bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Association Between Asthma and Osteoarthritis: A Nationwide Health and Nutrition Examination Survey
Authors: Koo Hyeon-Kyoung , Song Pamela , Lee Joo-Hyun 
Published: October 2020

Abstract
Backgrounds: Asthma and osteoarthritis (OA) are medical conditions that disable physical activity and deteriorate patients’ quality of life. Despite the high prevalence, there are limited studies focusing on the comorbid condition and association between asthma and OA. The aim of study was to assess the prevalence and identify the clinical considerations for this special population.Methods: Adult patients aged over 40 years who completed questionnaire assessments and spirometry were enrolled from Korean National Health and Nutrition Examination Survey. Asthma and OA were defined on the history of doctor-diagnosed disease. Radiographic severities of OA were measured using the Kellgren/Lawrence grading system. Chronic obstructive pulmonary disease (COPD) as a comparative respiratory disease was diagnosed on the basis of spirometric results.Results: A total of 9344 subjects were enrolled, and the prevalence of asthma and COPD were 4.6%±0.3% and 12.0%±0.5%, respectively. The prevalence of OA in the asthma group was 31.9%±2.8%, which was significantly higher than those in the COPD (17.8%±1.5%) or control (16.2%±0.6%) groups. OA was more prevalent in asthma patients after adjusting for age, sex, body mass index, and smoking status (OR, 1.65; 95% CI, 1.27-2.13). After further adjustment of this model for prescription of OA medication, OA was still independently associated with asthma (OR, 1.56; 95% CI, 1.10-2.20). In contrast, the relationship of OA medication with asthma was not significant (P=0.64). This relationship was evident in subjects with asthma without airflow limitation measured by spirometry (OR, 1.97; 95% CI, 1.32-2.93). Moreover, radiographic severity of knee OA correlated with asthma (OR, 1.10; 95% CI, 1.0-1.21). Conclusions: OA shows a high prevalence in patients with asthma, with the prevalence being higher than that in COPD patients or controls. The comorbid characteristics of these two conditions need to be considered in clinical practice.
Concurrent Brain Structural and Functional Alterations in Patients with Migraine without Aura: An fMRI Study
Authors: Li Zhengjie , Zhou Jun , Lan Lei , Cheng Shirui , Sun Ruirui , Gong Qiyong , Wintermark Max , Zeng Fang , Liang Fanrong 
Published: October 2020

Abstract
Objectives: To explore the possible concurrent brain functional and structural alterations in patients with migraine without aura (MwoA) patients compared to healthy subjects (HS). Methods: Seventy-two MwoA patients and forty-six HS were recruited. 3D-T1 and resting state fMRI data were collected during the interictal period for MwoA and HS. Voxel-based morphometry (VBM) for structure analysis and regional homogeneity (Reho) for fMRI analysis were applied. The VBM and Reho maps were overlapped to determine a possible brain region with concurrent functional and structural alteration in MwoA patients. Further analysis of resting state functional connectivity (FC) alteration was applied with this brain region as the seed.Results: Compared with HS, MwoA patients showed decreased volume in the bilateral superior and inferior colliculus, periaqueductal gray matter (PAG), locus ceruleus, median raphe nuclei (MRN) and dorsal pons medulla junction. MwoA patients showed decreased Reho values in the middle occipital gyrus and inferior occipital gyrus, and increased Reho values in the MRN. Only a region in the MRN showed both structural and functional alteration in MwoA patients. Pearson correlation analysis showed that there was no association between volume or Reho values of the MRN and headache frequency, headache intensity, disease duration, self-rating anxiety scale or self-rating depression scale in MwoA patients. Resting state functional connectivity (FC) with the MRN as the seed showed that MwoA patients had increased FC between the MRN and PAG.Conclusions: MRN are involved in the pathophysiology of migraine during the interictal period. This study may help to better understand the migraine symptoms.Trial registration: NCT01152632. Registered 27 June 2010.
Leveraging Methylation Alterations to Discover Potential Causal Genes Associated with the Survival Risk of Cervical Cancer in TCGA through a Two-stage Inference Approach
Authors: Zhang Jinhui , Wang Ting , Yu Xinghao , Huang Shuiping , Zhao Huashuo , Zeng Ping 
Published: October 2020

Abstract
Background：Multiple genes were previously identified to be associated with cervical cancer; however, the genetic architecture of cervical cancer remains unknown and many causal genes have yet been discovered.Methods: To explore causal genes related to cervical cancer, a two-stage causal inference approach was proposed within the framework of Mendelian randomization, where the gene expression was treated as exposure, with methylations located within that gene serving as instrumental variables. Five prediction models were first utilized to characterize the relationship between the expression and methylations for each gene; then the methylation-regulated gene expression (MReX) was obtained and the association was evaluated via Cox mixed-effects model based on MReX. We further implemented the harmonic mean p-value (HMP) combination to take advantage of respective strengths of these prediction models while accounting for dependency among the p-values.Results: A total of 14 causal genes were discovered to be associated with the survival risk of cervical cancer in TCGA when the five prediction models were separately employed. The total number of causal genes was brought to 23 when conducting HMP. Some of the newly discovered genes may be novel (e.g. YJEFN3, SPATA5L1, IMMP1L, C5orf55, PPIP5K2, ZNF330, CRYZL1, PPM1A, ESCO2, ZNF605, ZNF225, ZNF266, FICD and OSTC). Functional analyses showed these genes were enriched in tumor-associated pathways. Additionally, four genes (i.e. COL6A1, SYDE1, ESCO2 and GIPC1) were differentially expressed.Conclusion: Overall, our study discovered promising candidate genes that are causally associated with the survival risk of cervical cancer and thus provided new insights into the genetic etiology of cervical cancer.
Anlotininb as a Promising Inhibitor on Tumor Growth of Oral Squamous Cell Carcinoma Through Cell Apoptosis and Mitotic Catastrophe
Authors: Deng Zhaoming , Liao Wei , Wei Wei , Zhong Guihua , He Chao , Zhang Hongbo , Liu Qiaodan , Xu Xiwei , Liang Jun , Liu Zhigang 
Published: October 2020

Abstract
BackgroundOral squamous cell carcinoma (OSCC) has been one of the most malignant cancers in head and neck region. Anlotinib is a tyrosine kinase inhibitor targeting several receptors such as vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. Here we investigated whether Anlotinib have any antitumor effect on oral cancer and tried to explore and explain the possible mechanism.MethodsData from The Cancer Genome Atlas and the Gene Expression Omnibus and Gene Expression Omnibus database was collected to analyze the relationship between the expression of vascular epithelial growth factor receptor 2 and the overall survival rate of OSCC. Oral cancer cell lines Cal-27 and SCC-25 were cultured to conduct all the experiments. In vitro experiments such as CCK-8, colony formation, cell cycle assay and cell apoptosis assay were conducted to detect cell proliferation ability and the change of cell phase and apoptosis. Proteins concerning cell cycle and cell apoptosis were visualized via western blot. α-Tubulin were visualized via immunofluorescence to detect cells undergoing mitotic catastrophe. ResultsHigher expression of VEGFR-2 was significantly related to poorer prognosis. Experiment in vitro demonstrated that cell proliferation was significantly inhibited(p<0.05) after Anlotinib administration and G2/M arrest and apoptosis were both detected in both cell lines. Cycle-related proteins promoting cell cycle progression and proteins related to cell survival were downregulated in Anlotinib group compared to the control group. Cell-death-related biomarker and phosphorylated histone 3 were upregulated in expression in Anlotinib group. Abnormal spindle apparatus was observed in cells undergoing mitotic catastrophe. ConclusionAnlotinib could exert an antitumor effect on oral cancer cells lines via apoptotic pathway and mitotic catastrophe pattern, presenting a promising potential therapy for patients with OSCC.
Targeting the Kaposi’s Sarcoma-associated Herpesvirus Genome With the CRISPR-Cas9 Platform in Latently Infected Cells
Authors: Haddad Coral Orel , Kalt Inna , Shovman Yehuda , Xia Lei , Schlesinger Yehuda , Sarid Ronit , Parnas Oren 
Published: October 2020

Abstract
Background: Kaposi’s sarcoma-associated herpesvirus (KSHV) is a transforming gammaherpes. Like other herpesviruses, KSHV infection is for life long and there is no treatment that can cure of patients from the virus. In addition, there is urgent need to target viral genes to study their role during the infection cycle. The CRISPR-Cas9 technology offers a means to target viral genomes and thus may offer a novel strategy for viral cure as well for better understanding of the infection process. We evaluated the suitability of this platform for the targeting of KSHV. Methods: We have used BAC16 genome, which contains an expression cassette encoding hygromycin-resistance and a GFP marker gene. Three genes were targeted: gfp which serves as a marker for infection; orf45 encoding a lytic viral protein; and orf73, encoding LANA which is crucial for latent infection. The fraction of cells expressing GFP as well as viral DNA levels and LANA expression were monitored and viral genomes were sequenced. Results: We found that KSHV episomes can be targeted by CRISPR-Cas9. Interestingly, the quantity of KSHV DNA declined, even when target sites were not functionally important for latency. In addition, we show that antibiotic selection, used to maintain infection, interferes with the outcome of targeting.Conclusions: Our study provides insights to the use of this fundamental approach for the study and manipulation of KSHV. It provides guidelines for the targeting CRISPR-Cas9 to the viral genome and for outcomes interpretation.
Screen Time Duration and Timing: Effects on Obesity, Physical Activity, Dry Eyes, and Learning Ability in Elementary School Children
Authors: Mineshita Yui , Kim Hyeon-Ki , Chijiki Hanako , Nanba Takuya , Shinto Takae , Furuhashi Shota , Oneda Satoshi , Kuwahara Mai , Suwama Anzu , Shibata Shigenobu 
Published: October 2020

Abstract
Background: As internet use becomes more widespread, the screen time (ST) of elementary school students increases yearly. It is known that longer durations of ST can affect obesity, physical activity, dry eye disease, and learning ability. However, the effects of ST just before bedtime have not been clarified. Therefore, we examined ST duration and timing effects on elementary school children. Methods: We conducted a survey of 7,419 elementary school students in Tokyo, Japan using a questionnaire on food education. ST duration and timing (just before bedtime) served as the explanatory variables, and the relationship between obesity, physical activity, dry eyes, and learning ability was analyzed using logistic regression analysis. Gender, school year, height, and weight were considered confounding factors. First, we examined whether ST duration and timing were related to each objective variable, using a univariate model to examine all variables. Thereafter, we performed multivariate logistic regression analyses for all variables showing a significant difference in the univariate models.Results: The results showed that the relationship between the ST duration and obesity, physical activity, and learning ability was statistically significant. The relationship between ST timing and obesity, dry eyes, and learning ability was also statistically significant. Therefore, ST timing has a greater effect on dry eyes, and ST duration has a greater effect on academic performance. Conclusion: Our findings indicate that ST in school children is related to obesity, physical activity, dry eyes, and learning ability, and they suggest that not only the duration but also the timing of ST is important.
Analysis of the CHP Technological Innovation System in Iran using the Causal Layered Analysis (CLA)
Authors: Heirani Hossein , Moghaddam Naser Bagheri , Fazli Mohammad Hassan 
Published: October 2020

Abstract
Background: As many other countries, Iran has adopted policies consider energy technologies development. One of these technologies around which several national programs have launched is the Cogeneration of Heat and Power (CHP). Despite the variety of plans and actions in different governmental and non-governmental bodies, the fact is that the national targets have not been fulfilled as they were expected. Since the first step to make policies for technology development is recognizing the problems and bottlenecks hindering the development process, the main aim of this paper is to provide a model to analyze the failures of technology development process according to Technological Innovation System (TIS) approach. Besides, the CLA method has been used to decipher the profound and latent factors causing these problems. Results: By mixing up CLA and TIS approaches, this paper achieves a comprehensive model describing the causal relationship between multi-layered problems of technology development. Afterwards, by using structural equation modelling, the correlation amongst multi-layered problems was tested. While most studies have concentrated on the structural and functional problems of the TIS, the results of the model demonstrate a significant role of the discourses and visions. Although the structural problems have had the most significant effect on the functional problems, surprisingly, the second position is for the problems related to metaphors. This might be the most noticeable result of this research that the metaphoric and visionary factors can play a role as important as structures of the TIS. Conclusion: The results of the study indicate that the discursive and metaphoric factors have had the significant effect both directly on the failure of the CHP innovation system and indirectly through affecting structural elements. A notable policy suggestion is to change the discourse of centralized power generation and to make more effort regarding the energy efficiency in the society. Moreover, policies should create a positive and long-term vision for development of CHP plants.
Customized Reconstruction of Complex Soft Tissue Defect Around the Knee with Individual Design of Free Perforator Flap
Authors: Fu Jinfei , Qing Liming , Wu Panfeng , Zhou Zhengbing , Yu Fang , Tang Juyu 
Published: October 2020

Abstract
Background Reconstruction of complex soft tissue defect around the knee, particularly in involving with large soft tissue defect or disruption of extensor mechanism, always is a challenging problem. The purpose of this study was to introduce our clinical experience on using individual design of free perforator flap for complex soft-tissue reconstruction around the knee. Methods Between June 2010 and March 2017, 16 patients underwent the reconstruction of complex soft tissue defect in the knee region with free perforator flap, Various flap designs was performed basing on the location of wound, the require pedicle length, the tissue components that are deficient, the volume of such components and the risk of donor site morbidity.Results Complex soft tissue defect of the knee was reconstructed with anteriorlateral thigh perforator (ALTP) flap in 5 cases, modified ALTP flap in 2 cases, chimeric ALTP flap in 4 cases, dual skin paddles ALTP flap in 2 cases and chimeric thoracodorsal artery perforator (TDAP) flap in 2 cases. Multiple perforator flaps and vascularized fascia lata in combination were performed in one case. All flaps survived postoperative. None vascular congestion was observed. Only one case suffered partial necrosis. Primary closure of donor site was performed for all patients. The mean follow-up time was 16.5 months. Most cases showed satisfactory flap contour and acceptable function outcome. Conclusions Free perforator flap is a reliable option for repairing complex soft tissue defect in the knee region, especially when local and pedicled flaps are unavailable. Various flap designs allow for more individualized treatment approaches.
Findings on the relationship between cardiovascular disease and coronavirus disease 2019: a systematic review
Authors: Silva1 Yuri Henrique da , Júnior José Gildo de Moura Monteiro , Araújo Rosângela Ferreira Frade de 
Published: October 2020

Abstract
Coronavirus disease 2019 (COVID-19) presents as the main cause of death, respiratory and heart failures, especially in the elderly, immunosuppressed, and those with cardiovascular comorbidities. Therefore, a better understanding of these findings is needed. A systematic review was carried out looking for articles published between December 2019 and May 2020 on the MEDLINE / PubMed search platform using the following descriptors: ((((((((("cardiovascular disease") OR ("acute myocardial infarction")) OR ("coronary artery disease")) OR ("acute coronary syndrome")) OR ("atherosclerosis")) OR ("cardiac insufficiency")) OR ("pericarditis")) OR ("myocarditis")) AND ("COVID-19")) OR ("SARS-CoV-2")and considering inclusion and exclusion criteria.40% of patients infected with SARS-CoV-2 had hypertension or other cardiovascular comorbidities, while 27% presented cardiovascular complications, mainly acute cardiac injury, arrhythmia and heart failure. The hypotheses of involvement of an intense inflammatory response, decreased immunity and greater expression of ACE2 in the heart, associated with more severe heart conditions, were discussed in this study. The increase in cardiac and inflammatory markers was associated with worse clinical outcomes and risk of death, confirming the need to evaluate them since admission to the hospital. The 10 articles analyzed presented as a limitation the small number of patients inserted, to the detriment of the pandemic state. We warned about the need for better clinical management of patients with cardiovascular comorbidities, and the importance of including this group among the first to be immunized, aiming at reducing the number of fatal cases due to infection. Studies with greater coverage are needed for a better comprehension of the topics discussed here.
Sofosbuvir-based therapies achieved satisfactory virological response in Chinese with genotypes&nbsp;3 and 6 infection:&nbsp;a real-world experience from a centre
Authors: Tang Qiao , Wei Li , Liu Xiaoqing , Hu Peng 
Published: October 2020

Abstract
BackgroundAs previously shown by others, sofosbuvir-based regimens yield high sustained virological response rates in patients with HCV infection except for genotype 3b complicating with cirrhosis. The real-world study aims to explore efficacy and safety of sofosbuvir-based regimens in genotypes 3 and 6 infected patients, especially the impact of ribavirin co-administration on sustained virological response in cirrhotic patients with genotype 3b infection. MethodsA retrospective cohort study included 173 patients initiated on sofosbuvir-based regimens. Main endpoint of treatment was sustained virological response at post-treatment week 12 (SVR12).Results92 patients with sufficient follow-up were included. Overall, SVR12 rate was 96.7% (89/92), including 62 patients treated with addition of ribavirin to sofosbuvir-based regimens, given superior SVR12 rate (98.4%) than ribavirin free regimens (93.3%). SVR12 rates were 96.3% and 96.7% in patients infected with genotype3 (54) and genotype 6 (38) Among patients with genotype 3b infection, SVR12 was achieved in 97.1%, and 100% when complicating with cirrhosis. SVR12 rate was achieved in 96.6% among patients with cirrhosis (28/29), 100% with ribavirin co-administration regimens and 87.5% without ribavirin. Totally, three patients failed to achieve SVR12, including 2 non-cirrhotic patients with genotype 3b and 6a infection treated with sofosbuvir+ribavirin and sofosbuvir/velpatasvir regimen, one cirrhotic patient with genotype 3k infection treated with SOF/VEL regimen. No sever adverse events occurred.ConclusionsReal-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infection. Addition of ribavirin to sofosbuvir-based regimens may improve efficacy, especially in patients with genotype 3 infection and cirrhosis.Trial registrationNot applicable.
Mathematical Model for COVID-19 Management in Crowded Settlements and High-Activity Areas
Authors: Ssematimba Amos , Nakakawa Juliet , Ssebuliba Joseph , Mugisha Joseph Y. T 
Published: October 2020

Abstract
This paper develops and analyses a population density-dependent mathematical model to study the transmission dynamics of COVID-19 in crowded settlements such as refugee camps, schools, markets and churches. The model quantifies the potential impact of physical/social distancing and population density on the disease burden. It further determines the number of secondary infections that may arise from having one infectious individual in a high population-activity area. Results reveal that with no fatalities, the reproduction numbers associated with asymptomatic and symptomatic cases are inversely proportional to; the habitat area size, and the efforts employed in tracing and hospitalising these cases. The critical habitat area below which the disease dies out is directly proportion to the time taken to identify and hospitalise infected individuals. Results also show that disease persistence in the community is guaranteed even with minimal admission of infected individuals. In a high-activity area with 70,000 individuals, results indicate that if 10% of these individuals do not adhere to standard operating procedures (SOPs) when allocated an area of 1m2 per individual, then every infectious seeder will cause approximately one new infection within 12 hours of activity. On the other hand, if the area occupied by the 70,000 individuals is increased to 1km2 then even at the lowest explored level of adherence to SOPs, the arising number of new cases within 12 hours would be less than one per infectious seeder. We conclude that proper use of masks and physical distancing measures should be highly enforced in crowded settings.