bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-40: A New B Cell-Associated Cytokine Up-Regulated in Rheumatoid Arthritis Decreases Following the Rituximab Therapy and Correlates With Disease Activity, Autoantibodies, and NETosis
Authors: Navrátilová Adela , Andrés Cerezo Lucie , Hulejová Hana , Bečvář Viktor , Tomčík Michal , Komarc Martin , Veigl David , Tegzová Dana , Závada Jakub , Olejárová Marta , Pavelka Karel , Vencovský Jiří , Šenolt Ladislav 
Published: October 2021

BackgroundInterleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA).MethodsIL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined.ResultsIL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p&lt;0.0001). Similarly, IL-40 was increased in the serum of RA patients compared to HC, OA, or SLE (p&lt;0.0001 for all) and decreased after 16 and 24 weeks (p&lt;0.01 and p&lt;0.01) following rituximab treatment. No significant effect of adalimumab on IL-40 was observed. IL-40 levels in RA patients correlated with rheumatoid factor-IgM and anti-cyclic citrullinated peptides (anti-CCP) in the serum (p&lt;0.0001 and p&lt;0.01), as well as in the synovial fluid (p&lt;0.0001 and p&lt;0.001). Synovial fluid IL-40 was also associated with disease activity score DAS28 (p&lt;0.05), synovial fluid leukocyte count (p&lt;0.01), neutrophil attractants IL-8 (p&lt;0.01), MIP-1α (p&lt;0.01), and markers of neutrophil extracellular traps externalization (NETosis) such as proteinase 3 (p&lt;0.0001) and neutrophil elastase (p&lt;0.0001). Synovial fibroblasts exposed to IL-40 increased the secretion of IL-8 (p&lt;0.01), MCP-1 (p&lt;0.05), and MMP-13 (p&lt;0.01) compared to the unstimulated cells.ConclusionsWe show the up-regulation of IL-40 in RA and its decrease following B cell depleting therapy. The association of IL-40 with autoantibodies, chemokines, and markers of NETosis may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 in synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.
Implications of Isolated Para-Aortic Lymph Node Metastasis in Endometrial Cancer: A Large-Scale, Multicenter, and Retrospective Study
Authors: Li Wenting , Jiang Jie , Fu Yu , Shen Yuanming , Zhang Chuyao , Yao Shuzhong , Xu Congjian , Xia Min , Lou Ge , Liu Jihong , Lin Bei , Wang Jianliu , Zhao Weidong , Zhang Jieqing , Cheng Wenjun , Guo Hongyan , Guo Ruixia , Xue Fengxia , Wang Xipeng , Han Lili , Zhao Xia , Li Xiaomao , Zhang Ping , Zhao Jianguo , Ma Jiezhi , Yao Qin , Yang Xiaohang , Dou Yingyu , Wang Zizhuo , Liu Jingbo , Fang Yong , Li Kezhen , Wang Beibei , Chen Gang , Cheng Xiaodong , Sun Chaoyang , Kong Beihua 
Published: October 2021

Objective: To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy.Methods: Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated.Results: Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6–59.9], 74.2 95% CI: 65.6–81.4), and 45.8% (95% CI: 38.7–53.2), respectively.Conclusion: Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.
Role of Phospholipases A2 in Vascular Relaxation and Sympatholytic Effects of Five Australian Brown Snake, Pseudonaja spp., Venoms in Rat Isolated Tissues
Authors: Vuong Nhi Thuc , Jackson Timothy N. W. , Wright Christine E. 
Published: October 2021

Human envenoming by Australian brown snakes (Pseudonaja spp.) may result in potentially life-threatening hypotension and subsequent cardiovascular collapse. There have been relatively few studies of the cardiovascular and sympathetic effects of Pseudonaja spp. venoms. In this study, we have examined the effects of venom from five brown snake species—P. affinis, aspidorhyncha, inframacula, nuchalis, and textilis—on cardiac inotropic and chronotropic responses, vascular tone, and sympathetic nerve-induced vascular contractions in rat isolated tissues. The role of phospholipases A2 (PLA2s) in venom-induced effects was assessed with the sPLA2 inhibitor varespladib. In rat isolated left and right atria, there were no physiologically relevant effects of Pseudonaja venoms (0.1–30 µg/ml) on left atrial force of contraction (inotropy) or right atrial rate (chronotropy). In contrast, in isolated small mesenteric arteries precontracted with a thromboxane mimetic, each of the five brown snake venoms (at 30 µg/ml) caused marked vasorelaxation (−60 to –90% of contractile tone). Pretreatment with varespladib (1 µM) significantly inhibited the vasorelaxation caused by P. aspidorhyncha, P. nuchalis, and P. textilis venoms. Electrically induced sympathetic nerve-mediated contractions of mesenteric arteries were significantly attenuated by only P. textilis, and P. affinis venoms (30 µg/ml) and these sympatholytic effects were inhibited by varespladib (1 µM). Based on their inhibition with the sPLA2 inhibitor varespladib, we conclude that PLA2 toxins in P. aspidorhyncha, P. nuchalis, and P. textilis venoms are involved in brown snake venom-induced vasorelaxation and the sympatholytic effects of P. affinis, and P. textilis venoms. Our study supports the promising potential role of varespladib as an initial (pre-referral) and/or adjunct (in combination with antivenom) therapeutic agent for brown snake envenoming.
Long Non-coding RNA Rhabdomyosarcoma 2-Associated Transcript Regulates Angiogenesis in Endothelial Cells
Authors: Alaqeeli Maha , Mayaki Dominique , Hussain Sabah N. A. 
Published: October 2021

Background: Long non-coding RNAs (lncRNAs) are non-coding RNAs that have more than 200 nucleotides. They have recently emerged as important regulators of angiogenesis. To identify novel lncRNAs that may be involved in the regulation of angiogenesis, we detected the mRNA of 84 lncRNAs in human umbilical vein endothelial cells (HUVECs) exposed to hypoxia for 24h. One of these, rhabdomyosarcoma 2-associated transcript (RMST), is significantly upregulated by hypoxia. Little is known about the presence and roles of RMST in EC function.Objective: The main objective of the study was to investigate the regulation of RMST in ECs and to determine its role in EC survival, proliferation, migration, and differentiation.Methods: Using qPCR, basal mRNA levels of 10 RMST isoforms in HUVECs were measured. Levels were then measured in response to 24h of hypoxia, 7days of differentiation in a co-culture assay, and exposure to four different angiogenesis factors. Functional roles of RMST in EC survival, migration, and differentiation were quantified by using a loss-of-function approach (transfection with single-stranded antisense LNA GapmeRs). EC survival was measured using cell counts and crystal violet assays. Cell migration and differentiation were measured using scratch wound healing and Matrigel® differentiation assays, respectively.Results: Five RMST isoforms (RMST-202, -203, -204, -206, and -207) were detected in HUVECs and human microvascular endothelial cells (HMEC-1s). Other types of vascular cells, including human aortic valve interstitial cells and human aortic smooth muscle cells, did not display this expression profile. RMST was significantly upregulated in response to 24h of hypoxia and in response to 7days of HUVEC co-culture with human lung fibroblasts. RMST was significantly downregulated by angiopoietin-2 (Ang-2), but not by VEGF, FGF-2, or angiopoietin-1 (Ang-1). Selective knockdown of RMST demonstrated that it promotes EC survival in response to serum deprivation. It is also required for VEGF- and Ang-1-induced EC survival and migration, but not for differentiation.Conclusion: We conclude that RMST is expressed in human ECs and that this expression is upregulated in response to hypoxia and during differentiation into capillary-like structures. We also conclude that RMST plays important roles in EC survival and migration.
An Evaluation of Forced Distance Learning and Teaching Under Pandemic Conditions Using the Technology Acceptance Model
Authors: Drueke Barbara , Mainz Verena , Lemos Martin , Wirtz Markus Antonius , Boecker Maren 
Published: October 2021

Research: Due to the sudden outbreak of COVID-19 and the resulting pandemic situation, universities were forced to rapidly change their traditional pedagogical and didactical approach by shifting from mostly face-to-face teaching to entirely virtual and online teaching methods. Through this, a “forced” distance learning and teaching situation emerged. This study aimed at investigating the effect of these innovations on the implementation, acceptance, and use of the virtual teaching offer within the framework of the technology acceptance model (TAM).Methods: A total of 218 students and 69 lecturers of a German Medical Faculty completed online questionnaires on the acceptance, satisfaction, and usefulness of the forced distance learning (FDL) and teaching (FDT), respectively. An extended version of the TAM was used to assess the acceptance of the students and lecturers of FDL and FDT. In order to estimate the multivariate dependencies, path analysis was employed using structural equation modeling (SEM).Results: In general, students and lecturers reported being satisfied with the implementation of the FDL and FDT. Regarding the TAM model, the fit indices suggested an acceptable model fit for both groups. The model of the students revealed that the perceived usefulness had a strong predictive power on the attitude toward using and the perceived ease of use also predicted the attitude. The existing technical infrastructure as well as the general media affinity and pandemic-related worries proved to be positively associated with the perceived usefulness while data security worries and organization of online teaching predicted the perceived ease of use in students. The strong positive predictive power of the perceived usefulness for the attitude toward using was also evident in the model for the lecturers and the technical infrastructure predicted the perceived ease of use in the lecturers.Conclusion: The TAM is a suitable framework to represent the implementation, acceptance, and use of the virtual teaching offer during the special pandemic situation at the university. However, personal and structural context factors were important predictors for the perceived usefulness and the perceived ease of use in the student group. The forced situation for learning and teaching makes it more difficult to predict the actual use of virtual teaching offers solely based on attitude.
Subgroup Formation in Diverse Virtual Teams: The Moderating Role of Identity Leadership
Authors: op ‘t Roodt Helen , Krug Henning , Otto Kathleen 
Published: October 2021

Background: As today’s organizations are becoming increasingly globalized and adding the impetus to a more remote form of working due to the present COVID-19 pandemic, new ways of collaboration—like virtual teams—have gained importance. In the present study, we aim to investigate how virtual team outcomes are linked to perceived diversity and subgroup formation and attempt to gain some initial insight into the role of the social identity approach to leadership in virtual teams.Method: In the present cross-sectional study, a total of 102 virtual team members participated in an online survey measuring perceived diversity, identity leadership, subgroup formation, perceived performance, and team satisfaction, to examine the factors moderating the relationship between perceived diversity and subgroup formation as well as between perceived diversity and team performance and satisfaction.Results: Moderation analysis revealed that perceived diversity had a negative influence on performance ratings when subgroups were highly perceived to be present, but not if subgroup formation was rated as low. The relationship between perceived diversity and team satisfaction was not moderated by perceived subgroup formation. Furthermore, identity leadership was found to be positively related to team satisfaction and perceived performance, while subjective diversity was negatively associated with both team outcomes. Identity leadership moderated the relationship between perceived diversity and subgroup formation, in that high levels of identity leadership weakened the positive relationship.Conclusion: This study provides first evidence to the importance of the team leader’s role as a manager of a shared social identity in virtual teams where perceived differences can lead to subgroup splits, as identity leaders may hinder the emergence of subgroups in virtual teams.
Systematic Assessment of COVID-19 Pandemic in Bangladesh: Effectiveness of Preparedness in the First Wave
Authors: Saha Priom , Gulshan Jahida 
Published: October 2021

Background: To develop an effective countermeasure and determine our susceptibilities to the outbreak of COVID-19 is challenging for a densely populated developing country like Bangladesh and a systematic review of the disease on a continuous basis is necessary.Methods: Publicly available and globally acclaimed datasets (4 March 2020–30 September 2020) from IEDCR, Bangladesh, JHU, and ECDC database are used for this study. Visual exploratory data analysis is used and we fitted a polynomial model for the number of deaths. A comparison of Bangladesh scenario over different time points as well as with global perspectives is made.Results: In Bangladesh, the number of active cases had decreased, after reaching a peak, with a constant pattern of death rate at from July to the end of September, 2020. Seventy-one percent of the cases and 77% of the deceased were males. People aged between 21 and 40 years were most vulnerable to the coronavirus and most of the fatalities (51.49%) were in the 60+ population. A strong positive correlation (0.93) between the number of tests and confirmed cases and a constant incidence rate (around 21%) from June 1 to August 31, 2020 was observed. The case fatality ratio was between 1 and 2. The number of cases and the number of deaths in Bangladesh were much lower compared to other countries.Conclusions: This study will help to understand the patterns of spread and transition in Bangladesh, possible measures, effectiveness of the preparedness, implementation gaps, and their consequences to gather vital information and prevent future pandemics.
36-Month Evaluation of a Weight Management Programme in Chinese Overweight and Obese Adults
Authors: Yang Xi , Chattopadhyay Kaushik , Hubbard Richard , Li Jia-Lin , Li Li , Lin Yi 
Published: October 2021

Background: Few comprehensive lifestyle intervention programmes have been investigated on overweight and obese adults in China. This study was to evaluate the effect of a 36-month weight management programme on weight loss and its maintenance among overweight and obese patients in Ningbo, China.Methods: Adults with BMI ≥24kg/m2 enrolled in this programme, including nutritional, physical activity, psychological and endocrinological counselling sessions, from July 2015 to January 2020. Adults participated in face-to-face counselling sessions and group-based education. Then, participants joined 21-day intensive programme using Bohe health APP and WeChat group to get personal advice of nutrition and lifestyle. In the end, participants were requested to join 33-month follow-ups including face-to-face counselling and personal advice on WeChat group. The main outcome was to evaluate the changes in weight at each followup from baseline weight.Results: In total, 692 adults participated in this entire weight management programme. During follow-ups, 579, 475, 299, 219, and 135 adults participated at 3, 6, 12, 24, and 36 months, respectively. All participants had a significant initial weight loss at 3 months, then maintained the weight loss during 33-month follow-ups. At 36 months, 11.0%, 6.4%, and 3.5% of all participants achieved 5%, 10%, and 15% weight loss from the baseline weight, respectively. Adjusted weight at 36 months was significantly reduced from the baseline weight in both sex (−7.2 kg).Conclusion: This weight management programme is suggested to benefit to reduce initial body weight and maintain long-term weight loss among overweight and obese adults.
The Determinants of the Low COVID-19 Transmission and Mortality Rates in Africa: A Cross-Country Analysis
Authors: Bouba Yagai , Tsinda Emmanuel Kagning , Fonkou Maxime Descartes Mbogning , Mmbando Gideon Sadikiel , Bragazzi Nicola Luigi , Kong Jude Dzevela 
Published: October 2021

Background: More than 1 year after the beginning of the international spread of coronavirus 2019 (COVID-19), the reasons explaining its apparently lower reported burden in Africa are still to be fully elucidated. Few studies previously investigated the potential reasons explaining this epidemiological observation using data at the level of a few African countries. However, an updated analysis considering the various epidemiological waves and variables across an array of categories, with a focus on African countries might help to better understand the COVID-19 pandemic on the continent. Thus, we investigated the potential reasons for the persistently lower transmission and mortality rates of COVID-19 in Africa.Methods: Data were collected from publicly available and well-known online sources. The cumulative numbers of COVID-19 cases and deaths per 1 million population reported by the African countries up to February 2021 were used to estimate the transmission and mortality rates of COVID-19, respectively. The covariates were collected across several data sources: clinical/diseases data, health system performance, demographic parameters, economic indicators, climatic, pollution, and radiation variables, and use of social media. The collinearities were corrected using variance inflation factor (VIF) and selected variables were fitted to a multiple regression model using the R statistical package.Results: Our model (adjusted R-squared: 0.7) found that the number of COVID-19 tests per 1 million population, GINI index, global health security (GHS) index, and mean body mass index (BMI) were significantly associated (P &lt; 0.05) with COVID-19 cases per 1 million population. No association was found between the median life expectancy, the proportion of the rural population, and Bacillus Calmette–Guérin (BCG) coverage rate. On the other hand, diabetes prevalence, number of nurses, and GHS index were found to be significantly associated with COVID-19 deaths per 1 million population (adjusted R-squared of 0.5). Moreover, the median life expectancy and lower respiratory infections rate showed a trend towards significance. No association was found with the BCG coverage or communicable disease burden.Conclusions: Low health system capacity, together with some clinical and socio-economic factors were the predictors of the reported burden of COVID-19 in Africa. Our results emphasize the need for Africa to strengthen its overall health system capacity to efficiently detect and respond to public health crises.
Clinicopathological Characteristics and Survival Outcomes of Primary Renal Leiomyosarcoma
Authors: Chen Cheng , Jiang Xinjie , Xia Fei , Chen Xudong , Wang Weiguo 
Published: October 2021

Background: Primary renal leiomyosarcoma (LMS) is an exceedingly rare entity with a poor prognosis. We summarized the clinicopathological characteristics, treatment choice, and survival outcomes of LMS from the Surveillance, Epidemiology, and End Results (SEER) database.Methods: Renal LMS and kidney renal clear cell carcinoma (KIRC) data from 1998 to 2016 were collected from the SEER database. The continuous variables were analyzed using t-tests, while the categorical variables were analyzed using Pearson's chi-squared or Fisher's exact tests. Propensity score matching (PSM) was also performed. The cancer-specific survival (CSS) and overall survival (OS) curves were estimated using Kaplan-Meier analyses and compared by log-rank tests. The risk factors for CSS and OS were estimated using univariable and multivariable Cox proportional hazard regression models.Results: A total of 140 patients with renal LMS and 75,401 patients with KIRC were enrolled. These groups differed significantly in sex, race, tumor size, grade, SEER stage, surgery, radiation, and chemotherapy. Renal LMS exhibited poorer CSS and OS compared with KIRC before and after PSM. For renal LMS, the univariate Cox proportional hazard regression model indicated that larger tumor size, higher tumor grade, higher SEER stage, and chemotherapy were risk factors for CSS and OS, while surgery appeared to be a protective factor. However, only tumor grade, SEER stage, and receiving surgery remained independent prognostic factors in the multivariable Cox proportional hazard regression model. In addition, subgroup analyses indicated that surgery remained a protective factor for advanced renal LMS. However, there was no survival benefit for patients receiving chemotherapy.Conclusions: Primary renal LMS is an exceedingly rare entity with distinct clinicopathological features and a poor prognosis. A higher tumor grade and late stage may indicate a poor prognosis. Complete tumor resection remains to be the first treatment choice, while chemotherapy may be a palliative treatment for patients with advanced disease.