bluuebunny/crossref_metadata_2025 huggingface dataset:
Cessation of Resuscitation in Pulseless Electrical Activity Out of Hospital Cardiac Arrest: A Mixed Methods Study of Senior Paramedic Decision Making
Authors: Coppola Alison , Black Sarah , Endacott Ruth
Published: September 2020

BackgroundPulseless electrical activity, a non-shockable cardiac arrest, is treated using advanced life support resuscitation. Typically, survival rates are poor and there is a paucity of evidenced-based guidelines for paramedics on when to cease resuscitation. This led to one UK Ambulance Service developing a local guideline to support senior paramedics when making cessation decisions. This study aimed to describe the patient characteristics, clinical features and system factors of pulseless electrical activity and explore the experiences of senior paramedics making autonomous cessation decisions. Design and MethodsAn explanatory sequential mixed method design conducted in a single UK Ambulance Service. Data was retrieved for all adult Out of Hospital Cardiac Arrest patients from 1st December 2015 to 31st December 2018. Cases subject to a coronial or police investigation were excluded. Senior paramedics ceased resuscitation for 50 PEA patients, a consecutive sample, which was reviewed in detail using descriptive statistics. Independent t-test and Chi Square examined associations between variables known to prognosticate survival. Interviews were conducted with six senior paramedics who remotely supported on-scene paramedics and findings were analysed using content framework analysis. ResultsPatient characteristics: Mean age 78 years, male (n=30, 60%), co-morbidities (n=40, 80%), witnessed collapse (n=37, 74%), bystander BLS (n=30, 60%). Clinical features: defibrillation (n=22, 44%), ROSC (n=8, 16%), heart rate< 50 (n=46, 92%), mean ETCO2 2.3kPa. System factors: Advanced life support duration 59mins. A significant association between witnessed cardiac arrest and bystander basic life support was found (95% p=.00). Themes arising from interviews were defining resuscitation futility, the impact of ceasing resuscitation, conflicting views and clinical decision tools. ConclusionSenior paramedics interpreted and applied a multifactorial approach to ceasing resuscitation for patients with PEA. Patient characteristics, clinical features and system factors were balanced using clinical judgement, found to be vital to the decision-making process. This finding questions the appropriateness of paramedics making cessation decisions based on clinical features alone. As prognostic factors for survival were present, further investigation to identify the difference between an unsuccessful or futile resuscitation is required.
Key metabolism pathways and regulatory mechanisms of high polysaccharide yielding in Hericium erinaceus
Authors: Gong Ming , Zhang Henan , Wu Di , Zhang Zhong , Bao Dapeng , Zhang Jinsong , Yang Yan
Published: September 2020

Background
Hericium erinaceus, a rare edible and medicine fungus, is widely used in the food and medical field. H. erinaceus polysaccharide is the main bioactive compound that exerts high bioactive value in the medical and healthcare industries.
Results
Here, we obtained two mutated strains (HEB and HEC) with high polysaccharide yield using ARTP mutagenesis from the original H. erinaceus strain HEA which genome was also reported 38.16 Mb, encoding 9,780 predicted genes by single-molecule, real-time sequencing technology. The polysaccharide content in the fermented mycelia of HEB and HEC was improved 23.25% and 47.45%, and a new β-glucan fraction with molecular weight 1.056 × 106 Da was produced in HEC. The phylogenomic analysis showed that H. erinaceus had the closest evolutionary affinity with Dentipellis sp. Integrative analysis of transcriptome and proteomics showed the upregulation of the carbohydrate metabolism pathway modules in HEB and HEC, which might lead to the increased production of glucose-6P and, in turn promoted the repeating units synthesis of polysaccharide. qPCR and PRM analysis confirmed that most of the co-enriched and differentially co-expressed genes involved in carbohydrates metabolism shared a similar expression trend with the transcriptome and proteome data in HEB and HEC. Heatmap analysis showed a noticeably decreased protein expression profile of the RAS-cAMP-PKA pathway in HEC with a highly increased 47.45% of polysaccharide content. The S phase progression blocking experiment further verified that the RAS-cAMP-PKA pathway's dysfunction might promote high polysaccharide and β-glucan production in the mutant strain.
Conclusions
The study revealed the main mechanism of the increased polysaccharide synthesis induced by ARTP mutagenesis and explored the key genes and pathways of polysaccharide synthesis.
Prevalence and Possible Risk Factor of Premarital Sexual Behaviour among Nepalese Adolescents
Authors: Dahal Maginsh , Subedi Raj Kumar , Khanal Sudip , Adhikari Anup , Sigdel Manoj , Baral Kushalata , Sangroula Raj Kumar , Xu Cheng , Gu Aihua
Published: September 2020

Background: To determine the prevalence of premarital sex and its risk factors in Nepal.Methods: A cross-sectional study was carried out among adolescents in Nepal. A self-administered questionnaire was used to collect information from 6,147 unmarried adolescents. Random sampling by using a lottery method was applied to select 20 colleges from all three districts. All the students who were studying at those colleges were enrolled in the study. Simple and multivariate logistic regression analyses were carried out to analyse the associations of risk factors and premarital sex.Results: The prevalence of premarital sex was 38.1%. Male students were more likely to engage in premarital sex (adjusted odds ratio [AOR]=2.04, confidence interval [CI]=1.76-2.36) than female students. Alcohol consumption (AOR=1.26, CI=1.08-1.47), smoking (AOR=1.69, CI=1.41-2.02), drug use (AOR=1.85, CI=1.23-2.83), going to night clubs (AOR=1.46, CI=1.24-1.70), clothing style of girls AOR=1.35, CI=1.15-1.58), clothing style of boys (AOR=3.51, CI=2.74-4.53), and unmarried friends having sex (AOR= 1.51, CI=1.31-1.73) were found to be major influencing factors for premarital sex. Moreover, students who had never received sex education were 2.92 times more likely to engage in premarital sex (CI=2.22-3.85) than those who had previously received sex education.Conclusions: We found several risk factors associated with premarital sex in Nepal. Preventing premarital sex may require the promotion of sex education.
Electrical Switching of High-Performance Bioinspired Nanocellulose Nanocomposites
Authors: Jiao Dejin , Lossada Francisco , Guo Jiaqi , Skarsetz Oliver , Hoenders Daniel , Liu Jin , Walther Andreas
Published: September 2020

Nature fascinates with living organisms showing mechanically adaptive behavior. In contrast to gels or elastomers, it is profoundly challenging to switch mechanical properties in stiff bioinspired nanocomposites as they contain high fractions of immobile reinforcements. Here, we introduce facile electrical switching to the field of bioinspired nanocomposites, and show how the mechanical properties adapt to low direct current (DC). This is realized for renewable cellulose nanofibrils/polymer nanopapers with tailor-made interactions by deposition of thin single-walled carbon nanotube electrode layers for Joule heating. Application of DC at specific voltages translates into significant electro-thermal softening via dynamization and breakage of the thermo-reversible supramolecular bonds. The altered mechanical properties are reversibly switchable in power on/power off cycles. Furthermore, we showcase electricity-adaptive patterns and reconfiguration of deformation patterns using electrode patterning techniques. The simple and generic approach opens avenues for bioinspired nanocomposites for facile application in adaptive damping and structural materials, and soft robotics.
Inverse Association Between Triglyceride Glucose Index and Muscle Mass in Korean Adults: 2008–2011 KNHANES
Authors: Ahn Sung Ho , Lee Jun hyuk , LEE JI WON
Published: September 2020

Aim: The early detection and prevention of sarcopenia is increasingly emphasized considering that sarcopenia is an important risk factor for falls or cardiovascular disease. Recently, there have been emerging evidences that support the relationship between sarcopenia, insulin resistance, and inflammation. The TyG index, a novel surrogate marker of insulin resistance and systemic inflammation, has not yet been verified for an association with sarcopenia. This study aimed to examine the relationship between the TyG index and muscle mass in Korean adults.Methods: This study included 15,741 non-diabetic adults over 19 years old using data from the 2008–2011 Korea National Health and Nutrition Examination Survey. Participants were divided into three groups according to tertiles of the TyG index. Low skeletal muscle mass index (LMSI) was defined by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project criteria. Weighted multivariate logistic regression model was used to analyze the relationship between TyG index tertiles and LSMI.Results: The ORs (95% CIs) for LSMI of the second and third tertiles, compared to first tertile, were 1.300 (1.001–1.689) and 1.448 (1.104–1.900), respectively, after adjusting for confounding factors. Higher TyG index was also associated with increased odds of LSMI in subgroups such as adults under 65-year old who did not exercise regularly, who consumed less than 30g alcohol per day, who did not currently smoke, and who ate less than 1.5g protein/kg/day.Conclusion: The TyG index was significantly and positively associated with LSMI in Korean adults.
Developing and Validating Regression Models for Predicting Household Consumption to Introduce an Equitable and Sustainable Health Insurance System in Cambodia
Authors: Nakamura Haruyo , Amimo Floriano , Yi Siyan , Tuot Sovannary , Yoshida Tomoya , Tobe Makoto , Rahman Mizanur , Yoneoka Daisuke , Ishizuka Aya , Nomura Shuhei
Published: September 2020

BackgroundFinancial protection is a key health system objective and an essential dimension of universal health coverage. However, it is a challenge for low- and middle-income countries, where the general tax revenue is limited, and a majority of the population is engaged in the informal economy. This study developed and validated regression models for Cambodia to predict household consumption, which allows the country to collect insurance contributions according to one’s ability to pay. This strategy would maximize the contribution revenue, optimize the government subsidy, and simultaneously ensure equity in healthcare access.MethodsThis study used nationally representative survey data collected annually between 2010 and 2017, involving 38472 households. We developed four alternative prediction models for annual household consumption: ordinary least squares (OLS) method with manually selected predictors, OLS method with stepwise backward variable selection, mixed-effects linear regression, and elastic net regression, which resulted in an adaptive least absolute shrinkage and selection operator (LASSO) regression. Household-level socioeconomic characteristics were also included as the predictors. Subsequently, we performed out-of-sample cross-validation for each model. Finally, we evaluated the prediction performance of the models using mean absolute error, root mean squared error, and mean absolute percentage error (MAPE). ResultsOverall, we found a linearly positive relationship between observed and predicted household consumptions in all four models. While the prediction performance of the four alternative models did not substantially differ, Stepwise Linear Model showed the best performance with the lowest values in all three statistical measurements, including MAPE of 1.376%. The use of regularization and the mixed effects in the regression was not particularly effective in this environment. The household consumption was better predicted for those with lower consumption, and the predictive performance declined as the consumption level increased. Although the richer household consumptions were likely to be overestimated, the trend was less noticeable in Adaptive LASSO Model.ConclusionsThis study suggests the possibility of predicting household consumption at a reasonable level with the existing survey data. Such a prediction would enable the country to raise the secured health insurance revenue equitably. The prediction model should be tested in real settings and continuously improved.
Serological Determinants of COVID-19
Authors: Noce Annalisa , Santoro Maria Luisa , Marrone Giulia , D’Agostini Cartesio , Amelio Ivano , Duggento Andrea , Tesauro Manfredi , Daniele Nicola Di
Published: September 2020

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spreaded rapidly worldwide, as far as it has become a global pandemic. Therefore, the introduction of serological tests useful for the determination of IgM and IgG antibodies, it has become the main diagnostic tool, useful for tracking the spread of the virus and consequently its containment. In our study we compared point of care test (POCT) lateral flow immunoassay (FIA) vs automated chemiluminescent immunoassay (CLIA), in order to assess their specificity and sensibility against COVID-19 antibodies detection. Results: We find that different specificities and sensitivities for IgG and IgM tests. Notably IgM POCT FIA method vs CLIA method (gold standard) has a low sensitivity (0.526), while POCT FIA method vs CLIA method (gold standard) test has a much higher sensitivity (0.937); further, with respect of IgG, FIA and CLIA could arguably provide the same information. Conclusions: FIA method could be helpful in assessing in short time, the possible contagiousness of subjects that for work reasons cannot guarantee “social distancing”.
Multi-Color and Multi-Material 3D Printing of Knee Joint Models
Authors: Ruiz Oliver Grimaldo , Dhaher Yasin
Published: September 2020

BackgroundEvery year, 3DP provides more alternatives and solutions in the medical field. Applications such as custom-made prosthetics and implants, platforms for pharmaceutical research, and PSAMs are the immediate emerging trends. Certainly, 3DP advancement is the convergence of multiple factors including improvements in medical software, 3D printer evolution, availability of new printing materials, improved industry support, and increasing commitment from medical societies and regulators. The overarching theme of this study is centered on exploring possible PSAMs and 3DP applications for improving surgical outcomes in orthopedics, particularly in ACL-R as well as providing functional models for TKA.Methods3-Matic, Rhinoceros, and SolidWorks were used to create three 3D computer-generated PSAMs: (1) Knee Joint model, wherein collagen fibers matrix structure is mimicked, (2) ACL-R model using a BPTB graft, incorporating key surgical outcomes such as orientations-architecture and positions-dimensions of the tunnels, as well as a custom-made SG based on patella anatomy (3) TKA model considering custom-made CS implants with symmetric tibial bearing design. Before printing, mechanical uni-axial tensile tests of materials were conducted using an Instron S3300, following the ASTM designation D412-C. The printing materials selection process and matching with anatomical structures were based on the analysis of the mechanical pattern of the strain-stress curves from different combinations of Agilus30™. The Stratasys J750™ printer was used to manufacture the ACL-R model (previous study), the ACL-R model with SG, and the TKA model. ResultsThe combinations No. 1-4 were chosen for 3DP with elastic modules of 1.8-0.7 MPa and Pearson coefficients of 0.980-0.991 respectively. The PSAMs were tested manually simulating 50 flexo-extension cycles without presenting ruptures, custom-made SG matches perfectly with PT anatomy. ConclusionFunctional PSAMs were printed with high fidelity, considerable cost, and short duration from planning to manufacturing. These coincided completely with 3D computer-generated PSAMs replicating fibers and features of the Knee Joint anatomy. The proposed PSAMs can be considered as an alternative to replacing cadaver specimens for medical training, pre-operative planning, education purposes, and validation of predictive models. We highlight the potential of PolyJet manufacturing combined with specialized medical software as a path to change the way specialists and researchers plan, execute, and validate complex procedures.
Research on Forearm Lateral Movement and Wrist Swing’s Continuous Motion Estimation and Estimation Result Correction
Authors: zhang lei
Published: September 2020

ObjectiveAccording to the muscle Hill model to estimate the angle of continuous human movement, existing methods require more parameters, and these parameters are susceptible to the influence of different individuals, so there are often large errors in estimation results. MethodsTherefore, Back Propagation (BP) neural network model based on features of surface electromyography (sEMG) and the angle of human movement was established in this paper. By studying the role of muscles in joint rotation, appropriate muscle tissues were selected to place EMG sensors, and the model of sEMG features and joint angle was established. For the problem in which sEMG features couldn’t fully reflect all EMG information, an extraction method combining time domain, frequency domain and time-frequency domain features was proposed. Aiming at the problem that the Degrees of Freedom (DOFs) of the forearm lateral movement and the wrist swing were controlled by more muscles, which made the joint angle difficult to predict, a method for correcting the estimation angle error by Kalman filter was proposed. Two DOFs exoskeleton robot was designed, and the established model and prototype were used to perform the tracking experiment. ResultsThe average absolute errors of two DOFs are about 17.6° and 6.9°, respectively. ConclusionThe results suggested that BP neural network model designed couldn’t only achieve uniform velocity tracking of the upper limb, but also ensured that the angular error was within a reasonable value, which met basic requirements for continuous movement estimation of the human body by sEMG.
Colostrum Avoidance and Associated Factors Among Mothers of Children Aged Less Than 12 Months in Jinka Town, South Ethiopia, 2019
Authors: Hadona Elias Amaje , Weldehawariat Feleke Gebremeskel , Sorrie Muluken Bekele
Published: September 2020

Background: Colostrum avoidance is the common nutritional malpractices in developing countries including Ethiopia. Discarding colostrum is the main causes of respiratory disease and diarrheal disease during childhood and contributes to over a million avoidable infant deaths each year and remains a public health problem in developing countries. Despite the fact that it has a negative effect on child health, little is known about the extent of the problem and its contributing factors in South Ethiopia particularly in study area. The aim of the study was to determine the prevalence of colostrum avoidance practices and associated factors among Mothers of children aged less than 12 months in Jinka Town, South Ethiopia. Methods: A community based cross-sectional study was conducted at Jinka Town from March 1 to 30, 2019. A total of 420 mothers having children less than 12 months of age were selected by systematic sampling technique. The data were collected by using pretested interviewer administered and semi-structured questionnaires. The data was entered using EPIDATA 3.1 and exported to SPSS version 23 for analysis. Descriptive statistics, Binary and multivariable logistic regression analysis were done. An adjusted odds ratio with 95% CI at a p-value < 0.05 was estimated to identify statistically significant variables with colostrum avoidance practices. Results: The prevalence of colostrum avoidance practice was 9.8% [95% CI: (6.9–12.5)]. Delayed initiation of breast feeding [AOR= 9.08(95% CI 4.16-19.83)], Lack of breast feeding counselling [AOR= 2.33(95% CI 1.11-4.87)], Home delivery of index child [AOR= 2.48 (95% CI 1.16-5.27)] and Poor knowledge on breast feeding [AOR=4.55(95% CI 1.95-10.63)] were factors associated with colostrum avoidance practices. Conclusions: Colostrum avoidance practice among mothers of children aged less than 12 months in Jinka town was high. Delayed initiation of Breas feeding, lack of breast feeding counselling, Home delivery and knowledge on breastfeeding feeding practice were factors associated with colostrum avoidance practice. Promoting institutional delivery services and strengthening of breast feeding counselling during antenatal and postnatal care were recommended for the promotion of the nutritional value of colostrum and its health benefits.
TRF2 promotes dynamic and stepwise looping of POT1 bound telomeric overhang
Authors: Paul Tapas , Liou Wilson , Cai Xinyi , Opresko Patricia , Myong Sua
Published: September 2020

Human telomeres are protected by shelterin components including POT1 and TRF2 but the molecular mechanism remains elusive. Here, we report an unexpected activity of POT1 in imparting conformational dynamics of the telomere overhang, even at a monomer level. Such POT1 induced overhang dynamics is greatly enhanced when TRF2 engages with the telomere duplex. Strikingly, TRF2 brings a POT1 bound overhang to the duplex and induces a stepwise movement up and down the axis of telomere duplex, thereby generating a highly dynamic loop formation. Interestingly, TRF2, but not TRF2ΔB, recruits POT1 bound overhang to the telomere duplex-single stranded junction by discrete steps of movement with a step size of TTAGGG. The same steps are observed regardless of the length of the POT1 bound overhang, suggesting a tightly regulated mechanism. Based on our results, we propose a plausible dynamic mechanism of t-loop formation coordinated by POT1 and TRF2.
Dilated Cardiomyopathy in a child with COVID-19
Authors: Kishore Rashmi , Choudekar Avinash , Xess Ashit Bhusan , Dar Lalit , Anand Rahul Kumar , Saxena Anita , Kabra Sushil Kumar
Published: September 2020

The coronavirus disease (COVID-19) though primarily causes respiratory tract infection, various extra-pulmonary complications have also been reported. We hereby report dilated cardiomyopathy in a one-year old premorbidly healthy boy with COVID-19 infection who had a poor outcome.
Fe3O4@Polydopamine Nanoparticle-Loaded Human Umbilical Cord Mesenchymal Stem Cells Improve the Cognitive Function in Alzheimer's Disease Mice by Promoting Hippocampal Neurogenesis
Authors: Wang Yuxiang , Jiang Jinlan , Fu Xueqi , Zhang Jingtian , Song Jiayue , Duan Lian , Shao Pu , Xu Xuemin , Zeng Linlin , Zhang Fuqiang
Published: September 2020

BackgroundOne of the most promising treatments for neurodegenerative diseases is the stem cell therapy; however, there are still some limitations in the treatment of Alzheimer's disease (AD), and the specific molecular mechanism that affects the cognitive function remains unclear. Therefore, it is necessary to develop a strategy to increase the recruitment of stem cells to the lesion site for clinical application. Fe3O4 nanoparticles have good physiological stability, biocompatibility, and is conducive to the active uptake of stem cells.MethodsIn this study, superparamagnetic iron oxide nanoparticles composed of magnetic Fe3O4 and polydopamine (PDA) shells were used to label human umbilical cord mesenchymal stem cells (hUC-MSCs) in order to increase the targeting of hUC-MSCs. We first detected the effect of Fe3O4 nanoparticles on the proliferation and differentiation of hUC-MSCs, and identified the distribution of Fe3O4@PDA labeled hUC-MSCs in APP/PS1 transgenic mice. We also determined the effects of hUC-MSCs on OA-induced apoptosis in vitro, and Fe3O4@PDA labeled hUC-MSCs on the cognitive function of AD mice by water maze test. The effects of Fe3O4@PDA labeled hUC-MSCs on related-proteins in hippocampus of AD mice were determined by WB and immunohistochemistry.ResultsFe3O4@PDA labeling did not affect the biological characteristics of hUC-MSCs, but did increase the efficiency of hUC-MSCs entering the brain. Moreover, the results of the water maze test showed that compared with single hUC-MSCs, Fe3O4@PDA-labeled hUC-MSCs improved the cognitive ability of APP/PS1 transgenic mice more significantly. Other experimental data, including WB, immunohistochemistry, showed that the expression of essential proteins in the hippocampus, such as amyloid precursor protein (App), synaptophysin (SYN), brain-derivedneurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), etc., are affected by Fe3O4@PDA coated-hUC-MSCs. The study showed a well-established Aβ deposition by promoting neurogenesis and synaptic plasticity and increased protein levels of BDNF, SYN, and GFAP.ConclusionFe3O4@PDA is a promising magnetic nanomaterial, which can increase the targeting of stem cells. The regulation of hUC-MSCs could improve the memory and cognitive ability of AD mice byexcessive generation of neuroprotective factors, which might be considered a viable therapy to treat AD.
Accidental Hypothermia: Factors Related to a Prolonged Hospital Stay - Nationwide Observational Study in Japan -
Authors: Takauji Shuhei , Hifumi Toru , Saijo Yasuaki , Yokobori Shoji , Kanda Jun , Kondo Yutaka , Hayashida Kei , Shimazaki Junya , Moriya Takashi , Yagi Masaharu , Yamaguchi Junko , Okada Yohei , Okano Yuichi , Kaneko Hitoshi , Kobayashi Tatsuho , Fujita Motoki , Shimizu Keiki , Yokota Hiroyuki , Yamaguchi Arino
Published: September 2020

Background: Accidental hypothermia (AH) has a low frequency, and the length of hospital stay in patients with AH remains poorly understood. The present study explored which factors were related to long-term hospitalization among patients with AH using Japan’s nationwide registry data.Methods: The data from the Hypothermia STUDY 2018, which included patients ≥ 18 years old with a body temperature ≤ 35°C, were obtained from a multicenter registry for AH conducted at 89 institutions throughout Japan, collected from December 1, 2018, to February 28, 2019. The patients were divided into a “short-stay patients” group (within 7 days) and “long-stay patients” group (more than 7 days). A logistic regression analysis after multiple imputation was performed to obtain odds ratios (ORs) for prolonged hospitalization with age, frailty, cause of hypothermia, mechanism underlying hypothermia, temperature, pH, potassium level, and disseminated intravascular coagulation (DIC) score as independent variables.Results: In total, 656 patients were included in the study, of which 362 were eligible for the analysis. The median length of hospital stay was 17 days. Of the 362 patients, 265 (73.2%) stayed in the hospital for more than 7 days. The factors associated with prolonged hospitalization were frailty (OR, 2.11; 95% confidence interval [CI], 1.09-4.10; p = 0.027), the occurrence of indoor (OR, 3.20; 95% CI, 1.58-6.46; p = 0.001), alcohol intoxication (OR, 0.17; 95% CI, 0.05-0.56; p = 0.004), pH (OR, 0.07; 95% CI, 0.01-0.76; p = 0.029), potassium level (OR, 1.36; 95% CI, 1.00-1.85; p = 0.048), and DIC score (OR, 1.54; 95% CI, 1.13-2.10; p = 0.006). Conclusions: Frailty, indoor situation, alcohol intoxication, pH, potassium level, and DIC score were factors contributing to prolonged hospitalization in patients with AH. These factors can be valuable for the early detection of AH requiring a prolonged hospital stay.
Long Noncoding RNA GAS6-AS1 Inhibits Progression and Glucose Metabolism Reprogramming in Lung Adenocarcinoma Via Repressing E2F1-Mediated Transcription of GLUT1
Authors: Luo Jing , Wang Huishan , Wang Li , Wang Gaoming , Yao Yu , Xie Kai , Li Xiaokun , Xu Lin , Shen Yi , Ren Binhui
Published: September 2020

BackgroundGlucose metabolism reprogramming is one of the hallmarks of cancer cells. While functional and regulatory mechanism of long noncoding RNA (lncRNA) in the contribution of glucose metabolism in lung adenocarcinoma (LUAD) remains incompletely understood. The aim of this study was to uncover the roles for GAS6-AS1 in the regulation of progression and glucose metabolism in LUAD.MethodsThe tumor-suppressive function of GAS6-AS1 was determined by experiments in vitro and nude mice xenograft models. The role of GAS6-AS1 in regulating cancer glucose metabolism was proved by detecting glucose uptake, lactate production, pyruvate production and extracellular acidification rate (ECAR). RNA pull-down assay, RNA immunoprecipitation (RIP) assay, luciferase reporter assay and Chromatin Immunoprecipitation (ChIP) assay were used to identify the underlying molecular mechanisms of GAS6-AS1. And the expression level of GAS6-AS1 in LUAD tissues and cells was measured by quantitative real-time PCR.ResultsOverexpression of GAS6-AS1 suppressed tumor progression of LUAD both in vitro and in vivo. Metabolic-related assays revealed that GAS6-AS1 inhibited glucose metabolism reprogramming. Mechanically, GAS6-AS1 was found to repress the expression of glucose transporter GLUT1, a key regulator of glucose metabolism. Ectopic expression of GLUT1 restored the inhibition effect of GAS6-AS1 on cancer progression and glucose metabolism reprogramming. Further investigation identified that GAS6-AS1 directly interacted with transcription factor E2F1 and suppressed E2F1-mediated transcription of GLUT1. And GAS6-AS1 was downregulated in LUAD tissues and correlated with clinicopathological characteristics and survival of patients.ConclusionsTaken together, our results identified GAS6-AS1 as a novel tumor suppressor in LUAD and unraveled its underlying molecular mechanism in reprogramming glucose metabolism. GAS6-AS1 potentially served as a prognostic marker and therapeutic target in LUAD.
Confinement Effects and Acid Strength in Zeolites
Authors: Grifoni Emanuele , Piccini GiovanniMaria , Lercher Johannes , Glezakou Vassiliki-Alexandra , Rousseau Roger , Parrinello Michele
Published: September 2020

Chemical reactivity and sorption in zeolites is coupled to confinement and - to a lesser extent- to the acid strength of Brønsted acid sites (BAS). In presence of water the zeolite Brønsted acid sites eventually convert into hydronium ions. The gradual transition from zeolite Brønsted acid sites to hydronium ions conversion in zeolites of varying pore size is examined by ab initio molecular dynamics combined with enhanced sampling based on well-tempered metadynamics and a recently developed set of collective variables. While at low water content (1-2 water/BAS) the acidic protons prefer to be shared between zeolites and water, higher water contents (n>2) invariably lead to solvation of the protons within a localized water cluster adjacent to the BAS. At low water loadings the standard free energy of the formed complexes is dominated by enthalpy and is associated with the acid strength of the BAS and the space around the site. Conversely, the entropy increases linearly with the concentration of waters in the pores, favors proton solvation and is independent of the pore size/shape.
Acceptability of Menstrual Products Interventions for Menstrual Hygiene Management Among Women and Girls in Malawi
Authors: Kambala Christabel , Chinangwa Angela , Chipeta Effie , Torondel Belen , Morse Tracy
Published: September 2020

BackgroundA key challenge for menstruating girls and women in low-resource countries is the inadequate and unreliable supply of menstrual products. Although development partners are implementing menstrual product interventions to address this challenge in Malawi, there is a paucity of information on the distribution of menstrual products and the acceptability of these interventions among users.MethodsWe conducted in-depth interviews with girls (n=20) and women (n=26) and 4 focus group discussions (FGDs) with women (n=35) and 7 FGDs with girls (n=60) to explore the acceptability of menstrual products interventions in 8 districts. Teachers (n=12), community leaders (n=6), community health workers (n=8) and service providers (n=9) were also interviewed to explore implementation issues and their views regarding the effect of menstrual products interventions on girls and women. Data were analyzed using content analysis.ResultsCommon menstrual products being promoted include locally made reusable pads, commercially made disposable pads and menstrual cups. Overall, adult women preferred reusable pads and young girls preferred disposable pads. Reported benefits of using any type of material distributed included enhanced cleanliness and reduced school absenteeism for girls. While community leaders and teachers applauded the use of disposable menstrual products they expressed concern that they are not affordable for an average Malawian and bemoaned the indiscriminate disposal of used disposable pads. Women and girls highlighted their lack of facilities to effectively wash and dry reusable pads. Service providers bemoaned poor coordination and the lack of national standards to regulate the quality of menstrual products distributed at national level. Improved inclusion of males and health workers could enhance the sustainability of programmes. Conclusion While the available menstrual products interventions are acceptable among participants, we note several challenges including affordability, poor disposal methods, lack of attention on sanitation facilities and the lack of standard protocols to regulate the quality of menstrual products. Recommendations to address these issues are reported.
Reporting of Antinuclear Antibody HEp-2 Indirect Immunofluorescence Assay: A Performance Survey
Authors: Tebo Anne E , Schmidt Robert L , Kadkhoka Kamran , Peterson Lisa K , Chan Edward K. L. , Fritzler Marvin J , Wener Mark H
Published: September 2020

Background: To evaluate the interpretation and reporting of antinuclear antibodies (ANA) by indirect immunofluorescence assay (IFA) using HEp-2 substrate based on common practice and guidance by the International Consensus on ANA patterns (ICAP).Method: Participants included two groups [16 clinical laboratories (CL) and 8 in vitro diagnostic manufacturers (IVD)] recruited via an email sent to the Association of Medical Laboratory Immunologists (AMLI) membership. Twelve (n=12) pre-qualified specimens were distributed to participants for testing, interpretation and reporting HEp-2 IFA. Results obtained were analyzed for accuracy with the intended and consensus response for three main categorical patterns (nuclear, cytoplasmic and mitotic), common patterns and ICAP report nomenclatures. The distributions of antibody titers of specimens were also compared. Results: Laboratories differed in the categorical patterns reported; 8 reporting all patterns, 3 reporting only nuclear patterns and 5 reporting nuclear patterns with various combinations of other patterns. For all participants, accuracy with the intended response for the categorical nuclear pattern was excellent at 99% [95% confidence interval (CI): 97-100%] compared to 78% [95% CI: 67-88%] for the cytoplasmic, and 93% [95% CI: 86%-100%] for mitotic patterns. The accuracy was 13% greater for the common nomenclature [87%, 95% CI: 82-90%] compared to the ICAP nomenclature [74%, 95% CI: 68-79%] for all participants. Participants reporting all three main categories demonstrated better performances compared to those reporting 2 or less categorical patterns. The average accuracies varied between participant groups, however, with the lowest and most variable performances for cytoplasmic pattern specimens. The reported titers for all specimens varied, with the least variability for nuclear patterns and most titer variability associated with cytoplasmic patterns. Conclusions: Our study demonstrates significant accuracy for all participants in identifying the categorical nuclear staining as well as traditional pattern assignments for nuclear patterns. However, there was less consistency in reporting cytoplasmic and mitotic patterns, with implications for assigning competencies and training for clinical laboratory personnel.
Weakened seasonality of the African rainforest precipitation in boreal winter and spring driven by tropical SST variabilities
Authors: Wang Xin-Yue , Zhu Jiang , Xin Meijiao , Song Chentao , Li Yadi , Zhou Yi , Li Xichen
Published: September 2020

Precipitation in the equatorial African rainforest plays an important role in both the regional hydrological cycle and the global climate variability. Previous studies mostly focus on the trends of drought in recent decades or long-time scales. Using two observational datasets, we reveal a remarkable weakening of the seasonal precipitation cycle over this region from 1979 to 2015, with precipitation significantly increased in the boreal winter dry season (+ 0.45 mm/day) and decreased in the boreal spring wet season (-0.78 mm/day), which account for ~ 14% of their respective climatological means. We further use a state-of-the-art atmospheric model to isolate the impact of sea surface temperature change from different ocean basins on the precipitation changes in the dry and wet seasons. Results show that the strengthening precipitation in the dry season is mainly driven by the Atlantic warming, whereas the weakening precipitation in the wet season can be primarily attributed to the Indian Ocean. Warming Atlantic intensifies the zonal circulation over the African rainforest, strengthening moisture convergence and intensifying precipitation in the boreal winter dry season. Warming Indian Ocean contributes more to reducing the zonal circulation and suppressing the convection in the boreal spring wet season, leading to an opposite effect on precipitation. This result has important implication on local ecology as well as global climate system.
Prevalence and Risk Factors of Thrombotic Events on Patients with COVID-19: A Systematic Review and Meta-Analysis
Authors: Xiong Xiaoming , Chi Jianhua , Gao Qinglei
Published: September 2020

BackgroundCoagulation abnormalities in COVID-19 patients accompanied with poor prognosis.This study aimed to determine the prevalence and risk factors of thrombotic events on COVID-19 patients.MethodsWe systematically reviewed all the studies about thrombotic events on COVID-19 patients in PubMed, Embase, Web of Science, MedRxiv, bioRxiv, from Dec 1st, 2019 to July 5, 2020. The weighted mean difference (MD) or odds ratio (OR) or relative risk (RR) with 95% confidence intervals (CI) for clinical data in COVID-19 patients with or without thrombotic events was calculated. Results12 articles contained 1083 patients were included for meta-analysis. The prevalence of thrombosis was 22% (95% CI 0.08-0.40) in COVID-19 patients and increased to 43% (95% CI 0.29-0.65) after admission to the intensive care unit (ICU). Compared with non-thrombotic patients, thrombotic patients had higher levels of D-dimer (MD=2.79, 95% CI 2.27–3.31), lactate dehydrogenase (LDH) (MD=112.71, 95% CI 62.40–163.02), and white blood cells (WBC) (MD=1.14, 95% CI 0.47–1.81) while decreased lymphocytes (MD= -0.20, 95% CI -0.38 – -0.02). Age, platelet counts, and male sex tended to be risks while diabetes tended to be a protection for thrombosis for COVID-19 patients, although no statistical difference was achieved. Finally, patients with thrombosis were at a higher risk of death (OR=2.39, 95% CI 1.36–4.20).ConclusionsPrevalence of thrombosis in COVID-19 patients was high, especially in ICU, though pharmacologic thromboembolism prophylaxis was applied. Therefore, higher levels of D-dimer, LDH, WBC, and decreased lymphocytes needed to be paid close attention to in patients with COVID-19.
Knowledge Attitude and Practices (KAPs) on Control of Bovine African Trypanosomosis in Pastoral Communities Surrounding Murchison Falls National Park, Uganda
Authors: Kizza Daniel , Ocaido Michaeal , Mugisha Anthony , Nalule Sarah , Onyuth Howard , Musinguzi Simon Peter , Waiswa Charles
Published: September 2020

Background: A survey was done among pastoral communities surrounding Murchison Falls National Park, Uganda to assess knowledge, attitude and practices about the control of bovine traypanosomosis. Methods: This was done using participatory methods and structured questionnaire.Results: The majority of the participants had ever seen tsetse flies and had ever heard about trypanosomosis with no significant difference (P > 0.05) across the five sub counties About 116 participants (73.9%) stated that trypanosomosis was a major disease in their area and across the five sub counties significant difference (P < 0.05) was observed. Farmers grazing near national parks and animals sharing grazing land and watering points with wild life respectively were considered the main causes of Bovine trypanosomosis. A significant difference (P < 0.01) in knowledge of farmers about the causes and signs of trypanosomosis in the study sub counties was observed. There was a high significant difference (P < 0.01) in control practices of trypanosomosis used in the study sub counties with the majority of farmers (58.6%) using insecticide treated cattle and significantly differed across the sub counties.Conclusion: The majority of participants had ever heard/seen tsetse flies and had ever heard about Nagana. Grazing near national parks and animal sharing grazing land and watering points with wildlife were the main causes of trypanosomosis. Insecticide treated cattle and not grazing in areas infested with tsetse flies were the major control practices of trypanosomosis. Knowledge about the disease, farmers’ attitude and control practices have overtime contributed to the pastoral communities and their cattle developing the needed resilience for survival in this high risk area.
Therapeutic Targets of Fingolimod (FTY720) in the Brains of Alzheimer's Disease Patients and the Associated Biological Mechanisms: a Network Pharmacology Study
Authors: Yin Pengqi , Xue Yang , Li Guozhong , Zhong Di
Published: September 2020

BackgroundThe sphingosine-1-phosphate receptor (S1PR) modulator fingolimod (FTY720), which is commonly used as an immunomodulator in multiple sclerosis treatment, was recently reported to be effective in the treatment of Alzheimer’s disease (AD), but its mechanism of action remains elusive. In this study, network pharmacology methods were applied to detect the potential pharmacological mechanisms of fingolimod in the brains of these patients. MethodsThe pharmacological macromolecular targets of fingolimod and fingolimod phosphate were downloaded from Swisstarget. Systematic intersection analysis of the expression profiles of brain tissues (709 AD tissues and 534 control tissues) was performed, and AD-associated fingolimod targets (F-ADGs) in the frontal, temporal and entorhinal cortices were analysed. The Minimal Common Oncology Data Elements method was used to detect core F-ADGs. Gene function enrichment analyses of the core F-ADGs were performed. Correlation analyses were performed to identify core F-ADGs with expression levels that were associated with the severity of AD. CIBERSORTx (https://cibersortx.stanford.edu/) was used to estimate the percentages of various immune cell populations in the cortex of each AD patient. ResultsWe found the fingolimod targets S1PR1, GNG3, GNG11 and GABBR2 were simultaneously detected in all three cortical regions. The core F-ADGs in all three cortical regions were enriched in similar biological processes, such as the G protein-coupled receptor signalling pathway, synaptic transmission, and pathways related to the function of synapses, especially GABAergic synapses. Core F-ADGs in the temporal and entorhinal cortices were also enriched in functions related to calcium signalling and cholinergic synapses. Correlation analysis showed that the expression levels of 7 core F-ADGs (S1PR1, NPY, NPY2R, GNAI1, GNG5, FPR1 and GPR183) in the frontal cortex were correlated with the severity of AD. No differences in immune cell infiltration between AD patients and normal controls were observed in any of the three cortical regions. ConclusionsThe pharmacological macromolecular targets of fingolimod and fingolimod phosphate, including S1PR1, were abnormally expressed in the cortices of multiple AD patients. The pharmacological effect of fingolimod on AD may be attributed to its ability to regulate GABA synapses, calcium signalling, and cholinergic synapses, other than regulating immune cell infiltration.
Identification of Tumor Mutation Burden and Immune Infiltrates in Hepatocellular Carcinoma Based on Multi-Omics Analysis
Authors: Yin Lu , Zhou Liuzhi , Xu Rujun
Published: September 2020

BackgroundWe aimed to explore the tumor mutational burden (TMB) and immune infiltration in HCC and investigate new biomarkers for immunotherapy.MethodsTranscriptome and gene mutation data were downloaded from the GDC portal, including 374 HCC samples and 50 matched samples. Furthermore, we divided the samples into high and low TMB groups, and analyzed the differential genes between them with GO, KEGG, and GSEA. Cibersort was used to assess the immune cell infiltration in the samples. Finally, univariate and multivariate Cox regression analyses were performed to identify differential genes related to TMB and immune infiltration, and a risk prediction model was constructed.ResultsWe found 10 frequently mutated genes, including TP53, TTN, CTNNB1, MUC16, ALB, PCLO, MUC, APOB, RYR2, and ABCA. Pathway analysis indicated that these TMB-related differential genes were mainly enriched in PI3K-AKT. Cibersort analysis showed that memory B cells (P=0.02), CD8+ T cells (P=0.09), CD4+ memory activated T cells (P=0.07), and neutrophils (P=0.06) demonstrated a difference in immune infiltration between high and low TMB groups. On multivariate analysis, GABRA3 (P=0.05), CECR7 (P<0.001), TRIM16 (P=0.003), and IL7R (P=0.04) were associated with TMB and immune infiltration. The risk prediction model had an area under the curve (AUC) of 0.69, suggesting that patients with low risk had better survival outcomes.ConclusionsOur study demonstrated for the first time that CECR7, GABRA3, IL7R, and TRIM16L mutations were associated with TMB and promoted antitumor immunity in HCC.
Are we there yet? Analyzing scientific research related to COVID-19 drug repurposing
Authors: Park Namu , Ryu Hyeyoung , Ding Ying , Yu Qi , Bu Yi , Wang Qi , Yang Jeremy J , Song Min
Published: September 2020

Drug repurposing may be a pivotal means of fulfilling urgent needs for treatment of the novel coronavirus disease 2019 (COVID-19), but current studies on drug repurposing for COVID-19 seem to show a lack of consensus in their drug candidate focus. Using bibliometric methods in a non-expert perspective, in a review of 34 published articles on the COVID-19 and drug-repurposing, we investigated obvious and less obvious points of consensus on drug candidates. To establish these two types of consensus, we first implemented document clustering. Within a set of five clustered papers, we established an obvious consensus, relying solely on the occurrence of entities by using term frequency and inverse document frequency and a comparison of mentioned drugs, finding that remdesivir and chloroquine were discussed with a certain degree of agreement. For the less obvious consensus, we created a drug entity co-occurrence network to establish low-high centrality combinations to probe the crucial drugs found in article clustering that are not plainly apparent through the mere counting of the occurrence of drug entities occurrences. Lopinavir emerged as having possibly potent effects in spite of underuse, while the mainstream of studies focus more on drugs such as chloroquine that enjoy explicit consent. Using an entitymetrics perspective, we expect that our research will support investigations of drug repurposing, expediting the process of establishing treatment for COVID-19.