bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions and utilisation of complementary and alternative medicine practices among hospital patients in Bangladesh
Authors: SHAHJALAL MD. , Gow Jeffrey , Rahman Md. Ashfikur , Hossain Md. Jakir , Khan Md. Nafiul Alam , Alam Md. Sazzadul , Hossain Ahmed , Mahumud Rashidul Alam
Published: November 2021

Background Complementary and alternative medicine (CAM) has played an important role in providing universal access to essential health care services globally. Conventional medicine (CM) driven health care practices are well-developed in Bangladesh; however, millions of people utilise CAM-based healthcare services for specific health conditions or health benefits due to high out-of-pocket payment (74%) in Bangladesh, while the global average is only 32%. Lack of evidence exists about the perception and utilisation of CAM in Bangladesh. This study aimed to estimate the prevalence correlates of the perception and utilisation of CAM among patients who received health care at a tertiary hospital, Bangladesh. MethodsThis study comprised a cross-sectional study with 1,183 individuals from the cross-sectional survey among patients who received health care from Government Unani and Ayurvedic Medical College Hospital in Dhaka, Bangladesh. Logistic regression analyses were employed to estimate the adjusted effect of independent factors on CAM health care services utilisation. Results Thirty-three percent of patients utilised CAM health care services, while 67% of patients sought conventional treatment before turning to CAM. CAM health care utilisation was significantly associated with young adult patients aged 26 to 45 years (AOR=6.26, 95% CI:3.24-12.07), patients without education (AOR=2.99, 1.81-4.93), and being married (AOR=1.79, 1.08-2.97). The apparent effectiveness, lower side effects, adequate patient satisfaction, and recommendations from others were the most prevalent reasons for using CAM.ConclusionCM plays a dominant role in health care provision in Bangladesh, with high-level patient satisfaction and health benefits. These results could be valuable for health policymakers as they explore prospects for integrating CAM and conventional medical services.
RNA Binding Protein-Mediated Immunosuppressive Tumor Microenvironment Contributes to Poor Prognosis in High-Grade Gliomas
Authors: Tong Wangxia , Luo Ning , Lan Shengyong , Zhou Xinmei , Wen Xiaodong , Jiang Yuanjing , Feng Wenyong , Yang Tiantian
Published: November 2021

The abnormal expression of RNA binding proteins (RBPs) in tumors can regulate the functions of immune genes and affect immune microenvironment. The characterization of immune infiltration and its regulatory mechanism from the perspective of RBPs and RBP-regulated immune genes in high-grade gliomas were comprehensively studied by bioinformatics. Prognosis-related RBPs and associated immune genes were obtained from the cancer genome atlas database (TCGA). By clustering RBPs, the potential relationship between the different clusters of RBPs expression and immune infiltration was explored. Immune-related RBP constructs immunosuppressive microenvironment in glioma by regulating immune genes and immune-related genes. Immunosuppression was the predominant type of phenotype with poor prognosis, while immunoinflammation was the predominant type of immunoinflammatory phenotype with good prognosis. RBP can construct immunosuppressive microenvironment by regulating immunosuppressive cells and stromal activation-related factors through directly and indirectly ways. Stromal activation plays a bridging role in tumor immunosuppressive regulation. The immunophenotyp depends on different enrichment states of immune-related RBP, which can change dynamically with the change of tumor pathological grade and affect the prognosis of patients.Our study suggests glioma related RBPs can potentially establish an immunosuppressive microenvironment by regulating immune genes and immune-related genes, which can be directly affected by RBPs clusters with distinct prognosis.
Determination of the use of whey and propolis on some growth characteristics, on blood values and diarhea of the goat kids
Authors: MANAV Selda , YILMAZ Murat
Published: November 2021

This study was conducted to obtain an alternative more economical and healthier milk substitute feed by adding whey powder and propolis to cow's milk in goat kid rearing. 40 Saanen goat kids born in the same period and were divided into 4 groups 7 days after thei birth. The kids were divided into 4 groups 10 by 10 into control group (CG) who were kept together with their mothers and into experimental groups 1-2-3 (EG1,EG2, EG3) who were kept in seperate sections. Kids in all three experimental groups were fed only with the formula (cow milk+whey powder+water). In the EG2 and EG3, the kids were given 0. 4 cc and 0. 2 cc propolis respectively in addiditon of the formula once a day. Some growth and development parameters and rectal temperatures of the kids were measured once a week and morning and evening diarrhea scorings were taken in all groups. Some biochemical and hematological analyzes were performed. According to all the results obtained, the differences in the body temperatures and in the glucose and urea values among the groups were found to be significant and the other characteristics were statistically significant (P<0.05). The insignificant difference between the average growth and development parameters of the kids in the CGs in the CG was an important finding in growing kids more economically and reserving the goat milk for more profitable procedures. According to the diarrhea scores, it was observed that propolis was effective on diarrhea and it was concluded that it could be used in growing kids as a preventive measure. Feeding kids with the formula was found more economical than feeding them with mother-milk. As a result of this study, it could be suggested that the use of milk replacers containing whey and propolis will positively affect the growth, the development and the health of the goat’s kids.
Efficacy and safety of single-use flexible ureteroscope（ZebraScopeTM）for the treatment of upper urinary tract calculi ≤ 2 cm
Authors: Wang Shun , Jiang Kehua , Chen Xiaolong , Wang Qing , Liang Xiangyi , Tian Yuan , Chen Kun , Sun Fa
Published: November 2021

Purpose

To evaluate the clinical efficacy and safety of a Chinese single-use flexible ureteroscope (ZebraScopeTM) for the treatment of upper urinary tract calculi ≤2 cm based on a retrospective database.
Methods

Overall, 84 patients with upper urinary tract calculi who underwent FURS at our hospital from July, 2020 to January, 2021 were enrolled and reviewed. Demographic characteristics and perioperative data were evaluated and analyzed.
Results

We identified 84 patients: 51 male and 33 female. The mean age of the patients was(49.63±12.23)years, and the mean body mass index was༈24.44±3.62༉Kg/m2. The degree of hydronephrosis was absent, mild, moderate and severe in 24, 35, 21 and 4 patients, respectively. The average operation time was༈74.57±42.51༉min, and the average blood loss was༈5.28±4.99༉ml. The catheter retention time was༈1.71±0.99༉day and the double-J tube retention time was༈32.89±13.23༉day. The length of hospital stay was༈4.29±3.28༉day. The stone-free rate was 77.78% after 1-month, and the cost of hospitalization was ¥༈34619±8719.16༉. The overall complication rate was 4.76%. There were significant increase in leukocyte, neutrophils, and decrease in urea nitrogen, albumin and globulin after surgery (P༜0.05), while no significant difference were observed in hemoglobin and creatinine (P༞0.05).
Conclusion

The Chinese single-use ureteral flexible ureteroscope (ZebraScopeTM)can be considered effective and safe for the treatment of upper urinary tract calculi ≤ 2 cm.
Quantification of Spatial Pharmacogene Expression Heterogeneity in Breast Tumors
Authors: Powell Nicholas R , Silvola Rebecca M , Howard John S , Badve Sunil , Skaar Todd C , Ipe Joseph
Published: November 2021

Background: Chemotherapeutic drug concentrations vary across different regions of tumors and this is thought to be involved in development of chemotherapy resistance. Insufficient drug delivery to some regions of the tumor may be due to spatial differences in expression of genes involved in the disposition, transport, and detoxification of drugs (pharmacogenes). Therefore, in this study, we analyzed the spatial expression of 286 pharmacogenes in 6 breast cancer tissues using the recently developed Visium spatial transcriptomics platform to (1) determine if these pharmacogenes are expressed heterogeneously across tumor tissue and (2) to determine which pharmacogenes have the most spatial expression heterogeneity.Methods: The spatial transcriptomics technology sequences the transcriptome of 55 um diameter barcoded sections (spots) across a tissue sample. We analyzed spatial gene expression profiles of four biobank-sourced breast tumor samples in addition to two breast tumor sample datasets from 10X genomics. Results: Collectively, we identified 8887 spots in tumor regions, 3814 in stroma, 44 in lymphocytes, and 116 in normal regions based on pathologist annotation of the tissues. We showed statistically significant differences in expression of pharmacogenes in tumor regions compared to surrounding non-tumor regions. We also observed that the most heterogeneously expressed genes within tumor regions were involved in ROS handling and detoxification mechanisms. GPX4, GSTP1, MGST3, SOD1, CYP4Z1, CYB5R3, GSTK1, and NAT1 showed the most heterogeneous expression within tumor regions. Conclusions: The heterogeneous expression of these pharmacogenes may have important implications for cancer therapy due to their ability to impact drug distribution and efficacy throughout the tumor. Notably, our results suggest that chemoresistance caused by expression of GPX4, GSTP1, MGST3, and SOD1 may be intrinsic, not acquired, since the heterogeneity is not specific to chemotherapy-treated samples or cell type.
Tetramethylpyrazine Derivative T-006 Ameliorates the Amyloid-β Plagues of Transgenic Alzhermer's Mice by Modulation of TLR4-mediated MyD88/NF-κB Signaling
Authors: Chen Haiyun , Chang Xiao , Zhou Jiemei , Zhang Guiliang , Cheng Jiehong , Zhang Zaijun , Liu Zheng , Yan Chunyan
Published: November 2021

BackgroundMicroglial activation mediated neuroinflammation was considered as a vital trigger factor in the pathogenesis of Alzheimer’s disease (AD). T-006, a new tetramethylpyrazine derivative, has been recently found to alleviate cognitive deficits via inhibition of Tau expression and phosphorylation in AD transgenic mouse models. Here, we hypothesized that T-006 may ameliorate AD-like pathology by suppressing the neuroinflammation. MethodsAPP/PS1 transgenic AD mouse model was used here to evaluate the anti-inflammatory effect of T-006 and its underlying mechanisms, as well as its potential protective effects against lipopolysaccharide (LPS)-activated microglial-induced neurotoxicity.ResultsOur results indicated that T-006 significantly decreased the levels of total amyloid β peptide (Aβ) and glial fibrillary acidic protein (GFAP) as well as the ionized calcium binding adaptor molecule-1 (Ibα-1) expression in the APP/PS1 mice. Moreover, T-006 dramatically suppressed abnormal elevation of inflammatory mediators and reduced the levels of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88) and NF-κB signaling related proteins in lipopolysaccharide (LPS)-induced BV2 microglial cells. We also found that TAK242, a TLR4 inhibitor could abolish the down-regulation of T-006 on LPS-induced proinflammatory mediators and reversed the downstream proteins expression containing MyD88 and NF-κB signaling. Importantly, T-006 prevented against neuroinflammation induced neurotoxicity by mitigating reactive oxygen species (ROS) overproduction and mitochondrial membrane potential (MMP) dissipation. Conclusions﻿ T-006 exerts neuroprotective effect in treating AD by suppressing the neuroinflammation through modulation of TLR4-mediated MyD88/NF-κB signaling pathways.
Insight Into The Aquatic Toxicity And Ecological Risk of Bisphenol B, And Comparison With That of Bisphenol A
Authors: Wang Yue , Zhao Tianyi , Yang Xianhai , Liu Huihui
Published: November 2021

As one of the alternatives of 2,2-bis(4-hydroxyphenyl)propane (bisphenol A, BPA), 2,2-bis(4-hydroxyphenyl)butane (bisphenol B, BPB) has not gained sufficient concerns so far, due to the limited concentration and toxicity data available. In this study, the acute toxicity of BPB to three aquatic organisms, i.e., Tetradesmus obliquus, Daphnia magna and Danio rerio, was investigated, and it showed that Daphnia magna was the most sensitive organism with the half effective concentration (EC50) of 3.93 mg/L. Thereout, the screened Daphnia magna was exposed to BPB for 21 days to explore the chronic toxicity. Results indicated that BPB restricted the body length of parent Daphnia magna and reduced the total number of broods and neonates. The no-observed effect concentration of BPB to Daphnia magna was as low as 0.01 mg/L, which was two orders of magnitude lower than that reported 0.86–5.00 mg/L of BPA. Furthermore, the ecological risk of BPB was quantitatively assessed using the risk quotient (RQ) method. Obviously, although the environmental concentrations and detectable rate of BPB were much lower than that of BPA, its ecological risk was not necessarily lower. Hence, BPB should not be ignored in the future environmental monitoring and management.
Characteristics And Source Analysis of Greenhouse Gas Concentration Changes at Akedala Station in Central Asia
Authors: Zhao Zhujun , Zhongqi LU , Qing HE , Quanwei ZHAO , Jianlin WANG
Published: November 2021

Mole fractions of atmospheric carbon dioxide (CO2), methane (CH4) ,nitrous oxide (N2O) and sulphur hexafluoride (SF6) have been continuously measured since September 2009 at the Akdala station (47˚06′N, 87˚58′E, 563.3 masl) in China. The station is located in the Central Asia and northwest of China, and it is the only station in that region with background conditions for long-term greenhouse gas observations. Characteristics of the mole fractions, growth rates as well as influence of long-distance transport were studied considering data from September 2009 to December 2019. The greenhouse gases concentrations at Akedala Station show a trend of year-on-year growth, with CO2 concentrations ranging from 389.80×10-6 to 408.79×10-6 (molar fraction of substances, same below), CH4 concentrations ranging from1890.07×10-9 to 1976.32×10-9, N2O concentrations ranging from 321.26×10-9 to 332.03×10-9, and SF6 concentrations ranging from 7.04×10-12 to 10.07×10-12, the growth rate of which is similar to the decadal average growth rate in the northern hemisphere. There exist obvious seasonal variations, with CO2 concentrations showing high in winter and low in summer and CH4 showing a distinct “W”- shaped trend while N2O and SF6 showing little difference between the four seasons. A relatively strong correlation and homology exist among the four greenhouse gases except in summer, and the analysis based on backward trajectories model shows that the Akedala Station is influenced by the airflow from northwest or southwest throughout the year. The Akedala station is an important atmospheric background station in Central Asia, and its greenhouse gas concentration levels and variation characteristics are significantly different from those of the background stations in the monsoon region. It’s degree changes are closely related to local source emissions, monsoon transport, and atmospheric photochemical processes.
Characterization of HIV-1 molecular epidemiology and Transmitted drug-resistance in newly diagnosed HIV-infected patients in Sichuan, China
Authors: Zhou Chang , Liang Shu , Li Yiping , Zhang Yan , Li Ling , Ye Li , Yuan Dan , Su Ling
Published: November 2021

Background

Sichuan Province is one of the highest AIDS epidemic provinces in China, with a large number of floating population. The annual number of cases of HIV/AIDS reported in Sichuan has been the highest province in China for several successive years. There is a lack of widespread and representative data on the distribution of HIV subtypes in Sichuan. We aim to investigate the characteristics of HIV-1 molecular epidemiology and transmitted drug-resistance in newly diagnosed HIV-infected patients in Sichuan, China.
Method

Archived plasma samples (n = 1524) from HIV-1 newly-diagnosed individuals in April 2019 were selected by cross-sectional investigation from all 21 cities in Sichuan Province. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 polymerase (pol) gene sequences. We also analysed the association of demographic and virological factors with transmitted drug-resistance (TDR).
Results

Partial pol gene sequences were obtained from 1297 cases. HIV-1 epidemic strains in Sichuan province: the majority of subtypes were circulating recombinant form (CRF) 07_BC (675, 52.04%), CRF01_AE (343, 26.45%), CRF08_BC (115, 8.87%), CRF85_BC (67, 5.17%), subtype B (33, 2.54%), the other subtypes only accounted for 4.93%, and circulating recombinant forms (URFs) (23, 1.77%) were observed in the study, and the difference of age, ethnicity, education, occupation, region and transmission pathway of different subtypes were statistically significant, CRF08_BC was significantly drug-resistant. A total of 205 (43.78%) pol sequences were involved in the genetic transmission network, with 76 clusters ranging in size from 2 to 24 pol sequences. In addition, the level of TDR has reached a medium level, with 72 of 1297 (5.55%) cases carrying drug-resistance mutation sites, TDR mutation frequency to nonnucleoside reverse transcriptase inhibitors (NNRTIs, 3.85%) was much higher than nucleoside reverse transcriptase inhibitors (NRTIs, 0.31%) and protease inhibitors (PIs, 1.70%). The most common HIV-1 mutation pattern for NNRTI was V106 (1.31%, 17/1297) and E138 (1.16%, 15/1297), and for PI was M46 (0.69%, 9/1297).
Conclusion

The distribution of HIV-1 genotypes in Sichuan is more diverse and complex, and the Men who have sex with men (MSM) is underrated, arguing for behavior scaling up intervention in this specific population besides the elderly people with heterosexual transmission risk groups. The risk of TDR mutation frequency increased in newly diagnosed patients highlights the significance of genotypic drug resistance monitoring and molecular surveillance of pretreatment HIV-1 drug resistance. The regimen composed of TDF, 3TC and EFV was still currently the preferred solution used free first-line therapy.
Safety Profile of Mutant EGFR-Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer: Meta-Analysis and Literature to Review
Authors: Tauseef abubakar , Zafar Maryam , Silberstein Peter , Nahas Joseph , Frederickson Thomas , Abbas Anum , Alali Yaman , Hansen Sean , Abughanimeh omar , Mirza Mohsin
Published: November 2021

Despite the use of platinum-based chemotherapy, lung cancer continues to be the leading cause of cancer related death in the world. To overcome the rate of lung cancer related death, scientists discovered advanced therapies including mutant Epidermal Growth Factor Receptor-tyrosine kinase (EGFR-TK) inhibitors. Included in this study are nine phase 3 randomized controlled trials designed to study the safety profile of mutant EGFR-TK inhibitors in patients with advanced non-small cell lung cancer. The study showed that mutant EGFR-TK inhibitors have an incidence of adverse effects that is far less than platinum-based chemotherapy. Adverse effects reported were tolerable and easily manageable by slowing the infusion rate, decreasing the dosage, and skipping a dosage in symptomatic patients.
Fetal Exposure to Acetochlor Impaired Cognitive Function in Rats via Abnormal Gut Microbiome and Metabolic Disorders
Authors: Wei Wei , Wu Huanyu , Gu Wenbo , Xu Jiaxu , Hu Cong , Ma Yifan , Qi Guolian , Jiang Hongyan , Long Yujia , Jiang XiTao , Han Tianshu , Jiang Wenbo
Published: November 2021

Background: Current evidence has shown that acetochlor has adverse effects on health, which has been widely used in agricultural production, while the evidence on the effects of fetal acetochlor exposure on nervous system is quite limited. The fetus period is the most sensitive window period in the whole lifetime to external stimuli. Therefore, we established a rat model fetal exposed to acetochlor. Results: Impaired cognitive function, abnormal gut microbiome and significant changes in the hippocampus and colon could be observed in the acetochlor-exposed group. We also observed remarkable impairment in the hippocampal cells in the histomorphology observation. Fecal microbiota transplantion(FMT) was performed to elucidate whether the gut microbiome mediated the acetochlor-induced abnormal behavior. Then the proteomics analysis and metabonomics analysis in the hippocampus indicated that differential expression proteins were mainly enriched in amino acid neurotransmitter-related pathways, long-term potentiation, and synaptic-related pathways and differential metabolite were mainly enriched in mutiple neurotransmitter-related pathways. Then we observed remarkable changes in the Camk2b/Erk1/2/NF-κB pathway and Prkaca/p-CREB1/BDNF pathway in the FMT group, which may cause abnormal cognitive behaviors. Conclusions: Our results demonstrate that fetal exposure to acetochlor could induce abnormal behaviors in rats via disrupting the intestinal microbiome.
LENG8 regulation of mRNA processing is responsible for the control of mitochondrial activity
Authors: Zhao Yongxu , Wang Xiaoting , Liu Yuenan , Li Niannian , Wang Shengming , Sun Zhigang , Zhu Jingyu , Gao Zhenfei , Zhang Xiaoxu , Mao Linfei , Guan Jian , Yi Hongliang , Ding Qiurong , Liu Feng , Zhang Nan
Published: November 2021

The processing of mRNA is essential for the maintenance of cellular and tissue homeostasis. However, the precise regulation of this process in mammalian cells, remains largely unknown. Here we have found that LENG8 represents the mammalian orthologue of the yeast mRNA processing factor Thp3 and Sac3. We go on to demonstrate that LENG8 binds to mRNAs, associates with components of mRNA processing machinery (the TREX complex) and contributes to mRNA nuclear export to the cytoplasm. Loss of LENG8 , leads to aberrant accumulation of poly (A) + RNA in the nucleus, in both Hela cells and murine fibroblasts. Furthermore, the precipitation of LENG8, is associated with an enrichment of both mRNAs and lncRNAs, and approximately half of these are also bound by the TREX component, THOC1. However, LENG8 preferentially binds mRNAs encoding for mitochondrial proteins and depletion of this processing factor, causes a dramatic breakdown in mitochondrial ultrastructure and a reduction in mitochondrial respiratory activity. Conditional deletion of Leng8 in mouse adipose tissues lead to a decreased body weight, and increased adipose thermogenesis. Our work has found an evolutionarily conserved mRNA processing factor that can control mitochondrial activity.
Acute Diesel Exhaust Exposure Causes a Delayed Reduction in Cognitive Control
Authors: Faherty Thomas , Delgado-Saborit Juana Maria , Alfarra Rami , MacKenzie Angus R , McFiggans Gordon , Shapiro Kimron L , Raymond Jane E
Published: November 2021

Urban residents are frequently exposed to high levels of traffic-derived air pollution for short time periods, often (but not exclusively) during commuting. Although chronic air pollution exposure and health effects, including neurological effects on children and older adults, are known to be correlated, causal effects of acute pollution exposure on brain function in healthy young adults remain sparsely investigated. Neuroinflammatory accounts suggest effects could be delayed by several hours and could affect attention, especially in social contexts. Using a controlled atmosphere chamber, we exposed 81 healthy young adults to either diluted diesel exhaust (equivalent to polluted roadside environments) or clean air for one hour. Half of each group immediately completed a selective attention task to assess cognitive control; remaining participants completed the task after a 4-hour delay. Cognitive control was significantly poorer after diesel versus clean air exposure for those in the delay but not immediate test condition, suggesting an inflammatory basis for this acute negative effect of air pollution on cognition. These findings provide the first experimental evidence that acute diesel exposure, comparable to polluted city streets, causes a negative effect on cognitive control several hours later. These findings may explain commuter mental fatigue and support clean-air initiatives.
Delayed discharge for non-clinical reasons among stroke patients in a high-complexity hospital: A cross-sectional study
Authors: Pellico-López Amada , Fernández-Feito Ana , Cantarero David , Montes Manuel Herrero , Cuevas Joaquín Cayón- De las , Parás-Bravo Paula , Paz-Zulueta María
Published: November 2021

Delayed discharge for non-clinical reasons (bed-blocking) is characteristic of pathologies associated with ageing, loss of functional capacity and dependence such as stroke. The aims of this study were to describe the costs and characteristics of cases of patients with stroke and delayed discharge for non-clinical reasons (bed-blocking) compared with cases of bed-blocking (BB) for other reasons and to assess the relationship between the length of total stay (LOS) with patient characteristics and the context of care. A descriptive cross-sectional study was conducted at a high complexity public hospital in Northern Spain (2007-2015). 443 stroke patients presented with BB. Delayed discharge increased LOS by approximately one week. The mean age was 80.22 years, significantly higher than in cases of BB for other reasons. Patients with stroke and BB are usually older patients, however, when younger patients are affected, their length of stay is longer in relation to the sudden onset of the problem and the lack of adequate functional recovery resources or residential facilities for intermediate care.
Identification of Key Interactions of Benzimidazole Resistance-Associated Amino Acid Mutations in Ascaris β-Tubulins By Molecular Docking Simulations
Authors: Jones Ben P. , Vliet Arnoud H.M. , LaCourse E. James , Betson Martha
Published: November 2021

Ascaris species are soil-transmitted helminths that infect humans and livestock mainly in low and middle-income countries. Benzimidazole (BZ) class drugs have predominated for many years in the treatment of Ascaris infections, but persistent use of BZs has already led to widespread resistance in other nematodes, and treatment failure is emerging for Ascaris. Benzimidazoles act by binding to β-tubulin proteins and destabilising microtubules. Three mutations in the β-tubulin protein family are associated with BZ resistance. Seven shared β-tubulin isotypes were identified in Ascaris lumbricoides and A. suum genomes. Benzimidazoles were predicted to bind to all β-tubulin isotypes using in silico docking, demonstrating that the selectivity of BZs to interact with one or two β-tubulin isotypes is likely the result of isotype expression levels affecting the frequency of interaction. Ascaris β-tubulin isotype A clusters with helminth β-tubulins previously shown to interact with BZ. Molecular dynamics simulations using β-tubulin isotype A highlighted the key role of amino acid E198 in BZ-β-tubulin interactions. Simulations indicated that mutations at amino acids E198A and F200Y alter binding of BZ, whereas there was no obvious effect of the F167Y mutation. In conclusion, the key interactions vital for BZ binding with β-tubulins have been identified and show how mutations can lead to resistance in nematodes.
Designing and Implemenitin of an Evidence-Based Information Management and Practice Course for Librarians Based on ADDIE Model
Authors: Gavgani Vahideh Zarea , Hazrati Hakimeh , Sadeghi-Ghyassi Fatemeh , Esmaeilzad Sima , Mahami Mina
Published: November 2021

Background: Evidence-based practice is competency required by librarians to provide quality services in today’s rapidly growing world of information. This study aimed to instructional desianing and implementing of an evidence-based information management and practice course based on ADDIE Model.Methods: This action research was conducted based on ADDIE Model in 2019 in Tabriz University of Medical Sciences. The Analysis,Design, Development, Implementation and Evaluation was performed accordingly. The course was offered virtually through the Learning Mangement System of one of the top ranked universities in Iran. course evalouation was done based on Kirkpatrick’s model. A Likert-based satisfaction evaluation questionnaire was developed, which included three open-ended questions about strengths and weaknesses of the course and an open-end question for recommendations. After psychometric analysis, the questionnaires were distributed among the participants. The data were analyzed in SPSS 19 and reported by descriptive statistics (mean and SD).Results: After three sessions of focus group discussion, 10 lessons was determined inclouding: evidence-based practice in clinical medicine, critical thinking and mind map, searching and retrieving evidence, systematic reviews, critical appraisal of evidence, systematic search, levels of evidence, systematic questions, and meta-analysis. The syllabuses was categorized in 5 modules based on 5 steps of evidence-based practice guidline.The overall satisfaction about the training was reported excellent (83.52 ± 16.27), and addressed the highest satisfaction with the support services (94.52 ± 29.68).Conclusions: This syllabus is appropriate for short course education of evidence-based approach in librarianship as a branch of medical librarianship and information sciences. It also is suitable for professional continuing education of librarians.
Defining research priorities for youth public mental health: reflections on a co-production approach to transdisciplinary working
Authors: Taylor Andrea , McMellon Christina , French Tara , MacLachlan Alice , Evans Rhiannon , Lewis Ruth , McCann Mark , Moore Laurence , Murphy Simon , Simpson Sharon , Inchley Jo
Published: November 2021

Background

With most mental health problems established during childhood/adolescence, young people must be a key focus of public mental health (PMH) approaches. Despite the range of factors known to influence mental health, evidence for effective interventions is lacking for this age group. This study aimed to define priorities for future intervention-focussed research to support youth PMH by engaging with transdisciplinary stakeholder groups.
Methods

Our co-production approach involved priority-setting workshops with young people, researchers, practitioners and policymakers. Each workshop focussed on three thematic areas: social connections and relationships; schools and other education settings; key groups at greater risk of mental ill-health, specifically LGBTQ+ and care-experienced young people. Workshop outputs were synthesised to define research priorities.
Results

Ten priorities for youth PMH research were defined, covering the following areas: building supportive relationships; whole system approaches; social media; support at times of transition; improving links between different services; development and training for those who support young people; staff mental health; engaging with families; awareness of and access to services; out of school and community settings.
Conclusions

These research priorities can inform future intervention-development to support youth PMH. Our transdisciplinary approach means the identified research priorities are more likely to be relevant to young people’s experiences and needs, and to fit with the needs of those working in practice and policy to support young people.
Navigating Pandemic Responsiveness in an Acute Care Setting: A Community Hospital’s Operational Experience with COVID-19
Authors: McLean Jesse , Clark Cathy , McKee Aidan , Legue Suzanne , Cocking Jane , Lamarche Amanda , Heerschap Corey , Morris Sarah , Fletcher Tracey , McKee Corey , Kennedy Kristal , Gross Leigh , Broeren Andrew , Forder Matthew , Barner Wendy , Tebbutt Chris , Kings Suzanne , DiDiodato Giulio
Published: November 2021

Background

To ensure continuity of services while mitigating patient surge and nosocomial infections during the coronavirus disease 2019 (COVID-19) pandemic, acute care hospitals have been required to make significant operational adjustments. Here, we identify and discuss key administrative priorities and strategies used by a large community hospital located in Barrie, Ontario to manage COVID-19.
Methods

Guided by a qualitative descriptive approach, we conducted a thematic analysis of all COVID-19-related documentation discussed by the hospital’s Emergency Operations Centre (EOC) during the first pandemic wave. We solicited operational strategies from administrative leaders to construct a narrative for each theme.
Results

Seven recurrent themes critical to the hospital’s pandemic response emerged: 1) Organizational Structure: a modified EOC structure was adopted to increase departmental interoperability and situational awareness; 2) Capacity Planning: Design Thinking guided rapid infrastructure decisions to meet surge requirements; 3) Occupational Health and Workplace Safety: a multidisciplinary team provided respirator fit-testing, critical absence adjudication, and wellness needs; 4) Human Resources/Workforce Planning: new workforce planning, recruitment, and redeployment strategies addressed staffing shortages; 5) Personal Protective Equipment (PPE): PPE conservation required proactive sourcing from traditional and non-traditional suppliers; 6) Community Response: local partnerships were activated to divert patients through a non-referral-based assessment and treatment centre, support long-term care and retirement homes, and establish a 70-bed field hospital; and 7) Corporate Communication: a robust communication strategy provided timely and transparent access to rapidly evolving information.
Conclusions

The hospital benefited from an interconnected command structure that focused on inter-operability, communication, novel administrative tools, and community partnerships.
Reduction of Wastes and Costs Through the Modified Kanban System in Unit Storerooms of HGH: A Value-for-Money Quality Improvement Initiative
Authors: LOGRONO KENNETH JUN , ZU'BI BELAL SALEM
Published: November 2021

Most public health sectors in many countries were heavily burdened both financially and operationally as a result of the pandemic's new changes. Organizations have been pushed to develop innovative solutions to balance expenses and revenues through value-for-money initiatives as a result of erratic economic conditions.Purchasing and supply distribution to the point of care account for approximately 30–40% of the hospital's operating budget. The demand-based ordering system, also known as the par system, has inherently resulted in increased waste due to obvious estimations for the quantity of items. Increased waste and costs have become a widespread issue in the healthcare supply chain, which was identified as a priority for improvement.The project is aimed to reduce the costs by 50% by implementing the Kanban system in the unit storeroom of medical units within three months. The IHI Model of Improvement was undertaken to go through the implementation of the project. Several quality improvement tools were used to test different ideas of change and measurement of improvements were also made.Following the adoption of the modified Kanban System, the costs of consumable item supply decreased by 69% from 16,000 QAR to 5,000 QAR. The percentage of wastes has reduced significantly to 0% while limiting the percentage of out stocking to a median of 1%.Kanban as a lean method, reduces wastes by controlling the flow of consumables within a supply chain. Eliminating or reducing waste is a cornerstone of lean management. The project’s new evidence demonstrated significant and sustainable cost saving strategy by reducing waste and pre-quantifying items based on their usage and flow. The Kanban system ultimately improved nurses’ productivity, streamlined the unit’s stock supply, promoted value improvement, and helped increased end-user satisfaction.
Expression Pattern and Prognostic Value of p53-Pathway in Gastric Cancer
Authors: Li Wei , shi Changhong
Published: November 2021

Background: Gastric cancer is one of the most common cancer across the world. Increasing evidence suggest that p53-pathway plays a critical role in the initiation, progress and therapy of gastric cancer. However, the prognostic value of p53-pathway in gastric cancer is not fully understood. Methods: A total of 67 p53-pathway-related genes and corresponding clinical information of 415 gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. The consensus clustering algorithm were performed to analyze the expression level of all p53-pathway related genes. Based on the differentially expressed genes between different subgroups, Cox regression analysis were used to construct an independent prognostic signature, which was further validated in two external datasets. Results: 3 subgroups of patients with significant different survival outcome were identified according to the expression level of p53-pathway-related genes. Comparison of gene expression between those subgroups identified 12 differentially expressed genes, 3 (THBS1, SERPINE1 and GADD45B) of which were significantly associated with the overall survival outcome. We further constructed a 3-gene signature as independence prognosis signature with promising performance in survival prediction of gastric cancer. Conclusions: This study provides a potential prognostic signature for predicting prognosis of gastric cancer patients, which may benefit individual therapy of gastric cancer.
Optimization of Intraperitoneal Aerosolized Drug Delivery: A Computational Fluid Dynamics (CFD) and Experimental Study
Authors: Rahimi-Gorji Mohammad , Debbaut Charlotte , Ghorbaniasl Ghader , Cosyns Sarah , Willaert Wouter , Ceelen Wim
Published: November 2021

Intraperitoneal (IP) aerosolized anticancer drug delivery was recently introduced in the treatment of patients with peritoneal metastases. However, little is known on the effect of treatment parameters on the spatial distribution of the aerosol droplets in the peritoneal cavity. Here, computational fluid dynamics (CFD) modeling was used in conjunction with experimental validation in order to investigate the effect of droplet size, liquid flow rate and viscosity, and the addition of an electrostatic field on the homogeneity of IP aerosol. We found that spatial distribution is optimal with small droplet sizes (1-5 µm). Using the current clinically used technology (droplet size of 30 µm), the optimal spatial distribution of aerosol is obtained with a liquid flow rate of 0.6 mL s-1. Compared to saline, nebulization of higher viscosity liquids results in less homogeneous aerosol distribution. The addition of electrostatic precipitation significantly improves homogeneity of aerosol distribution, but no further improvement is obtained with voltages higher than 6.5 kV. The results of the current study will allow to choose treatment parameters and settings in order to optimize spatial distribution of IP aerosolized drug, with a potential to enhance its anticancer effect.
Propensity-score Matching Analysis for Marital Status and Survival of Oral and Oropharyngeal Squamous Cell Carcinoma Based on SEER Database
Authors: Ming Wei , Zuo Jingjing , Han Jibo , Wang Yan , Chen Jinhui
Published: November 2021

ObjectMarital status plays different roles as a risk factor on survival in various cancers . The study is aimed to analyze the impact of marital status on survival of oral and oropharyngeal squamous cell carcinoma(OPSCC) at population level based on SEER database using propensity-score matching method(PSM).Methods37,023 eligible patients were extracted from the Surveillance, Epidemiology, and End Results(SEER) database, and analyzed the impact of various marital status on cancer-specific survival(CSS) of OPSCC by Kaplan-Meier method and Cox regression model. Then we used propensity-score matching analysis to balance baseline characteristics between married, single, divorced and widowed patients. The impact of various marital status after pairwise matching using p-value adjusted and PSM on CSS was re-analyzed by Kaplan-Meier method.ResultsThe age, sex, race, tumor location, pathologic grades, SEER stages, treatments, composite socioeconomic status(C-SES), insurance, and marital status were identified as independent prognostic factors for CSS of OPSCC. Widowed patients presented the worst CSS, compared with married, single, and divorced patients(P<0.001). Subgroup analysis indicated that widowed patients always presented with the significantly decreasing risk of CSS compared with other marital status in different SEER stages(P<0.001), and different C-SES(P<0.001). After propensity-score matching, widowed patients were still found to be associated with significantly decreased CSS compared with other marital groups(P<0.001).Conclusion﻿Marital status was first analyzed after using PSM to balance clinicopathological and socioeconomic confounding factors and identified as an independent prognostic factor for CSS of OPSCC. Widowed patients was significantly associated with a decreasing CSS, which indicated that absence of spousal support and optimal psychosocial coping strategies may explain the phenomenons.
4SC-202 Exerts An Anti-tumor Effect in Cervical Cancer By Targeting PRLR Signaling Pathway
Authors: Zhang Huijuan , Li Mingxia , Yang Wen , Ye Mingxia , Li Hua , Meng Yuanguang
Published: November 2021

The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by flow cytometry and western blotting, respectively. Immunofluorescence and western blotting were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time- and dose-dependent manner. SiHa cells were treated with 1 or 5 μM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 significantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This finding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.
Structure Clearance Design in Wind Tunnel Tests with Implications for Aerodynamic Drag of High-Speed Trains
Authors: Huang Zhixiang , Huang Hanjie , Zeng Weiping , Chen Li , Zhu Renyu
Published: November 2021

The influences of vestibule diaphragm gap, wheel-rail clearance, and strut-plate gap on the aerodynamic drag of a 1/8th-scale high-speed train model were investigated in an 8 m×6 m wind tunnel. The Reynolds number was set to 2.2×106 based on train height. It was found that the variation of the vestibule diaphragm gap changed the aerodynamic drag distribution pattern of each car; the drag coefficient of the head and middle cars might change as high as 45%; however, the change in the drag coefficient of the total train was very small. The effects of the strut-plate gap on the aerodynamic drag of each car and the total train were small. The effect of the wheel-rail clearance on the drag of the head car was not significant. It was suggested that the vestibule diaphragm gap, strut-plate gap and wheel-rail clearance of the 1:8 scale high-speed train model should not be greater than 11, 10, and 9 mm, respectively.
A novel heterozygous ZBTB18 missense mutation in a family with non-syndromic intellectual disability and structural brain abnormalities
Authors: Li Nana , Wang Meixian , Zou Yanna , Liu Zhen , Deng Ying , Qin Hong , Qiu Xiaoqiong , Kang Hong , Wang Yanping , Zhu Jun , Agostino Mark , Heng Julian I-T , Yu Ping
Published: November 2021

Background
Intellectual Disability (ID) is a characterized by significantly impaired adaptive behavior and cognitive capacity. Currently, high throughput sequencing approaches have led to the identification of genetic causes for ID in 25-50% of cases, while the causes of inherited ID are less well known. Here, we have investigated the genetic cause for non-syndromic ID in a Han Chinese family.
Methods
Whole genome sequencing was performed on identical twin sisters diagnosed with ID, their respective children as well as their asymptomatic parents. Data was filtered for rare variants and in silico prediction tools used to establish pathogenic alleles. Candidate mutations were validated by Sanger sequencing. Molecular modelling was conducted to establish the effects of the mutation on the protein encoded by a candidate coding gene.
Results
A novel heterozygous variant in the ZBTB18 gene c.1323C>G (p.His441Gln) was identified. This variant co-segregated with affected individuals in an autosomal dominant pattern and was not detected in asymptomatic family members. Molecular studies reveal that a p.His441Gln substitution disrupts the coordination of a zinc ion within the second zinc finger and disrupts the capacity for ZBTB18 to bind DNA.
Conclusions
c.1323C>G mutation in ZBTB18 gene on 1 chromosome may be related with the phenotype of intellectual disability in this family. WGS is an efficient method to perform molecular diagnosis for hereditary ID. This is the first report of an inherited ZBTB18 mutation for ID and suggests that mutations that disrupt C2H2 motifs underlie human neurodevelopmental disorder.
A Water-Soluble Manganese(II) Octanediaoate/Phenanthroline Complex Acts as an Antioxidant and Attenuates Alpha-Synuclein Toxicity
Authors: Queiroz Daniela Dias , Ribeiro Thales de Paula , Gonçalves Julliana M. , Mattos Larissa M. M. , Gerhardt Ellen , Freitas Júlia , Palhano Fernando L. , Frases Susana , Pinheiro Anderson S. , McCann Malachy , Knox Andrew , Devereux Michael , Outeiro Tiago F. , Pereira Marcos D.
Published: November 2021

The overproduction of reactive oxygen species (ROS) induces oxidative stress, a well-known process associated with aging and several human pathologies, such as cancer and neurodegenerative diseases. A large number of synthetic compounds have been described as antioxidant enzyme mimics, capable of eliminating ROS and/or reducing oxidative damage. In this study, we investigated the antioxidant activity of a water-soluble 1,10-phenantroline-octanediaoate Mn2+-complex on cells under oxidative stress, and assessed its capacity to attenuate alpha-synuclein (aSyn) toxicity and aggregation, a process associated with increased oxidative stress. This Mn2+-complex exhibited a significant antioxidant potential, reducing intracelular oxidation and increasing oxidative stress resistance in S. cerevisiae cells and in vivo, in G. mellonella, increasing the activity of the intracellular antioxidant enzymes superoxide dismutase and catalase. Strikingly, the Mn2+-complex reduced both aSyn oligomerization and aggregation in human cell cultures and, using NMR and DFT/molecular docking we confirmed its interaction with the C-terminal region of aSyn. In conclusion, the Mn2+-complex appears as an excellent lead for the design of new phenanthroline derivatives as alternative compounds for preventing oxidative damages and oxidative stress - related diseases.