bluuebunny/crossref_metadata_2025 huggingface dataset:
Berberine Suppresses Bladder Cancer Cell Proliferation by Inhibiting JAK1-STAT3 Signaling via Upregulation of miR-17-5p
Authors: Xia Yangyang , Chen Shouzhen , Cui Jianfeng , Wang Yong , Liu Xiaochen , Shen Yangli , Gong Li , Jiang Xuewen , Wang Wenfu , Zhu Yaofeng , Sun Shuna , Li Jiaxiang , Zou Yongxin , Shi Benkang
Published: December 2020

Background: Berberine (BBR), an active component extracted from Coptis chinensis, has shown anti-tumor effects in multiple tumors. However, the underlying mechanisms haven’t been fully elucidated. In this study, the effects of BBR on bladder cancer (BCa) cells and the underlying mechanisms were investigated both in vivo and vitro. Methods: MTT, colony formation, EdU incorporation assays and xenograft tumor models were performed to evaluate the anti-proliferation effects of BBR on BCa cells in vivo and vitro. The roles of BRR in migration and invasion of BCa cells were investigated by wound-healing, transwell migration and invasion assays. The apoptosis and senescence induced by BBR were determined by flow cytometry, tunel assay and senescence-associated β-galactosidase (SA-β-gal) activity assay. Potential candidate targets were screened using western blot. The relationships between miR-17-5p and JAK1-STAT3 pathway were then predicted using in-silico analysis and identified by dual-luciferase reporter assay. The regulatory mechanism of miR-17-5p mediated suppression of JAK1-STAT3 pathway caused by BBR treatment was validated by qRT-PCR and western blot.Results: We found that BBR showed significant cytotoxic effects against bladder cancer (BCa) cell lines both in vivo and vitro, with much lower cytotoxic effects on human normal urothelial cell line SV-HUC-1. BBR treatment induced DNA replication defects and cycle cell arrest, resulting in apoptosis or cell senescence, depending on p53 status, in BCa cells. Mechanically, BBR exerted anti-tumor effects on BCa cells through inhibiting JAK1-STAT3 signaling via promoting expression of miR-17-5p, which directly bound to 3’ UTR of JAK1 and STAT3 and downregulated their expressions. Conclusion: Our results demonstrate that BBR exerts anti-tumor effects through perturbing JAK1-STAT3 signaling via upregulating expression of miR-17-5p in BCa cells, and BBR may serve as a potential therapeutic option for BCa treatment.
WITHDRAWN: GCC2 is a New Biomarker for Diagnosis of Early Non-Small Cell Lung Cancer and A Potential Target to Reverse Epithelial to Mesenchymal Transition
Authors: Jeong Hyesun , Choi Byeong Hyeon , Jung Jik-han , Shin Hyunku , Park JinA , Kang Ka-Won , Quan Yu Hua , Yu Jewon , Park Ji-Ho , Park Yong , Choi Yeonho , Kim Hyun Koo , Hong Sunghoi
Published: December 2020

Background: Nano-sized exosomes (30–150 nm) are cell membrane-encapsulated vesicles that contain nucleic acids and proteins. Specific markers detecting non-small cell lung cancer (NSCLC) cell-derived exosomes in the blood circulation remain unidentified. Here, we report a new biomarker distinguishing cancer from non-cancer exosomes that also involved in epithelial to mesenchymal transition for cancer treatment.Methods: Exosomes were isolated from plasma of patients with various pathological stages of NSCLC and NSCLC cell lines, human pulmonary alveolar epithelial cells by size exclusion chromatography and characterized by Nanoparticle Tracking Analysis and western-blotting. The exosomes were lysed and applied to proteomic analysis. The expression levels of the GCC2 proteins from NSCLC patients were analyzed by ELISA assays, and the effects by GCC2 shRNA were analyzed by real-time RT-PCR, cell migration and colony formation assays.Results: A protein GRIP and coiled-coil domain-containing 2 (GCC2), which is involved in endosome-to-Golgi transport, was identified by the proteomics analysis of exosomes isolated from NSCLC cell lines. The GCC2 protein expression levels were increased in the exosomes derived from patients with early-stage NSCLC compared with healthy controls. The receiver operating characteristic curve of exosomal GCC2 revealed 94.74% sensitivity and 75.00% specificity, and AUC of 0.875. GCC2 knockdown experiments by GCC2 shRNA showed reduced exosome secretion in cancer cell lines, which altered the molecular and cellular properties, such as the expression levels of mesenchymal-to-epithelial genes, and cellular growth and motility.Conclusion: GCC2 represents a promising biomarker for early diagnosis of NSCLC and a therapeutic target for future cancer treatment.
The Significance of Prognostic m6A RNA Methylation Regulators in Tumor Immune Environment and Immune Therapy of Hepatocellular Carcinoma
Authors: Xu Qianhui , Xu Hao , Deng Rongshan , Li Nanjun , Mu Ruiqi , Qi Zhixuan , Shen Yunuo , Wang Zijie , Wen Jingchao , Zhao Jiaxin , Weng Di , Huang Wen
Published: December 2020

Background: Hepatocellular carcinoma (HCC) ranks the sixth prevalent tumors with high mortality in the world. N6-methyladenosine (m6A) might act an important regulatory factor in tumorigenesis and progression. Here, we aimed to elucidate the potential player of m6A RNA methylation regulators in tumor immune microenvironment (TIME) and immune checkpoint blockade (ICB) therapy of HCC.Methods: Transcriptome data as well as corresponding patient clinical data obtained from publicly TCGA-LIHC databank were integrative analyzed. To reveal the landscape of TIME in HCC, ESTIMATE algorithm, ssGSEA method and CIBERSORT analysis were conducted. And the correlations of m6A regulators with ICB-related genes was analyzed. Taking advantage of consensus clustering, two different HCC categories were screened. We analyzed the correlation of clustering result with TIME and ICB treatment. Then we yielded a robust signature of six m6A regulators by employing univariate proportional hazards and LASSO analysis. Survival analysis (Kaplan-Meier method), ROC curve analysis and Cox regression analysis were further performed. Then, these results were validated in ICGC-LIRI cohort. Subsequently, the relationship of prognostic risk signature with immune infiltration and ICB therapy were analyzed. Finally, the impact of ZC3H13 upon TIME and ICB immunotherapy was uncovered. Results: We identified that 19 out of 21 m6A key regulators significantly overexpressed in tumor tissue relative to paired normal sample. The m6A regulators-based case clusters were significantly correlated with overall survival (OS), immune score, immunological signature, tumor infiltrating immune cells, and ICB-associated genes expression level. Six m6A-related genes signature (YTHDF1, YTHDF2, IGF2BP3, KIAA1429, METTL3, and ZC3H13) were generated, which possess robust and stable prognostic validity and could serve as an independent prognosis predictive factor. Besides, risk score significantly correlated with immune score, immune-related signature, infiltrating immune cells (i.e., B cells, etc.,) and ICB molecules (i.e., CTLA4, etc.,). Finally, we corroborated ZC3H13 had intimate relationship with TIME and ICB therapy in HCC. Conclusion: Collectively, we herein identified two distinct HCC subgroups and established m6A regulators-based signature as a robust prognostic indicator and elucidated the crucial role of m6A regulators (ZC3H13) in immune cell infiltration and immunotherapy, which might contribute to clinical management and prognosis prediction of HCC.
Bioreduction of Cr(VI) by Viable Cells and Cell-Free Extract of a Moderate Halophile, Halomonas Smyrnensis KS802 and Evaluation of Their in Vitro Efficacy in Tannery Effluent
Authors: Biswas Jhuma , Paul AK
Published: December 2020

The present study was aimed to characterize the chromate reducing ability of cells and cell-free extract (CFE) of Halomonas smyrnensis KS802 (GenBank Accession No. KU982965) and evaluate their effectiveness in tannery effluents. Viable cells of the strain reduced 200 µM Cr(VI) in basal medium for halophiles (MH) in 10 h and was inversely proportional to Cr(VI) concentrations. The rapid reduction by cells (10⁹ cells/mL) was achieved with 7.5% NaCl, at pH 7 and 37°C which increased with increasing cell density (10¹° cells/mL). While acetate, Cu³⁺, Fe³⁺, SO₄²⁻, and CO₃²⁻ were stimulating the reduction, the inhibitors retarded the process significantly. The NADH-dependent chromate reduction of the CFE was found to be constitutive with Km and Vmax values of 56.58 µM and 3.37 µM/min/mg protein respectively. The optimal reductase activity of the CFE was evident at 200 µM Cr(VI), 10% NaCl, pH 8.0 and at 45°C. A higher concentration of CFE and electron donors increased the enzyme activity but was impacted negatively by toxic metals and anions. Both the cells and CFE were capable of reducing Cr(VI) remarkably from tannery effluent. FTIR and XRD spectra of chromate reducing cells confirmed possible complexation of reduced Cr-species with functional groups on cell surface.
An Access Control Model for the Internet of Things Based on Zero-Knowledge Token and Blockchain
Authors: Song Lihua , Ju Xinran , Zhu Zongke , Li Mengchen
Published: December 2020

Information security has become the focus problem in the Internet of Things, and the traditional centralized access control model is faced with threats such as single point failure, internal attack, and central leak. In this paper, we proposed a model to improve the access control security of the Internet of Things, which is based on zero-knowledge proof and smart contract technology in the blockchain. Firstly, we deployed the attribute information of access control in the blockchain, which relieves the pressure and credibility problem brought by the third-party information concentration; Secondly, the encrypted access control token is used to gain the access permission of the resources, which makes the user's identity invisible and effectively avoids the attribute ownership exposure problem; Besides, the use of smart contracts solves the problem of low computing efficiency of Internet of Things devices and the waste of blockchain computing power resources; Finally, a prototype of Internet of Things access control system based on blockchain and zero-knowledge proof technology is implemented. The test analysis results show that the model achieves effective attribute privacy protection, compared with the Attribute-Based Access Control model of the same security level, the access efficiency increases linearly with the increase of access scale.
Long Bone Fracture Reduction and Deformity Correction Using the Hexapod External Fixator With a New Method: a Feasible Study and Preliminary Results
Authors: Liu Yanshi , Li Hong , Liu Jialin , Zhang Xingpeng , Yushan Maimaiaili , Liu Zhenhui , Ma Chuang , Yusufu Aihemaitijiang
Published: December 2020

Background: The hexapod external fixator (HEF), such as the Taylor spatial frame (TSF), offering the ability of simultaneous correction of the multidirectional deformities without frame modification, whereas there are so many parameters for surgeons to measure and subjective errors will occur inevitably. The purpose of this study was to evaluate the effectiveness of a new method based on computer-assisted three-dimensional (3D) reconstruction and hexapod external fixator for long bone fracture reduction and deformity correction without calculating the parameters needed by the computer program.Methods: This retrospective study consists of 25 patients with high-energy tibial diaphyseal fractures treated by the HEF at our institution from January 2016 to June 2018, including 22 males and 3 females with a mean age of 42 years (range 14-63 years). Hexapod external fixator treatments were performed due to primary and definitive management of multiplanar posttraumatic deformity and/or severe soft-tissue damage that were not suitable for internal fixation in the tibia. Computer-assisted 3D reconstruction and trajectory planning of the reduction by Mimics were applied to perform virtual fracture reduction and deformity correction. The electronic prescription derived from the length changes of the six struts were calculated by SolidWorks. Fracture reduction was conducted by adjusting the lengths of the six struts according to the electronic prescription. The standard anteroposterior (AP) and lateral X-rays after reduction were taken to evaluate the effectiveness.Results: All patients acquired excellent functional reduction (most cases achieved anatomical reduction) in our study. The mean coronal plane translation (1.0±1.1 mm), coronal plane angulation (0.8±1.2°), sagittal plane translation (0.8±1.0 mm) and sagittal plane angulation (0.3±0.8°) after correction were all less than those (6.1±4.9 mm, 5.2±3.2°, 4.2±3.5 mm, 4.0±2.5°) before correction (P<0.05).Conclusion: The computer-assisted three-dimensional reconstruction and hexapod external fixator-based method allows surgeons to conduct long bone fracture reduction and deformity correction without calculating the parameters needed by the computer program. Considering the radiologic exposure, this method is suggested to apply in those unusually complex cases with extensive soft tissue damage and internal fixation is impossible or inadvisable.
Reimagining Community Relationships for Organizational Learning: a Scoping Review With Implications for a Learning Health System
Authors: Milligan Crystal , Wong Dorothy , Berta Whitney
Published: December 2020

Background: Communities represent a highly relevant source of knowledge with regard to not only healthcare performance but also sociocultural context, yet their role in learning health systems has not been studied. Situating the learning health system as an organization, this paper explores the phenomenon of organizational learning from or with communities (defined as one of ‘the people,’ such as a town, a specific patient group or another group directly receiving a healthcare service).Methods: We conducted a scoping review to determine what is known about organizational learning from or with communities that the organization serves, and to contribute to a more comprehensive evidence base for building and operating learning health systems. In March 2019, we systematically searched six academic databases and grey literature, applying no date limits, for English language materials that described organizational learning in relation to knowledge transfer between an organization and a community. Numerous variables were charted in Excel and synthesized using frequencies and thematic analysis. We updated this search in August 2020. Results: In total, 42 documents were included in our analysis. We found a disproportionate emphasis on learning explicit knowledge from community rather than on tacit knowledge or learning in equal partnership with community. Our review also revealed inconsistently defined concepts, tenuously linked with their theoretical and empirical foundations. Our findings provide insight to understand the organization-community learning relationship, including motives and power differentials; types of knowledge to be learned; structures and processes for learning; and transformative learning outcomes.Conclusions: Our review makes a singular contribution to organizational learning literatures by drawing from diverse research disciplines such as health services, business and education to map what is known about learning from or with community. Broadly speaking, learning health systems literature would benefit from additional research and theory-building within a sociological paradigm so as to establish key concepts and associations to understand the nature of learning with community, as well as the practices that make it happen.
The Extent and Barriers in Providing Pharmaceutical Care Services by Community Pharmacists in Malaysia: a Cross-sectional Study
Authors: Loh Pengyeow , Chua Siew Siang , Karuppannan Mahmathi
Published: December 2020

Background: Since the introduction of pharmaceutical care concept by Hepler and Strand in 1990, community pharmacists worldwide have been realigning their roles from being product-focused to patient-orientated to improve patient's quality of life. The objectives of this study were to determine the type of services, with emphasis on the extent of pharmaceutical care services provided by community pharmacists and the barriers in providing such services in Malaysia.Methods: A cross-sectional observational study was conducted using an online questionnaire. Community pharmacists in Malaysia were invited to participate in the study via emails. The questionnaire was structured based on the Malaysian Community Pharmacy Benchmarking Guidelines, the five practice principles of pharmaceutical care by the American Pharmacists Association and other studies. The online questionnaire was opened for 6 months, from April to September 2018. A reminder to participate was sent via email to the community pharmacists every fortnight.Results: A total of 420 community pharmacists responded to the online questionnaire. Besides essential services such as treatment for minor illness, medicine dispensing and counselling, most of the respondents were providing health screening and monitoring (99.5%), selection and recommendation of health supplements (90.5%), patient medication review (68.8%), weight management (52.4%) and counselling on smoking cessation (51.0%). More than half (53.3%) of the respondents reported that they were providing pharmaceutical care services to patients with chronic diseases. Based on the practice principles of pharmaceutical care, the respondents were involved in patients' data collection (23.3%), medical information evaluation (18.6%), formulating a drug therapy plan (9.3%), implementing a drug therapy plan (4.5%), and monitoring and modifying the plan (18.3%). Lack of separation between prescribing and dispensing was perceived as the main barrier to the implementation of pharmaceutical care services by a majority of the respondents (84.0%).Conclusions: The present study found that pharmaceutical care services provided by community pharmacists in Malaysia were inadequate in comparison with international practice principles. Areas that need improvement included collaboration with patients' other health care providers; more proactive management of patient's medicine regimen; having proper patient monitoring and follow-up mechanisms, and documentation.
Association Between the Level of Plasma B-type Natriuretic Peptide and in-hospital Mortality in Patients With Acute Exacerbation of COPD Without a History of Coronary Ischemic Heart Disease: A Retrospective Study
Authors: Cui Jiyun , Liu Jie , Wang Jing , Chu Yanbiao , Lv Meng , Xing Chunyan , Lin Dianjie
Published: December 2020

BackgroundPrevious studies suggested that plasma B-type natriuretic peptide (BNP) level was often elevated in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and was associated with increased mortality. However, most studies did not consider the fact that conditions such as coronary ischemic heart disease can also increase BNP level. Therefore, we aimed to explore the association between BNP level and in-hospital mortality in patients with AECOPD without a history of coronary ischemic heart disease.MethodsIn this retrospective cohort study, data on patients with AECOPD but without a history of coronary ischemic heart disease who were admitted in a comprehensive hospital from January 2017 to December 2019 and were identified using International Statistical Classification of Diseases and Related Health Problems, Nineth Revision (ICD-9) codes were included. BNP level was determined within 24 hours after admission, and the value was log2 transformed. The primary outcome was in-hospital mortality, and the secondary outcome was a composite outcome of in-hospital mortality or invasive mechanical ventilation.ResultsA total of 300 patients were included in this study (mean ages, 76.88 years; SD, 9.87; men, 63.33%). Sixteen patients (5.33%) showed in-hospital mortality; 29(9.67%) and 22 (6.67%) patients were assisted with invasive mechanical ventilators and noninvasive positive pressure ventilators, respectively. Univariate cox regression analysis showed that the unadjusted HRs of the primary and secondary outcomes were 1.85 (95% CI, 1.39-2.47) and 1.42 (95% CI, 1.19-1.71), respectively. After adjustment for age, sex, past medical history, smoking status, drinking status, CURB65 (Confusion, Urea > 7mmol/L, Respiratory rate≥30/min, Blood pressure systolic < 90 mmHg or diastolic <60 mmHg and age > 65 years), arterial partial pressure of O2(PaO2), arterial partial pressure of CO2 (PaCO2), neutrophil count, and D-dimer level (only secondary outcome), the adjusted HRs of the primary and secondary outcomes were 2.44 (95% CI, 1.43-4.14) and 1.36 (95% CI, 1.07-1.74), respectively. The results of subgroup analysis by age, sex, and lung function were robust.ConclusionsThe plasma log2BNP level was significantly associated with in-hospital mortality and a composite outcome of in-hospital mortality or invasive mechanical ventilation
West Lake Staging: A New Staging System Orchestrated by X-Ray and MRI on Knee Osteoarthritis
Authors: Huang Jiaxin , Chen Xi , Xia Mengting , Lv Shuaijie , Tong Peijian
Published: December 2020

Background: Although widely used of Kellgren - Lawrence (KL) staging system on knee osteoarthritis (KOA), it still had some disadvantages. The purpose of this study was to investigate the differences on X-ray and MRI among each stage of KOA and further propose a new staging system called West Lake (WL) staging.Methods: A cross-sectional study was conducted on patients with KOA. KL stages were defined by two qualified orthopedic surgeons. Joint space widths (JSW) were measured on X-rays, whereas cartilage injuries (CI) and bone marrow lesions (BML) were evaluated on MRI. The differences of them across the groups were calculated by T-test. Receiver operating characteristic (ROC) curves were rendered to obtain the areas under the curves (AUC), Youden index and corresponding cut-off points. Agreement Index (KAPPA) was used to analyze the consistency of KL stages and WL stages assessed by two qualified orthopedic surgeons. Results: Eventually, a total of 220 patients met the criteria. There were significant differences on JSW, CI and BML between KL II/III as well as KL III/IV. In KL II/III, the AUC of JSW, CI, BML was 0.99, 0.76, 0.71 and the Youden index was 0.94, 0.38, 0.45, meanwhile the cut-off points were £5.1mm, >1, >2. In KL III/IV, the AUC of JSW, CI, BML was 0.96, 0.79, 0.74 and the Youden index was 0.84, 0.58, 0.38, meanwhile the cut-off points were £3.2mm, >3, >4. The Kappa coefficients of KL stages and WL stages were 0.31 and 0.76.Conclusion: The WL staging was described as follows: Grade 0, normal X-ray. Grade 1, X-ray shows osteophyte but no joint space narrow, normal MRI or MRI shows cartilage degeneration and only 1 or 2 sections are involved in BML. Grade 2, X-ray shows joint space narrow, MRI shows cartilage defect but no full-thickness cartilage defect, meanwhile 3 or 4 sections are involved in BML. Grade 3, X-ray shows serious joint space narrow even JSW disappeared, MRI shows full-thickness cartilage defect, more than 4 sections are involved in BML.Trial registration: The study was approved by the First Affiliated Hospital of Zhejiang Chinese Medical University (2018-ZX-026-01).
Smart Surveillance and Micromanagement Using Information Technology for Malaria Elimination in Mangaluru, India – an Analysis of Five Years Data
Authors: Baliga B. Shantharam , Baliga Shrikala , Jain Animesh , Kulal Naveen , Kumar Manu , Koduvattat Naren , Kumar B. G. Prakash , Kumar Arun , Ghosh Susanta Kumar
Published: December 2020

BackgroundMalaria control system (MCS), an Information technology (IT)-driven surveillance and monitoring intervention is being adopted for elimination of malaria in Mangaluru city, Karnataka, India since October 2015. This facilitated ‘smart surveillance’ followed by required field response within a timeline. The system facilitated data collection of individual case and data driven mapping and strategies for malaria elimination programme. This paper aims to present the analysis of post-digitization data of 5 years, discuss the current operational functionalities of MCS and its impact on the malaria incidence.MethodsIT system developed for robust malaria surveillance and field response is being continued in the 6th year. Protocol for surveillance control was followed as per the national programme guidilines mentioned earlier. Secondary data from the malaria control system is collated and analysed. Incidence of malaria, active surveillance, malariogenic conditions and its management, malariometric indices, shrinking malaria map were also analysed.ResultsSmart surveillance and subsequent response for control was sustained and performance improved in five years with participation of all stakeholders. Overall malaria incidence significantly reduced by 83% at the end of 5 years when compared with year of digitizarion (DY) (p<0.001). Early reporting of new cases (within 48 hrs) was near total followed by complete treatment and vector control. Slide positivity rate (SPR) decreased from 10.36 (DY) to 6.5 (PDY 5). Annual parasite incidence (API) decreased from 16.17 (DY) to 2.64 (PDY 5). There was a negative correlation between contact smears and incidence of malaria. Five-year data analyses indicated declining trends in overall malaria incidence and correlation between closure by 14 days. The best impact on reduction in incidence of malaria was recorded in pre-monsoon months (~85%) compared to lower impact in July-August months (~40%). ConclusionIT System helped to micromanage control activities such as robust reporting, incidence-centric active surveillance, early and complete treatment, documentation of full treatment of each malaria patient, targeted mosquito control measures in houses surrounding reported cases. The learnings and analytical output from the data helped to modify strategies for control of both disease and the vector, heralding the city into the elimination stage.
Transannular Patch Repair of Tetralogy of Fallot With or Without Monocusp Valve Reconstruction: A Meta-analysis
Authors: Wei Xiaodong , Li Tiange , Ling Yunfei , Chai Zheng , Cao Zhongze , Chen Kerun , Qian Yongjun
Published: December 2020

Background: Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart diseases. Pulmonary regurgitation is the most common and severe comorbidity after transannular patch (TAP) repair of TOF patients. It has not been confirmed whether a TAP repair with monocusp valve reconstruction would benefit TOF patients in perioperative period compared to those without monocusp valve reconstruction. The purpose of the study is to review and analyze all clinical studies that have compared perioperative outcomes of TOF patients undergoing TAP repair with or without monocusp valve reconstruction and conduct a preferable surgery.Methods: Eligible studies were identified by searching the electronic databases. The primary outcome was perioperative mortality. Secondary outcomes included cardiopulmonary bypass time, aortic cross-clamp time, ventilation duration, ICU length of stay, hospital length of stay, and perioperative right ventricular outflow tract (RVOT) pressure gradient. The meta-analysis and forest plots were drawn using Review Manager 5.3. Statistically significant was considered when p-value ≤ 0.05. Results: Eight studies were included which consisted of 7 retrospective cohort study and 1 randomized controlled trial. The 8 studies formed a pool of 526 TOF patients in total, in which are 300 undergoing TAP repair with monocusp valve reconstruction (monocusp group) compared to 226 undergoing TAP repair without monocusp valve reconstruction (non-monocusp group). It demonstrated significant differences between two groups in perioperative cardiopulmonary bypass time (21.86, 95% CI 16.51-27.21), perioperative aortic cross-clamp time (11.20, 95% CI 1.06 - 21.34), mean length of ICU stay (-1.55, 95% CI -3.90 - -0.81), and the degree of perioperative PR (OR=0.02, 95% CI 0.00 - 0.15).Conclusion: Transannular patch repair with monocusp valve reconstruction seems to have significant advantages on some perioperative outcomes of TOF patients. Large, multicenter, randomized, prospective studies focusing on differences between TAP repair with and without monocusp valve reconstruction are needed.
Genome-wide association mapping reveals potential novel loci controlling stripe rust resistance in a Chinese wheat landrace diversity panel from the southern autumn-sown spring wheat zone
Authors: Wang Yuqi , Yu Can , Cheng Yukun , Yao Fangjie , Long Li , Wu Yu , Li Jing , Li Hao , Wang Jirui , Jiang Qiantao , Li Wei , Pu Zhien , Qi Pengfei , Ma Jian , Deng Mei , Wei Yuming , Chen Xianming , Chen Guoyue , Kang Houyang , Jiang Yunfeng , Zheng Youliang
Published: December 2020

Background: Stripe rust, caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst), is a serious foliar disease of wheat. Identification of novel stripe rust resistance genes and cultivation of resistant cultivars are considered to be the most effective approaches to control this disease. In this study, we evaluated the infection type (IT), disease severity (DS) and area under the disease progress curve (AUDPC) of 143 Chinese wheat landrace accessions for stripe rust resistance. Assessments were undertaken in five environments at the adult-plant stage with Pst mixture races under field conditions. In addition, IT was assessed at the seedling stage with two prevalent Pst races (CYR32 and CYR34) under a controlled greenhouse environment.Results: Seventeen accessions showed stable high-level resistance to stripe rust across all environments in the field tests. Four accessions showed resistance to the Pst races CYR32 and CYR34 at the seedling stage. Combining phenotypic data from the field and greenhouse trials with 6404 markers that covered the entire genome, we detected 17 quantitative trait loci (QTL) on 11 chromosomes for IT associated with seedling resistance and 15 QTL on seven chromosomes for IT, final disease severity (FDS) or AUDPC associated with adult-plant resistance. Four stable QTL detected on four chromosomes, which explained 9.99%–23.30% of the phenotypic variation, were simultaneously associated with seedling and adult-plant resistance. Integrating a linkage map of stripe rust resistance in wheat, 27 QTL overlapped with previously reported genes or QTL, whereas four and one QTL conferring seedling and adult-plant resistance, respectively, were mapped distantly from previously reported stripe rust resistance genes or QTL and thus may be novel resistance loci.Conclusions: Our results provided an integrated overview of stripe rust resistance resources in a wheat landrace diversity panel from the southern autumn-sown spring wheat zone of China. The identified resistant accessions and resistance loci will be useful in the ongoing effort to develop new wheat cultivars with strong resistance to stripe rust.
Sedentary Behaviour Among General Practitioners: A Systematic Review
Authors: Mayne Richard S. , Hart Nigel D. , Heron Neil
Published: December 2020

BackgroundSedentary behaviour is when someone is awake, in a sitting, lying or reclining posture and is an independent risk factor for multiple causes of morbidity and mortality. A dose-response relationship has been demonstrated, whereby increasing sedentary time corresponds with increasing mortality rate. This study aimed to identify current levels of sedentary behaviour among General Practitioners (GPs), by examining and synthesising how sedentary behaviour has been measured in the primary care literature.MethodsA systematic review was conducted to identify studies relating to levels of sedentary behaviour among GPs. Searches were performed using Medline®, Embase®, PscycINFO, Web of Science and the Cochrane Library, from inception of databases until January 2020, with a subsequent search of grey literature. Articles were assessed for quality and bias, with extraction of relevant data.ResultsThe search criteria returned 1707 studies. 34 full texts were reviewed and 2 studies included in the final review. Both were cross-sectional surveys using self-reported estimation of sedentary time within the International Physical Activity Questionnaire (IPAQ). Keohane et al. examined GP trainees and GP trainers in Ireland. 60% reported spending in excess of 7 hours sitting each day, 24% between 4 and 7 hours, and 16% less than or equal to 4 hours. Suija et al. examined female GPs in Estonia. The mean reported daily sitting time was 6 hours and 36 minutes, with 56% sitting for over 6 hours per day. Both studies were of satisfactory methodological quality but had a high risk of bias.ConclusionThere is a paucity of research examining current levels of sedentary behaviour among GPs. Objective data is needed to determine GPs’ current levels of sedentary behaviour, particularly in light of the increase in remote consulting as a result of the COVID-19 pandemic.
Exploring natural allelic variations of the β-triketone herbicide resistance gene HIS1 for application in indica rice and particularly in two-line hybrid rice
Authors: Lv Qiming , zhang xiuli , yuan dingyang , Huang zhiyuan , peng rui , peng jiming , li zuren , Tang li , liu ducai , zhou xiaomao , wang lifeng , pan lang , shao ye , mao bigang , xin yeyun , zhu lihuang , zhao bingran , Bai Lianyang
Published: December 2020

Background: Benzobicyclon (BBC) is a β-triketone herbicide (bTH) used in rice paddy fields. It has the advantages of high efficiency, low toxicity, high crop safety, and good environmental compatibility, and shows efficacy against paddy weeds resistant to other types of herbicides. However, as some important indica rice varieties are susceptible to BBC, BBC is currently only registered and applied in japonica rice cultivation areas.Results: By analyzing haplotypes of the bTHs broad-spectrum resistance gene HIS1 and phenotypes for BBC in 493 major indica rice accessions in China, we identified a novel non-functional allelic variant of HIS1 in addition to the previously reported 28-bp deletion. Through detection with markers specific to the two non-functional mutations, it was clear that 25.4% of indica conventional varieties, 59.9% of fertility restorers, and 15.9% of sterile lines were susceptible to BBC. In addition, due to natural allelic variations of the HIS1 gene in the sterile and restorer lines, some two-line hybrid sterile lines were sensitive to bTHs, and the corresponding restorers were resistant. We showed the potential effectiveness of using bTHs to address the issue of two-line hybrid rice seed purity stemming from the self-crossing of sterile lines during hybrid rice seed production. Finally, allelic variations of the HIS1 gene may also play an important role in the mechanized seed production of hybrid rice.Conclusions: Our findings offer guidance for the application of BBC in indica rice areas and provide a non-transgenic approach to address the seed purity issue of two-line hybrid rice.
Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda
Authors: Nsobya Sam L , Walakira Andrew , Namirembe Elizabeth , Kiggundu Moses , Nankabirwa Joaniter I , Ruhamyankaka Emmanuel , Arinaitwe Emmanuel , Conrad Melissa D , Kamya Moses R , Dorsey Grant , Rosenthal Philip J
Published: December 2020

BackgroundRapid diagnostic tests (RDTs) play a key role in malaria case management. The most widely used RDT identifies Plasmodium falciparum based on immunochromatographic recognition of P. falciparum histidine-rich protein 2 (PfHRP2). Deletion of the paralogous pfhrp2 and pfhrp3 genes leads to false-negative PfHRP2-based RDTs, and has been reported in P. falciparum infections from South America and Africa. However, identification of pfhrp2/pfhrp3 deletions has usually been based only on failure to amplify these genes using PCR, without confirmation based on PfHRP2 protein expression, and understanding of the true prevalence of deletions is incomplete.MethodsDeletions of pfhrp2/pfhrp3 in blood samples were investigated from cross-sectional surveys in 2012-13 in three regions of varied malaria transmission intensity in Uganda. Samples with positive Giemsa-stained thick blood smears, but negative PfHRP2-based RDTs were evaluated by PCR amplification of conserved subunit ribosomal DNA for Plasmodium species, PCR amplification of pfhrp2 and pfhrp3 genes to identify deletions, and bead-based immunoassays for expression of PfHRP2.ResultsOf 3516 samples collected in cross-sectional surveys, 1493 (42.5%) had positive blood smears, of which 96 (6.4%) were RDT-negative. Of these 96 RDT-negative samples, P. falciparum DNA was identified by PCR in 56 (58%) and only non-falciparum plasmodial DNA in 40 (42%). In all 56 P. falciparum-positive samples there was a failure to amplify pfhrp2 or pfhrp3: in 25 (45%) pfhrp2 was not amplified, in 39 (70%) pfhrp3 was not amplified, and in 19 (34%) neither gene was amplified. For the 39 P. falciparum-positive, RDT-negative samples available for analysis of protein expression, PfHRP2 was not identified by immunoassay in only four samples (10.3%); these four samples all had failure to amplify both pfhrp2 and pfhrp3 by PCR. Thus, only four of 96 (4.2%) smear-positive, RDT-negative samples had P. falciparum infections with deletion of pfhrp2 and pfhrp3 confirmed by failure to amplify the genes by PCR and lack of expression of PfHRP2 demonstrated by immunoassay.ConclusionFalse negative RDTs were uncommon. Deletions in pfhrp2 and pfhrp3 explained some of these false negatives, but most false negatives were not due to deletion of the pfhrp2 and pfhrp3 genes.
Risk factors and comorbidities associated with magnesium deficiency in pregnant women and women with hormone-related conditions: Analysis of a large real-world dataset
Authors: Orlova Svetlana , Dikke Galina , Pickering Gisele , Yaltseva Natalya , Konchits Sofya , Starostin Kirill , Bevz Alina
Published: December 2020

BackgroundAn accumulating body of literature indicates that magnesium deficiency is associated with a number of hormone-related conditions (HRC) in women, and epidemiological studies are needed to assess its prevalence and risk factors. Here, we present a secondary analysis of data pooled from four large observational studies that assessed magnesium deficiency among pregnant women and women with HRC across the Russian Federation.MethodsThe main objective of this analysis was to estimate the prevalence of magnesium deficiency in this population and to describe risk factors and comorbidities associated with low serum magnesium. Univariate logistic regression analysis was performed to identify the risk factors and comorbid conditions associated with an increased risk of low serum magnesium level.ResultsA total of 983 pregnant women and 9444 women with HRC were eligible for analysis. Prevalence of hypomagnesemia (magnesium serum level cut-off <0.66 mmol/L/<0.8 mmol/L) was 34.0%/78.9% in pregnant women and 21.4%/54.8% in women with HRC. The highest prevalence of magnesium deficiency was observed for osteoporosis and climacteric syndrome. Risk factors included diastolic blood pressure, previous pregnancy complications, infections and edema for pregnant women, and age, body mass index, and various comorbidities for women with HRC.ConclusionsThese results confirm the high prevalence of hypomagnesemia in pregnant women and women with HRC and underline the importance of routine screening, since risk factors are mostly non-specific.
Post-exposure Prophylaxis Against SARS-CoV-2 in Close Contacts of Confirmed COVID-19 Cases (CORIPREV): Study Protocol for a Cluster-randomised Trial
Authors: Tan Darrell , Chan Adrienne K. , Jüni Peter , Tomlinson George , Daneman Nick , Walmsley Sharon , Muller Matthew , Fowler Rob , Murthy Srinivas , Press Natasha , Cooper Curtis , Lee Todd , Mazzulli Tony , McGeer Allison
Published: December 2020

Background: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case.Methods: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r versus no intervention, using an adaptive approach to sample size calculation. Participants will be individuals aged >6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35 and 90 include comprehensive epidemiological, clinical, microbiologic and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α=0.05, assuming p0=15%, 5 contacts per case and intra-class correlation coefficient (ICC)=0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Discussion: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection.Trial registration: This trial was registered at www.clinicaltrials.gov (NCT04321174) on March 25, 2020. https://clinicaltrials.gov/ct2/show/NCT04321174
Using Item Response Theory (IRT) to Improve the Efficiency of the Simple Clinical Colitis Activity Index (SCCAI) for patients with ulcerative colitis
Authors: Walsh Alissa , Cao Rena , Wong Darren , Kantschuster Ramona , Matini Lawrence , Wilson Jean , Cohort Oxford IBD , Kormilitzin Andrey , South Matthew , Travis Simon , Bauermeister Sarah
Published: December 2020

BackgroundThe SCCAI was designed to facilitate assessment of disease activity in ulcerative colitis (UC). We aimed to interrogate the metric properties of individual items of the SCCAI using item response theory (IRT) analysis, to simplify and improve its performance. MethodsThe original 9-item SCCAI was collected through TrueColours, a real-time software platform which allows remote entry and monitoring of patients with UC. Data were securely uploaded onto Dementias Platform UK Data Portal, where they were analysed in Stata 16.1 SE. A 2-parameter (2-PL) logistic IRT model was estimated to evaluate each item of the SCCAI for its informativeness (discrimination). A revised scale was generated and re-assessed following systematic removal of items. ResultsSCCAI data for 516 UC patients (41 years, SD=15) treated in Oxford were examined. After initial item deletion (Erythema nodosum, Pyoderma gangrenosum), a 7-item scale was estimated. Discrimination values (information) ranged from 0.41 to 2.52 indicating selected item inefficiency with three items <1.70 which is a suggested discriminatory value for optimal efficiency. Systematic item deletions found that a 4-item scale (bowel frequency day; bowel frequency nocturnal; urgency to defaecation; rectal bleeding) was more informative and discriminatory of trait severity (discrimination values of 1.50 to 2.78). The 4-item scale possesses higher scalability and unidimensionality, suggesting that the responses to items are either direct endorsement (patient selection by symptom) or non-endorsement of the trait (disease activity). Conclusion Reduction of the SCCAI from the original 9-item scale to a 4-item scale provides optimum trait information that will minimise response burden. This new 4-item scale needs validation against other measures of disease activity such as faecal calprotectin, endoscopy and histopathology.
Efficacy of Electroacupuncture in Preventing Nausea and Vomiting After Thyroidectomy: a Prospective Randomized Controlled Trial
Authors: Park Min-Su , Park Won Seo , Nam Dongwoo , Min Sun Young , Chae Sumin
Published: December 2020

Background: Postoperative nausea and vomiting (PONV) is regarded as a serious concern after thyroidectomy. Electroacupuncture (EA) shows potential to reduce general anesthesia-related side effects. The aim of this study was to evaluate the efficacy of EA in preventing PONV that commonly occurs in patients after thyroidectomy. Methods: This study was a prospective randomized controlled trial with a two-arm, parallel-group structure. Sixty-four participants were randomly assigned to the acupuncture (n=35) or control (n=29) group. Patients in the acupuncture group received EA and intradermal press needles at the ST36 and PC6 positions. The primary endpoint was the incidence and severity of PONV, and secondary endpoints were the length of hospital stay, pain severity, and postoperative in-hospital morbidity.Results: The total incidence of PONV was 40.6% (26/64). There was no difference in the incidence of PONV between the control (10/29, 34.5%) and acupuncture (16/35, 45.7%) groups (p = 0.362). Severity of PONV, as measured by VAS, was not different between the groups (p = 0.842). Length of hospitalization and postoperative complications were not different between the groups.Conclusion: In this randomized controlled trial, EA treatment after thyroidectomy is safe and comparable to conventional anti-emetic therapy. Trial registration: Clinical Research Information Service, KCT0001782. Registered on 26 January 2016.
Rare disease awareness and perspectives of physicians in China: a questionnaire-based study
Authors: Li Xuefeng , Zhang Xiangyu , Zhang Shu , Lu Zijuan , Zhang Jianyong , Zhou Jincheng , Li Bingzhe , Ou Li
Published: December 2020

Background: It is estimated that there are over 16.8 million rare disease patients in China, representing a significant challenge for the healthcare system and society. Rare disease patients often experience delayed diagnosis, misdiagnosis, or improper treatment, which may be due to the lack of rare disease awareness among physicians. Materials and Methods: A total of 224 physicians from different hospitals in China participated in the questionnaire, and 9 rare disease experts were interviewed with open-ended questions.Results: Most physicians (83.5%) were from Tertiary hospitals, which have over 500 beds. Only 5.3% of physicians were moderately or well aware of rare diseases. Most physicians (80.1%) had suspected their patients to have rare diseases less than 3 times. There was a strong support for special legislations for rare diseases and orphan drugs. Further, multinomial logistic regression (MLR) was used to determine whether hospitals, gender, and career length has an impact on perspectives and awareness. It was shown that male physicians were more likely to think newborn screening is important (p<0.05). The longer the career length is, the more likely physicians believe that their previous education has not provided sufficient information about rare diseases and that their hospital has paid enough attention to rare diseases. Physicians from Tertiary A hospitals were more likely to rate the affordability of orphan drugs high. In addition, nine experts believed that rare disease awareness is essential for early diagnosis and timely treatment. These experts also made recommendations on how to improve rare disease awareness through medical school education and continuing training. Conclusions: Our study highlighted the importance of improving rare disease awareness among physicians in China. Recommendations about how to improve rare disease awareness in medical school education and establish an online ‘information hub’ are made for considerations of policy-makers.