bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Modelling of nsSNPs in GABRA2 Gene in Epilepsy and Study of Their Impact On Structure and Stability of GABRA2 Protein
Authors: Agha Zehra , Azam Maleeha , Faryal Bushra 
Published: November 2021

Abstract
Epilepsy is a neurological condition characterized by abrupt, unprovoked, and recurrent seizures that are unpredictable in frequency. The objective of this analysis was to identify novel non-synonymous polymorphisms in the GABRA2 gene and determine their effect on protein structure and stability. Most pathogenic/deleterious nsSNPs were predicted using six different bioinformatic tools. Mutpred2, Mupro was used to check the impact of identified nsSNPS on protein structure and stability. The pathogenic score of SNPs was predicted using the FATHMM tool. The CONSURF webserver was used for conservation analysis of pathogenic SNPs.3-D structure of the protein was realized using SWISS-MODEL and residue position in protein visualized by Lite Mol. GeneMANIA and STRING databases were used to predict the function of interlinked gene interactions. Out of 228 nsSNPs retrieved from the dbSNP database, we identified a novel missense variant, F285S (rs41310789), as most deleterious and its possible association with epilepsy syndrome focal epilepsy. Stability and conservation analysis results interpret rs41310789 present in evolutionarily conserved regions of a gene and affect its structure. This analysis provides information regarding the impact of nsSNPs that might affect the structure and activity of GABRA2 protein. Thus, these coding variants should be taken into scrutiny while genetic screening of epileptic patients.
WWOX Regulates UV/Cold Shock-Mediated Calcium Influx and Nuclear Bubbling in Frostbite
Authors: Tsai Cheng-Chang , Chen Szu-Jung , Deng Wen-Ting , Liu Tsung-Yun , Lee Kuan-Ting , Lee Ming-Hui , Lin Sing-Ru , Chen Yu-An , Wang Lu-Hai , Su Li-Jen , Sheu Hamm-Ming , Chang Nan-Shan 
Published: November 2021

Abstract
UV/cold shock-mediated frostbite involves non-apoptotic nuclear bubbling cell death (BCD) and participation of functional WWOX in cells (WWOXf). In contrast, cells with WWOX deficiency or dysfunction (WWOXd) undergo pop-out explosion death (POD). Here, by time-lapse microscopy, when WWOXf cells were exposed to UV or UV/cold shock and then incubated at room temperature, these cells rapidly and sequentially underwent: 1) loss of mitochondrial membrane potential, 2) formation of a nitric oxide (NO)-containing nuclear bubble per cell, 3) WWOX-dependent increase in calcium (Ca2+) influx, 4) shutdown of mRNA and protein synthesis machinery, as determined by RT/PCR and gene chip analysis, and 5) eventual cell death without caspase activation, stress fiber formation and chromosomal DNA fragmentation. In contrast, WWOXd cells exhibited a faster kinetics of stress fiber formation, explosion and death without NO production. Ectopic WWOX restored calcium influx and nuclear bubbling in WWOXd cells. In hairless mice, UV/cold shock rapidly downregulated protein expression in the skin and then liver, which may lead to organ damages. UV/cold shock induced complex formation of antiapoptotic TRAF2 and proapoptotic WWOX and their co-translocation to the nucleus, where the complex dissociation occurred. The observations suggest that WWOX and TRAF2 dissociation is needed for nuclear bubbling and death.
Dual Targeting of FGFR3 and ERBB3 Enhances The Efficacy of FGFR Inhibitors in FGFR3 Fusion-Driven Bladder Cancer
Authors: Weickhardt Andrew J , Lau David K , Hodgson-Garms Margeaux , Lavis Austen , Jenkins Laura J , Vukelic Natalia , Ioannidis Paul , Luk Ian Y , Mariadason John M. 
Published: November 2021

Abstract
Background

Mutations and fusions in Fibroblast Growth Factor Receptor 3 (FGFR3) occur in 10-20% of metastatic urothelial carcinomas and confers sensitivity to FGFR inhibitors. However, responses to these agents are often short-lived due to the development of acquired resistance. The objective of this study was to identify mechanisms of resistance to FGFR inhibitors in two previously uncharacterised bladder cancer cell lines harbouring FGFR3 fusions and assess rational combination therapies to enhance sensitivity to these agents.
Methods

Acquired resistance to FGFR inhibitors was generated in two FGFR3 fusion harbouring cell lines, SW780 (FGFR3-BAIAP2L1 fusion) and RT4 (FGFR3-TACC3 fusion), by long-term exposure to the FGFR inhibitor BGJ398. Changes in levels of receptor tyrosine kinases were assessed by phospho-RTK arrays and immunoblotting. Changes in cell viability and proliferation were assessed by the Cell-Titre Glo assay and by propidium iodide staining and FACS analysis.
Results

Long term treatment of FGFR3-fusion harbouring SW780 and RT4 bladder cancer cell lines with the BGJ398 resulted in the establishment of resistant clones. These clones were cross-resistant to the clinically approved FGFR inhibitor erdafitinib and the covalently binding irreversible FGFR inhibitor TAS-120, but remained sensitive to the MEK inhibitor trametinib, indicating resistance is mediated by alternate activation of MAPK signalling. The FGFR inhibitor-resistant SW780 and RT4 lines displayed increased expression of pERBB3, and strikingly, combination treatment with an FGFR inhibitor and the ATP-competitive pan-ERBB inhibitor AZD8931 overcame this resistance. Notably, rapid induction of pERBB3 and reactivation of pERK also occurred in parental FGFR3 fusion-driven lines within 24 hours of FGFR inhibitor treatment, and combination treatment with an FGFR inhibitor and AZD8931 delayed the reactivation of pERBB3 and pERK and synergistically inhibited cell proliferation.
Conclusions

We demonstrate that increased expression of pERBB3 is a key mechanism of adaptive resistance to FGFR inhibitors in FGFR3-fusion driven bladder cancers, and that this also occurs rapidly following FGFR inhibitor treatment. Our findings demonstrate that resistance can be overcome by combination treatment with a pan-ERBB inhibitor and suggest that upfront combination treatment with FGFR and pan-ERBB inhibitors warrants further investigation for FGFR3-fusion harbouring bladder cancers.
Alteration Functional and Effective Connectivity Between Visual and Attention-Networks in Cognitively Impaired Patients With Temporal Lobe Epilepsy
Authors: Jiang Yanchun , Zhang Yanbo , Nie Liluo , Liu Huihua , Zheng Jinou 
Published: November 2021

Abstract
Purpose: This paper examines the changes in functional connectivity (FC) and effective connectivity (EC) of the visual (VIS)-network and attention network (AN) in patients with cognitive impairment caused by temporal lobe epilepsy (CI-TLE) through independent component analysis (ICA) and Granger causality analysis (GCA).Material and methods: Resting-state functional magnetic resonance imaging（rs-fMRI）data and Montreal cognitive assessment（CoMA） were collected from 32 patients with CI-TLE and 29 age-matched healthy controls.Results: In the VIS network of CI-TLE patients, FC decreased in the right inferior occipital gyrus (IOG) and the left lingual gyrus (LG) and in the right temporal-parietal junction (TPJ) in the Doral attention network (DAN). FC increased in the right middle frontal gyrus (MFG) and right precuneus gyrus (PG). In the DAN, FC decreased in the left superior parietal gyrus (SPG) and right inferior parietal gyrus (LG). GCA revealed the decreased EC from the left LG to the right IOG within the VIS network and from the right inferior parietal gyrus (IPG) of the DAN to the left LG of the VIS network. In contrast, CI-TLE patients demonstrated increased EC from the right SPG to the right IPG within DAN，and from the right IPG of the DAN to the right TPJ of the VAN, and from the right TPJ to the left PG within VAN. Compared with healthy controls , Voxel-wise GCA in CI-TLE patients showed positive EC from the left LG to the right SPG. In contrast, increased EC was exhibited from the right TPJ to the right caudate. Pearson analysis showed a negative correlation between the CoMA scores and GC values from the right IPG to the right TPJ.Conclusion: The results indicate intrinsic brain network connectivity dysfunction in CI-TLE patients and the causal connection abnormality in the resting-state VIS network and AN. Also, it was found that CI-TLE patients possibly have a compensatory mechanism in the above networks. These findings shed new insights on the neuroimaging marker of CI-TLE.
The dropout rate and associated factors of the continuum of maternal health care services before and during Covid-19 Pandemic among women who gave birth in the last two years in Addis Ababa, Ethiopia, 2021. A comparative cross-sectional study design
Authors: Desta Dawit Zenamarkos , Kebede Adane , Merid Mehari Woldemariam , Negash Wubshet Debebe , Asmamaw Desale Bihonegn 
Published: November 2021

Abstract
Background
A continuum of maternal health care is the continuity of care during pregnancy, delivery, and post-delivery period. However, the dropout rate of the continuum care and factors associated with it during the COVID-19 pandemic were not well documented in the study setting. Hence, this study was used to assess the dropout rate and associated factors of the continuum of care before and during the COVID-19 pandemic.
Methods
A community-based comparative cross-sectional study was conducted among 630 women who gave birth in the last two years in Addis Ababa. An interviewer-administered questionnaires were used to collect the data. The Epi data version 4.6 and STATA version 14 statistical Softwares were used for data entry and analysis, respectively. Binary logistic regression model was used to identify associated factors of the dropout rate of a continuum of care.
Result
The dropout rate of the continuum of maternal healthcare was 58.39% (95% CI: 52.56-64.00) and 73.24% (95% CI: 67.91-77.98) before and during the covid-19 pandemic respectively. Women who had no information about PNC (AOR =1.88, 95% CI: 1.01-3.50), not received appropriate care (AOR = 3.92, 95% CI: 1.84-8.37), no information about maternal health care (AOR=2.57, 95% CI: 1.28-5.16), birth preparedness and complication readiness (AOR=0.47, 95% CI: 0.26-0.86), and had history of pregnancy-related complications (AOR=2.07, 95% CI: 1.17-3.68), were dropped out from continuum of care during the covid-19 pandemic. whereas, unplanned pregnancy (AOR= 3.35, 95% CI: 1.60-7.04), not know postpartum danger signs (AOR=1.79,95% CI: 1.03-3.12), and no information about maternal health care (AOR= 1.85, 95% CI: 1.06-3.23) were dropped out from continuum of care before covid-19 pandemic.
Conclusion
This study underscores nearly three fourth and more than half of women during and before the covid-19 pandemic dropped out from the continuum of care, respectively. Information about maternal health care, birth preparedness and complication readiness, information about PNC, and knowing postpartum danger signs were significantly associated with the dropout rate of the continuum of care. Thus, adapting policy that supports service delivery modification during such pandemic, promoting birth preparedness and complication readiness is very crucial.
Differential Gene -Based Predictors of Neoadjuvant Chemotherapy Efficacy in Breast Cancer
Authors: Lu Mei , Zou JieYa , Guo Rong , Yang XiaoJuan , Wang Ji , Zhang Qian , Deng XuePeng , Tao JianFen , Nie JianYun , Yang ZhuangQing 
Published: November 2021

Abstract
Background and objectiveChemotherapy is the most common treatment in breast cancer , and neoadjuvant chemotherapy (NAC) is wildly used because of it’s efficiency and safety. To identify significantly differentially expressed genes and select the most suitable breast cancer patients for neoadjuvant chemotherapy (NAC) before treatment. MethodsWe collected a total of 60 breast cancer patient samples before and after NAC. All the samples were subjected to high-throughput RNA sequencing (RNA-seq). Then , we identified AHNAK, CIDEA, ADIPOQ, and AKAP12 as candidate genes related to tumour chemotherapeutic resistance. Next, we analysed the expression levels of AHNAK, CIDEA, ADIPOQ, and AKAP12 by logistic regression and based on the result, we constructed a predictive model visualized by a nomogram. ResultsThe RNA-seq results show that AHNAK, CIDEA, ADIPOQ and AKAP12 are upregulated in residual disease after NAC (P<0.05), and compared with the pathological complete response (pCR) group, the non-pCR group presented high AHNAK, CIDEA, ADIPOQ and AKAP12 expression levels (P<0.05). Logistic analysis showed that high AHNAK, CIDEA, ADIPOQ and AKAP12 expression levels significantly reduced the pCR rate of NAC for breast cancer (P<0.05). In addition, our prediction model , which included AHNAK, CIDEA, ADIPOQ and AKAP12 , showed a good fitting effect with the H1 test (χ2=6.3967, P=0.4945) and the receiver operating characteristic (ROC) curve (area under the curve (AUC) 0.8249, 95% CI 0.722–0.9271). ConclusionHigh expression of AHNAK, CIDEA, ADIPOQ and AKAP12 indicates poor treatment response in breast cancer patients treated with NAC . The efficacy prediction model based on these results is expected to be a new method to select the optimal population of breast cancer patients for NAC.
A Cost-Effectiveness Analysis of Neoadjuvant Therapy for Neuroendocrine Cervical Tumors
Authors: Lin Yingtao , Chen Ying , He Haixin , Chen Jian 
Published: November 2021

Abstract
Purpose. This study aimed to assess the cost-effectiveness of neoadjuvant therapy in combination with surgery and adjuvant therapy compared with either surgery alone or surgery plus adjuvant therapy for the treatment of neuroendocrine cervical tumors (NETs). Materials and methods. A single-institution retrospective analysis of 107 patients with NETs was performed based on the new International Federation of Gynecology and Obstetrics (FIGO 2018) staging system. We divided the patients who underwent radical surgery into two groups: neoadjuvant therapy (NACT) and non-neoadjuvant therapy (non-NACT) groups. We performed subgroup analysis of overall survival and cost-effectiveness by dividing the patients with stage I-IV disease into four subgroups. An assessment was constructed to reflect the costs and effectiveness of the treatment from the perspectives of both clinical practice and health economics.Results. The NACT group had -0.45 life-years (LYs) at an incremental cost of $15197.58, compared with the non-NACT group, which means that it is not cost-effective. However, subgroup analysis of patients with stage II disease showed that the NACT group had significantly better overall survival time than the non-NACT group (median overall survival had not been reached versus 29.23 months, p＜0.001). The NACT group had an incremental cost-effectiveness ratio (ICER) of $5921.43/LY compared with the non-NACT group for stage II disease. Probabilistic sensitivity analyses showed that when the willingness-to-pay (WTP) threshold reached $31118.29/LY, which is nearly three times China's per capita GDP 2020, the probability of NACT being cost-effective was 97% versus non-NACT group in the treatment of stage II neuroendocrine tumors of the uterine cervix. Conclusion. NACT is not a cost-effective treatment strategy compared with non-NACT in the treatment of NETs, but may be a cost-effective treatment option for stage II NETs.
Time-Dependent Effects of Exposure to Nature and Perceived Behavioral Control over Social Distancing in Shared Open Spaces on Psychological Distress of Residents during Pandemic of COVID-19
Authors: Mousavinia Seyyedeh Fatemeh 
Published: November 2021

Abstract
Background: Further research into the influence of the COVID-19 epidemic on mental health is needed. Some research has highlighted the positive effects of nature exposure on mental health, as well as the importance of subjective assessments of green spaces. Methods: Considering both private and semi-public environments, the current longitudinal study examines the moderating effects of exposure to nature and perceived behavioral control over social distancing on the relationship between perceived interior crowding, social isolation, and psychological distress. Finally, it investigates whether these connections change through time. During the Iranian national lockdowns, data from 718 middle-aged women who completed an online questionnaire survey in two waves were used. Results and Conclusion: The findings of structural equation modeling back up the idea that social isolation plays a key role in the association between perceived interior crowding and psychological distress. Multi-Group Analysis revealed that exposure to nature reduced the negative effects of perceived interior crowding on psychological distress, as predicted. Nevertheless, this relationship is time-dependent and nature exposure during the time did not necessarily assist in reducing negative impacts. The current research adds to the body of knowledge by identifying perceived behavioral control as a buffer against the adverse effects of social isolation on psychological distress over time. These findings provide for a better understanding of psychological processes and could help in the promotion of design policies in the event of a pandemic.
Mapping Trends and Hot-spots of Virtual Simulation Research in Nursing: a Bibliometric Analysis
Authors: Zhang Qian , Chen Jia , Liu Jing 
Published: November 2021

Abstract
Background: Virtual simulation has been widely used in nursing education and nursing training. This study aims to characterize publications in terms of countries, institutions, journals, authors, and collaboration relationships, and analyze the trends and hot-spots of virtual simulation in nursing.Methods: Publications concerning virtual simulation in nursing were retrieved from Web of Science. Microsoft Excel 2010, VOSviewer, and Citespace were used to analyze the characteristics of this field. Results: We identified 611 papers between 1999 and 2021. The number of publications grew slowly until 2019, and got a sharp increase in 2020 and 2021. The USA, Canada and Australia were three key contributors to this field. Centennial College, University of Ottawa, and Ryerson University were three major institutions with a larger number of publications. Verkuyl M was the most productive and highest cited author. Clinical Simulation in Nursing, Nurse Education Today, Journal of Nursing Education were the three productive journals. "virtual patients," "nursing students," "clinical simulation," and "communication skills" were the frontier topics in recent years.Conclusion: Virtual patients simulated more clinical situations to train nursing students, developing more reliable and objective assessment methods to validate learning outcomes might be the recent and future hot-topics.
Effect of Mechanical Ventilation During Cardiopulmonary Bypass On End-Expiratory Lung Volume in The Perioperative Period of Cardiac Surgery
Authors: Trancart Lea , Rey Nathalie , Scherrer Vincent , Wurtz Véronique , Bauer Fabrice , Aludaat Chadi , Demailly Zoe , Selim Jean , Compère Vincent , Clavier Thomas , Besnier Emmanuel 
Published: November 2021

Abstract
Background

Many studies explored the impact of ventilation during cardiopulmonary bypass period. However, its effect on Functional residual capacity or End Expiratory Lung Volume (EELV) has not been specifically studied. Our objective was to compare the effect of two ventilation strategies during cardiopulmonary bypass (CPB) on EELV.
Methods

observational monocenter study in a tertiary teaching hospital. Adult patients undergoing on-pump cardiac surgery by sternotomy were included and ventilated on the GE Carescape R860® ventilator. Maintenance of ventilation during CPB was left to the discretion of the medical team, with division between "ventilated" and "non-ventilated" groups afterwards. Iterative per and postoperative measurements of EELV were carried out by nitrogen washin-washout technique.
Results

40 patients were included, 20 in each group. EELV was not significantly different between the ventilated versus non-ventilated groups at the end of surgery (1796±586ml vs. 1844±524ml; p=1). No significant difference between the two groups was observed on oxygenation, duration of mechanical ventilation, need postoperative respiratory support, occurrence of pneumopathy and radiographic atelectasis.
Conclusion

Maintaining mechanical ventilation during CPB does not seem to allow a better preservation of EELV in our population.
Energy-ecological Efficiency of Dual-Fuel Serie Plug-in Hybrid Electric Vehicle Considering WTW Emissions
Authors: Soares Laene Oliveira , de Moraes Danielle Rodrigues , Hernández-Callejo Luis , Boloy Ronney Arismel Mancebo 
Published: November 2021

Abstract
This paper discussed the possibility of replacing the series plug-in hybrid electric vehicle using the single-fuel spark-ignition engine (SFSIE) fuelled with gasoline A and Brazilian gasoline by the series plug-in hybrid electric vehicle fuelled with 50% bioethanol and 50% biogas in dual-fuel mode. The simulation of bioethanol, biogas and gasoline A combustion were carried out through GASEQ software to calculate the energy-ecological efficiency of the SFSIE and the dual-fuel spark ignition engine (DFSIE). The well-to-pump (WTP) emissions of the sugarcane bioethanol and biogas production pathway were evaluated through GREET software. The tank-to-wheel (TTW) emissions were determined to each series PHEV operating modes. Thus, the well-to-wheel emissions were calculated through the sum of the WTP, TTW and electricity mix emissions. The results showed that the energy-ecological efficiency for the DFSIE was 10.7% and 24.1% higher than that found for SFSIE fuelled with gasoline and Brazilian gasoline, respectively. The losses during the biogas production aggravate linearly the WTP emissions, and consequently the WTW emissions of the series PHEV. Besides that, the DFSIE presented 15.5% and 12.8 less TTW emissions than the SFSIE fuelled with gasoline A and Brazilian gasoline, respectively. Comparing to the emission standards, the DFSIE presented TTW emissions 30.5% higher than the EU emission standard by 2021. Although the DFSIE does not meet none of the emission standards, this engine mode can be an alternative to at least reduce the tailpipe emissions.
Development and Validation of a Cloak-Shaped Device for Sham Pediatric Tuina: a Randomized Controlled Study
Authors: Cai Jianxiong , Dai Lin , Yin Lingjia , Lu Taoying , Wang Li , Zhang Yongping , Zhang Huiyan , Zhu Conghao , Li Meiling , Wu Darong 
Published: November 2021

Abstract
Background: To date, no well-recognized placebo device or procedure for pediatric Tuina (PT) has been reported. We developed a cloak-shaped device and designed an RCT to detect whether the device is effective as a placebo in PT research.Methods: It was a two-arm, parallel-group RCT design. Children were randomly assigned to the genuine Tuina or sham Tuina group at a 1:1 ratio. The genuine and sham Tuina interventions were delivered using the same standardized procedure by adopting a cloak-shaped device. The primary outcomes were the judgement rates of the type of Tuina that participants received based on caregivers’ and observers’evaluations. The analysis explored whether parents' attitude towards PT was related to their judgment rate.Results: A total of 60 participants were enrolled (37 boys [61.7%]; 16.0[2.3] months). Thirty children received genuine PT, and 30 received sham PT. There was no significant difference in parents' judgment of the interventions received between the two groups (χ2=0.65,P=0.421) or based on observers' judgments (χ2=0.07, P=0.795). In terms of parents' attitude towards PT or compliance with PT, parents whose children were in the genuine Tuina group were not significantly different from those in the sham group(z=0.01, P=0.99; z=0.34, P=0.73). Of the participants in the sham group, none of their parents recorded receiving the sham intervention.Conclusions: The placebo device for sham PT was found to be a credible control for PT. This study supports its use in prospective, sham-controlled, randomized trials.Trial registration: ClinicalTrials.gov, NCT03474172. Registered in March 2018.