bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Z Drugs Use and Risk of Cognitive Impairment in Older Patients With Chronic Insomnia
Authors: Guo Fang , Yi Li , Zhang Wei , Zhang Yong-bo
Published: September 2020

Background Benzodiazepines (BZDs) and Z drugs are widely used for patients with chronic insomnia. The long term use of BZDs in older patients can cause cognitive impairment and potentially increase the risk of dementia. However, evidence for an association with Z drugs is limited. This study aimed to investigate the association between the risk of cognitive impairment and exposure to Z drugs in older patients with chronic insomnia.Methods We recorded older patients with chronic insomnia who visited the outpatient department of neurology, Beijing Friendship Hospital, and assessed the global cognitive function (MoCA) and five cognitive domains (CVLT, TMT-B, BNT-30, CDT and DST). Multiple regression analysis was conducted to determine the independent factors of cognition, and evaluate the effect of Z drugs use (zolpidem and zopiclone) on cognition.Results A total of 88 subjects were identified. BZDs use (P=0.03, B=2.67, 95% CI 0.36-4.97) and BZDs exposure density (P=0.01, B=1.22, 95% CI 0.33-2.11) were independent risk factors of cognitive impairment in older patients with chronic insomnia. Neither Z drugs use (P=0.11) nor Z drugs exposure density (P=0.92) correlated with global cognitive function. Moreover, compared with BZDs users, there were positive associations between Z drugs use and memory (P=0.00), attention (P=0.00) and verbal function (P=0.04). Additionlly, education level (P=0.02, OR=0.74, 95% CI 0.57-0.95), duration of insomnia (P=0.04, OR=1.05, 95% CI 1.00-1.11) and severity of insomnia (P=0.03, OR=1.27, 95% CI 1.02-1.57) were also independent factors of global cognitive function.Conclusion We found no evidence that Z drugs use and Z drugs exposure density were associated with cognitive impairment in older patients with chronic insomnia. However, the use of BZDs and BZDs exposure density were associated with an increased risk of cognitive impairment. Thus, BZDs use should be avoided，and Z drugs should be prescribed with extreme caution in the elderly.
Complete Chloroplast Genome of Calligonum Mongolicum: Genome Organization, Codon Usage Pattern, Phylogenetic Relationships, Comparative Structure and Adaptive Evolution Analysis
Authors: Duan Huirong , Zhang Qian , Yang Hongshan , Tian Fuping , Hu Yu , Wang Chunmei , Lu Yuan , Yuan Huijun , Cui Guangxin
Published: September 2020

Background The perennial shrub of Calligonum mongolicum is a dominant native plant in all Calligonum species, which has the largest and most widespread geographic distribution in arid deserts of northern China. Understanding the phylogenetic relationship between C. mongolicum and closely related plant species will offer guidance on the classification and identification of inter-species and their varieties. The chloroplast (cp) genome is an optimal model to decipher phylogenetic relationships and genome evolution in related plant families. In the present study, the complete cp genome of C. mongolicum was sequenced, and the characteristics were described, then the genomic structure was compared to other three Polygonaceae species.Results The cp genome of C. mongolicum was 162,124 bp in length with a quadripartite structure. A total of 131 functional genes were annotated, 14 different genes of which harbored introns and exons, 50 long repeat sequences and 244 simple sequences repeats were identified. Synonymous codon usage (SCU) analysis exhibited A/T preference, and 7 codons were identified as the optimal codons. Multivariate statistical analysis of parity rule 2, ENC-plot, and neutrality plot were combined conducted to imply natural selection as the crucial constraint in SCU bias in C. mongolicum cp genome.The phylogenetic tree showed that Rumex acetosa was the most related plant to C. mongolicum. From the comparative analysis of genomic structures, the inverted repeat regions (IRa and IRb) were less divergent than other parts and coding regions was relatively conserved than non-coding regions. Compared to other species in the Polygonaceae, the borders of IRb/SSC and SSC/IRa in C. mongolicum changed greatly. Furthermore, adaptive evolution analysis of 75 orthologous protein-coding genes indicated that only the psbK gene was under positive selection, which might be crucial in the adaptive evolution of C. mongolicum.Conclusions Our results comprehensively depicts the architecture of C. mongolicum cp genome, and will lay a vigorous foundation for further study on molecular marker selection, phylogenetic analysis, and population researches in Calligonum species.
Effect of Oral Carnosine Supplementation on Urinary TGF-β in Diabetic Nephropathy: a Randomized Controlled Trial
Authors: Siriwattanasit Narongrit , Satirapoj Bancha , Supasyndh Ouppatham
Published: September 2020

Background: Activation of the transforming growth factor beta (TGF-b) pathway is a significant contributor to the pathogenesis of diabetic nephropathy. Carnosine is an amino acid that can inhibit TGF-b synthesis. We tested the hypothesis that carnosine supplement added to standard therapy will result in reduced urinary TGF-b levels among patients with diabetic nephropathy. Methods: We randomly assigned 40 patients with diabetic nephropathy and albuminuria 30-299 mg/day to treatment with carnosine (2 g/day) or placebo for 12 weeks. Urinary TGF-b level was determined using ELISA, urine albumin was ascertained by immunonephelometric assay, and renal function and metabolic profiles were determined at baseline and during 12 weeks of active treatment. Primary outcome was decrease in urinary levels of TGF-b.Results: The 2 groups were comparable for baseline characteristics, blood pressure, urine albumin, urine TGF-b and renal function measurements. Urinary TGF-b significantly decreased with carnosine supplement (-17.8% of the baseline values), whereas it tended to increase with placebo (+16.9% of the baseline values) (between-group difference P <0.05). However, blood urea nitrogen, serum creatinine, glomerular filtration rate and other biochemical parameters remained unchanged during the study period including urinary albuminuria. Both groups were well tolerated with no serious side-effects.Conclusions: These data indicated an additional renoprotective effect of oral supplementation with carnosine to decrease urinary TGF-b level that serves as a marker of renal injury in diabetic nephropathy. Trial registration Thai Clinical Trials, TCTR20200724002. Retrospectively Registered 24 July 2020.
A direct interareal feedback-to-feedforward circuit in primate visual cortex
Authors: Siu Caitlin , Balsor Justin , Federer Frederick , Angelucci Alessandra
Published: September 2020

The mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via feedforward (FF) and feedback (FB) circuits. Several theories of hierarchical computation ascribe the bulk of the computational work of the cortex to looped FF-FB circuits between pairs of cortical areas. However, whether such corticocortical loops exist remains unclear. In higher mammals, FF projections send afferents almost exclusively to a single higher-level area. However, it is unclear whether FB projections show similar area-specificity, and whether they influence FF-projection neurons directly or indirectly. Using viral-mediated monosynaptic circuit tracing in macaque visual cortex, we find that neurons sending FF projections to a higher-level area receive monosynaptic FB inputs exclusively from that area. We also find monosynaptic FB-to-FB neuron contacts as a second motif of FB connectivity. Our results support the existence of FF-FB loops in primate cortex, and suggest that FB can rapidly and selectively influence the activity of incoming FF signals.
Current laboratory and clinical practices in reporting and interpreting anti-nuclear antibody indirect immunofluorescence (ANA IIF) patterns: results of an international survey. 
Authors: Hoovels Lieve Van , Broeders Sylvia , Chan Edward K.L. , Andrade Luis , Cruvinel Wilson de Melo , Damoiseaux Jan , Viander Markku , Herold Manfred , Coucke Wim , Heijnen Ingmar , Bogdanos Dimitrios , Calvo-Alén Jaime , Eriksson Catharina , Kozmar Ana , Kuhi Liisa , Bonroy Carolien , Lauwerys Bernard , Schouwers Sofie , Lutteri Laurence , Vercammen Martine , Mayer Miroslav , Patel Dina , Egner William , Puolakka Kari , Tesija-Kuna Andrea , Shoenfeld Yehuda , de Sousa Maria José Rego , Hoyos Marcos Lopez , Radice Antonella , Bossuyt Xavier
Published: September 2020

BackgroundThe International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) has recently proposed nomenclature in order to harmonize ANA indirect immunofluorescence (IIF) pattern reporting. ICAP distinguishes competent-level from expert-level patterns. A survey was organized to evaluate reporting, familiarity, and considered clinical value of ANA IIF patterns. MethodsTwo surveys were distributed by European Autoimmunity Standardization Initiative (EASI) working groups, the International Consensus on ANA Patterns (ICAP) and UK NEQAS to laboratory professionals and clinicians. Results438 laboratory professionals and 248 clinicians from 67 countries responded. Except for dense fine speckled (DFS), the nuclear competent patterns were reported by >85% of the laboratories. Except for rods and rings, the cytoplasmic competent patterns were reported by >72% of laboratories. Cytoplasmic IIF staining was considered ANA positive by 55% of clinicians and 62% of laboratory professionals, with geographical and expertise-related differences. Quantification of fluorescence intensity was considered clinically relevant for nuclear patterns, but less so for cytoplasmic and mitotic patterns. Combining IIF with specific extractable nuclear antigens (ENA)/dsDNA antibody testing was considered most informative. Of the nuclear competent patterns, the centromere and homogeneous pattern obtained the highest scores for clinical relevance and the DFS pattern the lowest. Of the cytoplasmic patterns, the reticular/mitochondria-like pattern obtained the highest scores for clinical relevance and the polar/Golgi-like and rods and rings patterns the lowest. ConclusionThis survey confirms that the major nuclear and cytoplasmic ANA IIF patterns are considered clinically important. There is no unanimity on classifying DFS, rods and rings and polar/Golgi-like as a competent pattern and on reporting cytoplasmic patterns as ANA IIF positive.
Teaching Prenatal Care via Hybrid Simulation: A Descriptive Study at Hassan First University in Morocco
Authors: Changuiti Omaima , Chergaoui Samia , Marfak Abdelghafour , Gantare Abdellah , Saad Elmadani , Hilali Abderraouf , Youlyouz-Marfak Ibtissam
Published: September 2020

Introduction: The training of health professionals requires special attention because it has a direct impact on human life where error is intolerable. The projection of theoretical knowledge in a practical environment is an indispensable step in learning which requires the mobilization of innovative teaching methods. This paper reports impacts of hybrid simulation in prenatal consultation on the learning of midwifery students in initial training.Materials and methods: In order to assess simulation’s impact on the acquisition of technical and non-technical skills in initial training of midwives, A descriptive study was carried out using pre-tests, post-tests and evaluation grids during the hybrid simulation of prenatal consultation session, after dividing the sample into 2 groups; experimental and control group. All statistical analyzes for this study were done with SPSS software. The pair comparisons were carried out by the Wilcoxon test with a significance level =0.05.Results: There was a significant improvement in the results of the post-simulation tests when compared to the results of the pre-simulation tests for both groups. It was noticed a significant increase in mean score from the first simulation session (25.23  6.32) to a repeated simulation session (36.38  3.77; p<0.0001).Conclusion: Experiencing of a prenatal consultation hybrid simulation for first year midwifery students at the Higher Institute of Health Sciences in Morocco demonstrated its effectiveness and importance in midwifery learning. It is necessary to integrate simulation in Moroccan midwifery and nursing education in order to standardize their curriculum according to the international guidelines.
Analysis of Factors Influencing the Network Teaching Effect of College Students in a Medical School During the COVID-19 Epidemic
Authors: Yu Liang , Huang Long , Tang Hao-ru , Hu Die , Feng Wen-yu , Shi Liu-xia
Published: September 2020

Background: The purpose of this study is to understand the influencing factors of Chinese college students’ satisfaction with online teaching and psychological pressure on learning during the novel coronavirus epidemic.Methods: We assessed the effect of online teaching of 7084 medical students from wannan medical college in March 5 to April 2, 2020 using cluster sampling. The respondents were asked to complete a 7-item self-compiled online teaching satisfaction questionnaire. Chi-square test and multivariate logistic regression analysis are used.Results: Gender is female (OR=1.257, 95%CI: 1.132~1.396), grades are second and third grades (second grades:OR=1.228, 95%CI: 1.080~1.397; third grades: OR=1.197, 95%CI: 1.048~1.367), normal/unfamiliar learning platform operation (OR=3.692, 95%CI: 3.321~4.103) were risk factors for satisfactory teaching effect. In addition, students whose school year system is four-year (OR=0.870, 95%CI: 0.781~0.969) and grade 4 and above (OR=0.594, 95%CI: 0.485~0.727) were more satisfied with the teaching effect of teachers. And, during the period of the COVID-19 epidemic, the risk factors for college students to have psychological stress were: female (OR=1.258, 95%CI: 1.096~1.442), from rural areas (OR=1.511, 95%CI: 1.312~1.740), and the academic year system is four-year system (OR=1.191, 95%CI: 1.028~1.380), using mobile phones and other learning tools (OR=1.388, 95%CI: 1.205~1.600), general/unfamiliar with learning platform operations (OR=2.273), 95%CI: 1.888~2.735). While the protective factors for college students’ psychological stress included: grade three and four and above (OR=0.463, 95%CI: 0.387~0.554; OR=0.232, 95%CI: 0.187~0.286), and they think that the teaching effect is satisfactory (OR=0.314, 95%CI: 0.261~0.379).Conclusion: This survey shows that compared with male college students, female college students were more dissatisfied with the teaching effect of teachers and havd greater psychological pressure on learning. Psychological counseling should be strengthened for students in rural areas and those who were not familiar with the operating platform to relieve their psychological pressure on learning.
Different Morphs of Heterostylous Plant (Tirpitzia Sinensis) Associated With Floral Characters Have Various Adaptation Strategies to Pollinator to Ensure Reproductive Success
Authors: Hu Demei , Chen Yan , Xiang Mengda , Tang Hanqing , Tang Xiaoxin , Wang Xiaoyue
Published: September 2020

Background: Heterostylous plants are commonly associated with pollinators promoting disassortative pollination. How different morphs adapt to pollinators to ensure reproductive success and whether floral characters (such as pistil, stamen and nectar traits) are relevant to this process remain unclear. Results: Tirpitzia sinensis is distylous flowers. Its floral characters were measured. Field observation of effective pollinator and pollination efficiency to different morphs was conducted, and breeding systems were examined by hand pollination treatments. Our results showed that L-morph produced more but smaller pollen grains per anther than S-morph. T. sinensis secreted more nectar at night as a possible adaptation to hawkmoths (Macroglossum spp.) active at dusk. L-morph produced much nectar due to its large secretion volume at night. The nectar was rich in sucrose. The sucrose/hexose ratio was higher in the nectar of S-morph than in that of L-morph. S-morph had higher visit rate but lower pollination efficiency of hawkmoths compared with L-morph. T. sinensis was self-incompatible. Seed sets in nature did not differ between morphs. Conclusions: Our findings suggest that L-morph increases its pollination efficiency through outstanding stigma, many pollen grains per anther, and high amount of nectar. S-morph attracts many hawkmoths to pollinate due to its high sucrose/hexose ratio in its nectar.
Optimum utilization of antenatal and postnatal cares among young women in Tigray, Northern Ethiopia: A community based-cross sectional study
Authors: Ayele Brhane , Hadgu Tsegay , Gebretnsae Hailay , G/silassie Fanna , Negash Degnesh , Teklay Kibrom , Wubayehu Tewolde , Marra Michele , Ricceri Fulvio
Published: September 2020

Background: Optimum antenatal and postnatal care services are recognized to be among the most effective interventions to reduce maternal and newborn morbidity and mortality. However; optimum antenatal care (ANC) and postnatal care (PNC) service utilization among young women in Africa is very low, especially in rural zones. Therefore, this study was conducted to determine the magnitude of optimum ANC and PNC services utilization and the factors associated, in the Eastern Zone of Tigray, Northern Ethiopia. Methods: Using a cross-sectional study design, 352 young women aged 15 to 24 were interviewed. Among those, 101 and 100 were eligible and included for studying optimum ANC and PNC service utilization, respectively. Multivariable logistic regression models were performed to identify independent determinants of the two outcome variables (optimum ANC and PNC utilization). Results: Optimum ANC and PNC services utilization was reached in 75% (95%CI: 64.50-84.20) and 16% (95%CI: 9.00-24.00) of the cases, respectively. Being older (20-24 years old vs. 18-19: AOR=9.21; 95% CI: 1.62-52.25) and knowing the availability of adolescent and youth friendly health service (AYFHS) (AOR= 4.01; 95% CI: 1.08-14.89) were significantly associated with optimum ANC service utilization. Furthermore; knowing the availability of AYFHS (AOR=10.81; 95%CI: 1.57-71.18) and having the right to decide about her own health care spending (AOR=6.16; 95%CI: 1.22-31.05) were significantly associated with optimum PNC service utilization. Conclusion: In rural zones in Tigray, PNC services utilization is far away from the optimum, while ANC service utilization is closer, even if a significant number of young women did not receive optimum ANC services. The presence of an AYFHS and its knowledge are shown to be related to an increase of optimal services utilization and hence interventions need to be designed accordingly.
The role of CENPO expression in the progression of non-small cell lung cancer
Authors: Yang Yanlong , Chen Xiaobo , Sun Hongwen , Yu Qinghe , Yin Fang , Hu Zaoxiu , Sun Yongmeng , Pu Lisha , Zhu Xinming , Li Shen , Zhao Yunping
Published: September 2020

Background: The role of Centromere protein O (CENPO) in the development of non-small cell lung cancer (NSCLC) is unknown. This study aimed to investigate the potential roleof CENPO in the development of NSCLCMethods: The expression level of CENPO was investigated in both tissues and cell-lines. Celigo cell counting assay, wound-healing assay, Transwell assay and Flow cytometry was used to explore the effect of CENPO on proliferation, migration, invasion, apoptosis and cell cycle of NSCLC. The potential mechanism of CENPO was explored by Human Apoptosis Antibody, also, western blot was conducted to detect the expression of PI3K/Akt/mTOR pathway and cell-cycle related protein (mTOR, P-mTOR, CDK1, CDK6 and PIK3CA). Besides, the effect of CENPO on the growth of NSCLC solid tumors was demonstrated in vivo.Results: Our study suggested CENPO gene overexpression in NSCLC. Reduced CENPO expression substantially decreased the proliferation, migration and invasion ability, and promoting apoptosis and induces cell cycle arrest of NSCLC cell-lines. Preliminary mechanism research suggested reduced CENPO could active apoptosis pathway, suppressing PI3K/AKT/mTOR pathway and down-regulation cell-cycle related proteins.Conclusion: CENPO was up-regulated in NSCLC and played an important role in promoting the progress of NSCLC.
Prevalence and Correlates of Maternal Early Stimulation Behaviors during Pregnancy in Northern Ghana: A Cross-Sectional Survey
Authors: Mackness Jessica , Gallis John A , Owusu Raymond Kofi , Ali Mohammed , Abubakr-Bibilazu Safiyatu , Adam Haliq , Aborigo Raymond , Awoonor-Williams John Koku , Lillie Margaret , McEwan Elena , Hembling John , Vasudevan Lavanya , Baumgartner Joy Noel
Published: September 2020

Background: Per UNICEF’s Nurturing Care Framework, early child development (ECD) begins during pregnancy and many lower-resource settings need data to inform their programs for optimal child development. The maternal-fetal relationship can be partly examined via a series of bonding activities called early stimulation behaviors (ESB). This study describes early stimulation behaviors and the associated correlates among pregnant women in Ghana. Methods: This cross-sectional study used data from a cluster randomized trial in two districts of Northern Ghana. A total of 374 pregnant women were enrolled at baseline and administered a pre-intervention survey. Communication-related early stimulation behaviors were the primary outcome and was evaluated using three maternal-fetal bonding activities; did the woman self-report touching and/or talking, singing, and talking to her belly about family. A generalized estimating equation modified Poisson model was used for the bivariate and multivariable analysis.Results: About half of the participants reported performing communication-related ESB during pregnancy frequently or sometimes. Bivariate analysis revealed that negative life experiences including higher rates of emotional, physical and sexual intimate partner violence (IPV) and having moderate to severe depressive symptoms were associated with women performing early stimulation behaviors more often. In the multivariable model, physical intimate partner violence remained significantly associated with early stimulation behaviors. Conclusion: Research on early stimulation behaviors is still in a nascent phase. It is unclear why our results revealed an association between intimate partner violence and early stimulation behaviors; this could reflect a coping mechanism for the expectant mother. Further research is needed to better understand this association and explore potential long-term impacts of early stimulation behaviors during pregnancy on child development.Trial registration: Clinical Trials # NCT03665246, September 11, 2018
Sleeping Habits Amongst Riyadh Children: A Cross-Sectional and Validation Study
Authors: Al-Khudhairy May Wathiq , Al-Sufyani Sarah M , Al-Otaibi Hadeel T , Mahjoub Randa A , Al-Shehri Asma H
Published: September 2020

Background: To validate the Arabic translation of the Children’s Sleep Habit Questionnaire and determine the behavioral prevalence of sleep habits amongst school aged children in Riyadh, Saudi Arabia. Methods: This prospective cross sectional study involved a Linguistic validation involving 50 bilingual parent participants in each of the Arabic and English Surveys, with a cross sectional pilot involving 1546 parent participants regarding their children’s Sleeping Habits. The Children’s Sleep Habit Questionnaire was distributed via Survey Monkey and subjected to IBM-SPSS statistics. Parents of 1546 school aged children ranging from 3 years to 12 years of age completed the survey.Results: The Total score of all domains ranged between 11 and 70. Mean Score of 35-37 in 11 % of this population. The Children’s Sleep Habit Questionnaire scores were High in comparison to the Owen’s article; greater research is needed to determine the underlying causes of the increased likelihood of sleep disorders.Conclusion: Our findings, especially in sleep anxiety are alarming and warrant for more research to determine underlying causes of the more prevalent sleep disorders (Sleep Anxiety) and any other apparent or possible causes for sleep disturbances amongst children.
Efficacy and Safety of Insulin Glargine in Patients With Acute Stroke and Hyperglycemia Receiving Intensive Care: Randomized Controlled Study
Authors: Tang Sung-Chun , Shih Shyang-Rong , Lin Shin-Yi , Chen Chih-Hao , Yeh Shin-Joe , Tsai Li-Kai , Yang Wei-Shiung , Jeng Jiann-Shing
Published: September 2020

Background: This pilot study compared the basal–bolus regimens of long-acting insulin glargine (IG) and neutral protamine Hagedorn (NPH) insulin in efficacy and safety in acute stroke patients with hyperglycemia receiving intensive care (NCT02607943).Methods: This was a randomized, open-label, clinical trial. Stroke patients who were admitted to the intensive care unit within 72 h of onset and met the inclusion criteria were enrolled. They received either IG or NPH with added short-acting prandial regular insulin over a 72-h period. The primary endpoints were the percentage of glucose within the range of 80 to 180 mg/dL and the percentage of glucose reduction compared with pre-randomization glucose levels, assessed through continuous glucose monitoring (CGM).Results: A total of 50 patients were included, 26 and 24 were randomly assigned to the IG and NPH, respectively. The participant baseline characteristics were comparable between groups, except the IG had a significantly higher glucose level pre-randomization than the NPH (290.69 ± 82.31 versus 246.04 ± 41.76 mg/dL, P = .021). CGM data showed that the percentage of time with glucose levels between 80 and 180 mg/dL was 45.88 ± 27.04% in the IG and 53.56 ± 22.89% in the NPH (P = .341) and the percentage of glucose reduction was 31.47 ± 17.52% in the IG and 27.28 ± 14.56% in the NPH (P = .374). The percentage of time with hypoglycemia (< 60 mg/dl) was 0.14 ± 0.49% in the IG and 0.47 ± 1.74% in the NPH (P = .361). Parameters representative of glucose variabilities, and poststroke outcomes were not significantly different between the groups.Conclusions: Our study results suggest that early initiation of an IG-based basal–bolus regimen is safe and equally effective as an NPH-based basal-bolus regimen for patients with acute stroke and hyperglycemia requiring intensive care.Trial registration: ClinicalTrials.gov, NCT02607943. Registered 18 Nov 2015, https://clinicaltrials.gov/ct2/show/NCT02607943
Barriers and Challenges Affecting Parents Use of Adrenaline Auto-Injector in Children at Risk of Anaphylaxis
Authors: Elghoudi Ahmed , Dhaheri Klithem Al , Narchi Hassib
Published: September 2020

Background: Anaphylaxis is a life-threatening condition. As accidental exposure to the offending allergens usually happens in the community, in absence of medical personnel, adrenaline auto-injector (AAI), carried by parents, remains the first and only drug of choice. As studies have shown that AAI is commonly underused by parents, this study was undertaken to elucidate the causes of its underutilization in our community.Methods: A cohort of parents attending the paediatric allergy clinic at Al Ain hospital, in the United Arab Emirates (UAE), completed a questionnaire survey aimed to assess their understanding and knowledge of their child’s allergy management, including their aptitude with the use the AAI, as well as their competence and comfort to provide this treatment in an emergency. Results: A total of 47 parents, 83% of whom were Emirati, including 66% of mothers, participated in the study. Food allergy was the main indication for AAI prescription, with tree nuts 62%) and peanuts (38%) being the main culprits. The majority (94%) of parents were trained by a doctor on using the AAI, with most (79%) demonstrating a good knowledge of indications for administering the AAI. Although all parents expressed satisfaction with the training that they had received, they still admitted to a remaining lack of confidence with using an AAI. Conclusions: The continuous education and training of parents on how to use an AAI, still requires supplementary psychological support to overcome their fear and anxiety with using the device in an urgent situation. More research is needed to explore the reasons behind their fear and anxiety to plan effective interventions.
Drug-Induced Cell Viability Prediction from LINCS-L1000 through WRFEN-XGBoost Algorithm
Authors: Lu Jiaxing , Chen Ming , Qin Yufang
Published: September 2020

BackgroundDifferent cell lines have different perturbation signatures under the action of specific compounds. Based on these perturbation signatures, it is very important to predict the cell viability and explore the biological molecular mechanism of action hidden under the phenotype. In the process of testing drug responses to the cancer, traditional experimental methods have been greatly hampered by the cost and sample size. At present, the public availability of large amounts of gene expression data makes it a challenging task to use machine learning methods to predict the drug sensitivity.ResultsIn this study, we developed the WRFEN-XGBoost cell viability prediction algorithm based on the LINCS-L1000 perturbation signatures. We integrateed the LINCS-L1000, CTRP and Achilles datasets and adopted a weighted fusion algorithm based on random forest and elastic net for key gene selection. Then, we combined the FEBPSO-XGBoost algorithm to predict the cell viability under the drug induction. Compared to other methods, our model achieved good results with 0.83 Pearson correlation. At the same time, we completed the drug sensitivity validation on the NCI60 and CCLE datasets, which further demonstrated the effectiveness of our method. ConclusionsOur results indicated that the proposed method could provide help to find the effective anti-cancer drugs and contributed to the medical research.
Cryo-EM structure of an activated GPCR-G protein complex in lipid nanodiscs
Authors: Wagner Gerhard , Zhang Meng , Gui Miao , Wang Zi-Fu , Gorgulla Christoph , Yu James , Sun Zhen-Yu , Klenk Christoph , Merklinger Lisa , Morstein Lena , Hagn Franz , Plückthun Andreas , Brown Alan , Nasr Mahmoud , Wu Hao
Published: September 2020

G protein coupled receptors (GPCRs) are the largest superfamily of transmembrane proteins and the targets of over 30% of currently marketed pharmaceuticals. Although several structures have been solved for GPCR-G protein complexes, structural studies of the complex in a physiological lipid membrane environment are lacking. Here, we report cryo-EM structures of lipid bilayer-bound complexes of neurotensin, neurotensin receptor 1, and Gai1b1g1 protein in two conformational states, resolved to 4.1 and 4.2 Å resolution. The structures were determined in lipid bilayer without any stabilizing antibodies/nanobodies, and thus provide a native-like platform for understanding the structural basis of GPCR-G protein complex formation. Our structures reveal an extended network of protein-protein interactions at the GPCR-G protein interface compared to in detergent micelles, defining roles for the lipid membrane in modulating the structure and dynamics of complex formation, and providing a molecular explanation for the stronger interaction between GPCR and G protein in lipid bilayers. We propose a detailed allosteric mechanism for GDP release, providing new insights into the activation of G proteins for downstream signaling.
The Epidemiological and Spatio-temporal Characteristics of 2019 Novel Coronavirus Diseases (COVID-19) in Libya
Authors: Daw Mohamed A , El-Bouzedi Abdallah H , Ahmed Mohamed O
Published: September 2020

Background: COVID-19 is a global pandemic that affected all aspects of life. Studies on understanding the geographical and epidemiological characteristics become particularly important in controlling the spread of the pandemic. Such studies are lacking in Northern African countries particularly in Libya, which considered being, the second largest country in Africa with the longest coast facing Europe. The objectives of this study are to; determine the epidemiological parameters and spatiotemporal patterns of COVID-19 in this large country and outline the needed strategies to contain the spread and the consequences of the pandemic. Methods: This comprehensive study included all the confirmed cases of COVID-19 since its emergence in Libya, from early April 2020 until August 31th. The epidemiological characteristics of COVID-19 were analyzed and the spatial dynamic trends were explored. A region -based counts of weekly reported cases were used to characterize and quantify the spatial dynamics of COVID-19. Results: A total 3695 of confirmed cases of OVID-19 were collected, 2515(68.1%) were males and 1180(31.9%) female with a male-to-female(M:F) ratio 2.1:1. Aged between 2 -78 years old. Older age patients infected with COVID-19 are at higher severity and mortality. A broad geographic variability and Spatiotemporal spread variation of the COVID-19 pandemic in Libya was observed. Indicating a higher significant increase of COVID-19 from the middle of July particularly in the West and Southern regions although it was consistently observed in Meddle and Southern regions. Conclusion: Evaluating the epidemiological data and the spatiotemporal dynamic trends of COVID-19 at early stages are particularly important in understanding the pandemic spread. These parameters are essential in designing effective prevention and control programs aimed at reducing the impact of COVID- 19 pandemic particularly in countries with limited resources.
Cobalt-Catalyzed Diastereo- and Enantioselective Allyl Addition to Aldehydes and α-Ketoesters through Allylic C–H Functionalization
Authors: Zhang Haiyan , Huang Jun , Meng Fanke
Published: September 2020

Catalytic reactions that can generate nucleophilic allyl–metal intermediates directly from simple alkenes without prefunctionalization, and ones that produce various homoallylic alcohols diastereo- and enantioselectively are of great importance in organic synthesis. Transformations that accomplish these two tasks simultaneously are in high demand, particularly if the catalysts, substrates and reagents are inexpensive and easy to access. Here we report a catalytic process that chemoselective formation of nucleophilic allyl–cobalt complexes through oxidative allylic C–H cleavage of alkenes followed by site-, diastereo- and enantioselective addition to aldehydes and α-ketoesters. The enantioenriched products that are otherwise difficult to access are obtained in up to 96% yield, with >95:5 dr and 98:2 er. The cobalt-based catalyst is derived from a commercially available chiral phosphine ligand. The utility of the method is demonstrated through enantioselective formal synthesis of lithospermic acid and total synthesis of dihydrodehydrodiconiferylalcohol.
Radiation Induced Checkpoint Immunotherapy Response in Refractory Colorectal and Pancreatic Adenocarcinoma
Authors: Parikh Aparna , Szabolcs Annamaria , Allen Jill , Clark Jeffrey , Wo Jennifer , Thel Hannah , Hoyos David , Mehta Arnav , Arshad Sanya , Lieb David , Drapek Lorraine , Blaszkowsky Lawrence , Giantonio Bruce , Weekes Colin , Zhu Andrew , Goyal Lipika , Nipp Ryan , Dubois Jon , Seventer Emily van , Foreman Bronwen , Matlack Lauren , Ly Leilana , Meurer Jessica , Hacohen Nir , Ryan David , Yeap Beow , Corcoran Ryan , Greenbaum Benjamin , Ting David , Hong Theodore
Published: September 2020

Immune checkpoint blockade has limited efficacy in microsatellite stable (MSS) colorectal (CRC) and pancreatic (PDAC) cancer. Preclinical models have demonstrated the use of radiation to activate the innate immune response and stimulate responsiveness to immune checkpoint blockade. Here, we describe a Phase 2 trial of radiation therapy combined with combined anti-CTLA4 (ipilimumab) and anti-PD1 (nivolumab) antibodies in MSS CRC and PDAC. In the per protocol analysis disease control rate was 37% (10/27) in CRC and 29% (5/17) in PDAC with an overall response rate of 15% (4/27) and 18% (3/17), respectively. Whole exome and RNA sequencing of biopsies from 17 patients revealed low tumor mutational burden in all tumors, but a notable upregulation of interferon stimulated genes with concordant high expression of multiple repeat RNA transcripts in responders. Altogether, this study provides foundational human proof of concept of radiation with combination immune checkpoint blockade therapy in otherwise immunotherapy resistant cancers.
Circular RNA circZNF652 is overexpressed in osteoarthritis and positively regulates LPS-induced apoptosis of chondrocytes by upregulating PTEN
Authors: Yuan Xuefeng , Zhang Yingchi , Cai Cong , Liu Chaoxu , Xie Jie , Yi Chengla
Published: September 2020

Background
Circular RNA circZNF652 promotes LPS-induced inflammation, which contributes to the development of osteoarthritis (OA), indicating the potential involvement of CRNDE in OA. This study was carried to explore the involvement of circZNF652 in OA.
Methods
RT-qPCR was performed to analyze the expression of circZNF652 and PTEN mRNA in synovial fluid samples from 60 OA patients and 60 healthy controls. Correlations between circZNF652 and PTEN mRNA were analyzed by Pearson’s correlation coefficient. Overexpression and siRNA silencing of circZNF652 were achieved in chondrocytes, followed by performing RT-qPCR and Western blot to analyze the expression of PTEN. The role of circZNF652 and PTEN in regulating the apoptosis of chondrocytes induced by LPS was analyzed by cell apoptosis assay.
Results
We found that circZNF652 was overexpressed in OA and positively correlated with PTEN mRNA. In chondrocytes, circZNF652 overexpression increased the expression of PTEN, and circZNF652 siRNA silencing decreased the expression of PTEN. Moreover, circZNF652 and PTEN positively regulated the apoptosis of chondrocytes induced by LPS. PTEN overexpression reversed the inhibitory effects of circZNF652 siRNA silencing on cell apoptosis.
Conclusion
CircZNF652E is overexpressed in OA and positively regulates LPS-induced apoptosis of chondrocytes by upregulating PTEN.
Common Causes and Characteristics of Adverse Drug Reactions in Older Adults: A Retrospective Study
Authors: Woo Seong-Dae , Yoon Jiwon , Doo Go-Eun , Park Youjin , Lee Youngsoo , Lee So-Hee , Lee Young-Hee , Ye Young-Min
Published: September 2020

Background Aging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥ 65 years) in comparison to younger individuals (< 65 years).Methods Of 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. Subjects exposed to major culprits were extracted from cohorts transformed to the Observational Medical Outcomes Partnership Common Data Model during the study period.Results In total, 4,152 (22.0%) ADRs were reported for 3,437 older adults (mean age, 74.6 years and 57.3% female). Tramadol (rate ratio, 1.32; 95% confidence interval [CI], 1.21–1.44; P < 0.001) and fentanyl (1.49, 1.16–1.92, P = 0.002) posed higher risks of ADRs in the older adults, whereas nonsteroidal anti-inflammatory drugs (NSAIDs) (0.35, 0.30–0.40, P < 0.001) and iodinated contrast media (ICM) (0.82, 0.76–0.89, P < 0.001) posed lower risks. Ratios of serious ADRs to NSAIDs (odds ratio, 2.16; 95% CI, 1.48–3.15; P < 0.001) and ICM (2.09, 1.36–3.21, P = 0.001) were higher in the older adults than in the younger patients. Analgesics primarily elicited cutaneous ADRs in the younger patients and gastrointestinal reactions in the older adults. ICM more commonly led to anaphylaxis in the older adults than the younger patients (3.0% vs. 1.6%, P = 0.019).Conclusion For early detection of ADRs in older adults, better understanding of differences in the causes and characteristics thereof in comparison to the general population is needed.
Family Planning Utilization at First Sexual Initiation and Associated Factors among High School Youth Female Students in Northern Ethiopia
Authors: G/Slassie Tsega , Fisseha Girmatsion , G/Slassie Measho , Hagos Tigst
Published: September 2020

Background: In developing, countries young women have little awareness about safe sex practice and do casual sexual activities. The consequences such as teenage and unplanned pregnancy and birth, unsafe abortion, miscarriages, and maternal deaths due to unsafe sex practice make youth sexuality much more serious and common in developing countries. Therefore, this study aimed to assess family planning, utilization at first sexual initiation, and associated factors among high school youth female students in Alamata, Tigray, Northern Ethiopia. Methods: An institution-based cross-sectional study was employed in Alamata town, south Tigray region, Ethiopia from June 01-30, 2019. A Self-administered structured questionnaire was used to collect the data. Data were entered and analyzed using SPSS statistical package version 22. Descriptive statistics, bivariate and multivariable logistic regressions were used to assess the factor associated with family planning utilization at first sexual initiations.Results: A total of 538 youths female who initiated sexual activities with an average age of 18.2+1. 6 years participated in this study. More than half of youths 297 (55.2%) were grades 9-10 and 283 (52.6 %) were living with both their mother and father. About 122 (22.7%) of youths used family planning methods at their sexual debut. The most common methods used were emergency contraceptive pills 90 (73.8%) and male condom 32 (26.2%). For those who start sexual activities without using family planning, 42 (7.8%) experienced unwanted pregnancy. Students those who got >100birr monthly pocket money were 88% less likely to use a family planning method at first sex [AOR 0.124CI 95% (0.05-0.32)] and regards to religion students categorized as other religions were more likely to use family planning methods [AOR 1.67 CI 95% (1.17-2.57)].Conclusions: Most youth females are not using family planning at first sexual debut. This might expose them to different reproductive health problems. Therefore, an active effort to promote sexuality education and family planning use is recommended at the high school level.
High-Fidelity Simulation of Critical Deterioration Events in Pediatric Patients: A Learning Needs Assessment
Authors: Lee Jung , Lin Jainn Jim , Hsia Shao Hsuan , Huang Jing Long , Chiu Cheng Hsun , Lin Min Huey , Chuang Cheng Keng
Published: September 2020

BackgroundWe introduced high-fidelity simulation (HFS) using mannequins to teach pediatric residents about critical deterioration events (CDE; respiratory failure, circulatory shock, or both) in pediatric patients over a 1-year period. For an effective HFS program, a learning needs assessment is required. We assessed pediatric residents’ knowledge, attitudes, and perceptions of the new learning tool.MethodsA 20-item paper-based questionnaire survey was completed by pediatric residents of a tertiary medical center who participated in the HFS program.ResultsThirty-four (85%) of 40 pediatric residents responded to the survey. Their mean age was 29.35 ± 1.25 years, and 10 (29.4%) were male. The primary learning objective was the acquisition of technical skill. However, the residents considered HFS helpful for the acquisition of both technical and non-technical skills. A questionnaire with a seven-point Likert scale (1–7) was used to assess resident attitudes toward the HFS. The residents scored highly for active engagement with the HFS (mean score, 5.32 ± 1.45) and reported moderate stress levels (mean score, 4.35 ± 1.27). The residents (n = 34) considered HFS training before encountering a real patient with a similar presentation helpful (mean score, 6.32 ± 0.58), and also considered its future use for improving the management of CDE in pediatric patients important (mean score, 6.41 ± 0.7). The main barrier to HFS session attendance was lack of time (76.5%, n = 26).ConclusionsHFS is helpful for residents learning about CDE in pediatric patients, and should be integrated into their training curriculum. Sufficient time is needed for effective HFS learning.
Psychological and behavioral responses of nursing interns from 12 Chinese universities during the COVID-19 epidemic: a knowledge, attitude and practice survey
Authors: Chen Ying , Zhang Hailin , Xu Yuzi , Xu Fengqin , Wang Yinhe , Cao Yang
Published: September 2020

Background: Coronavirus disease 2019 (COVID-19) has spread globally and resulted in the COVID-19 pandemic worldwide. To depict the psychological and behavioral responses, and knowledge of nursing interns who are facing the COVID-19 epidemic in China, we conducted a knowledge, attitude, and practice (KAP) survey using a convenience sample in the First People’s Hospital of Lianyungang, Kangda College of Nanjing Medical University, Jiangsu Province, China.Methods: A combination of a face-to-face questionnaire survey and an online survey was used for nursing interns from 12 Chinese universities. The Symptom Checklist 90 was used to investigate anxiety and depression of the nursing interns during the COVID-19 epidemic. Self-designed questionnaires were used to investigate behavioral responses, COVID-19-related knowledge, and preventive measures.Results: During the COVID-19 epidemic, the mean score of anxiety of 237 surveyed nursing interns were not statistically significantly different with that of the Chinese norm (1.42 vs. 1.39, P = 0.354). However, the mean score of depression of them were lower than that of the Chinese norm (1.22 vs. 1.50, P < 0.001). However, no statistically significant difference in the anxiety or depression was found between demographic subgroups. The most common way for the nursing interns to seek for help was asking for instructor or other medical professionals (89.45%). When the nursing interns had suspected symptoms, they will most likely go to the hospital for treatment (97.89%). The nursing interns have good knowledge regarding the origin and prevention of COVID-19 (correct percentage > 94%), however less knowledge regarding treatment and incubation (correct percentage < 10%).Conclusion: The nursing interns showed relative lower depression in the face of COVID-19 public health emergencies, and took proper preventive measures during the epidemic, however, were lack of certain epidemiology knowledge about COVID-19.