bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Cardiovascular Outcomes of SGLT2 Inhibitors in Type 2 Diabetes Mellitus: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Jiang Yu , Yang Pingping , Fu Linghua , Sun Lizhe , Shen Wen , Wu Qinghua 
Published: March 2022

BackgroundA network meta-analysis of randomized controlled trials (RCTs) was conducted to explore the cardiovascular outcomes of all the kind and dosages of sodium-glucose cotransport-2 (SGLT2) inhibitors in type 2 diabetes mellitus (T2DM) patients.Method and ResultThe Cochrane Library, PubMed, and Embase databases were systematically searched for studies to compare the therapeutic effects of different SGLT2 inhibitors in T2DM patients. The effect measurements estimate chosen were odds ratios (ORs) and their corresponding 95% confidence interval (CI). Forty-seven RCTs involving a total of 70574 participants were eligible for direct and indirect comparisons. In direct comparison, treatment with dapagliflozin 5mg showed significantly lower risk of all-cause mortality compared with treatment with dapagliflozin 2.5mg (OR 0.09, 95% CI 0.01-0.70). According to NMA, interestingly, empagliflozin 10mg/25mg, and canagliflozin 100mg was associated with significantly lower risks of all-cause mortality compared with placebo (OR of 0.70, 95% CI 0.58-0.85; 0.69, 95% CI 0.57-0.84; and 0.83, 95% CI 0.73-0.95, respectively). Compared with placebo, dapagliflozin 10mg, empagliflozin 10mg and 25mg displayed the lower risks for cardiovascular events (OR 0.78, 95% CI 0.44-1.00; OR 0.47, 95% CI 0.22-0.93; and 0.43, 95% CI 0.24-0.74, respectively) by direct comparison. Moreover, canagliflozin 100/300mg showed significantly higher risks of cardiovascular events compared with empagliflozin 10mg (OR of 4.83, 95% CI 1.14-20.46 and 5.31, 95% CI 1.26-22.34, respectively) and empagliflozin 25mg (4.23, 95% CI 1.13-15.83 and 4.65, 95% CI 1.25-17.27, respectively) according to NMA. There were non-significant differences among all interventions in volume depletion in traditional pairwise meta-analysis. While in NMA, canagliflozin 100/300mg were associated with significantly increased risks of volume depletion compared with placebo (OR of 1.47, 95% CI 1.08-1.99 and 2.19, 95% CI 1.66-2.90, respectively).ConclusionIn the limitations of the NMA, this study showed that empagliflozin might be better than other SGLT2 inhibitors with low risks of all-cause mortality and cardiovascular events in patients with T2DM suggesting the need for ad hoc RCTs.
Perirenal Fat Thickness: A Surrogate Marker for Metabolic Syndrome in Chinese Newly Diagnosed Type 2 Diabetes
Authors: Guo Xiu Li , Tu Mei , Chen Yang , Wang Wei 
Published: March 2022

ObjectiveIncreasing evidence suggested that perirenal fat thickness (PrFT) was associated with metabolic risk factors. This study aimed to assess the association between PrFT and metabolic syndrome (MetS) in Chinese newly diagnosed type 2 diabetes (T2DM), further evaluating the ability of PrFT in identifying MetS.MethodA total of 445 Chinese newly diagnosed T2DM were enrolled in this study from January to June 2021. Demographic and anthropometric information were collected. PrFT was evaluated by CT scan on Revolution VCT 256. MetS was based on the Chinese Diabetes Society definition. Receiver operating characteristic (ROC) curve was conducted to assess the optimal cutoff value of PrFT in identifying MetS.ResultsOverall, the prevalence of MetS was 57.5% (95% CI: 54.0–64.0%) in men and 58.9% (95% CI: 52.3–65.5%) in women separately. The correlation analysis showed that PrFT was significantly correlated with metabolic risk factors like body mass index, waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, uric acid, and insulin resistance. PrFT was also shown to be independently associated with MetS after adjustment for other confounders. The odds ratios (ORs, 95% CI) were 1.15 (1.03–1.38) in men and 1.31 (1.08–1.96) in women (P &lt;0.05). The ROC curves showed a good predictive value of PrFT for MetS. The areas under the curve of PrFT identifying MetS were 0.895 (95% CI: 0.852–0.939) in men and 0.910 (95% CI: 0.876–0.953) in women (P &lt;0.001). The optimal cutoff values of PrFT were 14.6 mm (sensitivity: 83.8%, specificity: 89.6%) for men and 13.1 mm (sensitivity: 87.6%, specificity: 91.1%) for women.ConclusionsPrFT was significantly associated with MetS and showed a powerful predictive value for it, which suggested that PrFT can be an applicable surrogate marker for MetS in Chinese newly diagnosed T2DM.Clinical Trial RegistrationThis study was registered in clinicaltrials.gov (ChiCTR2100052032).
A Synoptic Framework for Forecasting the Urban Rainfall Effect Using Composite and K-Means Cluster Analyses
Authors: McLeod Jordan , Shepherd Marshall 
Published: March 2022

Observational and numerical modeling studies continue to affirm the existence of the “urban rainfall effect” (URE), or a discernible anomaly in warm season precipitation due to urbanization. However, the literature has been lacking a progression towards the predictability of the URE. Atlanta, Georgia has consistently appeared in the literature because of its well-studied urban rainfall anomalies. Using the Multi-sensor Precipitation Estimates (MPE) dataset and the ERA-Interim reanalysis dataset, an 18-year period (2002–2019) is examined. Three similar but distinct methods are used to define urban rainfall days (URDs), or periods when the precipitation in the urbanized areas of Atlanta are greater than the surrounding rural areas. A combination of compositing, wind rose, and k-means cluster analyses are employed to extract the synoptic framework supportive of the URE in Atlanta, Georgia. The synoptic-scale compositing analysis reveals that there are a consistent set of meteorological ingredients that are needed to produce an URD, including weaker-than-average southwesterly-to-northwesterly flow at 700 hPa, copious amounts of moisture throughout the tropospheric column, and a background low-level convergent flow. Composite atmospheric soundings reveal that there is enhanced moisture throughout the tropospheric column on URDs, leading to marginal instability that favors localized convection across the Atlanta metropolitan area. The study also provides clarity on how often the URE is present (roughly 8% of the time) during warm season days across the Atlanta metropolitan area. Taken together, this synoptic framework will aid in the forecasting of the URE in Atlanta and can be easily applied to other cities.
A Polymorphism in the BDNF Gene (rs11030101) is Associated With Negative Symptoms in Chinese Han Patients With Schizophrenia
Authors: Ping Junjiao , Zhang Jie , Wan Jing , Huang Caiying , Luo Jiali , Du Baoguo , Jiang Tingyun 
Published: March 2022

Objective: This study aimed to investigate the association between brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element binding protein (CREB) gene polymorphisms and schizophrenia.Methods: This study used a case-control design, and diagnoses were made based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. One hundred and thirty-four patients with schizophrenia were recruited from the Third People’s Hospital of Zhongshan City from January 2018 to April 2020. Sixty-four healthy controls were recruited from the same region. Genotypes at the BDNF gene single nucleotide polymorphisms rs11030101, rs2030324, and rs6265 and the CREB gene single nucleotide polymorphisms rs6740584 and rs2551640 were determined using a MassARRAY mass spectrometer. Linkage disequilibrium and haplotype analyses were performed, and genotype and allele frequencies were compared between groups. The positive and negative symptom scale (PANSS) was used to evaluate the association between the BDNF and CREB gene polymorphisms and schizophrenic symptoms.Results: There was no significant difference in genotype or allele frequencies for rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 between schizophrenic patients and controls (p &gt; 0.05). In addition, there were no significant differences in rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 genotype frequencies between the two groups in the dominant, recessive, or over-dominant models (p &gt; 0.05). Three loci in the BDNF gene and two loci in the CREB gene were in a state of strong linkage disequilibrium. The frequency of haplotype AAC (rs11030101/rs2030324/rs626), composed of three loci in the BDNF gene, was significantly increased in schizophrenic patients compared with control subjects. There were significant differences in the subscores of PANSSS for negative symptoms, in patients with different rs11030101 genotypes of the BDNF gene (p &lt; 0.05). There was also significant differences in the PANSS scores for the general symptom G12 (judgment and lack of insight) in patients with different rs6265 genotypes of the BDNF gene (p &lt; 0.05).Conclusion: The BDNF gene rs11030101/rs2030324/rs6265 AAC haplotype was potentially associated with an increased risk of schizophrenia. In addition, genotypes at the rs11030101 and rs6265 loci may affect the negative symptoms and general symptoms of schizophrenic patients, respectively.
Identification of Potential Diagnostic and Prognostic Biomarkers for Gastric Cancer Based on Bioinformatic Analysis
Authors: Niu Xiaoji , Ren Liman , Hu Aiyan , Zhang Shuhui , Qi Hongjun 
Published: March 2022

Background: Gastric cancer (GC) is one of the most prevalent cancers all over the world. The molecular mechanisms of GC remain unclear and not well understood. GC cases are majorly diagnosed at the late stage, resulting in a poor prognosis. Advances in molecular biology techniques allow us to get a better understanding of precise molecular mechanisms and enable us to identify the key genes in the carcinogenesis and progression of GC.Methods: The present study used datasets from the GEO database to screen differentially expressed genes (DEGs) between GC and normal gastric tissues. GO and KEGG enrichments were utilized to analyze the function of DEGs. The STRING database and Cytoscape software were applied to generate protein–protein network and find hub genes. The expression levels of hub genes were evaluated using data from the TCGA database. Survival analysis was conducted to evaluate the prognostic value of hub genes. The GEPIA database was involved to correlate key gene expressions with the pathological stage. Also, ROC curves were constructed to assess the diagnostic value of key genes.Results: A total of 607 DEGs were identified using three GEO datasets. GO analysis showed that the DEGs were mainly enriched in extracellular structure and matrix organization, collagen fibril organization, extracellular matrix (ECM), and integrin binding. KEGG enrichment was mainly enriched in protein digestion and absorption, ECM-receptor interaction, and focal adhesion. Fifteen genes were identified as hub genes, one of which was excluded for no significant expression between tumor and normal tissues. COL1A1, COL5A2, P4HA3, and SPARC showed high values in prognosis and diagnosis of GC.Conclusion: We suggest COL1A1, COL5A2, P4HA3, and SPARC as biomarkers for the diagnosis and prognosis of GC.
Prediction of Ventricular Arrhythmias by QRS/QTc - Ratio in Citalopram or Escitalopram Intoxication
Authors: Dietrichs Erik Sveberg , Smith Godfrey L. 
Published: March 2022

BackgroundThe U.S. Food and Drug Administration (FDA) has stated that citalopram and escitalopram should not be used at daily doses above 40 mg/20 mg due to risk for development of fatal ventricular arrhythmias like torsade de pointes (TdP). Yet, supratherapeutic serum concentrations of citalopram are common and predicting patients at risk for TdP is of high clinical value. Accordingly, we investigated whether QRS/QTc; developed for predicting TdP in hypothermic patients could be used in citalopram intoxication.MethodsA total of 16 publications describing patients suffering from complications due to citalopram or escitalopram treatment, or intoxication with the same substances, were included after a systematic search. The main criterion for inclusion was admission ECG, either with given QRS and QTc values or with attached ECG-files that enabled calculation.ResultsQRS/QTc rather that QTc alone emerged as a marker of ventricular arrhythmia in the 16 included case reports, with highly significant (p &lt; 0.0005) lower values in patients displaying ventricular arrhythmias.ConclusionCitalopram and escitalopram are extensively used in treatment of depressive disorders, and a large proportion of patients have supratherapeutic serum concentrations. Calculation of QRS/QTc in available case reports show that this novel ECG-marker has potential to predict patients at risk for developing ventricular arrhythmias.
The Diurnal Profile of Human Basal Pain Sensitivity and Skin Sympathetic Nerve Activity: A Healthy Volunteer Study
Authors: Zhu Ying , Yan Ai , Shu Bin , Chen Xuehan , Chen Yupei , Duan Guangyou , Huang He 
Published: March 2022

ObjectiveThe diurnal rhythm profile of human basal pain sensitivity and its association with sympathetic nerve activity are not fully understood. This study aimed to examine rhythmic changes in experimental pain sensitivity and skin sympathetic nerve activity in healthy volunteers.MethodsThirty healthy volunteers were included in the study. Experimental pain sensitivity, including pressure pain threshold and tolerance, cold pain threshold (CPT) and tolerance, skin sympathetic nerve activity, and cardiovascular parameters (including heart rate, cardiac output, and peripheral vascular resistance) at six time points throughout the day (08:00, 12:00, 16:00, 20:00, 00:00, and 04:00) were sequentially measured. Circadian rhythm analysis was performed on the mean values of the different measurements and individual subjects.ResultsSignificant differences were found in experimental pain sensitivity, skin sympathetic nerve activity, and non-invasive cardiovascular parameters at different time points (P &lt; 0.05). The minimum measured values of all four types of experimental pain sensitivity were consistently observed at 04:00. Rhythmical analysis showed that the mean values of pressure pain threshold (meta2d P = 0.016) and skin sympathetic nerve activity (meta2d P = 0.039) were significant. Significant diurnal rhythms in pain sensitivity and skin sympathetic nerve activity existed in some individuals but not in others. No significant correlation between experimental pain sensitivity and skin sympathetic nerve activity was found at any time point (P &gt; 0.05).ConclusionSignificant diurnal fluctuations were observed in different pain sensitivities and skin sympathetic nerve activity. No significant correlation between experimental pain sensitivity and sympathetic excitability at different times was found; the reasons for these phenomena remain to be further studied.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2000039709].
Acupuncture and Traditional Chinese Herbal Medicine Integrated With Conventional Rehabilitation for Post-stroke Functional Recovery: A Retrospective Cohort Study
Authors: Tseng Cheng-Yu , Hsu Pei-Shan , Lee Chang-Ti , Huang Hui-Fen , Lan Chou-Chin , Hsieh Tsung-Han , Liu Guan-Ting , Kuo Chan-Yen , Wang Ming-Chieh , Hsieh Po-Chun 
Published: March 2022

BackgroundStroke leads to tremendous impacts on patients and the healthcare system. It is crucial to explore the potential management of rehabilitation. Acupuncture and traditional Chinese herbal medicine (TCHM) integrated with conventional rehabilitation benefit post-stroke functional recovery.MethodsWe retrospectively reviewed the medical records of all patients included in the Integrated Traditional Chinese-Western Medicine care program for stroke (ITCWM-stroke care program) in 2019 in Taipei Tzu Chi Hospital to investigate the effects of acupuncture and TCHM integrated with conventional rehabilitation on National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores before and after the program.ResultsA total of 255 stroke inpatients were retrieved and divided into acupuncture and acupuncture + TCHM group by hemorrhagic and ischemic stroke types, respectively. All the patients were recruited in the program at the early subacute phase after stroke onset. Of the hemorrhagic and ischemic stroke subjects, the NIHSS and BI total scores were significantly improved in the acupuncture and acupuncture + TCHM groups. The subgroup analysis results showed that in subjects with a baseline BI score ≤ 40, the acupuncture + TCHM group significantly improved BI total score better than the acupuncture group in both hemorrhagic (p &lt; 0.05) and ischemic (p &lt; 0.05) stroke subjects.ConclusionAcupuncture and TCHM integrated with conventional rehabilitation significantly improve stroke patients’ functional recovery at the early subacute phase. Acupuncture + TCHM contributes to better activities of daily living (ADL) improvements in stroke patients with a baseline BI score ≤ 40. We suggest integrating acupuncture and TCHM into the post-stroke rehabilitation strategy, especially for stroke patients with poor ADL function.
Identification of Germline Mutations in Upper Tract Urothelial Carcinoma With Suspected Lynch Syndrome
Authors: Guan Bao , Wang Jie , Li Xuesong , Lin Lin , Fang Dong , Kong Wenwen , Tian Chuangyu , Li Juan , Yang Kunlin , Han Guanpeng , Wu Yucai , He Yuhui , Peng Yiji , Yu Yanfei , He Qun , He Shiming , Gong Yanqing , Zhou Liqun , Tang Qi 
Published: March 2022

ObjectiveWhole-exon sequencing (WES) is a commercially available tool for hereditary disease testing. However, little is known about hereditary upper-tract urothelial carcinoma (UTUC) in the Chinese population. This study aims to investigate the prevalence of Lynch syndrome (LS) in UTUC patients with high-risk features and identify the germline mutations of genetic predisposition gene mutations in those patients.MethodsIn total, 354 consecutive UTUC patients undergoing surgery were universally recruited, of whom 108 patients under 60 years old or with a personal/family history of cancer underwent universal immunohistochemistry staining to detect the expression of mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2). Patients with deficient or weak MMR protein staining or meeting the Amsterdam II criterion were defined as suspected LS patients, who further experienced microsatellite instability (MSI) (BAT25, BAT26, BAT40, D2S123, D5S346, D17S250) detection and performed WES analysis to explore germline pathogenic/likely pathogenic (P/LP) alterations.ResultsOf 108 patients, 90 (83.3%) cases were included due to younger than 60 years, and 18 cases due to personal/family history. IHC staining identified 21 patients with deficient MMR protein staining and 15 cases with weak MMR protein staining. Three cases met the Amsterdam II criterion but with proficient MMR protein staining. Finally, WES analysis was performed in 38 suspected LS patients and P/LP germline mutations were identified in 22 individuals. Genetic testing confirmed 5 LS cases, including 3 cases with novel mutations. MSI-harboring tumor was discovered in 4 LS cases, one of whom had weak MMR protein staining. Germline P/LP variants in DNA damage repair genes were found in 11 cases. In addition, we found that 11 patients had high- or moderate- penetrance P/LP mutations other than MMR genes. The common P/LP variants in high- or moderate-penetrance genes were 4 in ATM, 3 in MSH6 and KIT, and 2 in APC, NF1 and DICER.ConclusionsWe identified approximately 11% of UTUC cases as suspected LS and at least 1.4% patients with confirmed LS-associated UTUC. In addition, broader germline genetic testing could be considered to screen for cancer severity in hereditary UTUC patients.
The Relationship Between Short-Term Surrogate Endpoint Indicators and mPFS and mOS in Clinical Trials of Malignant Tumors: A Case Study of Approved Molecular Targeted Drugs for Non-Small-Cell Lung Cancer in China
Authors: Rui Mingjun , Wang Zijing , Fei Zhengyang , Wu Yao , Wang Yingcheng , Sun Lei , Shang Ye , Li Hongchao 
Published: March 2022

Objective: Due to the initiation of the priority review program in China, many antitumor drugs have been approved for marketing based on phase II clinical trials and short-term surrogate endpoint indicators. This study used approved targeted drugs for the treatment of non-small-cell lung cancer (NSCLC) in China as an example to evaluate the association between short-term surrogate endpoints [objective response rate (ORR) and disease control rate (DCR)] and median progression-free survival (mPFS) and median overall survival (mOS).Methods: Five databases, i.e., MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched, for phase II or phase III clinical trials of all molecular targeted drugs that have been marketed in China for the treatment of NSCLC. After screening the literature and extracting information, both univariate and multivariate linear regression were performed on the short-term surrogate indicators and mPFS and mOS to explore the relationship.Results: A total of 63 studies were included (25 studies with only ORR, DCR, and mPFS and 39 studies with ORR, DCR, mPFS, and mOS). In terms of the targeted drugs for the treatment of NSCLC, in addition to the good but not excellent linear relationship between DCR and mOS (0.4 &lt; R2adj = 0.5653 &lt; 0.6), all other short-term surrogate endpoint indicators had excellent linear relationships with mPFS and mOS (R2adj≥0.6), while mPFS and mOS had the most excellent linear relationships (R2adj = 0.8036).Conclusion: For targeted drugs for the treatment of NSCLC, short-term surrogate endpoint indicators such as ORR and DCR may be reliable surrogate indicators for mPFS and mOS. However, whether short-term surrogate endpoint indicators can be used to predict final endpoints remains to be verified.