bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bisindolylmaleimide IX: A novel anti-SARS-CoV2 agent targeting viral main protease 3CLpro demonstrated by virtual screening and in vitro assays
Authors: Gupta Yash , Maciorowski Dawid , Zak Samantha E. , Jones Krysten A. , Kathayat Rahul S. , Azizi Saara-Anne , Mathur Raman , Pearce Catherine M. , Ilc David J. , Husein Hamza , Herbert Andrew S. , Bharti Ajay , Rathi Brijesh , Durvasula Ravi , Becker Daniel P. , Dickinson Bryan C. , Dye John M. , Kempaiah Prakasha 
Published: October 2020

Abstract
The emergence of SARS/MERS drug-resistant SARS-CoV2 comes with higher rates of transmission and mortality. Like all coronaviruses, SARS-CoV-2 is a relatively large virus consisting of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral multiplication cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2’-O-MT. For virtual screening, the energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard(Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are approved by worldwide regulatory bodies. The screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP, and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand, and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. The top lead from each target pool was further subjected to molecular dynamics simulation using the Desmond module. Herein we report the evaluation of in-vitro efficacy of selected hit drug molecules on SARS-CoV-2 inhibition. Among eight molecules included in our evaluation, we found inhibitor of protein kinase C isoforms, Bisindolylmaleimide IX (BIM IX), as the potent inhibitor of SARS-CoV-2 in-vitro. Further, in-silico predicted target validation through enzymatic assays confirmed 3CLpro to be the target. Therefore, our data support advancing BIM IX for clinical evaluation as a potential treatment for COVID-19. This is the first study that has showcased the possibility of using bisindolylmaleimide IX to treat COVID-19 through this pipeline.
Chordoid Glioma of the Third Ventricular with Rare Patterns and Mutation in PRKCA: a case report and review of literature
Authors: ma xiaomei , zhu zhi , wang yin , li weiqing 
Published: October 2020

Abstract
Background: Chordoid gliomas are rare, low-grade neoplasms of the third ventricle. In the updated 4th edition of the 2016 WHO classification of tumours of the CNS, it described some three less common histological patterns and rare tissue patterns. Case presentation:Here we reported a case with all the uncommon patterns. It was a 52-year-old woman with dizziness and blurred vision. Imaging showed a solid tumor located in the third ventricle with a well-circumscribed border. Histological, almost tumor cells formed into atypical glands with different sizes and irregular shapes in an abundant of solid or loosely collagen matrix. Some tumor cells formed into papillary patterns, micro-papillary patterns. pseudoglandular patterns. Some focal tumor cells were spindle-shape. Only few epithelioid tumor cells formed into clusters and cords embedded into a myxoid stroma like the chordoma. No anaplastic features were identified in any lesion. Immunohistochemically, all the tumor cells were strong reactivity for TTF-1. Some tumor cells strong but focal reactivity for GFAP, NEU-N, and CD34. It showed a recurrent D463H missense mutation in PRKCA. All these findings confirm that the diagnosis was chordoid glioma of the third ventricular. Conclusions: There may be lots of histopathological features in one chordoid glioma case. It maybe suggested that PRKCA D463H mutation and TTF-1 positive may help to diagnose it.
Positive Mental Imagery in the Intervention of Negative Mood: A Randomized Controlled Trial
Authors: Zhou Wenjing , Li Peizhi , Lei Xu , yh yuan 
Published: October 2020

Abstract
Background

The aim of this study was to explore the intervention effect of positive mental imagery training on college students’ negative emotions in adults with depression trend.
Methods

A 2 (group: training group, non-training group) and 4 (time: pre-, post-, 1-week follow-up, and 6-week follow-up) mixed design was used in the present study, with the group as between-subjects factor and the time as within-subjects factor. Forty-nine participants with depressive tendency were randomly assigned to either the imagery training group or the non-training group. Except for negative interpretive bias were assessed before and after training, participants’ depression and anxiety symptoms, vividness and likelihood of mental imagery were assessed at all four time points.
Results

Compared to the pre-training, imagery group reported improvement in depression and trait anxiety scores and the likelihood of positive imagery across subsequent three assessments, and showed the improvement in the vividness of positive imagery at post-training. However, there was no significant between-group difference was found in negative interpretation bias.
Conclusions

The positive mental imagery training could effectively promote negative emotions and anxiety in adults with depression trend after 1-week training, and the effects of mental imagery could at least last for 6weeks, which provides a choice for self-regulation in daily life and is a promising way of mental health care. Often imagine a positive future, at least to some extent, good for our physical and mental health.
Bidirectional association of neurodevelopment with growth: A Prospective Cohort Study
Authors: Wei Xiaotong , Hu Jiajin , Yang Liu , Gao Ming , Li Lin , Ding Ning , Ma Yanan , Wen Deliang 
Published: October 2020

Abstract
Background

Evidence of the association between early life development in neurological and psychiatric with physical growth is controversial, and bidirectional effects have been poorly evaluated. The study aims to use the cross-lagged models and utilize data from the Born in Shenyang Cohort Study to characterize the bidirectional associations of the term-born infants' development in neurological and psychiatric in five domains and physical growth in the early life.
Methods

This study consists of 688 mother-child dyads from the Born in Shenyang Cohort Study. Infants' anthropometric and development in neurological and psychiatric outcomes were measured twice by the Gesell Development Scale and administered by staff at six and twelve months of age. Cross-lagged analyses and multiple linear regression analyses were used to explore the longitudinal relationships in both directions.
Results

In terms of longitudinal studies, the negative associations between gross motor and social behavior at six months with BMI Z -score at twelve months were found (gross motor: aβ=-0.20, 95% CI: -0.31 to- 0.09; social behavior: aβ=-0.23, 95% CI: − 0.33 to- 0.13). Instead, higher infant Z -scored BMI at six months predicted lower gross motor at twelve months (aβ=-0.08, 95% CI: -0.12 to- 0.04). The only bidirectional development in neurological and psychiatric, gross motor, had a more significant impact on infants’ BMI Z -score than the reverse (β=-0.21 vs. β=-0.09; P < 0.001). The similar associations had been found in weight gain velocity.
Conclusion

We found bidirectional relationships between infants’ gross motor with physical growth and suggested the term-born infants, who are on the edge of the developmental danger, should not be overlooked.
Cryo-EM Structure of a Tetrameric Photosystem I from Chroococcidiopsis TS-821, a Thermophilic, Non-heterocyst-forming Cyanobacteria
Authors: Semchonok Dmitry , Mondal Jyotirmoy , Cooper Connor , Schlum Katrina , Li Meng , Amin Muhamed , Sorzano Carlos Sanchez , Ramírez-Aportela Erney , Kastritis Panagiotis , Boekema Egbert , Guskov Albert , Bruce Barry 
Published: October 2020

Abstract
Photosystem I (PSI) is one of two the photosystems involved in oxygenic photosynthesis. PSI of cyanobacteria exists in monomeric, trimeric, and tetrameric forms, which is in contrast to the strictly monomeric form of PSI in plants and algae. The tetrameric organization raises questions about its structural, physiological, and evolutional significance. Here we report the ~3.9 Å resolution cryo-EM structure of tetrameric PSI from the thermophilic, unicellular cyanobacterium Chroococcidiopsis sp. TS-821. The structure resolves all 44 subunits and 448 cofactor molecules. We conclude that the tetramer is arranged via two different interfaces resulting from a dimer-of-dimers organization. The localization of chlorophyll molecules permits an excitation energy pathway within and between adjacent monomers. Bioinformatics analysis reveals conserved regions in PsaL subunit that correlate with the oligomeric state. Tetrameric PSI may function as a key evolutionary step between the trimeric and monomeric forms of PSI organization in photosynthetic organisms.
Whole exome sequencing identified novel mutation in SUOX gene causes extremely rare autosomal recessive isolated sulfite oxidase deficiency
Authors: Zhang Rui , Hao Yajing , Xu Ying , Qin Jiale , Wang Yanfang , Dey Subrata Kumar , Li Chen , Wang Huilin , Banerjee Santasree 
Published: October 2020

Abstract
BackgroundIsolated sulfite oxidase deficiency (ISOD) is the rarest types of life-threatening neurometabolic disorders characterized by neonatal intractable seizures and severe developmental delay with an autosomal recessive mode of inheritance. ISOD is extremely rare and only 29 mutations have been identified and reported worldwide. Germline mutation in SUOX gene causes ISOD. MethodsHere, we investigated a 5-days old Chinese girl, presented with intermittent tremor or seizures of limbs, neonatal encephalopathy, subarachnoid cyst and haemorrhage, dysplasia of corpus callosum, neonatal convulsion, respiratory failure, cardiac failure, hyperlactatemia, severe metabolic acidosis, hyperglycemia, hyperkalemia, moderate anemia, atrioventricular block and complete right bundle branch block. Karyotype and chromosomal microarray analysis were performed and identified no chromosomal abnormalities in the proband. Whole exome sequencing was performed for the proband. Sanger sequencing was performed for the proband and her family members. ResultsWhole exome sequencing identified a novel heterozygous deletion (c.1406_1421delCCTGGCAGGTGGCTAA) and a previously reported heterozygous substitution (c.1200C>G) in exon 6 of the SUOX gene in the proband. The novel heterozygous deletion leads to frameshift (p.Thr469Serfs*20) which results into the formation of a truncated sulfite oxidase of 488 amino acids. The substitution leads to a premature stop codon (p.Tyr400*) followed by the formation of a truncated sulfite oxidase of 399 amino acids. Hence, both the variants are loss-of-function variants. The proband’s father and mother is carrying the substitution and deletion in a heterozygous state respectively. These two variants were not identified in the elder brother of the proband as well as in the 100 healthy individuals. ConclusionHere, we reported the first variant of SUOX gene associated ISOD in Chinese population. Our study not only expand the mutational spectrum of SUOX gene associated ISOD, but also strongly suggested the application of whole exome sequencing for identifying the novel disease-causing mutation in candidate genes.
Mapping the Vector Abundance of Endemic Mosquito-Borne Diseases in Southern Quebec
Authors: Allostry Julie , Ludwig Antoinette , Kotchi Serge Olivier , Rousseu François , Fournier Richard 
Published: October 2020

Abstract
Background: Climate change is increasing the dispersion of mosquitoes and the spread of viruses of which some mosquitoes are the main vectors. This increases the risk of humans coming into contact with infected mosquitoes and developing diseases with sometimes fatal consequences. In Quebec, the surveillance and management of endemic mosquito-borne diseases, such as West Nile virus or Eastern equine encephalitis, could be improved by mapping the areas of risk supporting vector populations. However, there is currently no active tool tailored to Quebec that can predict annual mosquito population abundances. Methods: Our modelling approach is designed to meet this need. Four species of mosquitos were studied in this project for the period from 2003 to 2014 for the southern part of the province: Aedes vexans (VEX), Coquillettidia perturbans (CQP), Culex pipiens-restuans group (CPRg) and Ochlerotatus stimulans group (STMg) species. We used a mixed linear regression approach to model the abundances of each species or species groups as a function of meteorological and land cover variables. Results: The best models incorporate, for CPRg, the agricultural land, grassland and woodland classes and the average minimum temperature in September of the previous year; for STMg, the urban and woodland classes and the mean precipitation in June; for CQP, urban areas and the mean precipitation in January and August; and finally, for VEX, the agricultural land class and the mean precipitation in January, February and September. Conclusions: The models proved to be robust and precise over almost the entire study area, and the presence of significant climate variables for each of the species or species groups makes it possible to consider their use in predicting long-term spatial variations, based on climate and landscape change, in the abundance of mosquitoes potentially harmful to public health in southern Quebec.
Health States Utility Value in COVID-19
Authors: Alinia Cyrus , Yaghmaei Safura , Abdullah Farman Zahir , Ahmadi Asad , Samadi Nasrin , Pourteymour Sima , Mahmoudi Hassan , Moradi Ghobad , Piroozi Bakhtiar 
Published: October 2020

Abstract
Background: The main aim of the study was extract the health utility value of coronavirus 2019 (COVID-19) disease.Methods: In a cross-sectional study in Iran, 320 randomly selected treated patients from COVID-19 is studied. To collect the required data, we applied a questionnaire that included socio-demographic factors, clinical characteristics, and questions on the patients’ Health-Related Quality of Life (HRQoL). Time trade-off (TTO) approach is used to measure the lost HRQoL attributed to COVID-19. Besides, we applied a two-limit Tobit regression model to determine the effects of the socio-demographic factors on the patients’ health utility and used the visual analogue scale approach to estimate the perceived total current health status.Results: The overall mean (SE) and median (IQR) of the health utility values were 0.863 (0.01) and 0.909 (0.21), respectively. This values for those who were willing to trade time in exchange for perfect health estimated at 0.793 (0.01) and 0.848 (0.17), respectively. The lowest amount of utility value were belonged to the elderly (mean (SE) = 0.742 (0.04); median (IQR) = 0.765 (0.42)) and those lived in rural (mean (SE)) = 0.804 (0.03); median (IQR) = 0.877 (0.30)). The univariate analysis shows that age, location living, and household size factors have a statistically significant effect on the health utility. The regression model's findings indicate that the participants' age and hospitalization status were the key determinants of COVID-19 health utility value.Conclusion: COVID-19 is associated with a substantial and measurable diminution in HRQoL. This diminution in HRQoL can be directly compared with that induced by systemic health states.
A Randomized Controlled Trial on Mobile Phone Text Messaging to Improve Sexo-Reproductive Health Among Adolescent Girls in Cameroon
Authors: Wirsiy Frankline Sevidzem , Atuhaire Catherine , Ngonzi Joseph , Cumber Samuel Nambile 
Published: October 2020

Abstract
Background: We conducted a single-centered randomized controlled single-blinded trial (i.e trained interviewers; blinded to group allocation). The target population included adolescent girls in the Kumbo West Health District (KWHD) of Cameroon. This trial tested the efficacy of weekly educational one-way text messages to improve perception of adolescent girls on sexo-reproductive health. Methods: Allocation concealment (1:1) was determined by sequentially numbered sealed opaque envelopes. A total of 398 participants either received the mobile phone sexo-reproductive health text messages (199) or not (199). A blinded program secretary send out text messages and recorded delivery. Data was collected and managed at baseline and at 6 month intervals using an interviewer-administered questionnaire before and after intervention, then analysed using the independent T-test (mean differences) and ANOVA on SPSS version 21.Results: The mean knowledge, attitude and practice scores respectively increased significantly from 6.03, 4.01 and 3.45 at baseline to 7.99, 5.83 and 4.99 at the end of the study. After performing ANOVA for the overall correct knowledge, positive attitudes and good practices respectively for between and within the intervention groups, we obtained: (F=15.12, P=0.023), (F=60.21, P=0.001) and (F=57., P=0.013) which showed statistical significance thus indicating the overall improvement in adolescents girls perception as a result of the intervention and not by chance. Majority (65.3%) of the participants were satisfied with the Short Message Service (SMS). Conclusion: This trial has contributed to the body of knowledge and evidence on the use of mobile phone technology using educative SMS to improve adolescent girl’s perception on sexo-reproductive health in Cameroon. Trial Registration: Pan African Clinical Trials Registry, PACTR201805003259293. Registered 28 March 2018, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3259
Job Satisfaction of Midwives in the Context of a Midwife-Led Project – A Repeat Measure Mixed Methods Study
Authors: Grylka-Baeschlin Susanne , Aeberli Regula , Guenthard-Uhl Barbara , Kaeppeli Barbara Meier , Leutenegger Vanessa , Volken Thomas , Pehlke-Milde Jessica 
Published: October 2020

Abstract
Background: Job satisfaction of midwives is important to prevent skill shortage. Those working in midwife-led models of care were more satisfied than those working in standard care. Job satisfaction in the context of a midwife-led project was not researched previously. The aim of this study was to investigate job satisfaction before and after the implementation of a midwife-led intervention.Methods: Longitudinal observational study at three time points using quantitative and qualitative methods. A total of 43 midwives working in the labour ward participated in the online surveys and 5-7 in the focus group discussions. The surveys comprised questions from validated instruments. Descriptive and multivariable time series analysis were used for quantitative and content analysis for qualitative data.Results: Adjusted predicted scores decreased between t0 and t1 and subsequently increased at t2 without reaching baseline values (e.g ‘professional support subscales’: between t0 and t1: (0.65, 95% CI [0.45, 0.86] versus 0.26, 95% CI [0.08, 0.45], p=0.005) and t0 and t2 (0.65, 95% CI [0.45, 0.86] versus 0.29, 95% CI [0.12, 0.47], p=0.004). Focus group discussions revealed three themes: “Job satisfaction”, “Challenges with the implementation” and “Continuity of care”. Midwives perceived the additional tasks as stressors. Conclusion: The implementation of new interventions might increase work related stress and decrease job satisfaction in an early phase. This effect was stronger than the one of acquiring more autonomy and responsibility. Heads of institutions and policy makers should recognise the needs of support and additional resources for staff when planning new projects.
DNA Vaccination Target on Amyloid Oligomer also Reduce tau Pathology and Improve Synaptic Function in Aged 3xTg-AD Mice
Authors: sha sha , Xing xiaona , Wang Tao , Li Ying , Zhang RongWei , Shen Xueli , Cao Yunpeng , Qu Le 
Published: October 2020

Abstract
Background: Active immunotherapy has been widely used as a potential therapeutic method for both treatment and prevention of Alzheimer’s disease (AD). Amyloid deposition and tau hyperphosphorylation are main pathological hallmarks of AD. Reduction in both is required to regulate synaptic proteins neurotransmission which can finally protect cognitive function. Growing evidence suggests that the most toxic β-Amyloid peptide (Aβ) oligomers can be detected from the very beginning of AD development, so it is wise for us to develop effective therapy method focus on Aβ oligomers rather than monomers. Methods: The 3×Tg-AD mice were randomly divided into two groups immunized with p(Aβ3–10)10-MT and PBS respectively. The PBS group was used for positive group while C57/B6 mice was used for negative group. ELISA was used to detect the antibody titers and Morris Water Maze was to analysis the cognitive function. The Aβ ,Tau hyperphosphorylation, Neuron and synaptic protein were detected through immunohistochemistry and western blot. Results: Mice immunized with p(Aβ3–10)10-MT can not only reduce the levels of Aβ oligomers and plaque deposits but also protect neuron as well as synaptic function, finally prevent the decline spatial memory in transgenic mice. Conclusions: Our novel DNA genetic vaccine is highly safe and effective, thus providing strong evidence for the treatment and prevention of early AD.
Design, Synthesis and Antibacterial Activity of Novel Pyrimidine-Containing 4H-Chromen-4-one Derivatives
Authors: Su Shijun , Chen Mei , Tang Xuemei , Peng Feng , Liu Tingting , Zhou Qing , Luo Hui , He Ming , Xue Wei 
Published: October 2020

Abstract
A series of pyrimidine-containing 4H-chromen-4-one derivatives were designed and synthesized by combining bioactive substructures. All compounds were characterized using 1H NMR, 13C NMR, 19F NMR and HRMS. Preliminary biological activity results showed that most of title compounds displayed significant inhibitory activity against Xanthomonas axonopodis pv. Citri (Xac), Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (Rs). In particular, compound 4c demonstrated a good inhibitory effect against Xac and Xoo, with half-maximal effective concentration(EC50) values of 15.5 and 14.9 μg/mL respectively, and that of compound 4h showed the best antibacterial activity against Rs with an EC50 value of 14.7 μg/mL, These results were better than both bismerthiazol (BT, 51.7, 70.1 and 52.7 μg/mL, respectively) and thiodiazole copper (TC, 77.9, 95.8 and 72.1 μg/mL respectively). In vivo antibacterial activity results indicated that compound 4c displayed better curative(42.4%) and protective (49.2%) activities for reducing rice bacterial leaf blight than both BT (35.2, 39.1%) and TC (30.8, 27.3%). The mechanism of compound 4c against Xoo was analysed through scanning electron microscopy (SEM). Results showed that the compound destroied the bacterial cell membrane structure. These results indicated that pyrimidine-containing 4H-chromen-4-one derivatives are valuable in the research of new agrochemicals.