bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence on Article 5.3 of FCTC (Tobacco Industry Interference in tobacco control activities) in India- a Qualitative scoping study
Authors: Goel Sonu , Kar Sitanshu Sekhar , Verma Madhur , Sivanantham Parthibane , Naik Bijay Nanda
Published: October 2020

Background: Tobacco Industry (TI) strives to portray itself as being “socially responsible” and contest for pertinent decision-making positions, which it uses to deter, delay or dilute tobacco control measures. There is little documented evidence of Tobacco Industry Interference (TII) from India, the scope of their interference and challenges faced by the experts for effective tobacco control.Methods: A cross-sectional qualitative research design, based upon in-depth interviews (N=26), was used to explore the opinion of key stakeholders regarding TII in India. The interview schedule collected information about the participant’s roles and responsibilities in tobacco control, the nature of TII faced by the participant, means of influence by TI, barriers and challenges to tobacco control efforts using a set of questions. Results: Most of the respondents were engaged in tobacco control, training, advocacy, and awareness generation activities from the last 5-10 years or more. The respondents defined the TI and its scope as per their experience with the help of power ranking methodology. Most of them perceived TI as ‘Manufacturers’ while others consider them as ‘advertisers’, ‘public relation companies’, ‘wholesalers’, ‘vendors’, and ‘Government firms having TI stocks’ as TI. We identified six major domains (Influencing the policy and administrative decisions, Interference with implementation of tobacco control laws and activities, False propaganda and hiding the truth, manipulating front action groups (FAG), Rampant tobacco advertising and promotion activities, and others) under which TII activities were classified. Most respondents were of opinion that TI players were interfering in the policy decisions, implementation of the tobacco control laws and activities, and manipulating the FAG. A detailed taxonomic classification of the TII strategies that emerged from our analysis were linked to article 5.3 of FCTC. Conclusions: The activity documented a significant level of TII in different domains with stakeholders acting at various hierarchical levels. The study provide insights about the nefarious tactics of TI, enable stakeholders to anticipate and pre-empt the kinds of alliances the TI may attempt to build, stimulate academicians and researchers to undertake in-depth analysis into various strategies and underscore the need for ensuring transparency in official interactions with the TI and their representatives.
Awareness of COVID-19: What do Pakistanis perceive? A Large Survey of 1200 Residents
Authors: Ladiwala Zoya Fatima Rizwan , Dhillon Rubaid Azhar , Zahid Ibrahim , Irfan Omar , Khan Muhammad Sharjeel , Awan Safia , Khan Javaid Ahmad
Published: October 2020

Background: The Novel Coronavirus Disease (COVID-19) has created havoc globally as countries worldwide struggle to combat this pandemic. Since prevention and social isolation are known to be the only ways to prevent the spread of COVID-19, this has created challenges among the lower-middle income countries (LMIC) including Pakistan, as it battles between an under-resourced healthcare, an economic shutdown, and widespread myths and misconceptions. Therefore, we conducted a study to evaluate the knowledge, attitude and perceptions regarding COVID-19 as public understanding is vital to help facilitate the control of this outbreak. Methods: A pre-validated online questionnaire was distributed among the general population of Pakistan from 1st to 12th June 2020. Descriptive statistics were analyzed using SPSS v25. Adequate knowledge was assigned as a score of >4 (range: 0-8) and good perception as a score of >3 (range: 0-5). Chi‑square test was used to determine the significance of difference in knowledge and perception of COVID-19 among socio-demographics. Logistic regression analysis was run to identify factors associated with adequate knowledge and perception. P < 0.05 was considered as significant.Results: A total of 1200 respondents participated in this study with a wide range of age groups and education. Majority of the respondents had adequate knowledge (93.3%) with a mean score of 6.59 ± 1.35, and good perception (85.6%) with a mean score of 4.29 ± 0.82. Significant differences in knowledge and perception were observed among genders, age groups, education and between students and employees in the healthcare and non-healthcare department. A multivariable analysis revealed an advanced degree and a female gender to be significant predictors of adequate knowledge and perception. Conclusions: Albeit the surge of COVID-19 cases in Pakistan, the participants demonstrated an overall adequate knowledge and good perception towards COVID-19. Perhaps, a potential hint towards noncompliance practices in following preventive protocols requires further educational interventions that target safe health practices and complications of this infection.
An exploratory study to estimate cost-effectiveness threshold value for life saving treatments in western Iran
Authors: Moradi Najmeh , Woldemichael Abraha , Malekian Parisa , Rotavandi Delnia Moradi , Rezaei Satar
Published: October 2020

Background: Cost-effectiveness analysis provides a crucial means for evidence-informed decision-making on resource allocation. This study aims to elicit individuals' willingness to pay (WTP) for one additional quality-adjusted life-year (QALY) gained from life-saving treatment and associated factors in Kermanshah city, western Iran.Methods: We conducted a cross-sectional study on a total of 847 adults aged 18 years and above to elicit their WTP for one additional QALY gained by oneself and a family member using a hypothetical life-saving treatment. We used a multistage sampling technique to select the samples, and the Iranian version of EQ-5D-3L, and visual analogue scale (VAS) measures to obtain the participants’ health utility value. The Tobit regression model was used to identify the factors affecting WTP per QALY values.Results: The mean WTP value and standard deviation (SD) was US$ 862 (3,224) for the respondents. The mean utility values using EQ-5D-3L and VAS methods for respondents were 0.779 and 0.800, respectively. Besides, the WTP for the additional QALY gained by the individual participants using the EQ-5D-3L and VAS methods were respectively US$ 1,202 and US$ 1,101, while the estimated value of the family members was US$ 1,355 (SD= 3,993). The Tobit regression models indicated that monthly income, education level, sex, and birthplace were statistically significantly associated (p < 0.05) with both the WTP for the extra QALY values using the EQ-5D-3L and the VAS methods. Educational level and monthly income also showed statistically significant relationships with the WTP for the additional QALY gained by the family members (p < 0.05). Conclusion: Our findings indicated that the participants' WTP value of the additional QALY gained from the hypothetical life-saving treatment was in the range of 0.20 to 0.24 of the gross domestic product (GDP) per capita of Iran. This value is far lower than the World Health Organization (WHO) recommended CE threshold value of one. This wide gap reflects the challenges the health system is facing and requires further research for defining the most appropriate CE threshold at the local level.
Transcriptional response of Bacillus megaterium FDU301 to PEG200-mediated arid stress
Authors: Zhao Lei , Zhou Yanjun , Li Jianbei , Xia Yucheng , Wang Weiyun , Luo Xiuqi , Yin Juan , Zhong Jiang
Published: October 2020

Background For microorganisms on a paper surface, the lack of water is one of the most important stress factors. A strain of Bacillus megaterium FDU301 was isolated from plaques on a paper surface using culture medium with polyethylene glycol 200 (PEG200) to simulate an arid condition. Global transcriptomic analysis of B. megaterium FDU301 grown under normal and simulated arid conditions was performed via RNA-seq technology to identify genes involved in arid stress adaptation.Results The transcriptome of B. megaterium FDU301 grown in LB medium under arid (15% PEG200 (w/w)) and normal conditions were compared. A total of 2941 genes were differentially expressed, including 1422 genes upregulated and 1519 genes downregulated under arid conditions. Oxidative stress-responsive regulatory genes perR, fur, and tipA were significantly upregulated, along with DNA protecting protein (dps), and catalase (katE). Genes related to Fe2+ uptake (feoB), sporulation stage II (spoIIB, spoIIE, spoIIGA), small acid-soluble spore protein (sspD), and biosynthesis of compatible solute ectoine (ectB, ectA) were also highly expressed to various degrees. Oxidative phosphorylation-related genes (atpB, atpE, atpF, atpH, atpA, atpG, atpD, atpC) and glycolysis-related genes (pgk, tpiA, frmA) were significantly downregulated.Conclusion This is the first report about transcriptomic analysis of a B. megaterium to explore the mechanism of arid resistance. Major changes in transcription were seen in the arid condition simulated by PEG200 (15%), with the most important one being genes related to oxidative stress. The results showed a complex mechanism for the bacteria to adapt to arid stress.
The Influence of Empowered Work Environments on the Psychological Experiences of Nursing Assistants During COVID-19: A Qualitative Study
Authors: Travers Jasmine , Schroeder Krista , Norful Allison A. , Aliyu Sainfer
Published: October 2020

Background: Nursing Assistants (NA) who feel empowered tend to perform their duties better, have higher morale and job satisfaction, and are less likely to leave their jobs. Organizational empowerment practices in hospitals likely shape the psychological experiences of empowerment among these personnel; however, little is known about this relationship.Objective: We used qualitative inquiry to explore the relationship between organizational empowerment structural components and feelings of psychological empowerment among hospital frontline workers during a public health emergency. Methods: Kanter’s Theory of Structural Empowerment and Spreitzer’s Psychological Empowerment in the Workplace Framework were applied to identify the conceptual influences of organizational practices on psychological experiences of empowerment. In-depth interviews were conducted with a convenience sample of NAs, caring for hospitalized COVID-19 patients. Directed content analysis was performed to generate a data matrix consisting of the psychological experiences of meaning, competence, self-determination, and impact embedded under the organizational structural components of information, resources, support, and opportunity. Results: Thirteen NAs (mean age= 42 years, 92% female) completed interviews. Information, or lack thereof, provided to the NAs influenced feelings of fear, preparation, and autonomy. Resources (e.g., protocols, equipment, and person-power) made it easier to cope with overwhelming emotions, affected the NAs’ abilities to do their jobs, and when limited, drove NAs to take on new roles. NAs noted that support was mostly provided by nurses and made the NAs feel appreciated, desiring to contribute more. While NAs felt they could consult leadership when needed, several felt leadership showed little appreciation for their roles and contributions. Similar to support, the opportunity to take care of COVID-19 patients yielded a diverse array of emotions, exposed advances and gaps in NA preparation, and challenged NAs to autonomously develop new care practices and processes. Conclusion: Management and empowerment of healthcare workers are critical to hospital performance and success. We found many ways in which the NAs’ psychological experiences of empowerment were shaped by the healthcare system’s empowerment-related structural conditions during a public health emergency. To further develop an empowered and committed critical workforce, hospitals must acknowledge the organizational practice influence on the psychological experiences of empowerment among NAs.
Body Image, Life Satisfaction and Associated Factors Among Women in Sweden having Undergone Mastectomy after Breast Cancer
Authors: Lundberg Pranee C , Phoosuwan Nitikorn
Published: October 2020

Background: Women having undergone mastectomy due to breast cancer have experience which is very much individual and contextual. In order to facilitate efforts to understand the women and improve their quality of life, the aim of this study was to investigate body image, life satisfaction and associated factors among women having undergone mastectomy.Methods: Four hundred and eighty-one women in Sweden having undergone mastectomy after breast cancer were enrolled in a descriptive cross-sectional study. Each participant completed a questionnaire comprising socio-demographic characteristics, social support, body image and life satisfaction. Multiple linear regression analyses estimated relationships between socio-demographic characteristics, information support, social support, and treatment variables, and continuous outcome variables such as body image and life satisfaction).Results: Body image was associated with all dimensions of life satisfaction. Lower age, underlying disease, chemotherapy and breast reconstruction increased body image dissatisfaction, while treatment options were factors associated with life satisfaction. Total social support was a factor that increased life satisfaction in the dimensions of physical symptoms, sickness impact and quality of close friend relationship.Conclusion: The findings highlight that some socio-demographic characteristics, treatment options and social support were associated with body image dissatisfaction and life dissatisfaction among the women with breast cancer after mastectomy. This can increase healthcare professionals’ understanding of women with breast cancer after treatment. They should provide effective information, focus attention on the women’s needs, and prepare intervention programs that make the women cope with their life situations during follow-up care.
Association between triglyceride-glucose index and risk of incident diabetes: a secondary analysis based on a Chinese cohort study
Authors: Li Xiaoli , Li Guilong , Cheng Tiantian , Liu Jing , Song Guangyao , Ma Huijuan
Published: October 2020

Background: Recent studies have suggested the triglyceride-glucose index (TyG index) may serve as a suitable substitute for insulin resistance. However, evidence for the relationship between TyG index and risk of diabetes remains limited. This study sought to explore the association of baseline TyG index with risk of developing diabetes in Chinese adults.Methods: This retrospective cohort study was conducted using data from the health screening program in China. A total of 201,298 non-diabetic individuals were included. TyG index was calculated as Ln [fasting plasma glucose (mg/dl) × fasting triglyceride level (mg/dl)/2]. Diabetes was defined as fasting plasma glucose ≥126 mg/dl and/or self-reported diabetes. Cox proportion-hazard model was employed to evaluate the independent impact of baseline TyG index on future diabetes risk. Sensitivity and subgroup analyses were implemented to verify the reliability of results. Notably, data were downloaded from the DATADRYAD website, and used only for secondary analyses.Results: During an average follow-up of 3.12 years, among 201,298 individuals aged ≥20 years, 3,389 subjects developed diabetes. After adjusting for potential confounders, elevated TyG index were independently correlated with greater risk of incident diabetes (hazard ratio (HR), 3.34; 95% confidence interval (CI), 3.11–3.60). Compared with the lowest quartile (Q1), increasing TyG index (Q2, Q3, and Q4) was related to increased HR estimates of incident diabetes [HR (95% CI), 1.83 (1.49–2.26); 3.29 ( 2.70–4.01), and 6.26 (5.15–7.60), respectively]. Moreover, a nonlinear relationship was observed between TyG index and risk of diabetes and the slope of the curve increased accompanying the rise of TyG index. Subgroup analysis revealed the positive association was stronger among subjects with age < 40 years, body mass index ≥18.5 kg/m2 and < 24 kg/m2, or systolic blood pressure <140 mmHg, or in females.Conclusions: Elevated TyG index is independently correlated with increased risk of incident diabetes in Chinese adults, indicating it may represent a reliable predictor of diabetes in high-risk populations.
The Health Potential of Neighborhoods: A Population-Wide Study in The Netherlands
Authors: Dekker Louise H. , Rijnks Richard H , Mierau Jochen O.
Published: October 2020

The authors have requested that this preprint be removed from Research Square.
REDIAL-2020: A suite of machine learning models to estimate Anti-SARS-CoV-2 activities
Authors: KC Govinda , Bocci Giovanni , Verma Srijan , Hassan Md , Holmes Jayme , Yang Jeremy , Sirimulla Suman , Oprea Tudor
Published: October 2020

Strategies for drug discovery and repositioning are an urgent need with respect to COVID-19. We developed "REDIAL-2020", a suite of machine learning models for estimating small molecule activity from molecular structure, for a range of SARS-CoV-2 related assays. Each classifier is based on three distinct types of descriptors (fingerprint, physicochemical, and pharmacophore) for parallel model development. These models were trained using high throughput screening data from the NCATS COVID19 portal (https://opendata.ncats.nih.gov/covid19/index.html), with multiple categorical machine learning algorithms. The “best models” are combined in an ensemble consensus predictor that outperforms single models where external validation is available. This suite of machine learning models is available through the DrugCentral web portal (http://drugcentral.org/Redial). Acceptable input formats are: drug name, PubChem CID, or SMILES; the output is an estimate of anti-SARS-CoV-2 activities. The web application reports estimated activity across three areas (viral entry, viral replication, and live virus infectivity) spanning six independent models, followed by a similarity search that displays the most similar molecules to the query among experimentally determined data. The ML models have 60% to 74% external predictivity, based on three separate datasets. Complementing the NCATS COVID19 portal, REDIAL-2020 can serve as a rapid online tool for identifying active molecules for COVID-19 treatment. The source code and specific models are available through Github (https://github.com/sirimullalab/redial-2020), or via Docker Hub (https://hub.docker.com/r/sirimullalab/redial-2020) for users preferring a containerized version.
Investigating Public Values in Health Care Priority – Chileans´ Preferences for National Health Care
Authors: Núñez Alicia , Chi Chunhuei
Published: October 2020

Background: This study aims to assess preferences and values for priority setting in healthcare in Chile through an original and innovative survey method. Based on the answers from a previous survey that look into the barriers the Chilean population face, this study considers the preferences of the communities overcoming those barriers. As a result six programs were identified: (1) new infrastructure, (2) better healthcare coverage, (3) increasing physicians/specialists, (4) new informatics systems, (5) new awareness healthcare programs, and (6) improving availability of drugs. Methods: We applied an innovative survey method developed for this study to sample subjects to prioritize these programs by their opinion and by allocating resources. The survey also asked people´s preferences for a distributive justice principle for healthcare to guide priority setting of services in Chile. The survey was conducted with a sample of 1,142 individuals. Results: More than half of the interviewees (56.4%) indicated a single program as their first priority, while 20.1% selected two of them as their first priority. To increase the number of doctors/specialists and improve patient-doctor communication was the program that obtained the highest priority. The second and third priorities correspond to improving and investing in infrastructure and expanding the coverage of healthcare insurances. Additionally, the results showed that equal access for equal healthcare is the principle selected by the majority to guide distributive justice for the Chilean health system. Conclusions: This study shade lights on how a large population sample can participate in major decision making of national health policies, including making a choice of a distributive justice principle. Despite the complexity of the questions asked, this study demonstrated that with an innovative method and adequate guidance, average population is capable of engaging in expressing their preferences and values. Results of this study provide policy-makers useful community generated information for prioritizing policies to improve healthcare access.
Platelet-to-Lymphocyte Ratio and C-Reactive Protein as Markers for Colorectal Polyp Histological Type
Authors: Chen Rui , Wang Liguang , Zhao Qi , Li Zhen , Chen Man , Lian Guodong , Zhang Junyong
Published: October 2020

Background: The PLR and CRP level are markers that have been reported to predict the histological type of various tumors, and here, we evaluated their utility in predicting colorectal polyp histological types.Methods: We retrospectively reviewed 172 patients with colorectal polyps who underwent endoscopic polypectomy. The associations between histological type and clinicopathologic parameters were assessed by multivariate analysis. Results: The optimal PLR and CRP cut-off values were 113.32 and 0.39, respectively. The PLR (P=0.002) and CRP (P= 0.009) values were associated with the histological type according to the univariate analysis, whereas low PLR (P ≤0.001) and CRP (P =0.017) values were independent risk factors in the multivariate analysis together with maximum tumor diameter (P ≤0.001) and tumor number (P =0.0014).Conclusions: Preoperative PLR and CRP are correlated with the colorectal polyp histological type.
Molecular Subtypes Based on DNA Methylation Predict Prognosis in Lung Squamous Cell Carcinoma
Authors: Li XiuShen , Nie Ke-Chao , Zheng Zhi-Hua , Zhou Rui-Sheng , Huang Yu-Sheng , Ye Zeng-Jie , He Fan , Tang Ying
Published: October 2020

Background: Due to tumor heterogeneity, the diagnosis, treatment, and prognosis of patients with lung squamous cell carcinoma (LUSC) are difficult. DNA methylation can affect tumor heterogeneity by participating in gene expression. Methods: In this study, we collected the clinical information of LUSC patients in the Cancer Genome Atlas (TCGA) database and the relevant methylated sequences of the University of California Santa Cruz (UCSC) database to construct methylated subtypes and performed prognostic analysis. Results: 965 potential independent prognosis methylation sites were finally identified and the genes were identified. Based on consensus clustering analysis, seven subtypes were identified by using 965 CpG sites and corresponding survival curves were plotted. The prognostic analysis model was constructed according to the methylation sites’ information of the subtype with the best prognosis. Internal and external verifications were used to evaluate the prediction model. Conclutions: Models based on differences in DNA methylation levels may help to classify the molecular subtypes of LUSC patients, and provide more individualized treatment recommendations and prognostic assessments for different clinical subtypes. GNAS, FZD2, FZD10 are the core three genes that may be related to the prognosis of LUSC patients.
Post Traumatic Stress Disorder and Death Anxiety Symptoms During the Coronavirus Epidemic in 2019: A Cross-Sectional Study Based on the Affected Population
Authors: Zhang Qian , Zheng Rujun , Fu Yan , Mu Qianqian , Li Junying
Published: October 2020

Background Mental health is an important aspect of the management public health emergencies.While extensive research is being conducted on various aspects of the COVID-19 epidemic, one of the factors overlooked is death anxiety. Methods A cross-sectional study based on the results of an online survey. The survey was conducted one month after the outbreak (February 18–29, 2020) and repeated at the time of resuming activity (April 8–14, 2020). The 15-item Death Anxiety Scale (T-DAS) was used to assess the degree of death anxiety, and the revised 23-item Stanford Acute Stress Response Questionnaire (SASRQ) assessed PTSD symptom clusters. Through convenient sampling, a total of 7678 cases were collected. Results: Between the first and second surveys, the number of individuals with high death anxiety rose from 48.1–53.2%, while the incidence of PTSD increased from 7–10.4%. PTSD was found to be significantly associated with living community contact history, poor health status of participants, history of life-threatening experiences, high death anxiety level, and non-medical occupation. Compared with other occupations, medical staff suffer more lasting death anxiety during the COVID-19 epidemic. Conclusions: During the COVID-19 epidemic, adverse psychological symptoms were prevalent among the general population in China.High death anxiety also was an important factor affecting PTSD.Therefore, means to address death anxiety must be included in the plan for the management of psychological effects of public health emergency and high-risk groups such as medical personnel should receive targeted intervention.
Gold Nanoparticles Induce Cell Stress by Interfering with the Cellular Protein Quality Control System
Authors: Zhang Guofang , Song Qingle , Zhang Yuqian , Liang Ruijing , Chen Liang , Monteiro-Riviere Nancy , Boraschi Diana , Chang Yan-Zhong , Li Hongchang , Li Yang
Published: October 2020

The cellular protein quality control (PQC) system ensures the intracellular misfolded/unfolded proteins to be detected and eliminated. ER-associated degradation (ERAD) and unfolded protein response (UPR) are the key mechanisms of PQC, which maintain protein homeostasis and ensure cell survival. Here, we show that after internalization by human epithelial cells, gold (Au) nanoparticles (NPs) localized in endoplasmic reticulum (ER) and induced an accumulation of misfolded/unfolded proteins. Au NPs activated UPR, but suppressed ERAD shown by a reduced degradation rate of the ERAD marker CD3-δ-YFP, which triggered ER stress through IRE1-XBP1-Chaperones and PERK-eIF2α-ATF4-CHOP pathways. The Au NP-dependent ER stress consequently induced the intracellular accumulation of ROS, and caused cell apoptosis/death, concomitant to production/release of inflammatory cytokines and chemokines. This study for the first time shows that NPs can interfere with the cellular PQC system by impairing ERAD activity, which in turn initiates a cascade of events leading to cell death and inflammation.
Anion-Exchange-Mediated Internal Electric Field: Boosting Photogenerated Carrier Separation and Utilization
Authors: Li Yadong , Han Tong , Cao Xing , Sun Kaian , Peng Qing , Cheong Weng-Chon , Chen Zheng , Lin Rui , Zhao Di , Zhuang Zewen , Chen Chen , Wang Dingsheng
Published: October 2020

Constructing heterojunctions is a commonly used method for heterogeneous photocatalysts to modulate the internal electric field (IEF); however, this method suffers from narrow IEF distribution (primarily limited at the heterojunction interface) and long migration paths of photocarriers, and therefore results in suboptimal efficiencies in carrier separation and utilization. In this work, we report for the first time novel basic bismuth nitrate compound nanorods (denoted as BOH NRs) featuring surface-exposed open channels and a simple chemical composition; by simply modifying the bulk anion layers to overcome the limitations of heterojunctions, the bulk IEF could be readily modulated. A low exchange ratio (~10%) with halide anions (I–, Br–, Cl–) would give rise to a prominent elevation in carrier separation efficiency; for the reaction of photocatalytic oxidative coupling of benzylamine, the conversions over the modified catalysts are 1.6–2 times as high as that over pristine BOH. Benefiting from the unique crystal structure and the localization of valence electrons, the IEF intensity increases with the atomic number of introduced halide anions, leading to an enhanced efficiency of carrier separation and utilization. Our work here offers new insights into the design and optimization of semiconductor photocatalysts.
Anthelminthic Efficacy of Fenbendazole and Levamisole in Native Fowl in Northern Iran
Authors: Soudkolaei Saemi , Kalidari Gholam Ali , Borji Hassan
Published: October 2020

Background: With the number of free-range domestic chickens increasing, helminth parasites have potentially become more of a threat in commercial flocks in recent years, and routine poultry worming is needed to improve chicken products. The present study deals with a field trial to study the efficiency of two generally used anthelmintics as fenbendazole and levamisole, against gastrointestinal nematodes of domestic chickens in the north of Iran. Methods: Out of 45 domestic chickens flocks that agreed to the study, 20 flocks were selected to participate in fecal egg count reduction testing based on flock size from April 2017 to September 2018. The infected chickens were randomly distributed into three equal groups of each (n = 30). Ninety chickens in the infected groups received one of the following treatments (d 0 of treatment): Group 1: 5 mg kg−1 body weight (BW) of fenbendazole for three continuous days, Group 2: 16 mg kg−1 BW of Levamisole, and Group 3: placebo; water + DMSO (the control). The efficiency of the treatments was evaluated by comparing fecal egg count in the treated groups and control group.Results: Examination of 3 herds of chickens from the control group showed that the animals were infected with gastrointestinal nematodes by 95.0% with an average geometric value of 361 eggs per gram of feces. The substance fenbendazole at a dose of 5 mg/kg b/w for three days against gastrointestinal nematodes showed an efficiency of 83.7% (P ≥0.05), and the substance levamisole at a dose of 16 mg/kg b/w showed 71.8% (P ≥0.05) with geometric mean eggs in a gram of feces 100 and 199.6, respectively. In general, the initial substances of fenbendazole and leamisole showed significantly lower activity.. The result of this study revealed that fenbendazole was a better effective dewormer than levamisole on the three Iranian domestic chicken flocks, but it is not significant. Capillaria spp., were the most generally resistant nematodes followed by Trichostrongylus spp., and Amidostomum anseris.Conclusion: Our results indicated there is a reduction efficacy in fenbendazole and levamisole in three Iranian domestic chicken flocks. Given the results of our study, it appears possible that resistance may be expected in the helminth parasite of poultry. Additional studies with a larger scale are required to determine the prevalence of anthelminthic resistance in the poultry industry.
Identification of Co-Expressed Genes Promoting CD8+ T Cell Infiltration in Melanoma Tumor Microenvironments
Authors: Yan Kexin , Wang Yutao , Xiao Ting
Published: October 2020

Purpose: To identify CD8+ T cell-related factors and the co-expression network in melanoma, to illustrate the interactions among CD8+ T cell-related genes in the melanoma tumor microenvironment.Method: We obtained melanoma and para-carcinoma tissue mRNA matrices from TCGA-SKCM and GSE65904. The CIBERSORT algorithm was used to assess CD8+ T cell proportions and the “estimate” package was used to assess melanoma tumor microenvironment purity. Weighted gene co-expression network analysis was used to identify the most related co-expression modules in TCGA-SKCM and GSE65904. Subsequently, a co-expression network was built based on the common results in the two cohorts. Results: Nine co-expressed genes (CCL5, GAP5, GZMA, GZMH, IRF1, LAG3, PRF1, NKG7, PSMB10) were identified as CD8+ T cell-related genes that promoted infiltration of CD8+ T cells, which were enriched in the cellular response to interferon−gamma process and antigen processing and presentation of peptide antigen. In the low expression level group, inflammation and immune responses were weaker, and the tumor purity was higher, suggesting that these genes were immune protective factors that improved the prognosis of melanoma. Besides this, co-expression factors negatively correlated with angiogenesis factors and positively correlated with angiogenesis inhibitors. Conclusion: These nine co-expressed genes promote high levels of infiltration of CD8+ T cells by the cellular response to the interferon−gamma process. The mechanism might provide new pathways for treatment of patients who are insensitive to PD-1 immunotherapy due to low degrees of CD8+ T cell infiltration.
Genomic Characterization of A Multidrug-Resistant Citrobacter Freundii Strain ZT01-0079 Co-Producing blaNDM-1 and blaSHV-12 Using MiSeq and MinION
Authors: Zhang Tingyan , Lin Yanfeng , Li Zhonghong , Liu Xiong , Li Jinhui , Li Lizhong , Wang Kaiying , Liu Zhongdong , Lu Lanfen , Li Peng , Wang Hongyan
Published: October 2020

Background: The emergence of multi-drug resistant Citrobacter freundii poses daunting challenges to the treatment of clinical infections. The purpose of this study was to characterize the genome of a C. freundii strain with an IncX3 plasmid encoding both the blaNDM-1 and blaSHV-12 genes.Methods: Strain ZT01-0079 was isolated from a clinical urine sample. The Vitek2 system was used for identification and antimicrobial susceptibility testing. The presence of blaNDM-1 was detected by PCR and sequencing. Conjugation experiments and Southern blotting were performed to determine the transferability of the blaNDM-1- carrying plasmid. Nanopore and Illumina sequencing were performed to better understand the genomic characteristics of the strain.Results: Strain ZT01-0079 was identified as C. freundii, and the coexistence of blaNDM-1 and multiple drug resistance genes was confirmed. Electrophoresis and Southern blotting showed that blaNDM-1 was located on a ~53kb IncX3 plasmid. The NDM-1-encoding plasmid was successfully transferred at a frequency of 1.68×10−3. Both blaNDM-1 and blaSHV-12 were located on the self-transferable IncX3 plasmid.Conclusion: The rapid spread of the IncX3 plasmid highlights the importance of continuous monitoring of the prevalence of NDM-1-encoding Enterobacteriaceae. Mutations of existing carbapenem resistance genes will bring formidable challenges to clinical treatment.
How Can We Improve Patients’ Access to New Drugs Under Uncertainties? : South Korea’s Experience with Risk Sharing Arrangements
Authors: Lee Boram , Bae Eun-Young , Bae SeungJin , Choi HyunJin , Son Kyung-Bok , Lee Young-Sil , Jang Suhyun , Lee Tae-Jin
Published: October 2020

Background: New drugs including cancer drugs and orphan drugs are becoming increasingly more expensive. Risk sharing arrangements (RSAs) could manage the risk based on both financial impact and the health outcome of new drugs if reimbursed. To improve patients’ access to new drugs under uncertainties, many developed countries have adopted RSAs. In this study, we aimed to understand the effects of RSAs in South Korea on patients’ access.Methods: We reviewed current status of RSA drugs in South Korea. The number of appraisals and time gap between market approval and reimbursement per RSA drug were considered to quantify improvement of patients’ access as they showed how rapidly decisions on reimbursement of RSA drugs were derived. Then, we applied a comparative analysis to determine whether the RSA drugs in South Korea were reimbursed in the UK, Italy, and Australia. Most data for this study were obtained from websites of the governmental department/agencies responsible for appraisal of drug reimbursement in each country. And literatures related to RSAs were investigated as well.Results: The eligibility for Korean RSAs had two key components - drugs for cancer and rare diseases and not having other alternative treatments. As of the first half of 2019, there were 39 RSA drugs reimbursed in South Korea, the majority of which were financial-based schemes. Refund and expenditure cap were the representative types (89.7%). After introduction of RSAs, the time gap and number of appraisals were decreased. Based on the indications of RSA drugs, the level of drug coverage in South Korea was found lower than Italy, similar to the UK, and higher than Australia.Conclusions: RSAs in South Korea significantly enhanced patients’ access to new drugs and led to the alleviation of patients’ out-of-pocket expenses. The drug coverage of South Korea had a level comparable to that of other countries. This study provides implications for countries that have a dual mission of containing pharmaceutical expenditure and improving access to new drugs.
Synaptosomes: New Vesicles for Neuronal Mitochondrial Transplantation
Authors: Picone Pasquale , Porcelli Gaetana , Bavisotto Celeste Caruso , Nuzzo Domenico , Galizzi Giacoma , Biagio Pier Luigi San , Bulone Donatella , Carlo Marta Di
Published: October 2020

Background: Mitochondrial dysfunction is a critical factor in the onset and progression of neurodegenerative diseases. Recently, mitochondrial transplantation has been advised as an innovative and attractive strategy to transfer and replace damaged mitochondria. Here we propose, for the first time, to use rat brain extracted synaptosomes, subcellular fraction of isolated synaptic terminal that contain mitochondria, as mitochondrial delivery systems. Results: Synaptosomes preparation was validated by the presence of Synaptophysin and PSD95. Syn aptosomes were characterized in terms of dimension, zeta potential, polydispersity index and number of particles/mL. Nile Red or CTX-FITCH labeled synaptosomes were internalized in LAN5 recipient cells by a mechanism involving specific protein-protein interaction, as demonstrated by loss of fusion ability after trypsin treatment and using different cell lines. The loading and release ability of the synaptosomes was proved by the presence of curcumin both into synaptosomes and LAN5 cells. The vitality of mitochondria transferred by Synaptosomes was demonstrated by the presence of Opa1, Fis1 and TOM40 mitochondrial proteins and JC-1 measurements. Further, synaptosomes deliver vital mitochondria into the cytoplasm of neuronal cells as demonstrated by microscopic images, increase of TOM 40, cytochrome c, Hexokinase II mitochondrial proteins, and presence of rat mitochondrial DNA. Finally, by using synaptosomes as vehicle, healthy mitochondria restored mitochondrial function in cells containing rotenone or CCCp damaged mitochondria. Conclusions: Taken together these results suggest that synaptosomes can be a natural vehicle for the delivery of molecules and organelles to neuronal cells. Further, replacement of affected mitochondria with healthy ones could be a potential therapy for the treatment of neuronal mitochondrial dysfunction-related diseases.
Novel hyaluronic acid-coated polymeric micelles with ROS scavenging to encapsulate statins for alleviating atherosclerosis
Authors: Mu Dan , Li Jianhui , Qi Yu , Sun Xuan , Liu Yihai , Shen Song , Li Yuyu , Xu Biao , Zhang Bing
Published: October 2020

Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the SIM-loaded micelles demonstrated remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system can synchronically alleviate the accumulation of macrophages and oxidative stress, providing a promising and innovative option against atherosclerosis.
Attitudes of Junior Faculty Members Towards The Role of Faculty Development Program on Their Scholar Activities: The Experience in A Developing Country
Authors: Dabbagh Ali , Ahmadizadeh Seyyedeh Narjes , Behnaz Faranak , Fani Kamal , Ghasemi Mahshid , Goharani Reza , Jahangirifard Alireza , Malekianzadeh Bita , Massoudi Nilofar , Memary Elham , Moshari Mohammad Reza , Sabouri A. Sassan , Salaarian Sara , Sezari Parissa
Published: October 2020

The authors have requested that this preprint be removed from Research Square.
A Global Genome-wide Scan with Optimal Cutoff Mining for Emerging Biomarkers in Head and Neck Squamous Cell Carcinoma
Authors: Chi Li-Hsing , Wu Alexander TH , Hsiao Michael , Li Yu-Chuan (Jack)
Published: October 2020

BackgroundThe survival analysis of the Cancer Genome Atlas (TCGA) dataset is a well-known method to discover the gene expression-based prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC). In order to utilize a continuous gene expression for survival analysis, it is necessary to determine a cutoff point by the dichotomization of the patients. There is some optimization software for cutoff determination. However, those predetermined cutoffs by software usually set at the median, 1/4 quantile, or 3/4 quantile of RNA sequencing (RNA-Seq) value to find a significant P-value of the Kaplan-Meier curve. There are few clinicopathological features available on their pre-processed data sets.MethodsWe developed a comprehensive workflow by R script, running on the Rstudio platform. It includes data retrieving and pre-processing, feature selection, cutoff mining engine, Kaplan-Meier survival analysis, Cox proportional hazard modeling, and biomarker discovery.ResultsUsing this workflow on the TCGA HNSCC cohort, we scanned human protein-coding genes (20,500) programmatically. After adjustment with other confounders, we found that the clinical tumor stage and the surgical margin involvement are independent risk factors in patient survival. According to the resulting tables with Bonferroni adjusted P-value under optimal cutoff as well as hazard ratio (>=1.5), there were ten candidate biomarkers, named as DKK1, CAMK2N1, STC2, PGK1, SURF4, USP10, NDFIP1, FOXA2, STIP1, and DKC1, which are significantly associated with the poor prognosis of overall survival (OS). At the same time, the other ten genes were over-expressed in the better survival patients (with hazard ratio <=0.5), named as ZNF557, ZNF266, IL19, MYO1H, FCGBP, LOC148709, EVPLL, PNMA5, IQCN (previous name as KIAA1683), and NPB. Further validations are warranted. ConclusionsWe suggested this analysis tool equipped with an optimal cutoff finder will help with biomarker discovery of protein-coding genes, in terms of tumor-agnostic therapy.
Can Two supercutaneous locking plates be final treatment for complex tibia fracture? ----Clinical result of 39 cases and a finite element study
Authors: Ma Zhongyuan , Pei Zhiyong , Qu Yanzhen , Wu Hongbin
Published: October 2020

BackgroundSupercutaneous locking plate (SLP) has been tried to treat tibia fracture with certain success, but some inevitable problems: such as insufficient stability, screw tract inflammation and the impingement on knee and ankle joint movement have got in the way of its application. Few literature have focused on the possible solution for the above-mentioned problems, and few reports have tried the method of two SLPs.Methods43 patients received two SLPs as final treatment and 39 finished follow-up. 25 patients were open fracture and 18 of them needed skin graft, 11 patients had severe skin contusion, 3 patients had nearby soft tissue infection. Moore and Dahl pin site classification was used to record screw tract inflammation. Lysholm knee score and Kofoed ankle score were used to assess the knee and ankle function. An FE tibial fracture model was reconstructed to analyze the stiffness of different fixation.Results38 of 39 patients had bony union, the other one had clinical union. No bone infection or plate breakage was found while two screws were found broken at the rod-cap junction. FE analysis showed the structure axial stiffness (N/mm2) decreased with the plate-bone distance increased for one SLP, but two SLPs could greatly increase axial stiffness with the stiffness of SLP-2/4(364) was stronger than that of SLP-0(360.6). Function of knee and ankle was well accepted by most patients even with two plates on tibia, the lysholm knee score and kofoed ankle score was 78.9士5.0 and 72.3士7.0 respectively for two plates. When the number of plate decreased, lysholm knee score and kofoed ankle score further increased significantly. All patients had screw site inflammation: grade 2 in 25 cases; grade 3 in 14 cases. ConclusionsTwo SLPs can provide enough strength for bone union. Screw tract inflammation is inevitable, but infection could be foreseen and controlled. The impingement of SLP on knee and ankle joint movement is limited. Two SLPs maybe a good supplement treatment for complex tibia fracture.
Decades of Research Supporting Malaria Control and Elimination in China: A Bibliometric Analysis of Academic Articles Published in Chinese From 1980 to 2019
Authors: Du Yan-Qiu , Zhu Guo-Ding , Cao Jun , Huang Jia-Yan
Published: October 2020

Background: China has accumulated a lot of experience on malaria control and elimination in the past few decades. Many research papers have been published in Chinese journals. This study intends to quantitatively analyze these local journals based on the bibliometric analysis to obtain the development path and experience of malaria control and elimination in China.Methods: A long-term, multi-stage bibliometric analysis was implemented. Research articles published in Chinese journals from 1980 to 2019 were retrieved from Wanfang database and China National Knowledge Infrastructure (CNKI). Year of publication, journal name and keywords were extracted by the Bibliographic Items Co-occurrence Matrix Builder (BICOMB). We defined the K/A ratio (the percentage of a keyword frequency in the number of articles within a certain period) as an indicator for measuring the popularity of a keyword in different decades. And we used the software VOSviewer to make keyword co-occurrence network maps.Results: A total of 16,290 articles were included. The overall trend of articles continues to rise. However, the articles published in the past three years had continued to decline. There are two kinds of trends of the keyword frequency between different decades. The K/A ratio of keywords such as ‘Plasmodium falciparum’ continued to decline (17.05% in 1980s, 13.04% in 1990s, 9.86% in 2000s, 5.28% in 2010s), but ‘imported case’ and ‘surveillance’ continued to rise. Drug resistance always was a concern. The keyword co-occurrence network maps showed that the themes in malaria research were becoming more diverse, and the degree of multidisciplinary cooperation was gradually deepening.Conclusion: This bibliometric analysis reveals the trends in malaria research in China over the past 40 years. The results suggest the high attention on the investigation, multidisciplinary participation and drug resistance for researchers and policymakers in malaria-epidemic areas. And the results also provided domestic experts with qualitative evidence for the summary of China's experience on malaria control and elimination.