bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-factor Xa Activity Is Not Associated With Venous Thromboembolism in Critically Ill Patients Receiving Enoxaparin for Thromboprophylaxis: A Retrospective Observational Study
Authors: Dibiasi Christoph , Gratz Johannes , Wiegele Marion , Baierl Andreas , Schaden Eva 
Published: April 2022

BackgroundAnti-factor Xa activity has been suggested as a surrogate parameter for judging the effectiveness of pharmacological thromboprophylaxis with low molecular weight heparins in critically ill patients. However, this practice is not supported by evidence associating low anti-factor Xa activity with venous thromboembolism.MethodsWe performed a retrospective observational study including 1,352 critically ill patients admitted to 6 intensive care units of the Medical University of Vienna, Austria between 01/2015 and 12/2018. Included patients received prophylactically dosed enoxaparin (≤100 IU/kg body weight per day). We analyzed median peak, 12-h trough and 24-h trough anti-factor Xa activity per patient and compared anti-factor Xa activity between patients without vs. with venous thromboembolic events.Results19 patients (1.4%) developed a total of 22 venous thromboembolic events. We did not observe a difference of median (IQR) anti-factor Xa activity between patients without venous thromboembolism [peak 0.22 IU/mL (0.14–0.32); 12-h trough 0.1 IU/mL (&lt;0.1–0.17), 24-h trough &lt; 0.1 IU/mL (&lt;0.1– &lt;0.1)] vs. patients with venous thromboembolism [peak 0.33 IU/mL (0.14–0.34); 12-h trough 0.12 IU/mL (&lt;0.1–0.26); 24-h trough &lt; 0.1 IU/mL (&lt;0.1–&lt;0.1)].ConclusionPatients who developed venous thromboembolism had anti-factor Xa activities comparable to those who did not suffer from venous thromboembolism.
Grocott Methenamine Silver Staining Is the Optimal Approach to Histological Diagnosis of Pulmonary Cryptococcosis
Authors: Wang Suijing , Lai Jieyi , Wu Ruibin , Zhang Lihong , Huang Mayan , Xiao Yongbo , Zhang Xinke , Chen Jiewei 
Published: April 2022

BackgroundHistological staining methods for Cryptococcus identification vary in accuracy. This study aimed to investigate the clinical value of Grocott methenamine silver (GMS), periodic acid-Schiff (PAS), and Alcian blue (AB) staining in the diagnosis of pulmonary cryptococcosis (PC).MethodsFrom April 2004 to June 2021, the clinical and pathological data of 152 patients with PC were collected from the Department of Pathology, Sun Yat-sen University Cancer Center. The sensitivity and identifiability of GMS, PAS, and AB staining for histological diagnosis were systematically evaluated using statistical methods combined with the microscopic characteristics of PC cases.ResultsStatistical analysis showed that the detection rates of GMS, PAS, and AB staining were 100.0% (152/152), 94.7% (144/152), and 81.6% (124/152), respectively. McNemar’s test showed that the sensitivity of GMS was significantly higher than those of PAS (P = 0.008) and AB stains (P &lt; 0.001). Both PAS and AB stains had obvious non-specific staining, which interfered with the detection of Cryptococcus, and increased diagnostic difficulties. In contrast, in GMS staining, Cryptococcus spores were prominent with a clean background and were clearly observed at low or medium power magnification, with the identifiability significantly better than those of PAS or AB staining.ConclusionGMS staining had sensitivity up to 100%, and identifiability that was better than those of PAS and AB staining. GMS is the best method for histological diagnosis of PC.
Evidence of Omics, Immune Infiltration, and Pharmacogenomics for BATF in a Pan-Cancer Cohort
Authors: Jia Chenguang , Ma Yihui , Wang Mengyang , Liu Wen , Tang Feng , Chen Jincao 
Published: April 2022

Background: Cytotoxic CD8+ T-cell exhaustion is the major barrier for immunotherapy in tumors. Recent studies have reported that the basic leucine zipper activating transcription factor–like transcription factor (BATF) is responsible for countering cytotoxic CD8+ T-cell exhaustion. Nevertheless, the expression and roles of BATF in tumors have been poorly explored.Methods: In the present study, we conducted a multi-omics analysis, including gene expression, methylation status, DNA alterations, pharmacogenomics, and survival status based on data from the Cancer Genome Atlas (TCGA) database to discern expression patterns and prognostic roles of BATF in tumors. We also explored potential roles of BATF in a pan-cancer cohort by performing immune infiltration, Gene Ontology (GO) enrichment, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In vitro assay was also performed to explore roles of BATF in tumor cells.Results: We found that BATF was aberrantly upregulated in 27 types of tumors with respect to the corresponding normal tissues. Abnormal BATF expression in tumors predicted survival times of patients in a tissue-dependent manner. The results of GO, immune infiltration, and KEGG analysis revealed that increased BATF expression in tumors participated in modulating immune cell infiltration via immune-related pathways. BATF expression could also predict immunotherapeutic and chemotherapy responses in cancers. Moreover, knockdown of BATF suppresses tumor cell viability.Conclusion: Our present study reports the vital roles of BATF in tumors and provides a theoretical basis for targeting BATF therapy.
Multi-Omics Integration in Mice With Parkinson’s Disease and the Intervention Effect of Cyanidin-3-O-Glucoside
Authors: Wang Wang , Zhu Guoxue , Wang Yuwen , Li Wei , Yi Shilin , Wang Kai , Fan Lu , Tang Juanjuan , Chen Ruini 
Published: April 2022

BackgroundParkinson’s disease (PD) is a multifactorial degenerative disease of the central nervous system, which affects mostly older adults. To date, research has focused on the progression of PD. Simultaneously, it was confirmed that the imbalances in gut microbiota are associated with the onset and progression of PD. Accurate diagnosis and precise treatment of PD are currently deficient due to the absence of effective biomarkers.MethodsIn this study, the pharmacodynamic study of cyanidin-3-O-glucoside in PD mice was used. It intends to use the “imbalance” and “balance” of intestinal microecology as the starting point to investigate the “gut-to-brain” hypothesis using metabolomic-combined 16S rRNA gene sequencing methods. Simultaneously, metabolomic analysis was implemented to acquire differential metabolites, and microbiome analysis was performed to analyze the composition and filter the remarkably altered gut microbiota at the phylum/genera level. Afterward, metabolic pathway and functional prediction analysis of the screened differential metabolites and gut microbiota were applied using the MetaboAnalyst database. In addition, Pearson’s correlation analysis was used for the differential metabolites and gut microbiota. We found that cyanidin-3-O-glucoside could protect 1-methyl-4-phenyl-1,2,3,6− tetrahydropy ridine (MPTP)-induced PD mice.ResultsMetabolomic analysis showed that MPTP-induced dysbiosis of the gut microbiota significantly altered sixty-seven metabolites. The present studies have also shown that MPTP-induced PD is related to lipid metabolism, amino acid metabolism, and so on. The 16S rRNA sequencing analysis indicated that 5 phyla and 22 genera were significantly altered. Furthermore, the differential gut microbiota was interrelated with amino acid metabolism, and so on. The metabolites and gut microbiota network diagram revealed significant correlations between 11 genera and 8 differential metabolites.ConclusionIn combination, this study offers potential molecular biomarkers that should be validated for future translation into clinical applications for more accurately diagnosing PD. Simultaneously, the results of this study lay a basis for further study of the association between host metabolisms, gut microbiota, and PD.
Polymorphisms of Cytochromes P450 and Glutathione S-Transferases Synergistically Modulate Risk for Parkinson’s Disease
Authors: Fan Hui-Hui , Li Bao-Qing , Wu Ke-Yun , Yan Hai-Dan , Gu Meng-Jie , Yao Xing-Hao , Dong Hao-Jia , Zhang Xiong , Zhu Jian-Hong 
Published: April 2022

BackgroundEnvironmental substances such as pesticides are well-known in link with Parkinson’s disease (PD) risk. Enzymes including cytochromes P450 (CYPs), esterases and glutathione S-transferases (GSTs) are responsible for the xenobiotic metabolism and may functionally compensate each other for subtypes in the same class. We hypothesize that the genetic effects of each class modulate PD risk stronger in a synergistic way than individually.MethodsWe selected 14 polymorphic loci out of 13 genes which encode enzymes in the classes of CYP, esterase, and GST, and recruited a cohort of 1,026 PD and control subjects from eastern China. The genotypes were identified using improved multiplex ligation detection reaction and analyzed using multiple models.ResultsA total of 13 polymorphisms remained after Hardy-Weinberg equilibrium analysis. None of the polymorphisms were independently associated with PD risk after Bonferroni correction either by logistic regression or genetic models. In contrast, interaction analyses detected increased resistance to PD risk in individuals carrying the rs12441817/CC (CYP1A1) and rs2070676/GG + GC (CYP2E1) genotypes (P = 0.002, OR = 0.393, 95% CI = 0.216–0.715), or carrying the GSTM1-present, GSTT1-null, rs156697/AG + GG (GSTO2) and rs1695/AA (GSTP1) genotypes (P = 0.003, OR = 0.348, 95% CI = 0.171–0.706). The synergistic effect of GSTs on PD was primarily present in females (P = 0.003). No synergistic effect was observed within genotypes of esterases.ConclusionWe demonstrate a presence of synergistic but not individual impact on PD susceptibility in polymorphisms of CYPs and GSTs. The results indicate that the genetic interplay leads the way to PD development for xenobiotic metabolizing enzymes.
Efficacy of Cognitive-Behavioral Therapy for the Prophylaxis of Migraine in Adults: A Three-Armed Randomized Controlled Trial
Authors: Klan Timo , Gaul Charly , Liesering-Latta Eva , Both Bernhard , Held Isabella , Hennemann Severin , Witthöft Michael 
Published: April 2022

BackgroundBehavioral approaches are central to the preventive treatment of migraine but empirical evidence regarding efficacy and effectiveness is still sparse. This study aimed to evaluate the efficacy of a newly developed migraine-specific, integrative cognitive-behavioral therapy program (miCBT) combining several approaches (trigger and stress management, coping with fear of attacks, relaxation training) by comparing it with a single behavioral approach (relaxation training, RLX) as an active control group and a waiting-list control group (WLC).MethodsIn a three-armed open-label randomized controlled trial, 121 adults with migraine were assigned to either miCBT, RLX or WLC. The outpatient group therapy (miCBT or RLX) consisted of seven sessions each 90 min. Participants who completed the WLC were subsequently randomized to one of the two treatment groups. Primary outcomes were headache days, headache-related disability, emotional distress, and self-efficacy. The baseline was compared to post-treatment, and followed by assessments 4- and 12-months post-treatment to compare miCBT and RLX.ResultsMixed-model analyses (intention-to-treat sample, 106 participants) showed significantly stronger pre-post improvements in self-efficacy (assessed by the Headache Management Self-Efficacy Scale, HMSE-G-SF) in both treatment groups compared to the WLC (mean difference at post; miCBT: 4.67 [0.55–8.78], p = 0.027; RLX: 4.42 [0.38 to 8.46], p = 0.032), whereas no other significant between-group differences were observed. The follow-up analyses revealed significant within-group improvements from baseline to 12-month follow-up in all four primary outcomes for both treatments. However, between-group effects (miCBT vs. RLX) were not significant at follow-up.ConclusionThe miCBT has no better treatment effects compared to RLX in migraine-prophylaxis. Both treatments effectively increase patients' self-efficacy.Trial RegistrationGerman Clinical Trials Register (www.drks.de; DRKS-ID: DRKS00011111).
Accuracy of Calf Circumference Measurement, SARC-F Questionnaire, and Ishii's Score for Screening Stroke-Related Sarcopenia
Authors: Yao Ruihong , Yao Liqing , Yuan Changli , Gao Bu-Lang 
Published: April 2022

ObjectiveThe purpose of this study was to investigate the accuracy of sarcopenia diagnosis in patients with stroke using calf circumference (CC), SARC-F questionnaire, and Ishii's score in comparison with the Asian Working Group for Sarcopenia 2019 (AWGS) sarcopenia diagnostic criteria.Materials and MethodsIn this cross-sectional study, a total of 364 consecutive patients with stroke were enrolled and evaluated with the CC measurement, SARC-F questionnaire, and Ishii's score. The diagnostic accuracy was analyzed.ResultsBased on the AWGS criteria, sarcopenia was present in 180 (49.5%) patients, with an age range of 49–74 (mean 63 ± 14.7) years. In all patients, the cutoff value of CC in the accuracy of diagnosing sarcopenia was 30.5 cm, with an AUC of 0.85, sensitivity of 81.8%, specificity of 90.1%, Kappa value of 0.72, and Youden index of 0.72. In the accuracy of diagnosing sarcopenia in all patients, Ishii's score had a cutoff value of 118, AUC of 0.78, sensitivity of 90.1%, specificity of 36.0%, Kappa value of 0.4, and Youden index of 0.55. For accuracy of diagnosing sarcopenia, the SARC-F questionnaire had a cutoff value of 5, AUC of 0.731, sensitivity of 94.7%, specificity of 40%, Kappa value of 0.34, and Youden index of 0.41.ConclusionsBased on the AWGS criteria, calf circumference measurement has the optimal performance in screening stroke-related sarcopenia compared with the SARC-F questionnaire and Ishii's score. In patients with stroke, the cutoff value of calf circumference for sarcopenia is &lt; 31 cm in men and 30 cm in women, and with an AUC of 0.85.
The Overexpression of Insulin-Like Growth Factor-1 and Neurotrophin-3 Promote Functional Recovery and Alleviate Spasticity After Spinal Cord Injury
Authors: Talifu Zuliyaer , Qin Chuan , Xin Zhang , Chen Yixin , Liu Jiayi , Dangol Subarna , Ma Xiaodong , Gong Han , Pei Zhisheng , Yu Yan , Li Jianjun , Du Liangjie 
Published: April 2022

ObjectiveThis study was conducted to investigate the effects of the exogenous overexpression of nerve growth factors NT-3 and IGF-1 on the recovery of nerve function after spinal cord injury (SCI) and identify the potential mechanism involved.MethodsSixty-four female SD rats were randomly divided into four groups: an SCI group, an adeno-associated viral (AAV)-RFP and AAV-GFP injection group, an AAV-IGF-1 and AAV-NT-3 injection group, and a Sham group. After grouping, the rats were subjected to a 10-week electrophysiological and behavioral evaluation to comprehensively evaluate the effects of the intervention on motor function, spasticity, mechanical pain, and thermal pain. Ten weeks later, samples were taken for immunofluorescence (IF) staining and Western blot (WB) detection, focusing on the expression of KCC2, 5-HT2A, and 5-HT2C receptors in motor neurons and the spinal cord.ResultsElectrophysiological and behavioral data indicated that the AAV-IGF-1 and AAV-NT-3 groups showed better recovery of motor function (P &lt; 0.05 from D14 compared with the AAV-RFP + AAV-GFP group; P &lt; 0.05 from D42 compared with SCI group) and less spasticity (4–10 weeks, at 5 Hz all P &lt; 0.05 compared with SCI group and AAV- RFP + AAV-GFP group) but with a trend for more pain sensitivity. Compared with the SCI group, the von Frey value result of the AAV-IGF-1 and AAV-NT-3 groups showed a lower pain threshold (P &lt; 0.05 at 4–8 weeks), and shorter thermal pain threshold (P &lt; 0.05 at 8–10 weeks). IF staining further suggested that compared with the SCI group, the overexpression of NT-3 and IGF-1 in the SCI-R + G group led to increased levels of KCC2 (p &lt; 0.05), 5-HT2A (p &lt; 0.05), and 5-HT2C (p &lt; 0.001) in motor neurons. WB results showed that compared with the SCI group, the SCI-R + G group exhibited higher expression levels of CHAT (p &lt; 0.01), 5-HT2A (p &lt; 0.05), and 5-HT2C (p &lt; 0.05) proteins in the L2-L6 lumbar enlargement.ConclusionData analysis showed that the overexpression of NT-3 and IGF-1 may improve motor function after SCI and alleviate spasms in a rat model; however, these animals were more sensitive to mechanical pain and thermal pain. These behavioral changes may be related to increased numbers of KCC2, 5-HT2A, and 5-HT2C receptors in the spinal cord tissue. The results of this study may provide a new theoretical basis for the clinical treatment of SCI.
The Obesogenic Environment: Epigenetic Modifications in Placental Melanocortin 4 Receptor Gene Connected to Gestational Diabetes and Smoking
Authors: Franzago Marica , Porreca Annamaria , D’Ardes Mario , Di Nicola Marta , Di Tizio Luciano , Liberati Marco , Stuppia Liborio , Vitacolonna Ester 
Published: April 2022

BackgroundMaternal metabolic insults as well as Gestational Diabetes Mellitus (GDM) influence the fetal health and may affect ‘offspring’s susceptibility to chronic diseasesviaepigenetic modifications. GDM, the most common metabolic disorder in pregnancy, can be considered the result of complex interactions between genetic and environmental factors. A critical point in this view is the identification of genes which are epigenetically modified under the influence of GDM. The melanocortin 4 receptor (MC4R)gene plays a crucial role in nutritional health by suppressing appetite and participating in energy control regulation. The correlations between pregnant ‘women’s metabolic profiles and placental epigenetic modifications of this gene have been poorly investigated.ObjectiveThe aim of this study was to evaluate the effect of GDM and maternal clinical parameters at the third trimester of pregnancy to DNA methylation levels in the placenta at CpG sites ofMC4Rgene.Design and MethodsSocio-demographic and clinical characteristics, Mediterranean diet adherence, smoking habits, and physical activity were assessed at the third trimester of pregnancy of 60 Caucasian pregnant women, of which 33 with GDM. Clinical parameters of the newborns were recorded at birth.MC4RDNA methylation on maternal and fetal sides of the placenta was analyzed using bisulfite pyrosequencing.ResultsMC4RDNA methylation levels at CpG1 and CpG2 were lower on the fetal side of the placenta in GDM-affected women than in non-GDM-affected recruits (p= 0.033). Moreover, DNA methylation levels on the maternal side at CpG1 were positively related to glucose concentration at 2-h oral glucose tolerance test (OGTT). On the other hand, CpG2 DNA methylation was positively related to both 1-h and 2-h during OGTT. Maternal DNA methylation level at CpG2 was also associated with low density lipoprotein cholesterol (LDL-C) at the third trimester of pregnancy (rho = 0.340,p&lt; 0.05), while CpG1 methylation was negatively related to maternal weight variations at delivery (rho = −0.316,p&lt; 0.05). Significant associations betweenMC4RDNA methylation on the maternal side and lipid profile at third trimester of pregnancy in women smokers were found.ConclusionOur results suggest thatMC4Rmethylation profile in the placenta is related to maternal metabolic and nutritional conditions, potentially affecting fetal programming and the future metabolic health of the newborn.
Effect of Meal Texture on Postprandial Glucose Excursions and Gut Hormones After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy
Authors: Hedbäck Nora , Hindsø Morten , Bojsen-Møller Kirstine N. , Linddal Adelaide K. , Jørgensen Nils B. , Dirksen Carsten , Møller Andreas , Kristiansen Viggo B. , Hartmann Bolette , Holst Jens J. , Svane Maria S. , Madsbad Sten 
Published: April 2022

Background and aimsThe metabolic consequences after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are often studied using a liquid mixed meal. However, liquid meals may not be representative of the patients’ everyday diet. We therefore examined postprandial glucose and gut hormone responses using mixed meals differing only with respect to meal texture.MethodsTwelve RYGB-operated, 12 SG-operated, and 12 unoperated individuals (controls) were enrolled in the study. Participants were matched on age, sex, and body mass index. In randomized order, each participant underwent a liquid and a solid 4-h mixed meal test on separate days. The meals were isocaloric (309 kcal), and with identical macronutrient composition (47 E% carbohydrate, 18 E% protein, 32 E% fat, and 3 E% dietary fibers). The liquid meal was blended to create a smooth liquid texture while the other meal retained its solid components.ResultsPostprandial glucose concentrations (peak and incremental area under curve, iAUC) did not differ between the two meal textures in any group. In the control group, peak C-peptide was higher after the liquid meal compared with the solid meal (p = 0.04), whereas iAUCs of C-peptide were similar between the two meals in all groups. Peak of glucagon-like peptide-1 (GLP-1) was higher after the liquid meal compared with the solid meal in RYGB- and SG-operated individuals (RYGB p = 0.02; SG p &lt; 0.01), but iAUC of GLP-1 did not differ between meal textures within any group. Peak of glucose-dependent insulin tropic polypeptide (GIP) was higher after the liquid meal in the SG and control groups (SG p = 0.02; controls p &lt; 0.01), but iAUCs of GIP were equal between meals. There were no differences in total AUC of ghrelin between the liquid and solid meals within any of the groups.ConclusionA liquid and a solid meal with identical macronutrient composition result in similar postprandial glucose responses, both in operated and unoperated individuals. Small differences were observed for the postprandial peaks of C-peptide, GLP-1, and GIP concentrations. Overall, a liquid meal is suitable for evaluating glucose tolerance, β-cell function, and gut hormones responses, both after RYGB and SG and in unoperated individuals.Clinical Trial Registration[www.clinicaltrials.gov], identifier [NCT04082923].
Assessment of the Novel, Practical, and Prognosis-Relevant TNM Staging System for Stage I-III Cutaneous Melanoma
Authors: Hu Di , Liu Zeming , Chen Sichao , Huang Yihui , Zeng Wen , Wei Wei , Zhang Chao , Zhou Ling , Chen Danyang , Wu Yiping , Guo Liang 
Published: April 2022

BackgroundThe clinical TNM staging system does not differ between the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed.MethodsData were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy.ResultsThis retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values &lt; 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively.ConclusionWe developed a more practical and prognosis-relevant staging system than that of the 8th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma.