bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opposite Regulation of F508del-CFTR Biogenesis by Four Poly-Lysine Ubiquitin Chains
Authors: Wu Qingtian , Henri Yonta Tiakouang , Yao Ruixue , Ma Xuemei , Liu Lei , Vinye Nana Noutchie , Liang Xiubin , Zhao Gang , Hou Xia 
Published: November 2020

Abstract
Background: As a misfolding protein, more than 99% of F508del-CFTR (F508del) is degraded by the ubiquitin-proteasome system before its maturation, which results in almost no membrane expression of CFTR and thereby no chloride secretion across epithelial cells of cystic fibrosis patients. The conjugation of ubiquitin chains to the protein substrates is necessary for ubiquitin-mediated proteasomal degradation. Ubiquitin contains seven lysine (K) residues (K6, K11, K27, K29, K33, K48, and K63), all of them can be conjugated one to another forming poly-ubiquitin chains on substrates by mixing together or by only one type of lysine that provides sorting signals for different pathways. Results: Here we report that four lysine linked poly-Ub chains (LLPUCs) were involved in F508del biogenesis: two LLPUCs linked by K11 or K48 of Ub facilitated F508del degradation; whereas the other two linked by K63 and K33 of Ub protected F508del from degradation. LLPUC K11 is more potent for F508del degradation than K48. Moreover, E3 ligase CHIP and RNF5 catalyzed LLPUCs K48 formation and RNF5 also catalyzed LLPUC K11 formation on F508del. Importantly, Those LLPUCs provide F508del with different affinities to the proteasomal shuttle protein (Rad23a) and the proteasomal receptors (Adrm1 and S5a), offering a mechanistic insight of differential regulation F508del different by different LLPUCs. Conclusions: F508del utilizes four specific lysine-linked poly Ub chains and during its biogenesis for opposite destiny through different identification by proteasomal shuttle protein or receptors. These findings provide new insights to understand the CF pathogenesis and are expected to facilitate the development of therapies for this devastating disease.
Overestimated, still less than competent: A cross-sectional study concerning emergency department registered nurses’ disaster preparedness
Authors: Murphy Jason Patrick , Kurland Lisa , Rådestad Monica , Magnusson Sofia , Ringqvist Tove , Rüter Anders 
Published: November 2020

Abstract
BackgroundMajor incidents continue to pose a threat to health care systems by overwhelming them with a sudden surge of patients. A major factor impacting a hospital's surge capacity is the skills, abilities, and knowledge of emergency department registered nurses. The level of disaster nursing competency they possess affects patient safety and outcome. ED RNs' ability to accurately assess their competency and knowledge is imperative for mitigating the effect of major incidents. ED RN’s perception of overall disaster preparedness has not been thoroughly addressed. The aim of this study was to assess emergency department registered nurses' self-perceived disaster preparedness.MethodThe study was a cross-sectional study. A self-assessment questionnaire based on the results of a study identifying specific disaster nursing competencies for emergency department registered nurses was distributed to all emergency department registered nurses at six participating hospitals between January 10th to February 19th of 2019. A five-point Likert-type scale was used to assess competency.ResultsEmergency department registered nurses’ disaster preparedness according to the Total Disaster Competency mean, was low. Furthermore, the results indicate that ED RNs’ overestimate their disaster nursing competency when compared to the Total Disaster Competency score. When asked to estimate their overall the mean was ”less than competent” yet higher than the Total Disaster Competency score. Knowledge gaps concerning disaster preparedness plans were also identified. Additionally, this study identified factors associated with disaster preparedness and self-assessment ability.Conclusion ED RNs’ overestimate their disaster preparedness and may lack self-awareness concerning their disaster competencies. However, ED RNs with formal disaster education appeared to have better insight concerning their preparedness. Clinical experiences, higher levels of education, and training were positively associated with preparedness. A lack of self-awareness may negatively impact patient outcomes during a major incident.
One out of three bystanders of out-of-hospital cardiac arrests suffers pathological psychological processing a few weeks after the incident- results from a systematic telephone interview
Authors: Brinkrolf Peter , Metelmann Bibiana , Metelmann Camilla , Baumgarten Mina , Scharte Carolin , Zarbock Alexander , Hahnenkamp Klaus , Bohn Andreas 
Published: November 2020

Abstract
BackgroundWitnessing an out-of-hospital cardiac arrest (OHCA) is a traumatic experience. It is known, that some bystanders struggle with coping of these events. The impact of (part-) performing CPR vs. passive observing OHCA and of being a stranger as bystander vs. family and friends of the patient is still unknown.MethodsBetween December 2014 and April 2016 bystanders, who witnessed an OHCA of an adult patient (>18 years) were interviewed by telephone a few weeks after the event. In a semi-standardized questionnaire the paramount emotion at the time of the interview was asked. The statements given in response to open questions were rated into the categories “signs of pathological psychological processing”, “physiological psychological processing” and “good mental constitution” by independent researchers.ResultsObserving the exclusion criteria 89 telephone interviews could be included in the analyses. In 27 out of 89 cases (30.3%) signs of pathological psychological processing could be detected. Signs of pathological psychological processing were significantly less in bystanders, who received instructions by the dispatcher or autonomously performed CPR. No statistical significant differences in the psychological processing could be shown for gender, age, relationship to the patient, current employment in the health sector, location of cardiac arrest or number of additional bystanders.ConclusionsOne out of three bystanders of OHCA suffers sings of pathological psychological processing. This was independent of age, gender and relationship of the bystander to the patient. Bystanders who performed CPR with or without receiving instructions had a lower risk.
SIRT6&nbsp;Promotes&nbsp;Osteogenic Differentiation&nbsp;of&nbsp;Adipose-Derived&nbsp;Mesenchymal Stem Cells&nbsp;Through&nbsp;Activating&nbsp;Notch Signaling&nbsp;Via&nbsp;Antagonizing DNMT1
Authors: JIA BO , Chen Jun , Wang Qin , Sun Xiang , Han Jiusong , Guastaldi Fernando , Xiang Shijian , He Yan , Ye Qinsong 
Published: November 2020

Abstract
Background: Adipose-derived stem cells (ADSCs) are increasingly accepted as one of ideal seed cells for regenerative medicine for its potential to differentiate into multiple cell types, including osteogenic lineages. Sirtuin proteins 6 (SIRT6) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase and plays important roles in a variety of biological processes, including cell differentiation.Methods: Alkaline phosphatase (ALP) activity, ALP staining, and Alizarin Red Staining was performed to explore the roles of SIRT6 in the osteogenic differentiation of ADSCs. Western blot , RT-qPCR,Luciferase reporter assay and Co-Immunoprecipitation assay were applied to confirm the relationship between of Sirt6, DNA methyltransferases (DNMTs) and NOTCHs.Results: SIRT6 leads to increased alkaline phosphatase (ALP) activity, enhanced mineralization and upregulated expression of osteogenic-related genes of human adipose-derived mesenchymal stem cells (hADSCs) in vitro and in vivo. Further mechanistic studies showed that SIRT6 regulated osteogenic differentiation of hADSCs depending on its deacetylase activity. SIRT6 selectively prevents abnormal DNA methylation of NOTCH1, NOTCH2 in hADSCs by antagonizing DNMT1. DNMT1 expression was suppressed in SIRT6 overexpression hADSCs, and knockdown partially rescued abnormal DNA methylation of NOTCH1 and NOTCH2, leading to the increased capable of osteogenic differentiation. Conculsions: SIRT6 promotes the osteogenic differentiation of hADSCs.The SIRT6 protein suppresses DNMT level via physical interaction with the DNMT1 protein, deacetylating and destabilizing DNMT1 protein,leading the activation of NOTCH1 and NOTCH2.
Association of Whole Blood Copper, Magnesium and Zinc Levels with Metabolic Syndrome Components in 6–12-Year-Old Rural Chinese Children: 2010–2012 China National Nutrition and Health Survey
Authors: Zhang Huidi , Man Qingqing , Song Pengkun , Li Siran , Liu Xiaobing , Wang Lijuan , Li Yuqian , Yang Lichen 
Published: November 2020

Abstract
Background: Metabolic syndrome (MetS) is a major public health problem in the world and some studies indicated that it is significantly associated with the future risk of cardiovascular disease. There is also a certain prevalence of Mets in childhood and shows a trend of younger age. Previous studies on the relationship between elements and MetS were mostly seen in adults with single element analysis, and reports on children and the combined effects of multiple elements were very limited. With the data form 2010–2012 China National Nutrition and Health Survey, we aim to investigate the association between whole blood Cu, Mg and Zn in both single and combined effects and MetS components in 6–12-year-old rural Chinese children.Methods: A total of 911 children (51.2% male, 48.7% female) aged 6–12 years were enrolled. Basic characteristics, metals and MetS component parameters were collected. Multivariate logistic regression analysis was performed to examine the independent relationship between metals and MetS components.Results: Copper was positively associated with elevated waist (OR=2.00, 1.18–3.28) and negatively associated with elevated TG (OR=0.33, 0.16-0.65). When high Cu combined with Zn, the association with elevated waist and elevated TG both disappeared. In the combination of Cu and Mg, high Cu with high Mg had a positive association with elevated waist (OR=2.03, 1.26-3.27) and high Cu with low Mg had a negative asscoiation with elevated TG (OR=0.40, 0.16-0.95). Conclusions: Our study suggested that both the single and combined effects of Cu, Mg and Zn were associated with MetS components, especially in elevated waist and TG. And the comprehensive analysis of multiple elements was different from the results of single element analysis, which provide new avenues for the early screening of MetS. Additional research is needed to confirm these findings in other populations.
Preventable Multiple High-Risk Birth Behaviour and Infant Survival in Nigeria
Authors: Salawu Mobolaji Modinat , Afolabi Rotimi Felix , Gbadebo Babatunde Makinde , Salawu Adetokunbo Taophic , Fagbamigbe Adeniyi Francis , Adebowale Ayo Stephen 
Published: November 2020

Abstract
Background Globally, infant mortality has reduced considerably but has remained unacceptably high in sub-Saharan Africa, especially Nigeria where infant mortality rate is 67/1000 live births. To facilitate infant mortality reduction in Nigeria, an understanding of the synergistic effect of bio-demographic characteristics of mothers known as High Risk Birth Behaviours (HrBBs) is important. We therefore investigated the influence of HrBBs on infant survival in Nigeria.MethodsThis cross-sectional study design utilized data from the 2018 round of Nigerian Demographic Health Survey. The study participants were a representative sample of women of reproductive age (n=21350) who had given birth within the 5 years preceding the survey. HrBBs was measured through integration of information on maternal age at child’s birth, parity, and preceding birth interval with respect to the most recent child. The HrBBs was categorized as none, single and multiple. Data were analysed using descriptive statistics, Log-rank test and Cox proportional hazard model (α =0.05). Results The mean age of the women was 29.7 ± 7.2 and 4.1% had experienced infant death. Infant mortality was highest among women with multiple HrBBs (5.1%). Being a male, having small size at birth, failure to receive tetanus injection, non-use of contraceptives and living in the core-north (North West and North East) predisposed children to higher risk of dying before 12 months of age. The hazard ratio of infant mortality was significantly higher among infants of mothers in multiple HrBBs category (aHR=1.67; CI: 1.33-2.09) compared to their counterparts with no HrBBs. Conclusion Multiple HrBBs increase the chances of dying among infants in Nigeria. Screening women for HrBBs for special health attention during pregnancy, birth and postnatal period will alleviate infant death in Nigeria.
BLV-CoCoMo-qPCR-3: Improved BLV-CoCoMo-qPCR for Bovine Leukemia Virus Detection by Mixing Probes Targeting all BLV Variants
Authors: Borjigin Liushiqi , Yoneyama Shuji , Saito Susumu , Meripet Polat , Inokuma Michihito , Shinozaki Yasuo , Tanaka Naoko , Yamanaka Risa , Yasui Anna , Mimura Munehito , Murakami Hironobu , Takeshima Shin-nosuke , Aida Yoko 
Published: November 2020

Abstract
Background: The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, the most common neoplastic disease in cattle. The proviral load (PVL) is an important index for estimating disease progression. Previously, we developed a quantitative real-time PCR (qPCR) assay to measure the PVL of BLV using coordination of common motif (CoCoMo) degenerate primers that can amplify all known BLV strains. However, mutations, which potentially affect the detection ability, have been recently reported in the probe sequences of the long terminal regions (LTRs) of the BLV-CoCoMo-qPCR-2 assay. Here, we developed a new strategy to overcome these newly generated mutations located in the probe regions of this assay.Methods: We collected genomic DNA from 887 cows from 27 BLV-positive farms, using a nationwide survey conducted in 2011 and 2017 in Japan. BLV variants were investigated by quantifying the provirus using BLV-CoCoMo-qPCR-2 targeting the BLV LTR gene and the TaKaRa Cycleave PCR system targeting the BLV tax gene. Additionally, we sequenced the partial BLV LTR gene. The modified probes were designed to completely match the three BLV variants identified here, and the modified assay was established using mixed probes.Results: We found four single mutations within the probe region of the original BLV-CoCoMo-qPCR-2 assay, three of which negatively affected its sensitivity. Furthermore, we examined the optimum ratio of the concentration to be mixed with the wild type and three new BLV TaqMan probes were designed here using genomic DNAs extracted from cattle infected with the wild-type BLV strain and cattle infected with variants. Hence, we successfully established an improved BLV-CoCoMo-qPCR-3 assay that uses mixed probes corresponding to all three BLV variants. Conclusions: To overcome the loss of assay sensitivity due to newly emerging variants, we have established the BLV-CoCoMo-qPCR-3 assay that could amplify all BLV strains using newly designed mixed probes in addition to degenerate primers that were previously designed in our original assay. Our proposed method maintained the original sensitivity and reproducibility and can detect all mutant strains; thus, it is a useful tool to prevent the spread of BLV infections, especially those caused by newly emerging variants.
Mid- to Long-Term Follow-up Outcomes of One-Stage Posterior Lumbosacral or Lumbopelvic Fixation in the Management of Lumbosacral Junction Tuberculosis in Adults
Authors: Xu Zhenchao , Zhang Zhen , Chen Gang , Wang Xiyang 
Published: November 2020

Abstract
Background: This retrospective study aimed to evaluate the mid- to long-term outcomes of surgical management of lumbosacral junction tuberculosis in adults. Methods: A total of 38 adult patients were treated by one-stage posterior debridement, interbody fusion, lumbosacral or lumbopelvic fixation, and postural drainage. All cases were followed up for at least five years. Clinical and radiographic outcomes were gathered and analyzed.Results: All patients achieved clinical cure at the last follow-up. Erythrocyte sedimentation rates decreased to normal levels within three months postoperatively. Postoperative scores measuring pain (visual analog scale), neurological status (Japanese Orthopedic Association score), and patient quality of life (Oswestry Disability Index) all significantly improved compared to preoperative values. Patient-reported outcomes as measured by Kirkaldy-Willis criteria were excellent in 21 cases, good in 16 cases, and fair in 1 case; there were no poor outcomes. Lumbosacral angle increased from the preoperative values of 21.7° ± 1.8° to the postoperative values of 26.4° ± 1.4°, with an angle loss of 1.2° ± 0.7° at the last follow-up. Bone fusion occurred on average 12.8 ± 1.9 months after surgery. No nonunion, pseudarthrosis, loosening or fracture of instruments occurred at the last follow-up.Conclusion: For patients with lumbosacral junction TB, a treatment protocol including one-stage posterior debridement, interbody fusion, lumbosacral or lumbopelvic fixation, and postural drainage according to the severity of sacral destruction is a relatively nontraumatic and highly safe procedure. It can be used to reconstruct lumbosacral or lumbopelvic stability and facilitate the healing of TB.
Bibliometric Evaluation and Hot Spot Analysis of Developmental Dysplasia of the Hip
Authors: Fan YiNuo , Zhang Haitao , Guan Zhiying , Li Weifeng , Li Zhongfeng , He Wei , Chen Zhenqiu 
Published: November 2020

Abstract
Purpose: To analyze the research development process and research hotspots of DDH in order to guide the future research direction.Methods: Using the Web of Science database to search the relevant English literatures of DDH from 1994 to May 31,2020 and analyze them with Bibliometric analysis methods. The statistics and the analysis of the collected publications are for the sake of hierarchical refinement and quality assessment of the publications of different countries, authors, institutions, funding agencies, and journals. Using the VOS viewer software for visual conversion and researching direction and important fields of DDH simultaneously.Results: With a total of 2156 articles, the numbers of DDH published articles is increasing steadily. In funding agencies, the National Natural Science Foundation of China has funded most of the researches. In journals, the published articles of JOURNAL OF BONE AND JOINT SURGERY AMERICAN VOLUME are of the highest quality. For authors, KIM YJ is the author who not only published most of the articles, but also published the ones of the highest quality. In countries, the USA is ahead in the quantity and quality of published articles. In institutions, the published articles of UNIV BERN are of the highest quality. Through co-occurrence analysis, it can be seen that the research direction in the DDH field consists of four categories: Diagnosis, Complications, Hip replacement, and Staging treatment before hip replacement. Current research hotspots are mainly focused on treatment.Conclusions: At present, arthroplasty and osteotomy are research hotspots in recent years. It is recommended that researchers start the study of DDH from osteotomy, trying to optimize the adaptation age of various osteotomy to DDH and reduce its complications.
Midterm Results of Minimally Invasive Plating Osteosynthesis Versus Open Reduction and Internal Fixation for the Treatment of Mid-distal Humeral Shaft Fractures: A Case-match Controlled Comparison Study
Authors: Yin Bo , Gao Jie , Zeng Huayong , Lu Zheng , Cai Yanhong , He Yuanming , Liu Zhi , Li Lianhua 
Published: November 2020

Abstract
Background: Surgical treatment of humeral mid-distal shaft fractures is controversial. The purpose of this case-match controlled comparison study was to determine the safety and effectiveness of applying the MIPO technique compared with conventional ORIF for treating humeral mid-distal shaft fractures.Methods: This study was conducted from January 2012 to December 2016, and patients of mid-distal humeral shaft fractures were eligible for this study. The patients were followed up for a minimum period of 1 year. The clinical and radiographic outcomes were evaluated. The inclusion criteria were age between 18 to 60 years and acute displaced mid-distal humeral shaft fracture. The exclusion criteria were intra-articular fractures of the elbow, vascular insufficiency of the upper limb, pathological fracture and multiple or open fractures. The medical records and radiographs of all eligible patients during hospitalization and follow-up after discharge were reviewed. We use a 1:2 (MIPO/ORIF) case-match based on gender and age. All patients had at least 3 years of postoperative follow-up.Results: In total, 216 patients with mid-distal humeral shaft fracture underwent surgery at the departments of orthopedics of the Seventh Medical Center of PLA General Hospital and Beijing Chaoyang Hospital. Of them, 28 underwent MIPO and 56 case-matched controls underwent ORIF; all of them had complete 3-year follow-up data. No significant differences were observed in baseline characteristics between both groups. UCLA scores and MEPS were significantly higher in the MIPO group than in the ORIF group. Furthermore, UCLA score and MEPS grades in the MIPO group were significantly superior to those in the ORIF group. There was no statistically significant difference in major complication rates between both groups; however, the total major complication rate was significantly different between both groups.Conclusion: This study demonstrates that MIPO has a statistically significant clinical benefit over ORIF, including better shoulder and elbow joint function, with few overall major complications after at least 3 years of postoperative follow-up. MIPO is a safe and effective method for treating mid-distal humeral shaft fractures when surgery is indicated.
Screening and Identification of Significant Genes in Hepatocellular Carcinoma via Bioinformatical Analysis and Validation in Clinical Tissue
Authors: zhou jun guo , Wang Dongsheng , Zhong Xiaorong , Ying Wei , Feng Yanchao , Li Wenbo , Shi Lin , Huang Lizheng , Li Jianshui , Hou Lingmi , Leng wei Zheng 
Published: November 2020

Abstract
Background: To screen out significant genes associated with occurrence and development of hepatocellular carcinoma (HCC) via bioinformatical analysis and validation using clinical specimens. Methods: Gene expression chips were obtained from GEO database, differentially expressed genes (DEGs) between HCC and para-cancerous tissues were identified by GEO2R and Venn diagrams. What’s more, Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were carried out by DAVID. The protein-protein interaction (PPI) network and module analysis of DEGs were performed by STRING and Cytoscape to get hub genes. Subsequently, the influence of hub genes on overall survival and the expression levels were determined with Ualcan and GEPIA, and found the pathway via re-analysis of DAVID. Besides, immunohistochemistry staining were performed to verify the key genes, and follow-up results including prognoses and the clinicopathological features were statistically analyzed. Results: 49 up-regulated DEGs and 122 down-regulated DEGs were selected. There were to tally 33 Hub genes were screened out, while 28 of them were related to prognosis and high expression in HCC. Furthermore, CDK1 and RRM2 were significantly enriched in p53 signaling pathway. Meanwhile, CDK1, RRM2 were highly expressed in HCC tissues by immunohistochemistry staining. Additionally, CDK1 and RRM2 were negatively correlated with overall survival. Tumor size and AFP were significant prognostic factors, while CDK1 and RRM2 were independent prognostic factors. Conclusion: This study confirmed CDK1 and RRM2 as the key genes in HCC which could be potential biological target for diagnosis and treatment.