bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis for small molecule targeting of
Doublecortin Like Kinase 1 DCLK1
Authors: Patel Onisha , Roy Michael , Kropp Ashleigh , Dai Weiwen , Lucet Isabelle
Published: January 2021

Doublecortin-like kinase 1 (DCLK1) is a bi-functional protein classified as a Microtubule-Associated Protein (MAP) and as a serine/threonine kinase that plays a critical role in regulating microtubule assembly. This understudied kinase is upregulated or mutated in a wide range of cancers. Knockdown studies have shown that DCLK1 is functionally important for tumour growth. However, the presence of tissue and development specific spliced DCLK1 isoforms and the lack of systematic evaluation of their biological function have challenged the development of effective strategies to understand the role of DCLK1 in oncogenesis. Recently, DCLK1-IN-1 was reported as a potent and selective DCLK1 kinase inhibitor, a powerful new tool to dissect DCLK1 biological functions.
Here, we report the crystal structures of DCLK1 kinase domain in complex with two DCLK1-IN-1 precursors and DCLK-IN-1. Combined, our structural data analysis illuminates and rationalises the structure-activity relationship that informed development of DCLK1-IN-1 and provides the basis for DCLK1-IN-1 increased selectivity. We show that DCLK1-IN-1 induces a drastic conformational change of the N-lobe, which uncovered a new allosteric site. In addition, we demonstrate that DCLK1-IN-1 binds DCLK1 long isoforms with high affinity but does not prevent DCLK1 MAP function. Together, our work outlines the need for in-depth studies to rationally design of isoform-specific modulators and provides an invaluable structural platform to further the design of selective DCLK1 therapeutic agents.
Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-analysis
Authors: Degarege Abraham , Naveed Zaeema , Kabayundo Josiane , Brett-Major David
Published: January 2021

Objectives This systematic review and meta-analysis synthesized the evidence on the impact of demographics and comorbidities with clinical outcomes of COVID-19, including severe illness, admission to the intensive care unit (ICU), and death.MethodsThe PRISMA guidelines were followed to conduct and report this meta-analysis. The protocol is registered in PROSPERO International prospective register of systematic reviews (ID=CRD42020184440). Two authors independently searched literature from PubMed, Embase, Cochrane library and CINHAL on May 6, 2020; removed duplicates; screened titles, abstracts and full text using criteria; and extracted data from eligible articles. A random-effects model was used to estimate the summary odds ratio (OR). Variations among studies were examined using Cochrane Q and I2.ResultsOut of 4,275 articles obtained from the databases and screened, 71 studies that involved 216,843 patients were abstracted and then, where appropriate, analyzed by meta-analysis. The COVID-19 related outcomes reported were death in 26 studies, severe illness in 41 studies, and admission to ICU in 11 studies. Death was significantly correlated with hypertension (OR 2.60, 95% CI 1.95–3.25, I2 = 52.6%, n= 13 studies), cardiovascular disease (5.16, 4.10–6.22, 0.0%, 6), diabetes (2.11, 1.35–2.87, 67.4%, 12), chronic respiratory disease (2.83, 2.14–3.51, 0.0%, 9), cerebrovascular diseases (5.14, 1.08–9.19, 0.0%, 2), male sex (1.34, 1.18 – 1.50, 38.7%, 16), age older than 60 (6.09, 3.53 – 8.66, 95.5%, 6) or 65 years (3.56, 1.21 – 5.90, 18.2%, 6). Severe illness was also significantly associated with hypertension (1.70, 1.30 –2.10, 47.8%, 21), cardiovascular diseases (2.04, 1.01–3.08, 30.6%, 10), diabetes (1.65, 1.23–2.08, 24.9%, 18), male sex (1.35, 1.23 – 1.47, 0.0%, 32) and age at least 60 (4.91, 1.35 – 8.47, 0.0%, 4) or 65 (2.55,1.94 – 3.17, 24.5%, 9) years. Among hospitalized patients, the odds of admission to ICU was greater in individuals who had cardiovascular diseases (1.36,1.04–1.69, 0.0%, 4), diabetes (1.55, 1.20–1.90, 0.0%, 5) and chronic respiratory disease (1.52, 1.09–1.94, 0.0%, 5) than those who were not having these comorbidities. ConclusionsOlder age and chronic diseases increase the risk of developing severe illness, admission to ICU and death among COVID-19 patients. Special strategies are warranted to prevent SARS-CoV-2 infection and manage COVID-19 cases in those with vulnerabilities.
Demographic, Practice and Clinical Management Characteristics of Osteopaths Referring to, and Receiving Referrals from, Podiatrists: Secondary Analysis of a Nationally Representative Sample of Australian Osteopaths.
Authors: Fleischmann Michael , Vaughan Brett , Bird Adam , Grace Sandra , Fitzgerald Kylie , McLeod Gopi
Published: January 2021

Background Interprofessional care is paramount in contemporary healthcare practice. How different professions interact, and the characteristics of those practitioners who practice in an interprofessional way are rarely described in the literature. The aim of the current work was to identify the demographic, practice and clinical management characteristics of Australian osteopaths who report referring to, and receiving referrals from, podiatrists Methods The study was a secondary analysis of data from the Osteopathy Research and Innovation Network (ORION). Inferential statistics were generated to identify statistically significant demographic, practice and clinical management characteristics associated with referrals. Significant characteristics were then entered into a backward logistic regression model. Results Nine-hundred and ninety-two Australian osteopaths responded to the questionnaire. Sending referrals to a podiatrist was reported by 651 participants (65.6%) and receiving referrals from a podiatrist by 471 participants (47.5%). Australian osteopaths who reported referring to podiatrists were more likely to report receiving referrals from podiatrists (ORadj 10.82) and use diagnostic imaging (ORadj 9.87). Receiving referrals from a podiatrist was associated with sending referrals to a podiatrist (ORadj 10.04) and also being co-located with a podiatrist (ORadj 2.02). Conclusion This study provides initial evidence for the referral relationship between Australian osteopaths and podiatrists. Further work is now required to understand the nature of these referrals, including the complaints resulting in referral and outcomes of care. This information will be invaluable to those involved in health policy development and the professions advocating for their role in the wider healthcare system.
Causal Relationship between Educational Attainment and the Risk of Rheumatoid Arthritis: A Mendelian Randomization Study
Authors: Huang Guiwu , Cai Jiahao , Li Wenchang , Zhong Yanlin , Liao Weiming , Wu Peihui
Published: January 2021

Background Educational attainment is moderately heritable and positively associated with the risk of rheumatoid arthritis. However, the causality from educational attainment on rheumatoid arthritis remained unknown. Here, we aimed to determine whether educational attainment is causally associated with rheumatoid arthritis (RA) by using a Mendelian randomization (MR) approach.Methods Summary statistics data for RA were obtained from an available, published meta-analysis of genome-wide association studies (GWAS) that included 14,361 RA cases and 43,923 controls of European ancestry. The instrumental variables for educational attainment were obtained from a GWAS meta-analysis that included over 1 million individuals (N = 1,131,881) of European ancestry. MR analyses were performed using the inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Sensitivity analyses were performed to test the robustness of the association using the Cochran Q test, MR Egger intercept test, “leave-one-out” analysis and MR-PRESSO test.Results A total of 387 SNPs were employed as instrumental variables in our MR analysis. Genetically predicted higher educational attainment was associated with a significantly lower risk of RA using the IVW method (odds ratio [OR] = 0.42, 95% confidence interval [CI]: 0.34–0.52; p = 1.78×10−14). The weighted median and MR Egger methods yielded consistent results. The causality remained robust after discarding the outlier variants and SNPs associated with the confounding factors. "Leave-one-out" analysis confirmed the stability of our results. Additionally, the results demonstrated the absence of the horizontal pleiotropy.Conclusions The MR analysis supported a potential inverse causative relationship between educational attainment and the risk of RA.
Patient-Reported Noninfectious Comorbidities in Chinese HIV-Infected Patients: The Gaps Among Self-Awareness, Diagnosis, and Prevalence
Authors: Chen Jun , Lu Hongzhou , Liu Shuiqing , Liu Jun , Ding Haibo , Wang Rugang , Meng Zhihao , Zhang Peng , Wei Yinghua , Wang Lijing , Yang Jie , Zhang Jian , Zhao Qingxia , Chen Xiaohong , Ou Ruzhi , He Yuanhong , Chen Yahong , Chen Juan , Wang Min , Zhu Biao , Chen Yaokai , Jin Juan , Liu An , Zhou Yang , Gao Guijv , Ma Ping , Wei Hongxia , Su Feifei , Ruan Lianguo , Jiang Tianjun , Zheng Nanhong , Yu Jianhua , Xu Guangyong , Qian Feng , Huang Cenmian , Du Lingyao , Wang Na , Zhou Huiling , Peng Jie
Published: January 2021

Background: This study was performed to investigate the gaps among patient-reported data, physician-reported data, and laboratory test data in human immunodeficiency virus (HIV)-infected patients and to detect potential risk factors for the awareness gap. Methods: We included patients from 38 hospitals in China. Patient-reported data, physician-reported data, and laboratory test data on four typical noninfectious comorbidities (NICMs) (osteoporosis, kidney disease, neuropsychiatric comorbidities, and atherosclerotic cardiovascular disease (ASCVD)) were collected. We compared differences in and consistency of these types of data and investigated the associations between baseline characteristics and the awareness gap between patients and physicians. Results: This study included 1390 patients. The difference between the diagnosis rate and laboratory test positivity rate for all NICMs was significant. Patient-reported data on the three NICMs other than kidney disease were significantly different from the diagnosis rates. The agreement between patients and physicians for all NICMs was poor. The region, infection stage, hospital level, sex, and age influenced the awareness gap between patients and physicians. Conclusions: Our findings suggest that NICMs in HIV-infected patients in China are underestimated; gaps among patient awareness of disease exist, the clinical diagnosis rate, and the actual prevalence; patient characteristics influence the awareness gap between patients and physicians.
A Science-Policy Framework for a Green Economic Recovery After the COVID-19 Pandemic
Authors: Zachariadis Theodoros , Giannakis Elias , Taliotis Constantinos , Karmellos Marios , Fylaktos Nestor , Howells Mark , Blyth William , Hallegatte Stephane
Published: January 2021

As current production and consumption patterns of humanity exceed planetary boundaries, many opinion leaders have stressed the need to adopt green economic stimulus policies in the aftermath of the COVID-19 pandemic. Here, we provide an integrated multi-stakeholder framework to design an economic recovery strategy aligned with sustainability objectives. We first employ quantitative energy and economic models and then design a multi-criteria decision process in which we engage social actors from government, enterprises, and civil society. As a case study, we select green recovery measures that are relevant for a European Union country and assess their appropriateness with numerous criteria related to socio-economic and environmental sustainability and resilience. Results highlight trade-offs between immediate and long-run effects, between economic and environmental objectives, and between expert evidence and societal priorities. Importantly, we find that a ‘return-to-normal’ economic stimulus is not only environmentally unsustainable but also economically inferior to most green recovery schemes.
Periodontal Health and Chronic Obstructive Pulmonary Disease (COPD) Exacerbations: A Systematic Review
Authors: Kelly Niamh , Winning Lewis , Irwin Christopher , Lundy Fionnuala , Linden Dermot , McGarvey Lorcan , Linden Gerard , karim Ikhlas El
Published: January 2021

BackgroundA growing body of evidence suggests a role for oral bacteria in lung infections. This systematic review aimed to analyse the association between poor periodontal health and the frequency of chronic obstructive pulmonary disease (COPD) exacerbations. MethodsPubMed, Embase, Web of Science, CINAHL and Medline were searched for studies published until May 2020, with no language restriction. Studies reporting periodontal condition, or periodontal treatment outcomes, with data on the frequency of exacerbations of COPD, were identified. The primary outcome was the frequency of exacerbations and secondary outcomes included quality of life and hospitalisation. Studies were assessed for eligibility and quality by two assessors independently.Results Searches identified 532 records and 8 met the inclusion criteria. The data from intervention studies showed reduction in the frequency of exacerbations following periodontal treatment. Data from observational studies suggest association of worse plaque scores with exacerbation but not pocket depth or clinical attachment loss. Better periodontal health was also associated with reduced frequency of COPD exacerbations, hospitalisations and improved quality of life in COPD patients. Due to the high heterogeneity no meta-analysis was performed. The quality of some of the included studies was low and there was evidence of high risk of bias.ConclusionThe data supports possible association between poor periodontal health, the frequency of exacerbations and quality of life in COPD patients. The evidence is limited by high risk of bias suggesting need for well-designed and adequately powered randomised control trials.The PROSPERO registration number CRD42020180328
Diagnostic Utility of PD-L1 and TP-53 mRNA As Well As microRNAs Expression in Liquid Biopsy of NSCLC Patients – Pilot Study
Authors: Grenda Anna , Kuźnar-Kamińska Barbara , Krzyżanowska Natalia , Krawczyk Paweł , Janiszewska Mariola , Batura-Gabryel Halina , Milanowski Janusz
Published: January 2021

Introduction The expression of PD-L1 (programed cell death ligand 1) protein on neoplastic cells is a factor qualifying cancer patients for immunotherapy. However, the status of PD-L1 mRNA expression in plasma or serum has not been well studied in cancer patients. TP-53 (Tumor Protein p53) as tumor suppressor affects the expression of many genes, including microRNAs that regulate PD-L1 expression. Purpose of our study was to evaluate usefulness of analysis of PD-L1 mRNA, microRNAs and TP-53 mRNA expression in liquid biopsy in non-invasive diagnosis of non-small cell lung cancer patients (NSCLC).Material and methods We examined the expression the expression of TP-53 and PD-L1 mRNA as well as seven microRNAs (miR-17, miR-93, miR-142, miR-519, miR-526, miR-34a-5p and miR-34a-3p) in plasma obtained from 80 NSCLC patients and 39 healthy volunteers. We used quantitative PCR preceded by reverse transcription method.Results We observed PD-L1 mRNA expression only in 6 (7.5%) NSCLC patients. We showed that expression of TP-53 mRNA and each tested microRNAs were significantly higher in healthy person than in NSCLC patients. Based on the Receiver Operating Characteristic (ROC) analysis, we found that TP-53 mRNA and each of examined microRNAs expression were good diagnostic markers for non-invasive diagnosis of NSCLC. We found a significant, negative correlation between TP-53 mRNA and miR-17 (R=-045, p=0.0005) as well as miR-34a-5p (R=-0.32, p=0.04) expression in patients with advanced NSCLC.Conclusion The decreased expression of TP-53 mRNA may influence the disruption of microRNAs which could be involved in the regulation of PD-L1 expression in NSCLC patients
Neurological Manifestations as the Predictors of Severity and Mortality in Hospitalized Individuals with COVID-19: A Multicenter Prospective Clinical Study
Authors: Amanat Man , Rezaei Nima , Roozbeh Mehrdad , Shojaei Maziar , Tafakhori Abbas , Zoghi Anahita , Darazam Ilad Alavi , Salehi Mona , Karimialavijeh Ehsan , Lima Behnam Safarpour , Garakani Amir , Vaccaro Alexander , Ramezani Mahtab
Published: January 2021

Backgrounds: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. Methods: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for eight weeks after discharge and 16 weeks if their symptoms had no improvements. Results: We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n=10) and status epilepticus (n=1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after eight weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n=1) and Guillain-Barré syndrome (n=1) were also found during follow-up.Conclusion: Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.
The minimal COVID-19 vaccination coverage and efficacy to compensate for potential increase of transmission contacts, and increased transmission probability of the emerging strains
Authors: Tang Biao , Zhang Xue , Li Qian , Bragazzi Nicola , Golemi-Kotra Dasantila , Wu Jianhong
Published: January 2021

Background: Mass immunization is a potentially effective approach to finally control the local outbreak and global spread of COVID-19 pandemic. However, it can also lead to undesirable outcomes if mass vaccination results in increased transmission effective contacts and relaxation of other public health interventions due to the perceived immunity from the vaccine. Methods: We designed a mathematical model of COVID-19 transmission dynamics that takes into consideration the epidemiological status, public health intervention status (quarantined/isolated), immunity status of the population, and the strain variations. Comparing the control reproduction numbers and the final epidemic sizes (attack rate) in the cases with and without vaccination, we quantified some key factors determining when vaccination in the population is beneficial for preventing and controlling future outbreaks. Results: Our analyses predicted that there is a critical (minimal) vaccine efficacy rate (or a critical quarantine rate) below which the control reproduction number with vaccination is higher than that without vaccination, and the final attack rate in the population is also higher with the vaccination. We also predicted the worst case scenario occurs when a high vaccine coverage is achieved for a vaccine with lower efficacy rate and when the vaccines increase the transmission efficient contacts.Conclusions: The analyses show that an immunization program with a vaccine efficacy rate below the predicted critical values will not be as effective as simply investing in the contact tracing/quarantine/isolation implementation. We reached similar conclusions by considering the final epidemic size (or attack rates). This research then highlights the importance of monitoring the impact on transmissibility and vaccine efficacy of emerging strains.
Perceived Quality of Life and Associated Factors Among Patients with Severe Mental illness in Ethiopia: A Cross-sectional Study
Authors: Shumye Seid , Amare Tadele , Derajew Habtamu , Endris Merdia , Mengistu Nebiyu , Belayneh Zelalem
Published: January 2021

Background: Severe mental illness is strongly associated with an impaired quality of life. This intern can affect the treatment adherence and outcomes of the illness. However, due attention was not given this alarming issue Therefore; assessment of quality of life of patients with severe mental illness and its correlates is a yardstick measure for the effectiveness of the mental health service.Methods: An institutional based cross-sectional study was conducted from May 1 to 16, 2018 at Amanuel Mental Specialized Hospital. A systematic random sampling technique was used to get a total number of 394 samples. Data were collected using interview-administered questionnaires. World Health Organization Quality of Life Brief Version, The collected data were coded, entered into EpiDATA version 3.1 and analyzed by using SPSS version 20. Simple and multiple linear regression analysis were used to assess the contributing factors of quality of life in the participants and B coefficient with 95% CI confidence interval was used. The statistical significance was accepted at p-value < 0.05.RESULT: Mean quality of life score of patients with severe mental illness for each domain (mean± SD) was 41.3±7.5, 42.8±8.2, 38.9±8.9, and 41.8±6.5 for physical, psychological, social and environmental, respectively. Multiple regression analysis showed the age of participants was strongly positively correlated with all domains of quality of life. It predicts above 45% of the variability in each domain. Social support is also another strong predictor which was negatively correlated with all domains of quality of life, except physical. Conclusion: The study revealed that the mean score quality of life of patients with severe mental illness in each domain was low. This demonstrates a need for improving quality of among people with severe mental illness. Moreover, prevention and early intervention of co-morbid medical conditions is also recommended too.
Optimal design method of sealing depth in methane drainage boreholes to realize efficient drainage
Authors: Yi Minghao , Wang Liang , Hao Congmeng , Liu Qingquan , Wang Zhenyang
Published: January 2021

The purpose of underground methane drainage technology is to eliminate methane disasters and enable the efficient use of coal mine methane (CMM). The sealing depth is a key factor that affects the underground methane drainage performance. In this work, the layouts of bedding and crossing boreholes were considered to analyze the stress distribution and failure characteristics of roadway surrounding rocks through a numerical simulation and field stress investigation to determine a reasonable sealing depth. The results demonstrated that the depths of the plastic zone and elastic zone in the Xutuan and Qinan coal mines were 16 m and 20 m, respectively. Borehole sealing could minimize the air leakage through the fractures around the roadway when the sealing material covered the failure and plastic zones. In addition, the field test results of CMM drainage at different sealing depths indicated that the CMM drainage efficiency increased with an increase in the sealing depth and not change when the sealing depth exceeded the plastic zone. Moreover, sealing in the high permeability roadway surrounding rock did not strongly influence the borehole sealing performance. Considering these findings, a new CMM drainage system for a specific sealing depth and length was developed, which could effectively improve the CMM drainage efficiency and prolong the high concentration CMM drainage period. The proposed approach can be a valuable quantitative analysis method to select the optimized sealing parameters for underground methane drainage, which can considerably improve the drainage and utilization rates of CMM.
Future Challenges of Nursing in Health System of Iran
Authors: Barasteh Salman , rassouli Maryam , Karimirad Mohammad Reza , Ebadi Abbas
Published: January 2021

Background: Nursing development is considered as one of the most important ways to achieve the universal health coverage and sustainable develop goals in different countries. Nursing in Iran has the potential to provide services at all levels of universal health coverage. Therefore, planning for nursing in Iran needs to recognize the future challenges. This study aims to explore the future challenges of nursing in the health system of Iran from the view of expertsMethods: In this qualitative study, 11 semi-structured interviews were conducted with nursing experts by purposive sampling in 2017-2018. Interviews were recorded and transcribed and framework analysis method were used to analysis the data.Results: The results showed that a favorable future requires planning in three areas of nursing governance challenges, including centralized nursing stewardship, policy-making and legislation, monitoring and evaluation, and cooperation and communication with other institutions, inadequacy of professional development with social demands, including community-based nursing, nursing upgrades with disease patterns, expanding home care, expanding care centers, and use of technology, the challenge of human resource management, including nursing education tailored to the needs of the community, empowering nursing managers, recruiting and retaining nurses, and specialized nursing.Conclusions: A favorable future requires establishing a coherent nursing government, professional developing of nursing based on social demands, and enhancing human resources in line with the emerging needs of the future.
CpG Methylation of the GPX3 Promoter in Patients with Kashin-Beck Disease Potentially Promotes Chondrocyte Apoptosis
Authors: Zhang Rongqiang , Zhang Di , Yang Xiaoli , Zhang Dandan , Li Qiang , Wang Chen , Yang Xuena , Xiong Yongmin
Published: January 2021

Objective: To determine the methylation levels of CpGs in the GPX3 promoter region and explore their potential effects on the apoptosis of chondrocytes.Methods: Blood specimens were collected from 32 participants, including 16 KBD patients and 16 healthy subjects. Twenty-five CpGs in the promoter region of GPX3 were identified and detected by MALDI-TOF-MS. Methylation levels of CpGs were compared between KBD patients and healthy subjects as well as among the KBD patients with different degrees. C28/I2 human chondrocytes were treated with tBHP and Na2SeO3. Apoptosis in chondrocytes was examined under a fluorescence microscope.Results: The methylation levels of GPX3-8_CpG_11, GPX3-8_CpG_16, GPX3-8_CpG_20 in KBD patients were significantly higher than those of healthy subjects (P <0.05). The methylation levels of the other CpGs were not significantly different between the two groups (P> 0.05). The methylation level of GPX3-8_CpG_24 in KBD patients with degree III was significantly higher than those in KBD patients with degree I/II (P <0.05) MSP-PCR analysis indicated that the methylation rate of KBD group (9.41%) was significantly higher than that of healthy subjects (1.18%), and that GPX3 DNA methylation increased the risk of acquiring KBD 8 fold (OR = 8.000, 95% CI : 1.023-62.580); The mRNA expression of GPX3 in whole blood of KBD patients was lower than that of healthy subjects (P＜0.05); Compared with the control group, GPX3, GPX1 and GPX4 mRNA level of the tertbutyl hydroperoxide injury group decreased significantly (P <0.05), after supplementation with Na2SeO3. The logarithmic increase in mRNA levels of GPX3, GPX1 and GPX4 decreased the rate of apoptosis in chondrocytes.Conclusion: The methylation patterns of CpGs in GPX3 varied in KBD patients. The experiments indicated that the increased methylation of CpGs within the GPX3 promoter may down-regulate the expression of GPX3, thereby reducing the antioxidant function of GPX3 and promoting chondrocyte apoptosis, both of which accelerates the development of KBD.
Potato Growth, Photosynthesis, Yield, and Quality Response to Regulated Deficit Drip Irrigation under Film Mulching in A Cold and Arid Environment
Authors: Li Fuqiang , Deng Haoliang , Wang Yucai , Li Xuan , Chen Xietian , Liu Lintao , Zhang Hengjia
Published: January 2021

The effects of the amount and timing of regulated deficit drip irrigation under plastic film on potato (‘Qingshu 168’) growth, photosynthesis, yield, water use efficiency, and quality were examined from 2017 to 2019 in cold and arid northwestern China. A two-factor randomized design was used with two levels of regulated deficit irrigation (mild, moderate) applied in four stages of potato growth (seedling, tuber initiation, tuber bulking, starch accumulation). Growth and photosynthetic parameters were determined in each growth stage, and yield and quality were measured after harvest. The net photosynthetic rate, stomatal conductance, and transpiration rate decreased significantly under water deficit in the tuber formation and starch accumulation stages, and the decreases were greater with moderate than mild water deficit. Although water deficit reduced potato yields, potato subjected to mild water deficit in the seedling stage had the highest yield at 43,961.91 kg·ha−1, followed by those subjected to mild water deficit in the starch accumulation stage at 42,262.25 kg·ha−1, which were decreases of only 4.50% and 8.19%, respectively, compared with potato under full irrigation. The highest water use efficiency was in potatoes subjected to mild water deficit in the seedling stage (8.67 kg·m−3), with the second highest in those subjected to moderate water deficit in the seedling stage (8.28 kg·m−3), which were significant improvements by 10.87% and 5.84%, respectively, compared with full irrigation. The highest overall quality was in potatoes subjected to mild and moderate water deficit in the seedling stage. The starch content in potatoes with mild water deficit in the seedling stage increased by 3.34% compared with that under full irrigation. In addition, the protein and vitamin C contents in potatoes under moderate water deficit increased significantly by 0.77% and 21.59%, respectively, compared with the contents under full irrigation. Principal component analysis identified mild water stress in the seedling stage as the optimum regulated deficit irrigation regime for potato. Thus, the relative soil water content should be maintained at 55% to 65% of field capacity in the seedling stage but at 65% to 75% in the other growth stages. The results of this study provide theoretical and technical references for efficient water-saving cultivation and industrialization of potato in cold and arid northwestern China.
Comparative Role of Compost, Press Mud and Moringa Leaf Extract to Eliminate the Stress and Growth of Maize in Cadmium Polluted Soil
Authors: Bashir Saqib , Elshikh Mohamed Soliman , Alwahibi Mona S , Gulshan Allah , Iqbal Javaid , Hussain Arif , Bakhsh Ali , Ahmed Niaz , Khan Muhammad Jamal , Fahad Shah , Datta Rahul , Danish Subhan
Published: January 2021

Cadmium contamination in croplands is recognized as one of the major threats, seriously affecting soil health and sustainable agriculture around the globe. Cd mobility in wastewater irrigated soils can be curtailed through eco-friendly and cost effective organic soil amendments compost (CP), press mud (PM) and moringa leaf extract (ME) at 3% rate that eventually reduces its translocation from polluted soil to plant. This study explored the possible effects of various types of organic soil amendments on cadmium (Cd) phytoavailability in wastewater degraded soil and its subsequent accumulation in maize tissues. Maize plant was grown in Ghazi University as a test plant and Cd accumulation was recorded in its tissues, translocation from root to shoot, chlorophyll contents, plant biomass, yield and soil properties (pH, NPK, OM and Soluble Cd) were also examined. Results revealed that the addition of amendments significantly minimized Cd mobility in soil by 45.8%, 23% and 19.4% when CP, PM and ME were added at 3% over control. Comparing the control soil, Cd uptake effectively reduced via plants shoots by 33.3%, 27.7% and 19.4% when CP, PM and ME. In addition, NPK were significantly increased among all the added treatments in the soil-plant system as well as improved chlorophyll contents relative to non-treated soil. The Current study suggested that among all the amendments, compost at 3% rate performed well and might be considered a suitable approach for maize growth in polluted soil.
Correlation of sTILs Infiltration and UBR5 Expression on the Efficacy of Neoadjuvant Chemotherapy Efficacy and Prognosis in Early Triple Negative Breast Cancer
Authors: Pang Jian , Zhou Li , Liao Liqiu , Wang Shouman
Published: January 2021

Neoadjuvant chemotherapy (NAC) is widely used in patients with TNBC, but there are significant differences in the efficacy of chemotherapy in different patients. Stromal tumor infiltrating lymphocytes (sTILs) have been widely studied as biomarkers reflecting the therapeutic effect of NAC. As a tumor-associated gene, UBR5 has been found to be associated with chemotherapy sensitivity and prognosis of many cancers. This is the first time that we have combined UBR5 and sTILs to evaluate the chemotherapy efficacy of patients with TNBC treated with NAC and to study the correlation between sTILs and UBR5. MethodsSPSS was used to analyze the correlation between UBR5 and sTILs and clinicopathological data. Then doxorubicin and mitoxantrone treated mouse breast cancer cells to explore the relationship between UBR5 expression and chemotherapeutic drug sensitivity. Finally, R language analyzes the relationship between UBR5 and immune-related genes and immune score.ResultsIn patients with TNBC treated with NAC, the expression level of UBR5 and the degree of infiltration of sTILs are independent factors that affect whether the patient can achieve PCR and the expression between the two is negatively correlated. UBR5 expression can cause mouse breast cancer cells to develop resistance to doxorubicin and mitoxantrone. At the same time, UBR5 is also highly correlated with a variety of immune-related genes and immune scores.Conclusion﻿UBR5 and sTILs can jointly predict the efficacy of NAC in patients with TNBC. At the same time, the expression of UBR5 is also an important reason for chemotherapy resistance in patients with TNBC.
Early Onset Favipiravir Saves Lives
Authors: KARATAS Ercan , Aksoy Lacin , Kilic Pinar Elbir , Dogru Arzu , Ozaslan Ersin
Published: January 2021

Background
Favipiravir, an antiviral recommended for use in patients with tachypnea (respiratory rate 30 / min) in COVID-19 pneumonia, with SpO2 level below 90% in room air and with bilateral diffuse pneumonia on chest X-ray or tomography, or patients with treatment-resistant fever, is a new type of RNA-dependent RNA polymerase (RdRp) inhibitor. After the administration of Favipiravir, it contributed significantly to reducing mortality in patients with severe COVID-19 positive disease. We performed this study to determine the start time in Favipiravir's covid pneumonia.
Material and Method:
We evaluated the effect of a total of 5 days of oral treatment as a 2 × 1600 mg loading dose and a 2 × 600 mg maintenance dose of Favipiravir added to the standard COVID-19 treatment received by patients with laboratory-radiology-clinical findings who have advanced or severe COVID 19 pneumonia.
Results
180 patients hospitalized at Tuzla State Hospital and given Favipiravir treatment between 20/3/2020 and 30/5/2020 were examined. As of hospitalization, 17 of 101 patients (17%) who were given Favipiravir treatment in ≤ 3 days died, 30 of 79 patients (38%) who were given Favipiravir treatment for in > 3 days died (p:0.002). 33 of 47 patients (70%) who died were > 65 years old. Only 5 of the 47 (11%) patients who died had no comorbid disease. 35 had two or more comorbid diseases.
Conclusion
Patients with radiological findings indicating that COVID-19 will be severe and laboratory findings at the time of the first 3 days should be initiated with an effective dose of Favipiravir treatment without waiting for the clinical worsening.
Renal Shell injuries with Retaining renal shell fragments due to improvised explosive devices. Acute conservative approach and long term follow-up
Authors: Zor Murat , Topuz Bahadir , Kaya Engin , Yilmaz Sercan , Akay Sinan , Bedir Selahattin
Published: January 2021

Introduction: Among penetrating injuries, renal shrapnel injuries consist of a rarity of renal gunshot injuries. Due to the paucity of cases reported in the literature, there is no consensus regarding the management of renal shrapnel injuries and retaining renal shell fragments. In this study we aimed to report our non-operative management experience of renal shrapnel injuries who had also retaining renal shell fragments.Material and Methods: We retrospectively evaluated the medical records of renal shrapnel injuries that had also retaining renal shell fragments. All hemodynamically stable patients managed non-operatively and included to the study. The medical records of age, renal injury grade according to AAST, presenting pulse, systolic blood pressure, transfusion requirement, complications and need for adjuvant procedures, non-operative management success and mortality was reviewed. Complication rates due to retaining renal shell fragments were assessed by interviewing via telephone at the end of the first year of injury. The patients asked for plumbism symptoms and any surgical intervention for these foreign bodies.Results: A total of 8 patients with retaining renal shell fragments due to renal shrapnel injuries were included to the study. Mean patient age was 27,8 years. Mean follow-up period was 38.7±15.1 months. All patients were male. AAST renal injury scores were grade 1 one, grade 2 two, grade 3 four, grade 4 one patient. All patients were successfully managed non-operatively and discharged on the 7th day without any complication. No symptoms of plumbism and surgery necessity secondary to retaining renal shell fragments were seen in at least one year follow-up.Conclusion: Our study demonstrates that non-operative management of renal shrapnel injuries with retaining renal shell fragments lead low complication rates and high chance of renal preservation. However, we must keep in mind that this kind of management is safe in experienced trauma centers that have experienced staff.
Visualization of the Human Enteric Nervous System by Probe Confocal Laser Endomicroscopy: A First Real Time Observation of Hirschsprung’s Disease and Allied Disorders.
Authors: Harada Atsushi , Shimojima Naoki , Kobayashi Masakuni , Kamba Shunsuke , Hirobe Seiichi , Sumiyama Kazuki
Published: January 2021

Background: Our group previously proved that the human enteric nervous system can be visualized with confocal laser endomicroscopy after topical application of cresyl violet using surgically resected intestine specimens. The present report documents the first in vivo visualization of the human enteric nervous system with confocal laser endomicroscopy using local cresyl violet staining. The aim of this study was to evaluate the technical feasibility and clinical efficiency of confocal laser endomicroscopy in patients with Hirschsprung’s disease and allied disorders in vivo.Methods: Confocal laser endomicroscopy was performed in vivo in two patients to confirm the presence of the enteric nervous system during surgery in patients with Hirschsprung’s disease and allied disorders. Cresyl violet was gently injected from the serosal side into the muscular layer of the intestine, and scanning was performed within 30 minutes. Then, the scanned intestines were resected, and the visualized area of the specimens was pathologically evaluated.Results: The ganglion cell nuclei and the enteric nervous system network were clearly visualized intraoperatively in both cases. The morphological findings were similar to the pathological findings of the enteric nervous system in both cases although the period of visibility was brief. Conclusion: This study demonstrated the first, real-time observation of the enteric nervous system in humans using confocal laser endomicroscopy and the technical feasibility of visualizing the enteric nervous system in patients with Hirschsprung’s disease and allied disorders.
White Matter Hyperintensity in Different Migraine Subtypes
Authors: Dobrynina Larisa A. , Suslina Anastasia D. , Gubanova Mariia V. , Belopasova Anastasia V. , Sergeeva Anastasia N. , Evers Stefan , Gnedovskaya Elena V. , Krotenkova Marina V.
Published: January 2021

Background: The diagnostic value of white matter hyperintensities (WMH) in different types of migraine are unknown. Objective: To evaluate the WMH pattern of different subtypes in migraine patients with no vascular risk factors.Methods: 92 migraine patients (73 females, mean age 34.6±8.9; 61 episodic migraine, 31 chronic migraine, 36 migraine with aura, 56 migraine without aura) without vascular risk factors underwent brain MRI (3T). We also included a matched healthy control group with no migraine (n=24).Results: The prevalence of WMH in different types of migraine was similar and ranged from 38.7% to 44.4%; the control group showed no WMH at all. Lesions were located within frontal, parietal and temporal lobes (in order of decreasing incidence) in juxtacortical and/or deep white matter. WMH appeared as round or slightly elongated foci with a median size of 2.5 mm [1.5; 3]. Total number, size and prevalence of WMH by lobes and white matter regions were similar between groups, and no interaction with age or sex was found. The number of lesions within the frontal lobe juxtacortical white matter correlated with the age of patients (r= 0.331, p=0.001) and the duration since migraine onset (r=0.264, p=0.012). Conclusion: Patients with different migraine subtypes and without vascular risk factors are characterized by a similar pattern of WMH in the absence of subclinical infarctions or microbleedings. Therefore, WMH have no relevant prognostic value regarding the course of migraine and vascular complications. WMH pattern may be used to differentiate migraine as a primary disorder and other disorders with migraine-like headache and WMH.
Influence of Nickel Addition on the Stability, Trapping, and Diffusion Behaviour of Hydrogen in Vanadium: A First-Principles Investigation
Authors: Qin Jiayao , Liu Zhigao , Zhao Wei , Wang Dianhui , Zhang Yanli , Zhong Yan , Hu Chaohao , Wang Zhongmin , Liu Jiangwen
Published: January 2021

Hydrogen embrittlement causes deterioration of materials used in hydrogen energy systems. Alloying is an effective means for overcoming this issue. In this study, the first-principles calculation method was used to investigate the effects of alloying Ni on the stability, dissolution, trapping, and diffusion behaviour of interstitial/vacancy H atoms in V. The calculated phonon spectra and solution energies of the vacancy/interstitial H atoms revealed that the V–Ni phase was dynamically and thermodynamically stable, and Ni addition could reduce the stability of V hydrides and improve their resistance to H embrittlement. H atoms in the interstitials and vacancies preferentially occupied the tetrahedral interstitial site (TIS) and octahedral interstitial site (OIS) with the lowest solution energies and diffused along the TIS → TIS and OIS → OIS paths with the minimum diffusion barrier energies. The trapping energy of the vacancy H atoms indicated that the addition of Ni could reduce the H trapping capability of the vacancies and suppress the retention of H in V. Detailed analysis of the calculated H diffusion barriers indicated that the presence of monovacancy defects blocked the diffusion of H atoms more than the presence of interstitials, and Ni doping did not enhance the H diffusion coefficient.
Survival Predictors of Metastatic Adrenocortical Carcinoma: a SEER-based Retrospective Study
Authors: Yang Ningning , Wang Qingqing , Chen Fengxia , Ou Haibin , Zeng Yangyang , Zhou Yunfeng
Published: January 2021

Background: Metastatic adrenocortical carcinomas (MAC) have a poor prognosis. Advanced adrenocortical carcinoma often metastasizes to lung and liver. Prognostic factors of MAC have been rarely reported. This study aims to identify the association between specific metastasis and overall survival (OS) in MAC and determine the survival predictors for MAC patients.Methods: MAC patients' data was obtained from Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Survival differences were analyzed by Kaplan–Meier analysis and log-rank tests. Cox proportional hazard model was used to identify the prognostic factors associated with overall survival.Results: A total of 152 MAC patients were selected, among whom 77 patients (50.7%) were diagnosed with one metastatic site, 75 (49.3%) diagnosed with more than one distant metastasis. For the whole MAC cohort, multivariable analysis showed that year of diagnosis between 2013 and 2016, without liver metastasis, surgery and chemotherapy were significantly favorable predictors of OS. For patients with one metastatic site, lung metastases had a better survival outcome than liver metastases(p=0.037). Besides, compared with patients who didn’t received surgery, patients underwent surgery were correlated with longer OS (p=0.004). For patients with more than one site of distant metastases, married status, surgery, and chemotherapy predicted a better OS. Radiotherapy did not improve overall survival outcomes in the three cohort.Conclusion: Liver metastasis has a poor prognosis. Year of diagnosis, metastatic sites, surgery and chemotherapy were significant prognostic factors for OS in MAC patients. For patients with single metastasis, surgery was a favorable prognostic factor, while married patients, surgery and chemotherapy predicted a better survival outcome in patients with more than one metastasis. Based on the collective findings, surgery can be regarded as the preferred treatment option for all MAC patients. Besides, chemotherapy is also a good choice for patients with multiple metastases.
Discrimination of Skyrmion Chirality Via Spin-Orbit and -Transfer Torques for Logic Operation
Authors: Nakatani Yoshinobu , Yamada Keisuke , Hirohata Atsufumi
Published: January 2021

Recently many works on magnetic memories and logic circuits, which use a magnetic skyrmion have been reported. Previously we micromagnetically simulated a method to switch a chirality of a magnetic skyrmion formed in a magnetic thin film by introducing a pulsed heat spot. In this paper, we propose a method to discriminate the chirality of a skyrmion in a branched nanowire by using spin-orbit torque (SOT) and spin-transfer torque (STT), and confirm the validity of the method by using simulation. The simulated results show that the motion changes depending on the chirality when additional SOT is applied on a skyrmion moving in a branch by STT. This method can be used as a fundamental building block for electrical detection in memory and logic devices using the chirality of skyrmions as a data bit in addition to the presence (and polarity) of the skyrmions as conventionally used, which can be lead to multiple-valued operation.