bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Potential and Safety of the Cinnamomum zeylanicum Methanolic Extract Against Chronic Toxoplasma gondii Infection in Mice
Authors: Alanazi Abdullah D. , Almohammed Hamdan I. 
Published: June 2022

BackgroundThis experimental study determined the in vitro, in vivo, and toxicity effects of Cinnamomum zeylanicum methanolic extract (CZME) against Toxoplasma gondii infection.MethodsThe in vitro activity of CZME T. gondii tachyzoites was studied by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Infected mice were treated with CZME for two weeks at doses of 20, 40, and 60 mg/kg/day. Then, the therapeutic effects of CZME were evaluated by assessing the mean number and mean size of T. gondii tissue cysts, oxidant-antioxidant enzymes, pro-inflammatory cytokines, and mRNA expression levels of bradyzoite surface antigen 1 (BAG1) by real-time PCR.ResultsCZME significantly (p &lt;0.001) increased the mortality rate of parasites in a dose- and time-dependent response. The mean number of intracellular tachyzoites was significantly reduced after CZME therapy. The treatment of infected mice with CZME resulted in a significant (p &lt;0.001) downregulation of BAG1 and the level of lipid peroxidation (LPO) and nitric oxide (NO) as oxidative stress markers. However, a considerable rise (p &lt;0.05) was found in the levels of antioxidant markers such as glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD). In a dose-dependent response, after treatment of infected mice with CZME, the level of pro-inflammatory cytokines of IFN-γ, IL-1β, and IL-12 was considerably elevated. CZME had no significant cytotoxicity on Vero cells, with a 50% cytotoxic concentration of 169.5 ± 5.66 μg/ml.ConclusionThe findings confirmed the promising therapeutic effects of CZME on chronic toxoplasmosis in mice. Nevertheless, further investigations must confirm these results, elucidate its precise mechanisms, and examine its effectiveness in human volunteers.
Association of Healthy Lifestyle and Life Expectancy in Patients With Cardiometabolic Multimorbidity: A Prospective Cohort Study of UK Biobank
Authors: Cheng Xunjie , Ouyang Feiyun , Ma Tianqi , Luo Yi , Yin Jinghua , Li Jinchen , Zhang Guogang , Bai Yongping 
Published: June 2022

BackgroundThe prevalence of cardiometabolic multimorbidity (CMM), which significantly increases the risk of mortality, is increasing globally. However, the role of healthy lifestyle in the secondary prevention of CMM is unclear.MethodsIn total, 290,795 participants with CMM, which was defined as coexistence of at least two of hypertension (HTN), diabetes mellitus (DM), coronary heart disease (CHD), and stroke (ST), and those without these four diseases at baseline were derived from UK Biobank. The associations between specific CMM patterns and mortality, and that between healthy lifestyle (including physical activity, smoking, alcohol consumption, and vegetable and fruit consumption) and mortality in patients with specific CMM patterns were calculated using the flexible parametric Royston-Parmar proportion-hazard model. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated.ResultsDuring a median 12.3-year follow up period, 15,537 (5.3%) deaths occurred. Compared with participants without cardiometabolic diseases, the HRs for all-cause mortality were 1.54 [95% confidence interval (CI): 1.30, 1.82] in participants with HTN + DM, 1.84 (95% CI: 1.59, 2.12) in those with HTN + CHD, 1.89 (95% CI: 1.46, 2.45) in those with HTN + ST, and 2.89 (95% CI: 2.28, 3.67) in those with HTN + DM + CHD. At the age of 45 years, non-current smoking was associated with an increase in life expectancy by 3.72, 6.95, 6.75, and 4.86 years for participants with HTN + DM, HTN + CHD, HTN + ST, and HTN + DM + CHD, respectively. A corresponding increase by 2.03, 1.95, 2.99, and 1.88 years, respectively, was observed in participants with regular physical activity. Non-/moderate alcohol consumption and adequate fruit/vegetable consumption were not significantly associated with life expectancy in patients with specific CMM patterns.ConclusionCardiometabolic multimorbidity was associated with an increased risk of mortality. Regular physical activity and non-current smoking can increase life expectancy in patients with specific CMM patterns.
Copy Number Analyses Identified a Novel Gene: APOBEC3A Related to Lipid Metabolism in the Pathogenesis of Preeclampsia
Authors: Liu Nan , Guo Yu-Na , Wang Xiao-Jin , Ma Jue , He Yun-Ting , Zhang Fang , He Hao , Xie Jin-Liang , Zhuang Xu , Liu Meng , Sun Jian-Hua , Chen Yan , Lin Jian-Hua , Gong Li-Kun , Wang Bing-Shun 
Published: June 2022

BackgroundPreeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Whether genetic factors play a role in abnormal lipid metabolism during the incidence of preeclampsia has not been well investigated.MethodsPreeclampsia patients (n = 110) and healthy age- and gravidity-matched pregnant women (n = 110) were enrolled in this study. Peripheral blood specimens were used for genomic analysis (n = 10/group) or laboratory validation (n = 100/group). We retrospectively obtained the baseline clinical characteristics of 68 preeclampsia patients and 107 controls in early pregnancy (12–14 gestational weeks). Correlation analyses between differential genes and baseline lipid profiles were performed to identify candidate genes. In vitro and in vivo gain-of-function models were constructed with lentivirus and adeno-associated virus systems, respectively, to investigate the role of candidate genes in regulating lipid metabolism and the development of preeclampsia.ResultsWe observed that preeclampsia patients exhibited significantly elevated plasma TC (P = 0.037) and TG (P &lt; 0.001) levels and increased body mass index (P = 0.006) before the disease onset. Within the region of 27 differential copy number variations, six genes potentially connected with lipid metabolism were identified. The aberrant copies of APOBEC3A, APOBEC3A_B, BTNL3, and LMF1 between preeclampsia patients and controls were verified by quantitative polymerase chain reaction. Especially, APOBEC3A showed a significant positive correlation with TC (P &lt; 0.001) and LDL (P = 0.048) in early pregnancy. Then, our in vitro data revealed that overexpression of APOBEC3A disrupted lipid metabolism in HepG2 cells and affected both cholesterol and fatty acid metabolisms. Finally, in vivo study in a hepatic-specific overexpressed APOBEC3A mouse model revealed abnormal parameters related to lipid metabolism. Pregnant mice of the same model at the end of pregnancy showed changes related to preeclampsia-like symptoms, such as increases in sFlt-1 levels and sFlt-1/PLGF ratios in the placenta and decreases in fetal weight.ConclusionOur findings established a new link between genetics and lipid metabolism in the pathogenesis of preeclampsia and could contribute to a better understanding of the molecular mechanisms of preeclampsia.
Direct Oral Anticoagulants vs. Warfarin in Hemodialysis Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Elfar Sohil , Elzeiny Sara Mohamed , Ismail Hesham , Makkeyah Yahya , Ibrahim Mokhtar 
Published: June 2022

BackgroundThe use of Direct Oral Anticoagulants (DOACs) in patients who have both atrial fibrillation (AF) and end-stage renal disease (ESRD) requiring hemodialysis remains controversial, with warfarin remaining the mainstay of the treatment. As hemodialysis patients were excluded from most clinical DOACs trials, the evidence of their efficacy and safety is lacking in this cohort of patients.AimTo review the current evidence investigating safety profile and the efficacy of DOACs in comparison with warfarin in patients with AF and end-stage renal disease (ESRD) requiring hemodialysis.Methods and ResultsWe included five studies with a total of 34,516 patients in our meta-analysis. The outcomes were major bleeding, ischemic stroke, systemic embolization, hemorrhagic stroke, gastrointestinal bleeding, minor bleeding, and death. Of these patients, 31,472 (92.14%) received warfarin and 3,044 patients received DOACs (8.91%). No significant differences in the incidence of hemorrhagic stroke, major bleeding, hemodialysis access site bleeding, ischemic stroke, and GI bleeding were found between DOACs and warfarin. However, there were higher rates of systemic embolization, minor bleeding, and death events in patients who received DOACs than in the warfarin group (3.39% vs. 1.97%, P-value = 0.02), (6.78% vs. 2.2%, P-value 0.02), and (11.38% vs. 5.12%, P-value &lt; 0.006) respectively.ConclusionIn patients on dialysis who require anticoagulation for AF, warfarin could be associated with a significant reduction in minor bleeding, systemic embolization, and death compared to DOACs. These findings need to be validated by further prospective studies to address the best strategy to deal with the increased thrombotic and bleeding risks in such patients.
Pathogenetic Link of Cardiac Rupture and Left Ventricular Thrombus Following Acute Myocardial Infarction: A Joint Preclinical and Clinical Study
Authors: Ma Shan , Bai Ling , Liu Ping , She Gang , Deng Xiu-Ling , Song An-Qi , Du Xiao-Jun , Lu Qun 
Published: June 2022

BackgroundCardiac rupture (CR) and left ventricular thrombus (LVT) remain important complications of acute myocardial infarction (MI), and they are currently regarded as independent events. We explored the pathogenetic link between CR and LVT by investigating a murine model of MI with a high frequency of CR and in patients with acute MI.MethodsMI was induced in mice, the onset of CR was monitored, and the hearts of mice with or without fatal CR were histologically examined. Between 2015 and 2022, from patients admitted due to acute MI, the data of patients with CR or LVT were retrospectively collected and compared to uncomplicated patients (control).ResultsA total of 75% of mice (n = 65) with MI developed CR 2–4 days after MI. A histological examination of CR hearts revealed the existence of platelet-rich intramural thrombi in the rupture tunnel, which was connected at the endocardial site to platelet-fibrin thrombi within an LVT. In CR or non-CR mouse hearts, LV blood clots often contained a portion of platelet-fibrin thrombi that adhered to the infarct wall. In non-CR hearts, sites of incomplete CR or erosion of the infarct wall were typically coated with platelet thrombi and dense inflammatory cells. Of 8,936 patients with acute MI, CR and LVT occurred in 102 (1.14%) and 130 (1.45%) patients, respectively, with three cases having both complications. CR accounted for 32.8% of in-hospital deaths. The majority of CR (95%) or LVT (63%, early LVT) occurred within 7 days. In comparison to the control or LVT-late groups, patients with CR or early LVT reported increased levels of cellular and biochemical markers for inflammation or cardiac injury.ConclusionCR and LVT after MI are potentially linked in their pathogenesis. LVT occurring early after MI may be triggered by a thrombo-inflammatory response following wall rupture or endocardial erosion.
Efficacy and Safety of Shenqisuxin Granule for Non-ST-segment Elevation Acute Coronary Syndrome: Study Protocol for a Randomized, Double-Blinded, Placebo-Controlled Trial
Authors: Wu Xiaoping , Guo Ming , Shi Shihua , Shi Shengnan , Deng Yanping , Wang Shenglan , Wang Yabing , Wang Peili , Chen Keji 
Published: June 2022

IntroductionThe Chinese herbal compound formula, Shenqisuxin granule (SQSX), promotes neovascularization and prevents in-stent restenosis in modern pharmaceutical studies and is expected to provide an effective strategy for non-ST-segment elevation acute coronary syndrome (NSTEACS). Thus, this study aims to examine the efficacy and safety of SQSX for NSTEACS and initially reveal its mechanism.Methods/DesignThe study is a randomized, double-blinded and placebo-controlled trial. A total of 66 participants will be randomly allocated to one of the following two groups. Participants in the SQSX group will receive conventional treatment plus SQSX, while the placebo group will receive conventional treatment plus placebo, both for 14 days. The primary outcome, hs-CRP, and secondary outcome the Seattle Angina Questionnaire (SAQ) will be assessed at baseline, 7 ± 3 days and 14 ± 3 days. At all visit windows, other indicators including creatine kinase (CK), creatine kinase-myocardial band (CK-MB), cardiac troponins I (cTnI), 12-lead electrocardiograph and the syndrome scores of Qi deficiency and blood stasis will be tested and metagenomic sequencing for intestinal flora will be performed. Echocardiography and safety assessment will be performed at baseline and 14 ± 3 days. Adverse events will be monitored during the trial.DiscussionThe purpose of the study is to examine the efficacy and safety of SQSX to improve NSTEACS and initially reveal its mechanism.Trial RegistrationChina Clinical Trial Registry, ChiCTR2000029226. Registered on January 19, 2020.
Global Burden Attributable to High Low-Density Lipoprotein-Cholesterol From 1990 to 2019
Authors: Du Heyue , Shi Qingyang , Song Peige , Pan Xiong-Fei , Yang Xueli , Chen Lingmin , He Yazhou , Zong Geng , Zhu Ye , Su Baihai , Li Sheyu 
Published: June 2022

BackgroundHigh low-density lipoprotein-cholesterol (LDL-C) is a public health issue contributing to ischemic heart disease (IHD) and stroke.MethodIn this ecological study, we collected summary exposure values (SEVs), deaths, disability-adjusted life of years (DALYs), and Social Demographic Index (SDI) of high LDL-C from 1990 to 2019 using the query tool from the Global Burden of Disease (GBD) Collaborative Network. Outcomes include SEVs, deaths, and DALYs attributable to high LDL-C stratified by sex, age, region, SDI, countries, and territories. Estimated annual percentage changes (EAPCs) were applied to estimate annual trends of changes in these outcomes. We applied the weighted segmented regression with break-point estimation to detect the linear piecewise relationship between SDI and high LDL-C disease burden.ResultsGlobally, 3.00 million (95% uncertainty interval [UI], 2.35–3.76 million) people in 1990 and 4.40 million (95% UI, 3.30–5.65 million) people died from high LDL-C in 2019. The absolute annual burden from deaths and DALYs attributed to high LDL-C increased by 46% (95% UI, 35–56%) and 41% (95% UI, 31–50%) from 1990 to 2019. The age-standardized SEV, death, and DALY was decreased by 9% (95% UI, −11 to −8%), 37% (95% UI, −41−33%), and 32% (95% UI, −37 to −28%), respectively, during the study period. There was a negative association between SDI and high LDL-C-related age-standardized death and DALY rates when SDI surpassed 0.71 and 0.71, respectively.ConclusionAlthough the overall age-standardized burden of high LDL-C is controlled in the past 30 years, it remains increasing in moderate SDI countries, and decreasing trends are disappearing in high SDI countries. New challenges require new actions stratified by countries with different SDI levels.
Social Accountability in Medical Education: Students’ Perspective
Authors: Masud Nazish , Alenezi Shahad , Alsayari Ohoud , Alghaith Deemah , Alshehri Rana , Albarrak Danah , Al-Nasser Sami 
Published: June 2022

BackgroundGlobally, there is a rising interest in the concept of social accountability (SA). The literature evaluating SA of medical schools is limited; however, some international studies have revealed a lack of understanding of SA by medical students. This study evaluated the perception of SA among medical students at a governmental university in Saudi Arabia.MethodA cross-sectional study with 336 currently enrolled medical students was conducted from September 2020 to May 2021. The data were collected using an electronic survey comprised of the THEnet questionnaire that included 12 items to assess the perception of SA and some demographic variables. The total score was categorized into four groups and compared with the demographic profile of students.ResultsOut of the 336 participants, the mean age was 21.26 ± 0.5 years, with most students in the 19–21 age group (n= 154, 46%), and 189 (56.3%) were males. In addition, preclinical and clinical students had similar representation: 170 (51%) and 166 (49%), respectively. Most participants (173, 52%) scored in the 18–36 range, reflecting good perceived SA. The demographic profile of students (i.e., age, GPA, and year of study) was significantly associated with perceived SA (p= 0.003, 0.002, and &lt; 0.001, respectively).ConclusionThe study concludes that most medical students had a good level of perceived SA about their institution. The preclinical year students exhibited a better perception of SA. The final-year students were more critical about the SA of the institution compared to other students.
A Bibliometric Analysis on Motivation Between 2016 and 2020 of Physical Education in Scopus Database
Authors: Chen Chi-Jung , Lee Hung-Ying , Lin Ren-Jie , Farng Jenn-Kuen 
Published: June 2022

PurposeIn the field of physical education (PE), which encompasses a wide range of variables, the question of motivation has become increasingly important. The bibliometric methods can help researchers and educators understand the related research of motivation. The purpose of this study was to explore the bibliometric characteristics of motivation in the field of PE from 2016 to 2020 that try to discover the related research context and topics.MethodsBy using the keywords “motivation” and “physical education,” the bibliographic records and references have been retrieved from the Scopus databases (date of search: September 7, 2021). The Vosviewer software tool and Bibliometrix R package were used for information analysis and visualization. The themes include the annual publication, countries/regions, journals, authors, co-occurrences, and theme trends. Finally, it is presented with the characteristics of the big picture of bibliometrics.ResultsFrom the analysis of the above theme, this study showed that there were 623 studies published over the 5 years, with the number gradually increasing in 2017 and peaking in 2020. The number of citations was the highest in 2016. In terms of total publications, Spain, the United States, and Australia are the top three countries/regions. Most of the articles were published in sport pedagogy and public health relevant journals. The four main research directions were identified: Education, activity, health, and self-determination theory.ConclusionThis study helped us to comprehend the consistent publishing and rapid development of motivation in PE research. Via the bibliometric analysis, we can also incorporate previous research and predicted trends. All these works can help us to understand the basic psychological needs, leadership styles, and teacher support of PE teachers, and the intrinsic and extrinsic motivations of students at different ages. It is suggested that the in-depth study could be conducted on a single variable or emerging issues for future investigation. Researchers can keep tracking and reviewing motivation-related models.
Divergent Associations Between Serum Androgens and Ovarian Reserve Markers Revealed in Patients With Polycystic Ovary Syndrome
Authors: Li Youran , Zhai Yanhong , Li Lin , Lu Yifan , Su Shaofei , Liu Ying , Xu Zhengwen , Xin Mingwei , Zhang Qiaoli , Cao Zheng 
Published: June 2022

BackgroundThe role of excess androgen in ovarian reserve remains unclear in patients with polycystic ovary syndrome (PCOS). Our study highlights the associations of serum androgen levels and ovarian reserve markers in PCOS and non-PCOS women.MethodsTotally 584 menstrual abnormalities women of 20-45 years were retrospectively evaluated at the Beijing Obstetrics and Gynecology Hospital between January 2021 to October 2021. The enrolled patients were classified into two groups: the PCOS group (n=288) and the non-PCOS group (n=296) based on the Rotterdam consensus for PCOS diagnosis. The serum androgens, including testosterone (T), free testosterone (FT, calculated), bioavailable testosterone (Bio-T, calculated), androstenedione (A2), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) were assessed with an in-house developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The associations between the serum androgens and the hormone markers commonly used for evaluating ovarian reserve function, such as anti-mullerian hormone (AMH) and the ratio of luteinizing hormone (LH)/follicle stimulating hormone (FSH) were explored.ResultsThe serum T, FT, Bio-T, A2, DHT, DHEA, DHEAS, AMH and LH/FSH of the PCOS group were 51.7 ± 23.2 ng/dL/mL, 8.5 ± 5.0 pg/mL, 210.1 ± 127.7 pg/mL, 1.9 ± 0.8 ng/mL, 0.2 ± 0.1 ng/mL, 6.4 ± 4.2 ng/mL, 2431.0 ± 1030.7 ng/mL, 6.7 ± 3.8 ng/mL, and 1.8 ± 1.4 respectively, which were significantly higher than those in the non-PCOS group (p&lt;0.05). In the group of PCOS patients, T and A2 levels were positively associated with AMH in both multivariate linear regression analysis and Pearson’s correlation analysis. Similar but weaker associations were observed in the non-PCOS patients. In the PCOS patients with hyperandrogenemia (HA), the AMH level was significantly higher in the subjects with T increased than in the subjects with non-T androgen(s) increased (A2, DHT, DHEA or DHEAS).ConclusionsThe serum androgen levels are positively associated with ovarian reserve markers in both of the PCOS and the non-PCOS patients in our study. In the PCOS group, the highest AMH level was observed in the subjects with the T elevation subgroup, suggesting that T is more closely related with the increase of AMH when compared with other androgens investigated.