvia, Samarasinghe Supun , Silva Nadeeshika ,   Baltic International Academy,Latvia
Published: May 2021

The Latvian SMEs are under pressure due to highly competitive foreign‐multinational‐	firms in the Latvian food market. The present paper consists of a pilot study which was aimed to reveal the factors influential for Latvian food SME development. This exploratory study was conducted on a deductive approach where the hypotheses were generated through literature, then those hypotheses can be either accepted or rejected by the survey data analysis. The authors have constructed an online mediated questionnaire based on scientific literature and expertise view. The survey was aimed at businesspeople & top‐level managers of Latvian food SMEsin the Riga region. The most influential factors for Latvian food SMEs' development were identified as “innovation” and “skills” which have high positive impacts on Latvian food SMEs' development. In the future, the most contributing areas (variable indicators) of these influential factors can be further explored with a higher sample size which is beneficial to identify potential innovative strategies related to innovation and skills.