bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between Subclinical Hypothyroidism in Pregnancy and Hypertensive Disorder of Pregnancy: A Systematic Review and Meta-Analysis
Authors: Han Yue , Wang Jun , Wang Xiaoying , Ouyang Ling , Li Yan 
Published: March 2022

ObjectiveStudies have shown a high incidence of subclinical hypothyroidism in pregnancy, but the adverse pregnancy outcomes caused by it are not clear. Therefore, we conducted a systematic review and meta-analysis to evaluate the relationship between subclinical hypothyroidism in pregnancy and hypertensive disorders of pregnancy(HDP) to guide clinical practice.MethodWe searched the MEDLINE (PubMed), Cochrane Central, EMBASE, Web of Science, and SCOPUS databases and screened all studies evaluating the relationship between subclinical hypothyroidism in pregnancy and hypertensive disorders of pregnancy. Two researchers independently evaluated the quality of all eligible original studies using the Newcastle-Ottawa Scale (NOS). We also performed a meta-analysis using STATA15.1. Sensitivity analyses were also performed by examining the effects of individual studies as well as using different effect models and detecting any publication bias using the harbord test.ResultsTwenty-two studies were included in the final meta-analysis. Our results indicated that pregnant women with subclinical hypothyroidism had an increased risk of HDP (OR = 1.54(95% CI: 1.21-1.96) I²=67.1%), compared with euthyroidism. Subclinical hypothyroidism in pregnancy was not associated with hypertensive disorders of pregnancy at TSH diagnostic cut-off of less than 3.0 mIU/L (P = 0.077). Curiously, the risk of HDP increases when the TSH diagnostic cut-off value is higher or lower than 4 mIU/L. Although only 9 studies were above the threshold, the risk of developing HDP was still 1.69 times, which was highest in all subgroup analyses. This is consistent with the newly recommended diagnostic cut-off value of 4 mIU/L for TSH by the ATA. Our results consider that the risk of hypertensive disorder complicating pregnancy is increased regardless of the diagnosis of subclinical hypothyroidism at any stage of pregnancy. Unfortunately, there is insufficient evidence to support that patients can benefit from treatment with levothyroxine.ConclusionThe results of this meta-analysis indicate that subclinical hypothyroidism in pregnancy is associated with an increased risk of developing HDP, and this association exists regardless of the gestational period. However, the available evidence cannot support these patients receiving thyroxine intervention can benefit from it, so routine screening is only recommended for pregnant women with risk factors for hypothyroidism. Further research is needed to validate more scientific and rigorous clinical studies to clarify the relationship between subclinical hypothyroidism and HDP to improve patient prognosis.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021286405)
Predictive Factors for Catecholamine-Induced Cardiomyopathy in Patients with Pheochromocytoma and Paraganglioma
Authors: Wang Yi , Yu Xuerong , Huang Yuguang 
Published: March 2022

ObjectiveTo investigate possible predictive factors of catecholamine-induced cardiomyopathy in pheochromocytoma and paraganglioma (CICMPP) patients.MethodsIn all, 50 CICMPP patients and 152 pheochromocytoma and paraganglioma (PPGL) patients without CICMPP who were treated in our institution between August 2012 and April 2018 were included in this retrospective study to assess predictors of CICMPP.ResultsPatients with CICMPP reported younger onset age, more clinical symptoms and signs, more family history of hypertension, and higher maximum systolic, diastolic, and mean BP and maximum HR. Medical evaluation also showed higher level of blood hematocrit, blood glucose, 24-h urine catecholamines, larger diameter of the tumor and more comorbidities, von Hippel-Lindau syndromes, and metastatic tumors in these patients. Multivariable analysis identified maximum resting HR over 115 beats/min (OR 10.05, 95% CI 3.71–27.20), maximum resting systolic BP over 180 mmHg (OR 7.17, 95% CI 2.22–23.23), blood glucose over 8.0 mmol/L (OR 6.52, 95% CI 2.25–18.86), more than 3 symptoms and signs (OR 6.05, 95% CI 1.86–19.64), and onset age under 40 years (OR 3.74, 95% CI 1.37–10.20) as independent predictors of CICMPP. Female sex (OR 5.06, 95% CI 1.19–21.54), complaint of chest pain (OR 5.84, 95% CI 1.27–26.90), and extra-adrenal tumor (OR 8.64, 95% CI 1.82–40.94) were independent predictors of Takotsubo cardiomyopathy in CICMPP.ConclusionMaximum resting HR ≥115 beats/min, maximum resting systolic BP ≥180 mmHg, blood glucose ≥8.0 mmol/L, number of symptoms and signs ≥3, and onset age ≤40 years were found to be predictive factors for CICMPP.
Mechanism of Endoplasmic Reticulum Stress Pathway in the Osteogenic Phenotypic Transformation of Aortic Valve Interstitial Cells
Authors: Tao Yiming , Geng Yimin , Dang Wenpei , Xu Xinxin , Zhao Hui , Zou Lijuan , Li Yongsheng 
Published: March 2022

Background and PurposeCalcific Aortic Valve Disease (CAVD) is a crucial component of degenerative valvular disease in old age and with the increasing prevalence of the aging population. we hope that by modeling valvular osteogenesis and intervening with endoplasmic reticulum stress inhibitor TUDCA to observe the effect of endoplasmic reticulum stress on valve osteogenesisMethodsIn this study, rabbit heart valvular interstitial cells (VICs) were isolated and cultured. They treated with ox-LDL (Oxidized Low Density Lipoprotein) stimulation to establish a model of valvular osteogenic transformation. BMP2 (Bone Morphogenetic Protein 2), PERK (Protein kinase R-like endoplasmic reticulum kinase), CHOP (CCAAT/enhancer-binding protein homologous protein) and transcriptional regulatory factor ATF4 (Activating Transcription Factor 4 )were recorded after intervention with ER stress inhibitor TUDCA. The effects of er stress on valvular osteogenic transformation were analyzed.ResultAfter stimulation of VICs with ox-LDL, the expression levels of BMP2, PERK, CHOP, and ATF4 increased. However, TUDCA treatment can alleviate the increased expression levels of BMP2, PERK ATF4, and CHOP under ox-LDL stimulation to a certain extent.ConclusionThe endoplasmic reticulum stress signaling pathway is involved in ox-LDL-induced calcification of rabbit valve interstitial cells. Inhibition of endoplasmic reticulum stress using TUDCA can improve the progression of rabbit aortic valve calcification.
Mechanism and Experimental Verification of Luteolin for the Treatment of Osteoporosis Based on Network Pharmacology
Authors: Liang Guihong , Zhao Jinlong , Dou Yaoxing , Yang Yuan , Zhao Di , Zhou Zhanpeng , Zhang Rui , Yang Weiyi , Zeng Lingfeng 
Published: March 2022

PurposeTo explore the molecular mechanism of luteolin in the treatment of osteoporosis (OP) by network pharmacological prediction and experimentation.MethodsThe target proteins of luteolin were obtained with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). OP-related proteins were extracted from the Comparative Toxicogenomics Database (CTD) and GeneCards and DisGeNET databases. We imported the common protein targets of luteolin and OP into the STRING database to obtain the relationships between the targets. The common target proteins of luteolin and OP were assessed by KEGG and GO enrichment analyses with the DAVID database. Animal experiments were conducted to verify the effect of luteolin on bone mineral density in ovariectomised (OVX) rats. Finally, the effects of luteolin on key signalling pathways were verified by cell experiments in vitro.ResultsForty-four targets of luteolin involved in the treatment of OP, including key target proteins such as TP53, AKT1, HSP90AA1, JUN, RELA, CASP3, and MAPK1, were screened. KEGG enrichment analysis found that luteolin inhibits OP by regulating the PI3K-Akt, TNF, oestrogen and p53 signalling pathways. The results of animal experiments showed that bone mass in the low-dose luteolin group (Luteolin-L group, 10 mg/kg), high-dose luteolin group (Luteolin-H group, 50 mg/kg) and positive drug group was significantly higher than that in the OVX group (P&lt;0.05). Western blot (WB) analysis showed that the protein expression levels of Collagen I, Osteopontin and RUNX2 in bone marrow mesenchymal stem cells (BMSCs) cultured with 0.5, 1 and 5 μM luteolin for 48 h were significantly higher than those in the dimethyl sulfoxide (DMSO) group (P&lt;0.05). In vitro cell experiments showed that the p-PI3K/PI3K and p-Akt/Akt expression ratios in BMSCs cultured with 0.5, 1 and 5 μM luteolin for 48 h were also significantly higher than those in the DMSO group (P&lt;0.05).ConclusionsLuteolin has multitarget and multichannel effects in the treatment of OP. Luteolin could reduce bone loss in OVX rats, which may be due to its ability to promote the osteogenic differentiation of BMSCs by regulating the activity of the PI3K-Akt signalling pathway.
Bacteriological Quality of Bottled Drinking Water and Municipal Tap Water in Northeastern Ethiopia
Authors: Keleb Awoke , Ademas Ayechew , Sisay Tadesse , Lingerew Mistir , Adane Metadel 
Published: March 2022

Objective: Water-borne diseases cause high morbidity and mortality in developing countries, like Ethiopia. Diarrheal disease and typhoid are one of the top five diseases that cause significant public health burden and economic cost in Dessie city. Thus, monitoring the quality of drinking water is crucial to prevent waterborne disease. This study aimed to determine the bacteriological quality of bottled drinking water and municipal tap water in Northeastern Ethiopia for proper planning, monitoring, and intervention purpose.Methods: A laboratory-based cross-sectional study was conducted on 248 municipal tap water samples from point of collection (MTPOC), 248 water samples from a household water storage container (HHSC), 38 bottled water samples before packaging from manufacturing facilities (BPMF), and 38 bottle water samples from point of sale (POS) in Dessie city between March 15 to May 15, 2021. Water samples were collected by trained data collectors using a standard sampling protocol. Data were entered into Microsoft Excel and exported to SPSS version 25.0 for data cleaning and analysis. The commonest microbiological parameters, total coliforms (TC) and Escherichia coli (E. coli) were tested using the standard procedure. One-way ANOVA was used to compare the mean log concentration of E. coli and TC between sampling points and the Tukey post hoc test was also computed to identify statistically significant differences among sample types. The 95% confidence interval [CI] and p &lt; 0.05 were taken as statistically significant.Results: About 15.8 and 36.8% of the samples from BPMF and 26.3 and 55.3% of samples from POS were positive for E. coli and TC respectively while 47.2 and 65.7% of water sample from MTPOC and 48.8 and 98.8% of samples from HHSC were positive for E. coli and TC respectively. The mean log concentration of E. coli from the sample of MTPOC was significantly higher than BPMF. Similarly, water samples from HHSC had significantly higher E. coli and TC concentrations than BPMF and POS. Water samples from HHSC had also a significantly higher prevalence of log concentrations of TC than MTPOC.Conclusion: Most values were beyond maximum tolerable limits recommended by World Health Organization (WHO). Thus, good water handling practices and water quality monitoring are essential to prevent bacteriological contamination.
Cross-Talk Between m6A- and m5C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients
Authors: Song Wei , Ren Jun , Xiang Rensheng , Yuan Wenzheng , Fu Tao 
Published: March 2022

BackgroundN6-methyladenosine (m6A) and 5-methylcytosine (m5C) can modify long non-coding RNAs (lncRNAs), thereby affecting tumorigenesis and tumor progression. However, there is a lack of knowledge regarding the potential roles and cross-talk of m6A- and m5C-related lncRNAs in the tumor microenvironment (TME) and their effect on prognosis.MethodsWe systematically evaluated the expression patterns of m6A- and m5C-related lncRNAs in 1358 colorectal cancer (CRC) samples from four datasets. Consensus clustering was conducted to identify molecular subtypes of CRC, and the clinical significance, TME, tumor-infiltrating immune cells (TIICs), and immune checkpoints in the different molecular subtypes were analyzed. Finally, we established a m6A- and m5C-related lncRNA signature and a prognostic nomogram.ResultsWe identified 141 m6A- and m5C-related lncRNAs by co-expression analysis, among which 23 lncRNAs were significantly associated with the overall survival (OS) of CRC patients. Two distinct molecular subtypes (cluster A and cluster B) were identified, and these two distinct molecular subtypes could predict clinicopathological features, prognosis, TME stromal activity, TIICs, immune checkpoints. Next, a m6A- and m5C-related lncRNA signature for predicting OS was constructed, and its predictive capability in CRC patients was validated. We then constructed a highly accurate nomogram for improving the clinical applicability of the signature. Analyses of clinicopathological features, prognosis, TIICs, cancer stem cell (CSC), and drug response revealed significant differences between two risk groups. In addition, we found that patients with a low-risk score exhibited enhanced response to anti-PD-1/L1 immunotherapy. Functional enrichment analysis showed that these lncRNAs related to the high-risk group were involved in the development and progression of CRC.ConclusionsWe conducted a comprehensive analysis of m6A- and m5C-related lncRNAs in CRC and revealed their potential functions in predicting tumor-immune-stromal microenvironment, clinicopathological features, and prognosis, and determined their role in immunotherapy. These findings may improve our understanding of the cross-talk between m6A- and m5C-related lncRNAs in CRC and pave a new road for prognosis assessment and more effective immunotherapy strategies.
Evolution of Cryoglobulinemia in Direct-Acting Antiviral-Treated Asian Hepatitis C Patients With Sustained Virological Responses: A 4-Year Prospective Cohort Study
Authors: Chang Ming-Ling , Cheng Jur-Shan , Chuang Ya-Hui , Pao Li-Heng , Wu Ting-Shu , Chen Shiang-Chi , Chang Ming-Yu , Chien Rong-Nan 
Published: March 2022

BackgroundHow cryoglobulinemia evolves after sustained virological response (SVR) following direct-acting antiviral (DAA) treatment in Asian hepatitis C virus (HCV)-infected patients remains elusive.MethodsA prospective cohort study was conducted in 422 Taiwanese patients (358 completed DAA therapy and 353 experienced SVRs). Serum cryoglobulins were surveyed at baseline and every 3-6 months posttherapy.ResultsOf 422, 227 (53.8%) had cryoglobulinemia, 8 (1.89%) had cryoglobulinemic vasculitis. Of 227, 54 (23.8%), 57 (25.1%) and 116 (51.1%) had 1, 2 and 3 cryoglobulins, respectively; those with 3 cryoglobulins had the highest alanine aminotransferase, immunoglobulin G (IgG) and fibrosis-4 index. During a 4-year follow-up, among SVR patients, cryoglobulinemia rates decreased from 56.4% to 15.4%, single cryoglobulin rates increased (21.6% to 63.9%) and 3 cryoglobulin rates decreased (55.7% to 11.1%). Compared with baseline values, among SVR patients with baseline cryoglobulinemia, complement component 4 levels increased, and IgG and IgM levels decreased until 48 weeks posttherapy for those without posttherapy cryoglobulinemia. All 8 cryoglobulinemic vasculitis patients exhibited SVRs; 5 (62.5%) achieved complete clinical response 12 weeks posttherapy, of whom, 2 (40%) experienced clinical relapse 24~48 weeks posttherapy. Baseline IgM levels were associated with posttherapy cryoglobulinemia in SVR patients (cut-off values at 12, 24, 48 weeks and 4 years posttherapy: 130, 105, 118 and 168 mg/dL, respectively).ConclusionsAmong DAA-treated SVR patients, in 4 years, cryoglobulinemia rates decreased from 56.4% to 15.4%, multiple cryoglobulin rates decreased, cryoglobulinemia signals reversed, 62.5% of cryoglobulinemic vasculitis patients achieved complete clinical response (40% had relapse), and baseline IgM levels indicated posttherapy cryoglobulinemia.
Pathophysiological, Cellular, and Molecular Events of the Vascular System in Anaphylaxis
Authors: Nuñez-Borque Emilio , Fernandez-Bravo Sergio , Yuste-Montalvo Alma , Esteban Vanesa 
Published: March 2022

Anaphylaxis is a systemic hypersensitivity reaction that can be life threatening. Mechanistically, it results from the immune activation and release of a variety of mediators that give rise to the signs and symptoms of this pathological event. For years, most of the research in anaphylaxis has focused on the contribution of the immune component. However, approaches that shed light on the participation of other cellular and molecular agents are necessary. Among them, the vascular niche receives the various signals (e.g., histamine) that elicit the range of anaphylactic events. Cardiovascular manifestations such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and cardiac alterations are crucial in the pathophysiology of anaphylaxis and are highly involved to the development of the most severe cases. Specifically, the endothelium, vascular smooth muscle cells, and their molecular signaling outcomes play an essential role downstream of the immune reaction. Therefore, in this review, we synthesized the vascular changes observed during anaphylaxis as well as its cellular and molecular components. As the risk of anaphylaxis exists both in clinical procedures and in routine life, increasing our knowledge of the vascular physiology and their molecular mechanism will enable us to improve the clinical management and how to treat or prevent anaphylaxis.Key MessageAnaphylaxis, the most severe allergic reaction, involves a variety of immune and non-immune molecular signals that give rise to its pathophysiological manifestations. Importantly, the vascular system is engaged in processes relevant to anaphylactic events such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and decreased cardiac output. The novelty of this review focuses on the fact that new studies will greatly improve the understanding of anaphylaxis when viewed from a vascular molecular angle and specifically from the endothelium. This knowledge will improve therapeutic options to treat or prevent anaphylaxis.
High Performance Copper Based Metal Organic Framework for Removal of Heavy Metals From Wastewater
Authors: Haso Hussien Waritu , Dubale Amare Aregahegn , Chimdesa Mitiku Abdisa , Atlabachew Minaleshewa 
Published: March 2022

The biggest challenge of this century is the generation of wastewater which is released to the environment due to industrial expansion. Industrial development has caused the release of various pollutants including heavy metals such as Cd, Pb, and Cr into the environment. In this study, copper diphenylamine metal-organic framework (Cu-DPA MOF) has been synthesized via hydrothermal method and its adsorption capacity toward the removal of heavy metals from wastewater was examined. The removal efficiency of heavy metals by Cu-DPA MOF was tested at optimized adsorption parameters such as optimal adsorbent dosage, pH, initial metals concentration, and adsorption time. The heavy metals concentration in the wastewater before treated with the as-synthesized MOF was determined to be 0.3027, 0.0098, and 0.1021 mg/L for Cr, Cd, and Pb, respectively. The corresponding concentrations of heavy metals in wastewater were reduced to 0.0015, 0.00024, and 0.00016 mg/L when treated with the as-synthesized MOF. As a result, a maximum removal efficiency of 97.6%, 99.5%, and 99.5% was achieved for Cd, Cr, and Pb metals, respectively. This is possibly due to the high porous nature and huge surface area of the as-synthesized MOF. The adsorption data were best fitted with Freundlich isotherm throughout this study. The study sheds light on the design of adsorbents with high removal efficiency of pollutants found in the environment.
Survival Outcome of Surgical Resection vs. Radiotherapy in Brain Metastasis From Colorectal Cancer: A Meta-Analysis
Authors: Chang Yu , Wong Chia-En , Lee Po-Hsuan , Huang Chi-Chen , Lee Jung-Shun 
Published: March 2022

BackgroundThe incidence of brain metastasis from colorectal cancer (CRC) increases along with the greater survival rate for CRC because of the advances in therapeutic modalities. Local treatment strategies for brain metastasis include surgical resection and radiotherapy. Nevertheless, given the incongruent literature, the optimal therapeutic approach remains to be investigated. This study aims to systematically compare the real-world survival outcome of surgical resection and radiotherapy in patients with brain metastasis from CRC.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines (PROSPERO, ID: CRD42021240200), the Cochrane Library, Embase, and Medline were searched from the inception of the database to August 2021. Meta-analyses were conducted with results pooled using hazard ratios with corresponding 95% CIs to evaluate the overall survival (OS) following local treatment for brain metastasis from CRC. Summary effects were evaluated using a series of random-effect models.ResultsIn this review, 17 retrospective studies comprising 1,438 participants were included. In comparison with radiotherapy, the OS of patients who received brain metastasectomy was generally longer (HR, 0.53; 95% CI, 0.47–0.60). Extracerebral metastases (HR, 1.58; 95% CI, 1.34–1.86) and multiple brain metastases (HR, 1.38; 95% CI, 1.10–1.72) were associated with worse survival outcomes.ConclusionsFor patients with brain metastasis from CRC, the current real-world evidence demonstrated the survival benefit of aggressive neurosurgical management in suitable patients. Additionally, patients with extracerebral metastases and multiple brain metastases had worse survival outcomes.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=240200.
Construction and Interpretation of Prediction Model of Teicoplanin Trough Concentration via Machine Learning
Authors: Ma Pan , Liu Ruixiang , Gu Wenrui , Dai Qing , Gan Yu , Cen Jing , Shang Shenglan , Liu Fang , Chen Yongchuan 
Published: March 2022

ObjectiveTo establish an optimal model to predict the teicoplanin trough concentrations by machine learning, and explain the feature importance in the prediction model using the SHapley Additive exPlanation (SHAP) method.MethodsA retrospective study was performed on 279 therapeutic drug monitoring (TDM) measurements obtained from 192 patients who were treated with teicoplanin intravenously at the First Affiliated Hospital of Army Medical University from November 2017 to July 2021. This study included 27 variables, and the teicoplanin trough concentrations were considered as the target variable. The whole dataset was divided into a training group and testing group at the ratio of 8:2, and predictive performance was compared among six different algorithms. Algorithms with higher model performance (top 3) were selected to establish the ensemble prediction model and SHAP was employed to interpret the model.ResultsThree algorithms (SVR, GBRT, and RF) with high R2 scores (0.676, 0.670, and 0.656, respectively) were selected to construct the ensemble model at the ratio of 6:3:1. The model with R2 = 0.720, MAE = 3.628, MSE = 22.571, absolute accuracy of 83.93%, and relative accuracy of 60.71% was obtained, which performed better in model fitting and had better prediction accuracy than any single algorithm. The feature importance and direction of each variable were visually demonstrated by SHAP values, in which teicoplanin administration and renal function were the most important factors.ConclusionWe firstly adopted a machine learning approach to predict the teicoplanin trough concentration, and interpreted the prediction model by the SHAP method, which is of great significance and value for the clinical medication guidance.