bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using concept maps to evaluate preservice biology teachers’ conceptualization of COVID-19 as a complex phenomenon
Authors: Bielik Tom , Jagemann Johannes , Krell Moritz , Krüger Dirk , Ben Zvi Assaraf Orit 
Published: May 2023

IntroductionThe COVID-19 pandemic showed the critical importance of supporting teachers’ and students’ systems thinking when making sense of complex phenomena. This study sets to explore preservice biology teachers’ (PBTs) mental models of COVID-19 as complex phenomenon using concept maps.Methods27 PBTs concept maps of COVID-19 outbreak were collected and taken for analysis. Structural and complexity attributes were identified in participants’ concept maps and the relationships between them were tested, providing statistical analyses using exemplary concept maps.ResultsThe results suggest that the appearance of many concepts in a map (structural attribute) does not necessarily indicate high level of complexity, but rather the amount of simple structural relationships (complexity attribute). On the other hand, the results indicate that higher structural sophistication (e.g., high number of connections and junctions) could be associated with the complexity level of the map.DiscussionThis study provides a practical method for evaluating the complexity level of PBTs’ systems thinking, suggests a possible link between structural and complexity attributes in their concept maps, and demonstrates the need to further support PBTs in developing their systems thinking skills in the context of complex biological phenomena.
Jinlida granules combined with metformin improved the standard-reaching rate of blood glucose and clinical symptoms of patients with type 2 diabetes: secondary analysis of a randomized controlled trial
Authors: Kang Xiaomin , Sun Yuting , Duan Yingying , Zhang Yuqing , An Xudong , Jin De , Lian Fengmei , Tong Xiaolin 
Published: May 2023

BackgroundPrevious studies found that Jinlida granules could significantly reduce blood glucose levels and enhance the low-glucose action of metformin. However, the role of Jinlida in the standard-reaching rate of blood glucose and improving clinical symptoms has yet to be studied. We aimed to elaborate on the efficacy of Jinlida in type 2 diabetes (T2D) patients who experience clinical symptoms based on secondary analysis of a randomized controlled trial.MethodsData were analyzed from a 12-week, randomized, placebo-controlled study of Jinlida. The standard-reaching rate of blood glucose, the symptom disappearance rate, the symptom improvement rate, the efficacy of single symptoms, and the total symptom score were evaluated. The correlation between HbA1c and the improvement of clinical symptoms was analyzed.ResultsFor 12 weeks straight, 192 T2D patients were randomly assigned to receive either Jinlida or a placebo. The treatment group showed statistically significant differences in the standard-reaching rate of HbA1c &lt; 6.5% (p = 0.046) and 2hPG (&lt; 10 mmol/L, 11.1 mmol/L) (p &lt; 0.001), compared with the control group. The standard-reaching rate of HbA1c &lt; 7% (p = 0.06) and FBG &lt; 7.0 mmol/L (p = 0.079) were not significantly different between the treatment and control groups. Five symptoms exhibited a statistical difference in symptom disappearance rate (p &lt; 0.05). All the symptoms exhibited a significant difference in symptom improvement rate (p &lt; 0.05). The mean change in total symptom score from baseline to week 12 was −5.45 ± 3.98 in the treatment group and −2.38 ± 3.11 in the control group, with statistically significant differences (p &lt; 0.001). No significant correlations were noted between symptom improvement and HbA1c after 12 weeks of continuous intervention with Jinlida granules or placebo.ConclusionJinlida granules can effectively improve the standard-reaching rate of blood glucose and clinical symptoms of T2D patients, including thirst, fatigue, increased eating with rapid hungering, polyuria, dry mouth, spontaneous sweating, night sweat, vexing heat in the chest, palms, and soles, and constipation. Jinlida granules can be used as an effective adjuvant treatment for T2D patients who experience those symptoms.
Association between serum-free thyroxine level and all-cause mortality in critically ill patients: a retrospective study from MIMIC-IV
Authors: Dai Juan-Juan , Du Ding-Fu , Ma Gang , Jiang Ming-Jie 
Published: May 2023

BackgroundLow thyroxine (T4) levels have been observed in critically ill patients; however, controversial results regarding T4 supplemental therapy are reported. The association between serum free T4 (FT4) levels and mortality in critically ill patients has not been fully established and needs to be clarified.MethodsData from the Medical Information Mart for Intensive Care (MIMIC)-IV were collected and analyzed. The association between FT4 level and 30-day mortality after ICU admission was analyzed using Kaplan–Meier curves, spline smoothing fitting, martingale residuals of the null Cox model, and restricted cubic spline (RCS). Logistic regression, Cox regression, and receiver operating characteristic curve (ROC) were used to uncover the relationship and predictive value of serum FT4 and 30-day mortality in critically ill patients.ResultsIn the final analysis, 888 patients were enrolled, and the serum FT4 levels were divided into four groups. A significant difference in 30-day mortality was observed between the four groups. Kaplan–Meier curves also presented significantly higher 30-day mortality in groups 1 and 2 (p &lt; 0.0001). Further multivariance logistic regression showed that group 1 with FT4 levels lower than 0.7 μg/dl can predict 30-day mortality (odds ratio (OR) = 3.30, 95% confidence interval (CI) = 1.04–11.31). Spline smoothing fitting analysis showed a “V”-shaped line between 30-day mortality and FT4 level within 0–3 μg/dl. Further RCS analysis showed that the risk of death decreased rapidly as FT4 levels increased when serum FT4 levels were lower than 1.2 μg/dl and started to become flat afterward. The area under the ROC of the lower FT4 level to predict 30-day mortality was 0.833 (95% CI = 0.788–0.878). Both multivariant Cox regression and logistic regression showed that FT4 levels lower than 1.2 μg/dl can independently predict 30-day mortality when adjusted for other potential confounders (HR = 0.34, 95% CI = 0.14–0.82; OR = 0.21, 95% CI = 0.06–0.79, respectively), but its predictive power disappeared when adjusted for T3 or total T4.ConclusionSerum FT4 levels were significantly negatively associated with 30-day mortality when they were lower than 1.2 μg/dl and could predict the risk of 30-day mortality. A higher FT4 level is potentially related to increased 30-day mortality.
Diagnostic value of serum cathepsin S in type 2 diabetic kidney disease
Authors: Ren Xuejing , Wang Wanqing , Cao Huixia , Shao Fengmin 
Published: May 2023

BackgroundIdentification of risk factors that have causal effects on the occurrence of diabetic kidney disease (DKD), is of great significance in early screening and intervening for DKD, and in delaying the progression of DKD to end-stage renal disease. Cathepsin S (Cat-S), a novel non-invasive diagnostic marker, mediates vascular endothelial dysfunction. The diagnostic value of Cat-S for DKD has rarely been reported in clinical studies.ObjectiveTo analyze whether Cat-S is a risk factor for DKD and evaluate the diagnostic value of serum Cat-S for DKD.MethodsForty-three healthy subjects and 200 type 2 diabetes mellitus (T2DM) patients were enrolled. T2DM patients were divided into subgroups according to various criteria. Enzyme-linked immunosorbent assay was used to detect serum Cat-S levels among different subgroups. Spearman correlation analysis was used to analyze correlations between serum Cat-S and clinical indicators. Multivariate logistic regression analysis was performed to analyze risk factors for the occurrence of DKD and decreased renal function in T2DM patients.ResultsSpearman analysis showed that serum Cat-S level was positively correlated with urine albumin creatinine ratio (r=0.76, P&lt;0.05) and negatively correlated with estimated glomerular filtration rate (r=−0.54, P&lt;0.01). Logistic regression analysis showed that increased serum Cat-S and cystatin C(CysC) were independent risk factors for DKD and decreased renal function in T2DM patients (P&lt;0.05). The area under the receiver operating characteristic (ROC) curve was 0.900 of serum Cat-S for diagnosing DKD, and when the best cut-off value was 827.42 pg/mL the sensitivity and specificity were 71.6% and 98.8%, respectively. Thus, serum Cat-S was better than CysC for diagnosing DKD (for CysC, the area under the ROC curve was 0.791, and when the cut-off value was 1.16 mg/L the sensitivity and specificity of CysC were 47.4% and 98.8%, respectively).ConclusionIncreased serum Cat-S were associated with the progression of albuminuria and decreased renal function in T2DM patients. The diagnostic value of serum Cat-S was better than that of CysC for DKD. Monitoring of serum Cat-S levels could be helpful for early screening DKD and assessing the severity of DKD and could provide a new strategy for diagnosing DKD.
Circulating levels of cytokines and risk of cardiovascular disease: a Mendelian randomization study
Authors: Wei Tao , Zhu Zhanfang , Liu Lin , Liu Bo , Wu Min , Zhang Wei , Cui Qianwei , Liu Fuqiang , Zhang Ronghuai 
Published: May 2023

BackgroundEpidemiological studies have linked various circulating cytokines to cardiovascular disease (CVD), which however remains uncertain whether these relationships represent causality or are due to bias. To address this question, we conducted a Mendelian randomization (MR) analysis to systematically investigate the causal effects of circulating cytokine levels on CVD development.MethodsThis study leveraged the summary statistic from respective genome-wide association study (GWAS) of 47 cytokines and four types of CVD. The cis-quantitative trait locus (cis-QTL) definition, derived from a GWAS meta-analysis comprising 31,112 participants of European descent, served as instruments for cytokines. A two-sample MR design was employed, followed by comprehensive sensitivity analyses to validate the robustness of results.ResultsThe results of inverse-variance weighted method using cis-protein QTL (cis-pQTL) instruments, showed the causal effects of four cytokines (i.e., IL-1ra, MCSF, SeSelectin, SCF) on the risk of coronary artery disease (CAD). We also identified causal relationships between two cytokines (i.e., IL-2ra, IP-10) and heart failure (HF), as well as two cytokines (i.e., MCP-3, SeSelectin) and atrial fibrillation (AF), after controlling for false discovery rate (FDR). The use of cis-expression QTL (cis-eQTL) revealed additional causal associations between IL-1a, MIF and CAD, between IL-6, MIF, and HF, as well as between FGFBasic and AF. No significant sign was survived for stroke with FDR applied. Results were largely consistent across sensitivity analyses.ConclusionThe present study provides supportive evidence that genetic predisposition to levels of certain cytokines causally affects the development of specific type of CVD. These findings have important implications for the creation of novel therapeutic strategies targeting these cytokines as a means of preventing and treating CVD.
Intra-subject variability in oscillometry correlates with acute rejection and CLAD post-lung transplant
Authors: Vasileva Anastasiia , Hanafi Nour , Huszti Ella , Matelski John , Belousova Natalia , Wu Joyce K. Y. , Martinu Tereza , Ghany Rasheed , Keshavjee Shaf , Tikkanen Jussi , Cypel Marcelo , Yeung Jonathan C. , Ryan Clodagh M. , Chow Chung-Wai 
Published: May 2023

BackgroundChronic lung allograft dysfunction (CLAD) is the major cause of death post-lung transplantation, with acute cellular rejection (ACR) being the biggest contributing risk factor. Although patients are routinely monitored with spirometry, FEV1 is stable or improving in most ACR episodes. In contrast, oscillometry is highly sensitive to respiratory mechanics and shown to track graft injury associated with ACR and its improvement following treatment. We hypothesize that intra-subject variability in oscillometry measurements correlates with ACR and risk of CLAD.MethodsOf 289 bilateral lung recipients enrolled for oscillometry prior to laboratory-based spirometry between December 2017 and March 2020, 230 had ≥ 3 months and 175 had ≥ 6 months of follow-up. While 37 patients developed CLAD, only 29 had oscillometry at time of CLAD onset and were included for analysis. These 29 CLAD patients were time-matched with 129 CLAD-free recipients. We performed multivariable regression to investigate the associations between variance in spirometry/oscillometry and the A-score, a cumulative index of ACR, as our predictor of primary interest. Conditional logistic regression models were built to investigate associations with CLAD.ResultsMultivariable regression showed that the A-score was positively associated with the variance in oscillometry measurements. Conditional logistic regression models revealed that higher variance in the oscillometry metrics of ventilatory inhomogeneity, X5, AX, and R5-19, was independently associated with increased risk of CLAD (p &lt; 0.05); no association was found for variance in %predicted FEV1.ConclusionOscillometry tracks graft injury and recovery post-transplant. Monitoring with oscillometry could facilitate earlier identification of graft injury, prompting investigation to identify treatable causes and decrease the risk of CLAD.
Return to work after sepsis—a German population-based health claims study
Authors: Fleischmann-Struzek Carolin , Ditscheid Bianka , Rose Norman , Spoden Melissa , Wedekind Lisa , Schlattmann Peter , Günster Christian , Reinhart Konrad , Hartog Christiane S. , Freytag Antje 
Published: May 2023

BackgroundLong-term impairments after sepsis can impede the return to work in survivors. We aimed to describe rates of return to work 6 and 12 months postsepsis.MethodsThis retrospective, population-based cohort study was based on health claims data of the German AOK health insurance of 23.0 million beneficiaries. We included 12-months survivors after hospital-treated sepsis in 2013/2014, who were ≤60 years at the time of the admission and were working in the year presepsis. We assessed the prevalence of return to work (RTW), persistent inability to work and early retirement.ResultsAmong 7,370 working age sepsis survivors, 69.2% returned to work at 6 months postsepsis, while 22.8% were on sick leave and 8.0% retired early. At 12 months postsepsis, the RTW rate increased to 76.9%, whereas 9.8% were still on sick leave and 13.3% retired early. Survivors who returned to work had a mean of 70 (SD 93) sick leave days in the 12 months presepsis (median 28 days, IQR 108 days).ConclusionOne out of four working age sepsis survivors does not resume work in the year postsepsis. Specific rehabilitation and targeted aftercare may be opportunities to reduce barriers to RTW after sepsis.
IncHI1 plasmids are epidemic vectors that mediate transmission of tet(X4) in Escherichia coli isolated from China
Authors: Zhang Yan , Zhang Jie , Cai Ping , Lu Yang , Sun Ruan-Yang , Cao Meng-Tao , Xu Xiao-Li , Webber Mark A. , Jiang Hong-Xia 
Published: May 2023

IntroductionThis study aimed to investigate the genetic factors promoting widespread Q6 dissemination of tet(X4) between Escherichia coli and to characterize the genetic contexts of tet(X4).MethodsWe isolated E. coli from feces, water, soil and flies collected across a large-scale chicken farm in China in 2020. Antimicrobial susceptibility testing and PFGE typing were used to identify tigecycline resistance and assess clonal relationships among isolates. Plasmids present and genome sequences were analyzed by conjugation, S1 pulsed-field gel electrophoresis (PFGE), plasmid stability testing and whole-genome sequencing.ResultsA total of 204 tigecycline-resistant E. coli were isolated from 662 samples. Of these, we identified 165 tet(X4)-carrying E. coli and these strains exhibited a high degree of multidrug resistance. Based on the geographical location distribution of the sampled areas, number of samples in each area and isolation rate of tigecycline-resistant strains and tet(X4)-carrying isolates, 72 tet(X4)-positive isolates were selected for further investigation. Tigecycline resistance was shown to be mobile in 72 isolates and three types of tet(X4)-carrying plasmids were identified, they were IncHI1 (n = 67), IncX1 (n = 3) and pO111-like/IncFIA(HI1) (n = 2). The pO111-like/IncFIA(HI1) is a novel plasmid capable of transferring tet(X4). The transfer efficiency of IncHI1 plasmids was extremely high in most cases and IncHI1 plasmids were stable when transferred into common recipient strains. The genetic structures flanked by IS1, IS26 and ISCR2 containing tet(X4) were complex and varied in different plasmids.DiscussionThe widespread dissemination of tigecycline-resistant E. coli is a major threat to public health. This data suggests careful use of tetracycline on farms is important to limit spread of resistance to tigecycline. Multiple mobile elements carrying tet(X4) are in circulation with IncHI1 plasmids the dominant vector in this setting.
Association between migraine and Alzheimer’s disease: a nationwide cohort study
Authors: Kim Jaeho , Ha Woo Seok , Park Sang Hyun , Han Kyungdo , Baek Min Seok 
Published: May 2023

Background and objectiveMigraine is a common chronic neurological disease characterized by pulsating headaches, photophobia, phonophobia, nausea, and vomiting. The prevalence of dementia in individuals aged over 65 years in Korea is more than 10%, and Alzheimer’s disease (AD) dementia accounts for most cases. Although these two neurological diseases account for a large portion of the medical burden in Korea, few studies have examined the relationship between the two diseases. Therefore, this study investigated the incidence and risk of AD in patients with migraines.MethodsWe retrospectively collected nationwide data from a national health insurance claims database governed by Korea’s National Health Insurance Service. Among Koreans in the 2009 record, patients with migraine were identified according to the International Classification of Diseases, 10th revision (ICD-10) code G43. First, we screened the database for participants aged over 40 years. Individuals diagnosed with migraine at least twice over more than 3 months in a year were considered to have chronic migraine in this study. Further, all participants with an AD diagnosis (ICD-10 code: Alzheimer’s disease F00, G30) were investigated for AD dementia development. The primary endpoint was AD development.ResultsThe overall incidence of AD dementia was higher in individuals with a history of migraine than in those with no migraine history (8.0 per 1,000 person-years vs. 4.1 per 1,000 person-years). The risk of AD dementia was higher in individuals diagnosed with migraine (hazard ratio = 1.37 [95% confidence interval, 1.35–1.39]) than in the control group after adjustments for age and sex. Individuals with chronic migraine had a higher incidence of AD dementia than those with episodic migraine. Younger age (&lt;65 years old) was associated with an increased risk of AD dementia compared to older age (≥65  years old). Higher body mass index (BMI) (≥25 kg/m2) was also associated with an increased risk of AD dementia compared to lower BMI (&lt;25 kg/m2) (p &lt; 0.001).ConclusionOur results suggest that individuals with a migraine history are more susceptible to AD than those without a migraine history. Additionally, these associations were more significant in younger and obese individuals with migraine than in individuals without migraine.
Identification and cross-validation of autophagy-related genes in cardioembolic stroke
Authors: Yang Yufang , Zhang Min , Li Ziqing , He Shen , Ren Xueqi , Wang Linmei , Wang Zhifei , Shu Shi 
Published: May 2023

ObjectiveCardioembolic stroke (CE stroke, also known as cardiogenic cerebral embolism, CCE) has the highest recurrence rate and fatality rate among all subtypes of ischemic stroke, the pathogenesis of which was unclear. Autophagy plays an essential role in the development of CE stroke. We aim to identify the potential autophagy-related molecular markers of CE stroke and uncover the potential therapeutic targets through bioinformatics analysis.MethodsThe mRNA expression profile dataset GSE58294 was obtained from the GEO database. The potential autophagy-related differentially expressed (DE) genes of CE stroke were screened by R software. Protein–protein interactions (PPIs), correlation analysis, and gene ontology (GO) enrichment analysis were applied to the autophagy-related DE genes. GSE66724, GSE41177, and GSE22255 were introduced for the verification of the autophagy-related DE genes in CE stroke, and the differences in values were re-calculated by Student’s t-test.ResultsA total of 41 autophagy-related DE genes (37 upregulated genes and four downregulated genes) were identified between 23 cardioembolic stroke patients (≤3 h, prior to treatment) and 23 healthy controls. The KEGG and GO enrichment analysis of autophagy-related DE genes indicated several enriched terms related to autophagy, apoptosis, and ER stress. The PPI results demonstrated the interactions between these autophagy-related genes. Moreover, several hub genes, especially for CE stroke, were identified and re-calculated by Student’s t-test.ConclusionWe identified 41 potential autophagy-related genes associated with CE stroke through bioinformatics analysis. SERPINA1, WDFY3, ERN1, RHEB, and BCL2L1 were identified as the most significant DE genes that may affect the development of CE stroke by regulating autophagy. CXCR4 was identified as a hub gene of all types of strokes. ARNT, MAPK1, ATG12, ATG16L2, ATG2B, and BECN1 were identified as particular hub genes for CE stroke. These results may provide insight into the role of autophagy in CE stroke and contribute to the discovery of potential therapeutic targets for CE stroke treatment.