bluuebunny/crossref_metadata_2025 huggingface dataset:
The Persistence of Child and Adolescence Mental Healthcare: Results from Registry Data
Authors: Dijk Hermien , Freriks Roel , Alessie Rob , Mierau Jochen
Published: June 2020

Background: Previous studies on the persistence of child and adolescent mental healthcare do not consider the role of time-invariant individual characteristics. Estimating persistence of healthcare using standard linear models yields biased estimates due to unobserved heterogeneity and the autoregressive structure of the model. This study provides estimates of the persistence of child and adolescent mental healthcare taking these statistical issues into account. Methods: We use registry data of more than 80,000 Dutch children and adolescents between 2000 and 2012 from the Psychiatric Case Registry Northern Netherlands (PCR-NN). In order to account for autocorrelation due to the presence of a lagged dependent variable and to distinguish between persistence caused by time-invariant individual characteristics and a direct care effect we use difference GMM-IV estimation. In further analyses we assess the robustness of our results to policy reforms, different definitions of care and diagnosis decomposition. Results: All estimation results for the direct care effect (true state-dependence) show a positive coefficient smaller than unity with a main effect of 0.215 (p < 0.01), which indicates that the process is stable. Persistence of care is found to be 0.065 (p < 0.05) higher for females. Additionally, the majority of persistence of care appears to be associated with time-invariant characteristics. Further analyses indicate that (1) policy reforms only slightly affected persistence of care, (2) results are robust to different definitions of care and (3) persistence of care does not differ significantly across subgroups. Conclusions: The results indicate that the majority of mental healthcare persistence for children and adolescents is due to time-invariant individuals characteristics. Additionally, we find that in the absence of further shocks a sudden increase of 10 care contacts in the present year is associated with approximately 3 additional care contacts at some point in the future. This result provides essential information about the necessity of budget increases for future years in the case of exogenous increases in healthcare use.
The predictive value of lymphocyte-to-monocyte ratio in the prognosis of acute coronary syndrome patients: A systematic review and meta-analysis
Authors: Quan Xiao-Qing , Wang Run-Chang , Zhang Qing , Zhang Cun-Tai , Sun Lei
Published: June 2020

Background: The association between the lymphocyte-to-monocyte ratio (LMR) and prognosis in the patients with acute coronary syndrome (ACS) is not fully understood. We performed this systematic review and meta-analysis to evaluate the correlation between LMR and mortality or major adverse cardiac events (MACE) in patients with ACS.Methods: A systematic search was performed in PubMed, MEDLINE, EMBASE, the Cochrane Library, Scopus, and Web of science. The association between LMR and mortality/MACE was analyzed in patients with ACS. The search was updated to April 15, 2020. Results: A total of 5 studies comprising 4343 patients were included in this meta-analysis. The results showed that lower LMR predicted higher short-term mortality/MACE (hazard ratio [HR] = 3.44, 95% confidence interval [CI]: 1.46–8.14, P < 0.05) and long-term mortality/MACE (HR = 1.70, 95% CI: 1.36– 2.13, P < 0.05). In the subgroup analysis, there was still statistical significance of long-term mortality/MACE in all subgroups.Conclusions: This study suggested that lower LMR value might be associated with higher short-term and long-term mortality/MACE in ACS patients. Especially for younger ACS patients, low LMR was more closely associated with poor prognosis.
The influence of dietary supplementation with the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) on the chemotaxis, phagocytosis and respiratory burst of peripheral blood granulocytes and monocytes in calves
Authors: Wójcik Roman , Małaczewska Joanna , Zwierzchowski Grzegorz , Miciński Jan , Kaczorek-Łukowska Edyta
Published: June 2020

Background A healthy immune system plays a particularly important role in newborns, including in calves that are far more susceptible to infections (viral, bacterial and other) than adult individuals. Therefore, the present study aimed to evaluate the influence of HMB on the chemotactic activity (MIGRATEST® kit), phagocytic activity (PHAGOTEST® kit) and oxidative burst (BURSTTEST® kit) of monocytes and granulocytes in the peripheral blood of calves by flow cytometry.Results An analysis of granulocyte and monocyte chemotactic activity and phagocytic activity revealed significantly higher levels of phagocytic activity in calves administered HMB than in the control group, expressed in terms of the percentage of phagocytising cells and mean fluorescence intensity (MFI). HMB also had a positive effect on the oxidative metabolism of monocytes and granulocytes stimulated with PMA (4-phorbol-12-β-myristate-13-acetate) and Escherichia coli bacteria, expressed as MFI values and the percentage of oxidative metabolism.Conclusion HMB stimulates non-specific cell-mediated immunity, which is a very important consideration in newborn calves that are exposed to adverse environmental factors in the first weeks of their life. The supplementation of animal diets with HMB for both preventive and therapeutic purposes can also reduce the use of antibiotics in animal production.
Frequency of kdr mutations in the voltage-sensitive sodium channel (VSSC) gene in Aedes aegypti from Yogyakarta and implications for Wolbachia-infected mosquito trials
Authors: Wuliandari Juli R. , Hoffmann Ary A. , Tantowijoyo Warsito , Endersby-Harshman Nancy M.
Published: June 2020

Background : In the inner city of Yogyakarta, Indonesia, insecticide resistance is expected in the main dengue vector, Aedes aegypti , because of the intensive local application of pyrethroid insecticides. However, detailed information about the nature of resistance in this species is required to assist the release of Wolbachia mosquitoes in a dengue control program so that we can ensure that insecticide resistance in the strain of Ae. aegypti being released matches that of the background population. Methods: High-resolution melt genotyping was used to screen for kdr mutations associated with pyrethroid resistance in the voltage-sensitive sodium channel (V SSC ) gene in Ae. aegypti of some areas in the inner city of Yogyakarta. Results: The results show that the V1016G mutation predominated, with individuals homozygous for the 1016G allele at a frequency of 82.1% and the mutant allele G at a frequency of 92%. Two patterns of co-occurrence of mutations were detected in this study, homozygous individuals V1016G/S989P; and heterozygous individuals V1016G/F1534C/S989P. We found the simultaneous occurrence of kdr mutations V1016G and F1534C at all collection sites, but not within individual mosquitoes. Homozygous mutants at locus 1016 were homozygous wildtype at locus 1534 and vice versa, and heterozygous V1016G were also heterozygous for F1534C. The most common tri-locus genotype co-occurrences were homozygous mutant 1016GG and homozygous wild-type FF1534, combined with homozygous mutant 989PP (GG/FF/PP) at a frequency of 38.28%. Conclusions: Given the relatively small differences in frequency of resistance alleles across the city area, locality variations in resistance should have minor implications for the success of Wolbachia mosquito trials being undertaken in the Yogyakarta area.
Echography analysis of musculoskeletal, heart and liver alterations associated with endothelial dysfunction in obese rats
Authors: Coria Alejandra Martínez , Estrada-Cruz Norma Angélica , Ordoñez María Inés Pérez , Montes-Cortes Daniel H. , Manuel-Apolinar Leticia
Published: June 2020

Background: Modern imaging plays a central role in the care of obese patients, and there is an integral focus on its use and accessibility in individuals who have alterations of various in various organs. The objective in this study was to perform an echographic analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle (LV) in obese rats . Methods: Sprague Dawley rats (250±5g) were obtained and divided into two groups: the control (C) group was fed with a standard diet, and the obese (Ob) group was fed hyper caloric diet with a high fructose-fat content for 4 months. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography, abdominal ultrasound and musculoskeletal system studies were performed in the lower extremities. Results: The body weight in the Ob group was increased compared to that in the control group, (p<0.001); in addition, increased glucose, cholesterol and triglyceride concentrations (p<0.05) as well as increased levels of the adhesion molecules ICAM-1 and, VCAM-1 (p<0.01) were found in the Ob group vs the C group. On ultrasound, 75% of the Ob group presented fatty liver and distal joint abnormalities. Conclusion: Obese rats exhibit endothelial dysfunction and musculoskeletal changes, also, fatty liver and articular cysts in the posterior region of the distal lower- extremity joints.
Prospective Cardiovascular Magnetic Resonance Imaging in Adults with Alström Syndrome: Silent Progression of Diffuse Interstitial Fibrosis.
Authors: Baig Shanat , Dowd Rory , Edwards Nicola C , Hodson James , Fabritz Larissa , Vijapurapu Ravi , Liu Boyang , Geberhiwot Tarekegn , Steeds Richard P
Published: June 2020

Background Alström syndrome (ALMS) is a rare ciliopathy characterised by early onset insulin resistance, obesity, and dyslipidaemia and is a model for diseases that have huge social, health and economic impact. Cardiomyopathy develops in the majority, with high rates of morbidity and mortality, the definitive features of which are coarse replacement fibrosis and diffuse myocardial fibrosis (DIF). The pathogenesis of heart failure is thought to involve fibroblast accumulation and expansion of the extracellular matrix with excess protein deposition, leading to distorted organ architecture and impaired contractile function. Consecutive adults with genetically proven ALMS attending the National Centre for Rare Disease in Birmingham, England were studied. All patients underwent serial CMR, echocardiography and venous blood sampling, with computed tomography coronary angiography (CTCA) performed to assess severity of CAD. The aims of this study were: 1) to evaluate changes over time in DIF by cardiovascular magnetic resonance tissue characterization in ALMS; 2) to examine whether changes in DIF are associated with alteration in systolic or diastolic function; and 3) to evaluate the frequency and severity of coronary artery disease as a confounder for progression of ischaemic versus non-ischaemic fibrosis. Results In total, 30/32 adults (63% male; 67% White British) participated. The median age at first scan was 21.3 years (interquartile range: 19.0-32.6) and participants were followed for a maximum of 67 months. Only 4 patients had significant coronary artery stenosis on post-mortem, invasive coronary angiography or CTCA. Mid short axis myocardial T1 times, myocardial extracellular volume, and left ventricular mass increased significantly over time, by an average of 21.8ms (95% CI 17.4 – 26.1; p<0.001), 1.1 percentage points (0.6 – 1.6, p<0.001), and 2.8 g/m2 (1.9 – 3.7; p<0.001) per year, respectively. These changes were not associated with significant deterioration in myocardial structure or function.Conclusions This is the first comprehensive prospective study demonstrating progression of DIF in ALMS over time, although no structural or functional consequences were noted within a median three and a half years’ follow up. Further study is warranted to define whether DIF is a by-stander or the driver to impaired contractile function, heart failure and death.
Betalain exerts a protective effect against glaucoma is majorly through the association of inflammatory cytokines
Authors: Wang Jiadi , Zhang Dandan , Cao Conghong , Yao Jing
Published: June 2020

The present research aimed at evaluating the protective role of betalain on the in vitro glaucoma model using PC12 neuronal cells. The cultured neuronal cells in a customized pressurized chamber were analyzed for the onset of glutathione, myeloperoxidase (MPO), cathepsin, expression of inflammatory enzymes such as cyclooxygenase (COX-1), lipooxygenase (5- LOX), sPLA2 caveolin-1, glaucoma markers and other inflammatory cytokines in the presence and absence of betalain. The results have shown that a significant increase in the expression of oxidative stress with increased activity of cathepsin B and D. On the other hand, the activity of inflammatory enzymes such as COX-1, 5- LOX, sPLA2 were significantly increased in pressure exposed cells. In addition, glaucoma simulated cells demonstrated a significant increase in the VEGF, TGF-β, BDGF, and neuroserpin compared to control. Moreover, cells predisposed to hydrostatic pressure demonstrated an increase in (p<0.01) inflammatory cytokines such as IL-6, CXCR4, IL-17, IL-1β, and TNF-α levels. However, cells pre-treated with betalain improved the glutathione levels with attenuated MPO activity. Simultaneously, the levels of inflammatory cytokines and other glaucoma marker genes found restored in drug pre-treated cells. Thus, the results of the present study demonstrate that the use of betalain on ocular cells can prevent the progression of the disease that can be a suggestive therapeutic for controlling glaucoma like conditions.
Trends of alcohol use, dietary behaviour, interpersonal violence, mental health, oral and hand hygiene behaviour among adolescents in Lebanon: cross-sectional national school surveys from 2005, 2011 and 2017
Authors: Pengpid Supa , Peltzer Karl
Published: June 2020

Background: Health risk behaviours during adolescence can have long-term negative consequences. Little is known, however, about the recent health risk behaviour trends in adolescents in Lebanon, This investigation aimed to report the trends in the prevalence of various health risk behaviours, such as alcohol use, dietary behaviour, interpersonal violence, mental health, oral and hand hygiene, among adolescents in Lebanon.Methods: Cross-sectional nationally representative data were analysed from 13,109 adolescents (14 years median age) that participated in three waves (2005, 2011 and 2017) of the “Lebanon Global School-Based Student Health Survey (GSHS)”.Results: Significant improvements were found among both boys and girls in the decline of interpersonal violence (bulling victimization, being physically attack and involvement in physical fighting), poor washing of hands after using the toilet, and suicide plan, and among girls only loneliness, worry-induced sleep disturbance and suicidal ideation. Significant increases were found among both boys and girls in the prevalence of inadequate fruit consumption, and among boys only unintentional injury and not always washing hands before eating.Conclusion: Several decreases but also increases of health risk behaviours were found over three assessment points during a period of 12 years calling for continued health enhancing activities in this adolescent population.
Cost-Effectiveness Analysis of A Program to Delay Progression to Dialysis and Death Among CKD Patients in Lima, Peru
Authors: Saldarriaga Enrique M , Bravo-Zúñiga Jessica , Hurtado-Roca Yamilee , Suarez Víctor
Published: June 2020

Background. The Renal Health Program (RHP) was implemented in 2013 as a secondary prevention strategy to reduce the incidence of patients starting dialysis and overall mortality. A previous study found that adhered patients have 58% protection against progression to dialysis compared to non-adhered. Objective. We aim to estimate the lifetime economic and health consequences of the RHP intervention to determine its cost-effectiveness in comparison with usual care. Methods. We use a Markov model of three health stages to simulate for 30 years the cost associated with RHP and usual care, as well as years lived free of dialysis (YL) and Quality Adjusted Life Years (QALY). Costs were estimated from the payer perspective. We conduct a Probabilistic Sensitivity Analysis (PSA) to assess the robustness of our estimates. Results. We found that the RHP is a cost-saving alternative compared to usual care, with a per person difference of $-782.73in costs and 0.04 in QALYs. The Incremental Cost-Effectiveness Ratio (ICER) per QALY is $-21,660. From a PSA, RHP holds cost-saving under 999 out of 1,000 evaluated scenarios. Discussion. Our results show the lifetime economic value of a case-management intervention for CKD patients to delay its progression to dialysis. The RHP is cost-saving compared to usual care, with a negative ICER per QALY robust to different scenarios. We aim these results to help in the decision-making process of scaling-up and investment of similar strategies in Peru. Our results help to increase the evidence in Latin America where there is a lack of information in the long-term consequences of prevention and early referral strategies in CKD patients.
Carfilzomib Induced Cardiotoxicity in a Multiple Myeloma Patient
Authors: Toro Arnold Mendez , Diaz-Brochero Candida , Acosta-Gutierrez Estivalis
Published: June 2020

Proteasome inhibitors such as carfilzomib are indicated in multiple myeloma patients showing relapse and/or refractoriness of clonal activity after initial treatment. However, this therapy has been associated with a significative incidence of cardiotoxicity, especially in patients with known cardiovascular risk factors. Here we report a case of a 60-year-old woman with multiple myeloma, who developed congestive severe heart failure with positive myocardial lesion biomarkers and LVEF and strain reduction, after treatment with carfilzomib. Therefore chemotherapeutic drug was discontinued and neurohormonal blocking and diuretic therapy was started resulting in amelioration of symptoms, without changes in LVEF but with significant GLS improvement. This case illustrates the behavior of carfilzomib induced cardiotoxicity and the expected response to the appropriate pharmacological management. Although high-grade cardiotoxicity is relatively rare in patients with non previous cardiac risk factors, it was a predictable side effect of carfilzomib use. Recognition of this syndrome is critical to instauration of appropriate therapy and prevention of morbimortality.
A Report About a 23-year-old Young Mother Suffering From Rare Insular Thyroid Carcinoma
Authors: chen haibin , liu zhongmin , liang xiaoyan , wu rui
Published: June 2020

Background Insular carcinoma of thyroid (ICT) is a rare malignant tumor with poor differentiation of the thyroid , most patients are middle-aged and elderly women. Here is a report of a case involving a young woman suffering from insular thyroid carcinoma.Case report This report is about a 23-year-old young mother who already has three children of hers. she accidentally discovered a left neck mass with slight pain from local compression about half a year ago and did not seek medical treatment. She came to the hospital this time because the neck mass recently increased rapidly and she felt pressure on the trachea, affecting swallowing. Ultrasonography showed that the maximum diameter of the hypoechoic nodules was 61*46mm in the left and no lymph nodes enlargement were seen on both sides.The patient had a partial left thyroidectomy and histopathological results revealed ICT. Therefore, she completed total thyroidectomy and cervical lymph node dissection. The postoperative process was relatively smooth and the patient was successfully discharged.Conclusion：Not all patients with insular thyroid carcinoma have similar imaging findings, so Fine Needle Aspiration Cytology(FNAC)pathological diagnosis is necessary before surgery.
An Educational Intervention for Improving Knowledge of Syrian School children About Avulsion
Authors: zaher nancy Al , Dashash Mayssoon
Published: June 2020

Objective:The prognosis of replantation of an avulsed tooth is affected by the first aid management in the first 15 minutes after traumatic incident. Knowledge of the optimal management is crucial to successful replantation. The aim of this study was to investigate the effectiveness of educational intervention using the Arabic poster prize in improving the knowledge of primary schoolchildren about firstaid management of avulsion.Methods: An interventional educational study was undertaken. A total of 550 schoolchildren aged 9-12 years participated in this study. Thirteen public primary schools in Damascus city were chosen. A questionnaire was developed to measure the knowledge of schoolchildren about avulsion management. The translated IADT education poster about avulsion management was adopted .The content of this poster was explained to the children. Two months later, the subjects were re-evaluated using the same questionnaire. Paired sample t-test was used to compare the improvement of knowledge before and after.Result:A total of 537 schoolchildren completed the questionnaires in which (N=305(57% were females and (N=232) 43% were males. The findings demonstrated significant improvement in the participants’ responses after 8 weeks(P<0.05). The mean score of knowledge increased significantly from 3.71 in baseline to 4.03 after 8 weeks(P<0.003). Conclusion: The educational intervention showed significant improvement intheirknowledge of children about avulsion after education.This interventional method can be suggested as a practical valuable tool that can be generalized to cover all children in Syrian society in the hope to prevent negative consequences of avulsion.
Complex Lumbosacral Fracture-Dislocation with Sacral Fracture: Report of a Case and Review of the Literature
Authors: Qu Liyan , Song Jiashi , Li Fangcai , Liu Bing
Published: June 2020

Purpose: Traumatic lumbosacral fracture-dislocation is a very rare pattern of injury. We report a patient who has been suffered from a traffic accident and resulted in concomitant severe injuries: complex lumbosacral fracture-dislocation with pelvic ring disruption and vertical shear sacral fracture; Pneumothorax. Methods: She was transferred to the emergency department at the local provincial hospital and treated with the pelvic external fixation and closed drainage of thoracic cavity. For the further therapy, she was transferred to our hospital. The neurological examination revealed incomplete S1 paraplegia in the right lower extremity, the left lower extremity was normal, and rectal tone was existed. Standard x-rays and computed tomography revealed L5-S1 fracture-dislocation and fractures of the L5 transverse processes. Results: She was treated with S1 laminectomy and L5-S1 interbody fusion using lumbo-iliac internal fixation. Conclusions: Available literatures on lumbosacral fracture-dislocation were also reviewed which illustrate the pathogenic, clinical, radiological and therapeutic aspects of lumbosacral fracture dislocation.
Synthesis and Characterization of Human Skin-Compatible Conductive Flexible Cellulose Carbon Nanohorn Sheets
Authors: Selvam Karthik Paneer , Nagahata Taichi , Kato Kosuke , Koreishi Mayuko , Nakamura Toshiyuki , Nakamura Yoshimasa , Nishikawa Takeshi , Satoh Ayano , HAYASHI Yasuhiko
Published: June 2020

Background: Conductive sheets of cellulose and carbon nanomaterials and its human skin applications are an interesting research aspect as they have potential for applications for skin compatibility. Hence it is needed to explore the effects and shed light on these applications.Method: To fabricate wearable, portable, flexible, lightweight, inexpensive, and biocompatible composite materials, carbon nanohorns (CNHs) and hydroxyethylcellulose (HEC) were used as precursors to prepare CNH-HEC (Cnh-cel) composite sheets. Cnh-cel sheets were prepared with different loading concentrations of CNHs (10, 20 50,100 mg) in 200 mg cellulose. To fabricate the bio-compatible sheets, a pristine composite of CNHs and HEC was prepared without any pretreatment of the materials. Results: The obtained sheets are conductive (1.83×10-5­ S) and bio-compatible with human skin. Analysis for skin-compatibility was performed for Cnh-cel sheets by h-CLAT in vitro skin sensitization tests to evaluate the activation of THP-1 cells. It was found that THP-1 cells were not activated by Cnh-cel; hence Cnh-cel is a safe biomaterial for human skin. It was also found that the composite allowed only a maximum loading of 100 mg to retain the consistent geometry of free-standing sheets of < 100 µm thickness. Since CNHs have a unique arrangement of aggregates (dahlia structure), the composite is homogeneous, as verified by transmission electron microscopy (TEM) and, scanning electron microscopy (SEM), and other functional properties investigated by Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), conductance measurement, tensile strength measurement, and skin sensitization.Conclusion: It can be concluded that cellulose and CNHs sheets are conductive and compatible to human skin applications.
Identification of novel genes associated with diagnosis and prognosis in glioblastoma
Authors: Li Gaowei , Cai Linjun , Tang Xin , Huang Jianhan , Zhou Liangxue
Published: June 2020

Background: Glioblastoma (GBM) is the most lethal primary brain cancer and its survival rate is very low. Comprehensive genomic characteristics and high degree of heterogeneity of GBM are main causes that contribute to the absence of effective therapeutic targets and prognostic markers and eventual treatment failures. Here, Gene set enrichment analysis (GSEA) was used to explore comprehensive genomic characteristics and high degree of heterogeneity of GBM. Our study will help explain potential tumorigenesis mechanism and contribute to development of targeted therapeutics and prediction of patient prognosis.Methods: Gene expression profile of GSE50161 was downloaded from Gene Expression Omnibus (GEO) database and GSEA was performed to evaluate the microarray data at level of gene sets of GO, KEGG and hallmark of Molecular Signatures Database (MSigDB). Core enrichments of selected hallmark gene sets were applied for clinical prognosis verification in Gene Expression Profiling Interactive Analysis (GEPIA). Genes associated with significant overall survival (OS) and unreported before were recognized as novel; the expression levels of novel genes in GBM samples and every novel gene between normal brain and GBM samples were compared. Receiver operating characteristic (ROC) and Pearson correlation analysis were also performed to evaluate the diagnostic biomarkers of GBM and correlations among novel genes respectively.Results: We obtained 511 and 494 GO gene sets, 12 and 10 KEGG gene sets, and 2 and 8 hallmark gene sets in normal and GBM samples respectively. Five novel genes SERPINA5, TENM2, ARAP3, THBD, TCF19 associated with GBM prognosis were selected and four novel genes SERPINA5, TENM2, ARAP3, TCF19 performed well for GBM diagnosis prediction were obtained. In addition, we also found that four novel genes SERPINA5, ARAP3, THBD, TCF19 that high expressed in GBM samples were all positively correlated with each other and correlation between ARAP3 and TCF19 was the strongest.Conclusions: Our study will help deeper understand the molecular heterogeneity and develop of targeted therapeutics of GBM; five novel related to prognosis genes (of which four are also related to diagnosis) may be applied to more accurate clinical decision-making process.
First, Do No Harm: Unintended Consequences of Skill-Based Training in Global Health
Authors: Fant Colleen , Morgan Jennifer , Galvin Shannon , Peralta Feyce M. , Swaroop Mamta , Milad Magdy P. , Doobay-Persaud Ashti
Published: June 2020

Background: Many medical trainees participate in international clinical rotations in resource-limited settings and they frequently describe pressure to perform outside their scope of clinical practice. Educators must provide trainees with tools to manage dilemmas prior to departure and should also review relevant procedural skills that may be useful. The Northwestern University McGaw Global Health Clinical Scholars program (GHCS), created to provide global health skills across medical disciplines and promote clinical self-awareness, incorporates a skills and ethics simulation curriculum for participating trainees and this study aims to evaluate the impact on trainee self-perceptions.Methods: Training sessions were held between 2015 and 2017 for trainees participating in the GHCS program. The sessions were: ethics, obstetrics/gynecology/pediatrics, and surgery/anesthesia. Pre- and post- surveys assessed comfort and resources to navigate ethical dilemmas including participant beliefs about benefits versus harms of performing skills potentially outside of their scope and their willingness to perform these skills, if they were the only provider present.Results: There were 56 responses from 68 trainee session experiences. After the ethics session, participants reported more confidence dealing with issues around scope of practice, professionalism, and harm (p<0.05). After the skills sessions, the majority of participants stated the benefits outweighed harms of performing skills and were more likely to perform all skills if they were the sole provider.Discussion/Conclusions: Despite having a dedicated ethical simulation reviewing basic ethical frameworks, including scope of practice, skill-based trainings resulted in increased stated willingness of trainees to perform skills outside of their scope of training.
Relationships of Coping Styles and Psychological Distress Among Patients with Insomnia Disorder
Authors: Li Yinghui , Cong Xiaoyin , Chen Suzhen , Li Yong
Published: June 2020

Background: Insomnia appears to be one of the most frequent sleep complaints in the general population. It has significant negative impact on daily functioning. however, there has been little research that described the effect of coping style in insomnia disorder.Methods: The Simplified Coping Style Questionnaire (SCSQ) was used to evaluate 79 adult patients with insomnia disorder alongside 80 healthy controls. Additionally, sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist-90-Revised (SCL-90R) was utilized to determine the status of depression, anxiety and other psychological symptoms.Results: Positive coping style score was significantly lower, whereas negative coping style score and nine symptomatic dimensions of SCL-90R were significantly higher in insomnia patients than in controls. Positive coping style score was adversely related to PSQI score, obsessive-compulsive, depression, anxiety and phobic anxiety, whereas negative coping style score was positively related to PSQI score, somatization and interpersonal sensitivity. Further multiple stepwise regression analysis showed that PSQI total score was independently and positively correlated with negative coping style score.Conclusions: Insomniacs use more negative coping styles and less positive ones. Positive coping is adversely associated with insomnia symptoms and psychological distress, whereas negative coping is positively related to those symptoms.
Quantifying the impact of severe bushfires on biodiversity to inform conservation
Authors: Baranowski Kelsee , Faust Christina , Eby Peggy , Bharti Nita
Published: June 2020

The unusually severe 2019-2020 Australian bushfire season destroyed large areas of habitat along the southeastern coast. We assess the differences between this fire season and previous ones to understand their impacts and potential recovery. We used thermal satellite data to quantify the extent of eastern Australian bushfires from 2012-2020. During the 2019-2020 anomalous fire season, 134 mega-fires, each over 10,000 ha, burned 62.5% of the total affected area, including critical forested landscapes. Previous fire seasons were characterized by smaller, scattered fires in mostly non-forested areas. The anomalous fire season had direct negative impacts on wildlife including grey-headed flying foxes, which experienced substantial declines in immediately available foraging forest habitat, particularly key winter resources. We identified important areas for managing wildlife resources and supporting ecosystem health in the coming decades. Our research also identifies key monitoring areas to improve our understanding of ecosystem recovery and resilience in changing fire regimes.
A Novel Immuno-RNase Based on Engineered RNase A Variants for Targeted Cancer Therapy
Authors: Azghandi Masoume Vakili , Nassiri Mohammadreza , Kayser Veysel , Javadmanesh Ali , Ghovvati Shahrokh
Published: June 2020

The authors have requested that this preprint be removed from Research Square.
Mining Novel Specific Rumen Bacteria to Enhance the Bioactive Function of Mulberry Leaf in Promoting Host Antioxidant Activity and Immunomodulatory
Authors: Wang Bing , Luo Hailing
Published: June 2020

Background: Rumen is a natural fermentation system and the microorganisms inside can effectively utilize plant bioresource and interact with host metabolism. Here, analysis of rumen microbiome, together with animal performance and serum metabolism in a lamb model were performed to identify the potential use of mulberry leaf silage (MS) to replace alfalfa silage (AS) as a new functional feed resource and to mining the novel specific mulberry leaf associated rumen bacteria interact with host metabolism. Results: The lambs fed with MS diet showed improved antioxidant capacity and immune function compared to those fed AS diet. The MS diet significantly altered rumen microbiota α- and β-diversity and taxonomic composition. Microbial analysis revealed that Bifidobacterium, Lactobacillus and Schwartzia were enhanced, and Ruminococcaceae UCG-010 and Lachnospiraceae_XPB1014_group were down-regulated in the rumen of MS group. A strong association was also found between these rumen microbial taxa and host antioxidant capacity and immunomodulatory. Conclusion: These findings indicated that mulberry leaf silage can be a high-quality feed source or bioactive pharmaceutical that is responsible for ruminants health benefits by modifying the rumen microbial community with potentially enhanced probiotics and inhibited biohydrogenation and methane emission.
MHC class I evolution; from Northern pike to salmonids
Authors: Grimholt Unni , Lukacs Morten
Published: June 2020

Background
Salmonids are of major importance both as farmed and wild animals. The financial importance to aquacultural industry as well as to rural communities that profit from wild salmon fishing is substantial. With the changing environment comes changes in pathogenic pressures so understanding the immune system of all salmonid species is of essence. Major histocompatibility complex (MHC) genes are key players in the adaptive immune system signalling infection to responding T-cells populations. Their key role in inducing immunity and their link to disease resistance instigate studies on structure, function and evolution. Northern Pike, a basal sister clade to salmonids, represent a species which has not experienced the fourth salmonid specific whole genome duplication.
Results
Comparing the gene organization and evolution of MHC class I gene sequences in Northern pike versus salmonids displays a complex picture of how many of these genes evolved. Salmonid Ia and Ib Z lineage genes are not orthologs to the Northern pike Z lineage sequences. Instead, the salmonid genes have experienced unique gene duplications in the two duplicated regions as well as in the Salmo and Oncorhynchus branch. Potentially, transposase elements enabling these duplications were already present in the Northern pike Z lineage gene.
Conclusions
Although both Northern pike as well as salmonids have expanded their U and Z lineage genes, these gene duplications have occurred separately in pike and in a salmonid ancestor. However, the similarity between these duplications suggest the transposable machinery was present in a common ancestor. The salmonid MHCIa and MHCIb regions were mostly formed during the 80MYA since the split from pike and before the Oncorhynchus and Salmon branch separated. As seen in tetrapods, the non-classical U lineage genes are diversified duplicates of their classical counterpart. One MHCI lineage, the L lineage, experienced massive species-specific gene duplications after Oncorhynchus and Salmo split approximately 25 MYA. Based on what we currently know about L lineage genes, this diversity will most likely affect immune responses in individual species.
High Hba1c is Associated With Decreased 6-month Survival and Poor Outcomes After Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Study
Authors: Lee Junhaeng , Oh Joo Suk , Zuh Jong Ho , Hong Sungyoup , Park Sang Hyun , Kim Ji Hoon , Kim Hyungsoo , Seo Mingu , Kim Kiwook , Lee Doo Hyo , Jung Hyun Ho , Park Jungtaek , Oh Young Min , Choi Semini , Choi Kyoung Ho
Published: June 2020

Background: To evaluate the associations between glycated hemoglobin (HbA1c) at admission and 6-month mortality and outcomes after out-of-cardiac arrest (OHCA) treated by hypothermic targeted temperature management (TTM).Methods: This single-center retrospective cohort study included adult OHCA survivors who underwent hypothermic TTM from December 2011 to December 2019. High HbA1c at admission was defined as a level higher than 6%. Poor neurological outcomes were defined as cerebral performance category scores of 3-5. The primary outcome was 6-month mortality. The secondary outcome was the 6-month neurological outcome. Descriptive statistics, log-rank tests, and multivariable regression modelling were used for data analysis.Results: Of the 302 patients included in the final analysis, 102 patients (33.8%) had HbA1c levels higher than 6%. The high HbA1c group had significantly worse 6-month survival (12.7% vs. 37.5%, p < 0.001) and 6-month outcomes (89.2% vs. 73.0%, p = 0.001) compared to the non-high HbA1c group. Kaplan-Meier analysis and the log-rank test showed that the survival time was significantly shorter in the patients with HbA1c >6% than in those with HbA1c ≤6%. In the multivariable logistic regression analysis, HbA1c >6% was independently associated with 6-month mortality (OR 5.85, 95% CI 2.26-15.12, p < 0.001) and poor outcomes (OR 4.18, 95% CI 1.41-12.40, p < 0.001).Conclusions: This study showed that HbA1c higher than 6% at admission was associated with increased 6-month mortality and poor outcomes in OHCA survivors treated with hypothermic TTM. Poor long-term glycemic management may have prognostic significance after cardiac arrest.
Cancer Associated Macrophage-Like Cells and Prognosis of Esophageal Cancer after Chemoradiation Therapy
Authors: Gironda Daniel Joseph , Adams Daniel Lee , He Jianzhong , Xu Ting , Gao Hui , Qiao Yawei , Komaki Ritsuko , Reuben James M. , Liao Zhongxing , Blum-Murphy Mariela , Hofstetter Wayne L. , Tang Cha-Mei , Lin Steven H.
Published: June 2020

Background: Cancer Associated Macrophage-Like cells (CAMLs) are polynucleated circulating stromal cells found in the bloodstream of numerous solid-tumor malignancies. Variations within CAML size have been associated with poorer progression free survival (PFS) and overall survival (OS) in a variety of cancers; however, no study has evaluated their clinical significance in esophageal cancer (EC). Methods: To examine this significance, we ran a two-year prospective pilot study consisting of newly diagnosed stage I-III EC patients (n=32) receiving chemoradiotherapy (CRT). CAML sizes were sequentially monitored prior to CRT (BL), ~2 weeks into treatment (T1), and at the first available sample after the completion of CRT (T2). Results: We found CAMLs in 88% (n=28/32) of all patient samples throughout the trial, with a sensitivity of 76% (n=22/29) in pre-treatment screening samples. Improved 2 year PFS and OS was found in patients with CAMLs <50μm by the completion of CRT over patients with CAMLs ≥50μm; PFS (HR=12.0, 95%CI=2.7-54.1, p=0.004) and OS (HR=9.0, 95%CI=1.9-43.5, p=0.019). Conclusions: Tracking CAML sizes throughout CRT as a minimally invasive biomarker may serve as a prognostic tool in mapping EC progression, and high prevalence of these cells prior to treatment suggest diagnostic value for at-risk populations.
Karyomorphological Study of Taraxacum in Northeast China
Authors: Wu Jie , Yanping Xing , Haotao Chen , Qun Liu , Ran Li , Jing Li , Wei Ning , Wei Cao
Published: June 2020

Background: Dandelions ( Taraxacum ) comprise more than 2,000 species distributed worldwide, including 70 species in China and over 20 species in Northeast China. It is an edible plant used also in traditional Chinese medicine.
Methods: Chromosome number was determined by conventional tableting, and karyotypes were analyzed. We determined the number of mitotic chromosomes, karyotype characteristics, and morphology of Taraxacum germplasm resources collected in Northeast China. The data were compared with those in the Chromosome Counts Database (CCDB) using principal component analysis (PCA) and cluster analysis.
Results: The collected Taraxacum species included diploids, triploids, and tetraploids, with chromosome numbers of 2n = 16, 24, and 32, respectively. The karyotypes showed metacentric and submetacentric chromosomes and satellites. The absolute length of a single chromosome was 3.56–31.68 μm, and the karyotype asymmetry coefficient was 59.68%–67.45%. PCA of karyotype data showed that chromosome size, long arm length, and short arm length formed PC1. Cluster analysis based on karyotype data of the 18 species supported the taxonomic classification of this genus in the Flora of China .
Conclusions: Our results indicate that karyotype analysis can be used as cytological evidence for Taraxacum taxonomy. We also determined that among the 18 Taraxacum species, triploid species were more evolved than diploid and tetraploid species. We believe that our results provide a basis for further research in Taraxacum germplasm resources and lay the experimental foundation for further development of Taraxacum in traditional Chinese medicine.
Matched Cohort Study on the Efficacy of Tocilizumab in Patients with COVID-19 
Authors: Molinero Alejandro Rodríguez , Pérez-López Carlos , Gálvez-Barrón César , Miñarro Antonio , Macho Oscar , López Gabriela , Robles Maria Teresa , Dapena Dolors , Martínez Sergi , Rodríguez Ezequiel , Collado Isabel
Published: June 2020

Background: Tocilizumab has been proposed as a treatment for the new disease COVID-19, however, there is not enough scientific evidence to support this treatment. The objective of this study is to analyze whether the use of tocilizumab is associated with respiratory improvement and a shorter time to discharge in patients with COVID-19 and lung involvement.Methods: Observational study on a cohort of 418 patients, admitted to three county hospitals in Catalonia (Spain). Patients admitted consecutively were included and followed until discharge or up to 30 days of admission. A sub-cohort of patients treated with tocilizumab and a sub-cohort of control patients were identified, matched by a large number of risk factors and clinical variables. Sub-cohorts were also matched by the number of other treatments for COVID-19 that patients received. Increment in SAFI (inspired oxygen fraction / saturation) 48 hours after the start of treatment, and time to discharge, were the primary outcomes. Mortality, which was a secondary outcome, was analyzed in the total cohort, by using logistic regression models, adjusted by confounders.Results: There were 96 patients treated with tocilizumab. Of them, 22 patients could be matched with an equivalent number of control patients. The increment in SAFI from baseline to 48 hours of treatment, was not significantly different between groups (tocilizumab: -0.04; control: 0.09; p=0.636). Also, no difference in time to discharge was found between the two sub-cohorts (logrank test: p=0.472). The logistic regression models, did not show an effect of tocilizumab on mortality (OR 0.99; p=0.990)Conclusions: We did not find a clinical benefit associated with the use tocilizumab, in terms of respiratory function at 48 hours of treatment, or time to discharge.
The Effect of miR122 and miR185 on Hepatic Differentiation of Human Umbilical Cord Mesenchymal Stem Cells
Authors: YU Qun , LV Sha , SU Wen Jun , YIN Yan Feng , GUAN Zheng , ZHANG Lei
Published: June 2020

Background: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been considered as a promising cell source in liver diseases. miRNAs have been shown to play an important role in hepatic differentiation of hUC-MSCs. The study seeks to explore whether miR122 and miR185 could affect induction of hUC-MSCs into hepatic differentiation. Methods: miR122 and miR185 stable overexpression by hUC-MSCs were firstly created, then hUC-MSCs were cultured by hepatic differentiation conditional medium. After 28 days culture in hepatic inducing conditional medium, hepatic markers expressed by these cells were detected by qRT-PCR and western-blot. The cell functions were also evaluated by PAS staining and ICG phagocytosis. Results: Our results demonstrated that at the end of 28 days, hUC-MSCs overexpressing miR122 had increasing expression of hepatocyte markers including AFP, ALB, CK18, CK19 and HNF4α in both mRNA level and protein ecpression, while in the miR185 overexpression group, hUC-MSCs showed decreasing expression of hepatocyte markers. Moreover, there was also improvement of glycogen deposits as well as ICG phagocytosis ability in the hepatic inducing miR122 overexpression cells, while in the hepatic inducing miR185 overexpression group, hUC-MSCs showed decreasing glycogen deposits and ICG phagocytosis ability. Conclusions: We thus speculate that it is possible to promote hepatic differentiation of hUC-MSCs by overexpression of miR122 and this effect may be inhibited by miR185 overexpression. It seems miR122 and miR185 have an antagonistic effect on hUC-MSCs hepatic differentiation. Overexpression of certain kind of miRNA in cells by transfection or other gene modification skills could be an effective way to modulate stem cell fate.
No Difference in Physical Activity Associated with Cannabis Use Status in a Nationally Representative Sample of U.S. Adults
Authors: Ong Lydia Q. , Bellettiere John , Alvarado Citlali , Chavez Paul , Berardi Vincent
Published: June 2020

Background: Prior research examining the relationship between cannabis use, sedentary behavior, and physical activity has generated conflicting findings, potentially due to biases in the self-reported measures used to assess physical activity. This study aimed to more precisely explore the relationship between cannabis use and sedentary behavior/physical activity using objective measures. Methods: Data were obtained from the 2005-2006 National Health and Nutrition Examination Survey. 2,092 participants (ages 20-59; 48.8% female) had accelerometer-measured sedentary behavior, light physical activity, and moderate-to-vigorous physical activity. Participants were classified as a current cannabis user if they reported any use over the previous 30 days. Multivariable linear regression estimated minutes engaged in sedentary behavior/physical activity for current versus non-current cannabis users. Logistic regression modeled self-reported moderate-to-vigorous physical activity in relation to current cannabis use. Results: Fully-adjusted regression models indicated that current cannabis users’ objectively-measured sedentary behavior/physical activity did not significantly differ from non-current users. There were no significant associations between self-reported moderate-to-vigorous physical activity and cannabis use. Conclusions: This study is the first to evaluate the relationship between cannabis use and accelerometer-measured sedentary behavior and physical activity. Such objective measures should be used in other cohorts to replicate our finding that current cannabis use is not significantly associated with sedentary behavior/physical activity in order to fully assess the potential public health impact of recent increases in cannabis use.