bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling Vitamins as Wonder Molecules for Covid-19 Management via Structure-based Virtual Screening
Authors: Pandya Medha , Shah Sejal , Menamadathil Dhanalakshmi , Gadnayak Ayushman , Juneja Tanzil , Patel Amisha , Das Kajari , Das Jayashankar 
Published: January 2021

Abstract
The emergence situation of coronavirus disease 2019 (COVID-19) pandemic has realised the global scientific communities to develop strategies for immediate priorities and long-term approaches for utilization of existing knowledge and resources which can be diverted to pandemic preparedness planning. Lack of proper vaccine candidate and therapeutic management has accelerated the researchers to repurpose the existing drugs with known preclinical and toxicity profiles, which can easily enter Phase 3 or 4 or can be used directly in clinical settings. We focused to justify even exploration of supplements, nutrients and vitamins to dampen the disease burden of the current pandemic may play a crucial role for its management. We have explored structure based virtual screening of 15 vitamins against non-structural (NSP3, NSP5, ORF7a, NSP12, ORF3a), structural (Spike & Hemagglutinin esterase) and host protein furin. The in silico analysis exhibited that vitamin B12, Vitamin B9, Vitamin D3 determined suitable binding while vitamin B15 manifested remarkable H-bond interactions with all targets. Vitamin B12 bestowed the lowest energies with human furin and SARS-COV-2 RNA dependent RNA polymerase. Furin mediated cleavage of the viral spike glycoprotein is directly related to enhanced virulence of SARS-CoV-2. In contrast to these, vitamin B12 showed zero affinity with SARS-CoV-2 spike protein. These upshots intimate that Vitamin B12 could be the wonder molecule to shrink the virulence by hindering the furin mediated entry of spike to host cell. These identified molecules may effectively assist in SARS-CoV-2 therapeutic management to boost the immunity by inhibiting the virus imparting relief in lung inflammation.
Calcium-dependent serine-threonine phosphatase, calcineurin inactivation mediated by baicalein attenuates prion protein-mediated neuronal cell damage
Authors: Hong Jeong-Min , Moon Ji-Hong , Oh Young Min , Park Sang-Youel 
Published: January 2021

Abstract
Background: Prion diseases are a group of unvaryingly fatal neurodegenerative disorders characterized by neuronal cell death. Calcineurin and autophagy mediate prion-induced neurodegeneration, suggesting that inhibition of calcineurin and autophagy could be a target for therapy. Baicalein has been reported to exert neuroprotective effects against calcium-dependent neuronal cell death. Results: In the present study, we investigated whether baicalein attenuates prion peptide-mediated neurotoxicity and reduces calcineurin. We found that baicalein treatment inhibits prion protein-induced apoptosis. Baicalein inhibited calcium up-regulation and protected the cells against prion peptide‑induced neuron cell death by calcineurin inactivation. Furthermore, baicalein increased p62 protein levels and decrease LC3-II protein levels indicating autophagic flux inhibition and baicalein inhibited prion protein-induced neurotoxicity through autophagy flux inhibition. Conclusions: Taken together, this study demonstrated that baicalein attenuated prion peptide-induced neurotoxicity via calcineurin inactivation and autophagic flux reduction, and also suggest that baicalein may be an effective therapeutic drug against neurodegenerative diseases, including prion diseases.
Menopause Is a Natural Stage of Aging: A Qualitative Study
Authors: Ilankoon IMPS , Samarasinghe Kerstin , Elgán Carina 
Published: January 2021

Abstract
Background Menopause is a biopsychosocial phenomenon encompassing the transition in a woman’s life from being fertile to infertile. Although menopause may result in extremely unpleasant physical symptoms there is evidence of a low rate of reported menopausal symptoms amongst women in Asian cultures. Women’s experiences, views, and responses to menopause which influences women’s daily life and well-being, may vary between different societies and cultures. This study aimed to explore and describe menopausal experiences among women in Sri Lanka. Methods A qualitative exploratory research was conducted among postmenopausal women of 46-55 years of age in the western province of Sri Lanka. Individual interviews with a purposive sample of 20 women were conducted, and data analysis was done using manifest and latent content analysis. Results The results consist of an overall theme, “Menopause is a natural stage of aging” and three categories “Entering a new stage”, “Managing menopause” and “Not the end of life” which emerged from 34 codes. The overall theme highlights that changes in menopause were experienced as a natural change in life, with health problems that are normal for this change and handled with different self-care practices. The category “Entering a new stage” describes the women becoming aware of menopause and its bodily changes. The category “Managing menopause” describes women’s experiences of being able to find their own remedies to ease the menopausal symptoms and by engaging in religious activities and focusing on interaction with people. The category, “Not the end of life” describes women's views of themselves as still valuable because menopause was experienced as a natural part of their lives. Conclusion Women in Sri Lanka managed menopausal problem mainly on their own as they viewed the menopause as a natural stage of aging risking unnecessary suffering and failure to detect preventable complications. Enabling support groups for menopausal women and improving on their health-seeking behaviour by encouraging them to take part in screening for cervical and breast cancer would improve their condition. Further information on additional hormone therapy with a, subsequent follow-up and evaluation by community health nurses and/or midwives, would facilitate Sri Lankan women's transition to menopause.
Comparison of three treatment methods for simple bone cyst in children
Authors: Zhang Ke Xue , Chai Wei , Zhao Jia Jia , Deng Jun Hao , Peng Zhan , Chen Ji Ying 
Published: January 2021

Abstract
Background The unicameral bone cyst (UBC) is a kind of benign tumor whose clinical treatments and efficacy are controversial. The purpose of this study was to evaluate the efficacy of the elastic stable intramedullary nail (ESIN), the injection of autologous bone marrow (ABM), and the combination of ESIN and ABM in the treatment of bone cyst in children. Methods 83 cases with simple bone cyst were analyzed retrospectively. 28 cases were treated with ABM. 28 cases were treated with ESIN. 27 cases were treated with ABM and ESIN. All cases were diagnosed through X-ray, CT, or MRI scans. For the suspicious ones, the pathological biopsy was performed for an accurate diagnosis. X-ray examinations were carried out for the postoperative follow-up. Capanna criteria for bone cyst was used for postoperative evaluation of three methods. Results All cases accomplished the follow-up. The effective rate of the ABM+ESIN group was significantly higher than that of the ABM group (P<0.05), and the cure rates of the ESIN group and the ABM+ESIN group were higher than that of the ABM group (P<0.05, respectively). The cure time in the ESIN group was lower than that of the other two groups (P<0.05, respectively). The times for admission were 2.0±0.0 in the ESIN group, 5.7±1.9 in the ABM group, and 4.7±2.4 in the ABM+ESIN group (P<0.05 when compared with each other). Conclusions The method of ABM combined with ESIN for children’s bone cyst has the highest effective rate and curative rate. For the individual method, ESIN has a higher effective rate and curative rate than that of ABM. Meanwhile, it has the fewest time of hospitalization.
The value of Bayesian predictive projection for variable selection: An example selecting lifestyle predictors of young adult well-being
Authors: Bartonicek Adam , Wickham Shay Ruby , Pat Narun , Conner Tamlin S. 
Published: January 2021

Abstract
BackgroundVariable selection is an important issue in many fields such as public health and psychology. Researchers often gather data on many variables of interest and then are faced with two challenging goals: building an accurate model with few predictors, and making probabilistic statements (inference) about this model. Unfortunately, it is currently difficult to attain these goals with the two most popular methods for variable selection methods: stepwise selection and LASSO. The aim of the present study was to demonstrate the use predictive projection feature selection – a novel Bayesian variable selection method that delivers both predictive power and inference. We apply predictive projection to a sample of New Zealand young adults, use it to build a compact model for predicting well-being, and compare it to other variable selection methods. MethodsThe sample consisted of 791 young adults (ages 18 to 25, 71.7% female) from New Zealand who had taken part in the Dunedin Daily Life Study in 2013-2014. Participants completed a 13-day online daily diary assessment of their well-being and a range of lifestyle variables (e.g., sleep, physical activity, diet variables). The participants’ diary data was averaged across days and analyzed cross-sectionally to identify predictors of average flourishing. Predictive projection was used to select as few predictors as necessary to approximate the predictive accuracy of a reference model with all 28 predictors. Predictive projection was also compared to other variable selection methods, including stepwise selection and LASSO.ResultsThree predictors were sufficient to approximate the predictions of the reference model: higher sleep quality, less trouble concentrating, and more servings of fruit. The performance of the projected submodel generalized well. Compared to other variable selection methods, predictive projection lead to models with either matching or slightly worse performance but with much fewer predictors.ConclusionPredictive projection was used to efficiently arrive at a compact model with good predictive accuracy. The predictors selected into the submodel – felt refreshed after waking up, had less trouble concentrating, and ate more servings of fruit – were all theoretically meaningful. Our findings have important implications for applications of variable selection in health research.
Health services utilization and out-of-pocket (OOP) expenditures in public and private facilities in Pakistan: An empirical analysis of the 2013-14 OOP Health Expenditure Survey
Authors: Khalid Faraz , Raza Wajeeha , Hotchkiss David R. , Soelaeman Rieza H. 
Published: January 2021

Abstract
Background As low- and middle-income countries progress toward Universal Health Coverage, there is an increasing focus on measuring out-of-pocket (OOP) expenditure and health services utilization within countries. While there have been several reforms to improve health services coverage and financial protection in Pakistan, there is limited empirical research comparing OOP expenditure and health services utilization between public and private facilities and exploring their determinants, a knowledge gap addressed in this study. Methods We used data from 2013-14 OOP Health Expenditure Survey, a population-based household survey carried out for Pakistan’s National Health Accounts. The analysis included 7,969 encounters from 4,293 households. We conducted bivariate analyses to describe patterns of care utilization, estimated annualized expenditures by type and sector of care, and assessed expenditure composition. We used multivariable logistic regression modeling to identify factors associated with sector of care and generalized linear model (GLM) with log link and gamma distribution to identify determinants of OOP expenditures stratified by type of care (inpatient and outpatient). Results Most encounters (82.5%) were in the private sector and were for outpatient visits (85%). Several public-private differences were observed in annualized expenditures and expenditure components. Logistic regression results indicate males, wealthier individuals, Punjab and Sindh residents, and those in smaller households were more likely to access private outpatient care. In the inpatient model, rural residents were more likely to use a private provider, while Khyber Pakhtunkhwa residents were less likely to use private care. GLM results indicate private sector inpatient expenditures were approximately PKR 6,660 (USD 61.8) higher than public sector expenditures, but no public-private differences were observed for outpatient expenditures. Several demographic factors were significantly associated with outpatient and inpatient expenditures. Of note, expenditures increased with increasing wealth, decreased with increasing household size, and differed by province and region. Conclusions This is the first study comprehensively investigating how healthcare utilization and OOP expenditures vary by sector, type of care, and socio-economic characteristics in Pakistan. The findings are expected to be particularly useful for the next phase of social health protection programs and supply side reforms, as they highlight sub-populations with higher OOP and private sector utilization.
Evaluating the Performance of Diagnostic methods for soil transmitted helminths in the Amhara National Regional State, Northwest Ethiopia
Authors: Niguse Abebe Fenta , Hailu Tadesse , Alemu Megbaru , Nibret Endalkachew , Amor Arancha , Munshea Abaineh 
Published: January 2021

Abstract
Background: Soil-transmitted helminths are more prevalent in tropics and sub-tropics including Ethiopia. Despite their high prevalence, direct saline microscopy with its low sensitivity has been used as a diagnostic method in almost all health facilities in Ethiopia. Alternative diagnostic methods which have higher sensitivity are not yet implemented. Therefore, this study aimed to compare and evaluate the performance of diagnostic methods for soil transmitted helminths. Methods: A cross-sectional study among 520 school children was conducted from October to December, 2019 in Amhara National Regional State. The study participants were selected using systematic random sampling technique. Stool samples were processed via formol ether concentration, Kato-Katz, spontaneous tube sedimentation and agar plate culture techniques. Data was entered into Epi-data version 3.1 and analysis was done using SPSS version 20.0. The sensitivity, specificity, and negative predictive value were calculated against the combined result. Strength of agreement of the diagnostic methods was determined by Kappa value. Results: The Overall prevalence of soil transmitted helminths was 40.8% using combination of methods. The prevalence 24.4%, 22.5%, and 32.4%, respectively was recorded by using formol ether concentration, Kato-Katz and spontaneous tube sedimentation. The highest prevalence of hookworm (29.2%) was detected by the agar plate culture. The sensitivity and negative predictive value of formol ether concentration were 57.9 % and 78.4%, for Kato-Katz thick smear 55.2% and 76.4%, for spontaneous tube sedimentation were 79.2% and 87.5% to soil transmitted helminths detection, respectively. The sensitivity and negative predictive value of agar plate culture to hookworm detection were 86.4% and 93.5%, respectively. Conclusion: Spontaneous tube sedimentation shows higher sensitivity in the detection of soil transmitted helminth infections. Agar plate culture (APC) method also indicated better performance for hookworm detection than other methods. Therefore, the employment of spontaneous tube sedimentation technique for routine laboratory and agar plate culture for research purposes will significantly aid in accurate diagnosis of parasitic infections.
Utility of Abdominal Drain in Gastrectomy (ADiGe) Trial: study protocol for a multicenter non-inferiority randomized trial
Authors: Weindelmayer Jacopo , Mengardo Valentina , Veltri Alessandro , Baiocchi Gian Luca , Giacopuzzi Simone , Verlato Giuseppe , de Manzoni Giovanni 
Published: January 2021

Abstract
Background: Prophylactic use of abdominal drain in gastrectomy has been questioned in the last 15 years and a 2015 Cochrane meta-analysis on four RCTs concluded that there was no convincing evidence to the routine drain placement in gastrectomy. Nevertheless, the Authors evidenced the moderate/low quality of the included studies and highlighted how 3 out of 4 four came from Eastern countries. After 2015 only retrospective studies have been published, all with inconsistent results.Methods: ADiGe (Abdominal Drain in GastrEctomy) Trial is a multicenter prospective randomized non-inferiority trial with a parallel design. It aimed to verify whether avoiding routine use of abdominal drain is burdened with complications, particularly an increase in postoperative invasive procedures. Patients with gastric cancer, scheduled for subtotal or total gastrectomy with curative intent, are eligible for inclusion, irrespective of previous oncological treatment. The primary composite endpoint is reoperation or percutaneous drainage procedures within 30 postoperative days. The primary analysis will verify whether the incidence of the primary composite endpoint is higher in the experimental arm, avoiding routine drain placement, than control arm, undergoing prophylactic drain placement, in order to falsify or support the null hypothesis of inferiority. Secondary endpoints assessed for superiority are overall morbidity and mortality, Comprehensive Complications Index, incidence and time for diagnosis of anastomotic and duodenal leaks, length of hospital stay, readmission rate.Assuming one-sided alpha of 5%, and cumulative incidence of the primary composite endpoint of 6.4% in control arm and 4.2% in the experimental one, 364 patients allow to achieve 80% power to detect a non-inferiority margin difference between the arm proportions of 3.6%. Considering a 10% drop-out rate, 404 patients are needed. In order to have a balanced percentage between total and subtotal gastrectomy, recruitment will end at 202 patients for each type of gastrectomy. The surgeon and the patient are blinded until the end of the operation, while postoperative course is not blinded to patient and caregivers.Discussion: ADiGe Trial could contribute to critically re-evaluate the role of prophylactic drain in gastrectomy, a still widely used procedure.Trial registration: Prospectively registered (last updated on October 29, 2020) at Clinicaltrials.gov with the identifier NCT04227951, https://clinicaltrials.gov/ct2/show/NCT04227951.
Development of an Engineered Peptide Antagonist against Periostin to Overcome Doxorubicin Resistance in Breast Cancer
Authors: Oo Khine Kyaw , Kamolhan Thanpawee , Soni Anish , Thongchot Suyanee , Mitrpant Chalermchai , O-charoenrat Pornchai , Thuwajit Chanitra , Thuwajit Peti 
Published: January 2021

Abstract
Background: Chemoresistance is one of the main problems in treatment of cancer. Periostin (PN) is a stromal protein which is mostly secreted from cancer associated fibroblasts in the tumor microenvironment and can promote cancer progression including cell survival, metastasis, and chemoresistance. The main objective of this study was to develop an anti-PN peptide from the bacteriophage library to overcome PN effects in breast cancer (BCA) cells. Methods: A twelve amino acids bacteriophage display library was used for biopanning against the PN active site. A selected clone was sequenced and analyzed for peptide primary structure. A peptide was synthesized and tested for the binding affinity to PN. PN effects including a proliferation, migration and a drug sensitivity test were performed using PN overexpression BCA cells or PN treatment and inhibited by an anti-PN peptide. An intracellular signaling mechanism of inhibition was studied by western blot analysis. Lastly, PN expressions in BCA patients were analyzed along with clinical data. Results: The results showed that a candidate anti-PN peptide was synthesized and showed affinity binding to PN. PN could increase proliferation and migration of BCA cells and these effects could be inhibited by an anti-PN peptide. There was significant resistance to doxorubicin in PN-overexpressed BCA cells and this effect could be reversed by an anti-PN peptide in associations with phosphorylation of AKT and expression of survivin. In BCA patients, serum PN showed a correlation with tissue PN expression but there was no significant correlation with clinical data. Conclusions: This finding supports that anti-PN peptide is expected to be used in the development of peptide therapy to reduce PN-induced chemoresistance in BCA.
Triple null mutations in starch synthase SSIIa gene homoeologs lead to high amylose and resistant starch in hexaploid wheat
Authors: Schoen Adam , Joshi Anupama , Tiwari Vijay K , Gill Bikram S. , Rawat Nidhi 
Published: January 2021

Abstract
Background: Lack of nutritionally appropriate foods is one of the leading causes of obesity in the US and worldwide. Wheat (Triticum aestivum) provides 20% of the calories consumed daily across the globe. The nutrients in the wheat grain come primarily from the starch composed of amylose and amylopectin. Resistant starch content, which is known to have significant human health benefits, can be increased by modifying starch synthesis pathways. Starch synthase enzyme SSIIa, also known as starch granule protein isoform-1 (SGP-1), is integral to the biosynthesis of the branched and readily digestible glucose polymer amylopectin. The goal of this work was to develop a triple null mutant genotype for SSIIa locus in the elite hard red winter wheat variety ‘Jagger’ and evaluate the effect of the knock-out mutations on resistant starch content in grains with respect to wild type. Results: Knock-out mutations in SSIIa in the three genomes of wheat variety ‘Jagger’ were identified using TILLING. Subsequently, these loss-of function mutations on A, B, and D genomes were combined by crossing to generate a triple knockout mutant genotype Jag-ssiia-∆ABD. The Jag-ssiia-∆ABD had an amylose content of 35.70% compared to 31.15% in Jagger, leading to ~118% increase in resistant starch in the Jag-ssiia-∆ABD genotype of Jagger wheat. The single individual genome mutations also had various effects on starch composition. Conclusions: Our full null Jag-ssiia-∆ABD mutant showed a significant increase in RS without the shriveled grain phenotype seen in other ssiia knockouts in elite wheat cultivars. Moreover, this study shows the potential for developing nutritionally improved foods in a non-GM approach. Since all the mutants have been developed in an elite wheat cultivar, their adoption in production and supply will be feasible in future.
Efficacy and Safety of the Syrup "KalobaTUSS®" as a Treatment for Cough in Children: a randomized, double blind, placebo-controlled clinical trial
Authors: Carnevali Ilaria , Paglia Rita La , Pauletto Laura , Raso Floriana , Testa Marco , Mannucci Carmen , Sorbara Emanuela Elisa , Calapai Gioacchino 
Published: January 2021

Abstract
Background: Acute cough in children often causes discomfort to children and parents, reducing their quality of life. Despite the extensive utilization of over-the-counter remedies for cough, the efficacy of most of these treatments in children has not been confirmed.Methods: We conducted a randomized, double blind, placebo-controlled clinical trial of 106 children with acute cough to evaluate the efficacy and safety of KalobaTUSS®, a paediatric cough syrup based on acacia honey and on Malva sylvestris extract, Inula helenium extract, Plantago major extract, and Helichrysum stoechas extract by using a validated 6 points Likert scale.Results: Children were orally treated with KalobaTUSS® or placebo for eight days. Children receiving KalobaTUSS® showed an early and significant reduction in night-time and day-time cough scores measured using a specific scale and a shorter duration of cough than children treated with the placebo.Conclusions: KalobaTUSS® is well tolerated and produces positive effects by reducing the severity and shortening the duration of cough in children.Trial Registration: Clinicaltrials.gov no. NCT04073251. Retrospectively registered.