bluuebunny/crossref_metadata_2025_split huggingface dataset:
1,25-dihydroxyvitamin D as Predictor of Renal Worsening Function in Chronic Kidney Disease. Results From the PASCaL-1,25D Study
Authors: Galassi Andrea , Fasulo Eliana Maria , Ciceri Paola , Casazza Roberta , Bonelli Fabrizio , Zierold Claudia , Calleri Mariella , Blocki Frank A. , Palmieri Maria Assunta , Mastronardo Claudio , Cozzolino Mario G. 
Published: March 2022

BackgroundHeterogeneous progression of chronic kidney disease (CKD) toward dialysis advocates improving in renal care management. Diagnosis and staging of CKD relies on estimated glomerular filtration rate (eGFR) and albuminuria. Tubular biomarkers emerged as new predictors of worsening renal function (WRF), due to partial inaccuracy of eGFR and existing WRF in non-proteinuric patients. Active vitamin D is synthesized in renal tubules and participates to mineral adaptation in CKD. Circulating 1,25-dihydroxyvitamin D [1,25(OH)2D] was poorly investigated as a biomarker of endocrine tubular function and predictor of WRF.ObjectiveInvestigate capability of 1,25(OH)2D to predict parathormone (PTH) increase and WRF in CKD stage 3–4.MethodsPASCaL-1,25D was an observational, prospective, monocentric study. Primary outcomes were absolute and 20% increase in PTH, and WRF defined as 20% reduction in eGFR or dialysis initiation at 6 months.ResultsSeventy-one patients completed follow up. Absolute increase in PTH (1–84) was independently predicted by lower 1,25(OH)2D levels (p = 0.0134). No association was detected between 1,25(OH)2D and iPTH increase. Higher 1,25(OH)2D was associated with reduced risk of WRF at univariate analysis [OR 0.89 (95% CI 0.86–0.93), p = 0.006]. The 1,25(OH)2D/PTH (1–84) ratio was associated with non-significant 84% risk reduction for WRF [OR 0.16 (95% CI 0.06–0.41), p = 0.05]. Low 1,25(OH)2D reached 100% sensitivity in predicting WRF in CKD stage 3 (AUC 9.909, p &lt; 0.0001) and non-elderly patients (AUC 0.883, p &lt; 0.0001). Machine learning models retained 1,25(OH)2D/PTH (1–84) as relevant predictor of WRF together with eGFR and albuminuria. Age influenced interaction between renal and mineral biomarkers.Conclusion1,25(OH)2D deserves attention as biomarker of tubular health, and sensible predictor of WRF on the short run among non-elderly patients affected by stage 3 CKD. The 1,25(OH)2D/PTH (1–84) ratio may represent a composite biomarker of tubular reserve/endocrine response to the transition from adaptive to maladaptive equilibrium in CKD-MBD.
Circulating D-Dimers Increase the Risk of Mortality and Venous Thromboembolism in Patients With Lung Cancer: A Systematic Analysis Combined With External Validation
Authors: Li Jing , Yan Shanle , Zhang Xiaohui , Xiang Mengqi , Zhang Chuanhua , Gu Ling , Wei Xiaoying , You Chuanyun , Chen Shenhua , Zeng Daxiong , Jiang Junhong 
Published: March 2022

BackgroundD-dimer is a fibrin-degrading substance that is soluble and whose degradation is produced by plasma protein-mediated degradation of cross-linked fibrin. Previous investigations have shown a link between D-dimer and the mortality in lung cancer patients. However, different investigations varied whether D-dimer could predict prognosis in these patients.MethodsA meta-analysis and systematic review of all available cohort studies were performed on the link between circulating D-dimer levels and survival of lung cancer patients. Relevant studies were searched in Embase, Cochrane Library, and PubMed databases. Data from 540 lung cancer patients from the First Hospital of Soochow University and Sichuan Cancer Hospital were used for external validation.ResultsWe finally obtained 19 eligible cohort studies with pooled HR showing that high D-dimer levels contribute to death in tumor group (HR 1.62, 95% CI: 1.39–1.88, I2 = 75.0%). Further stratified analysis showed that higher circulating D-dimer in the advanced lung cancer group was linked to a 1.91-fold risk (HR = 2.91, 95% CI: 2.24–3.78, I2 = 6.0%). Incorporation of other variables, including days of follow-up, country, design, public year, population, disease status, and quality score, into the meta-regression model, indicated that disease status was an additional source of heterogeneity (p &lt; 0.001). External validation of 540 patients also showed that high levels of D-dimer showed a higher risk of overall mortality (HR 1.39, 95% CI: 1.13–1.72, p = 0.002) and VTE events (HR 3.98, 95% CI: 1.99–8.70, p = 0.002) in lung cancer patients.ConclusionsHigh circulating plasma D-dimer levels independently predict long-term prognosis and the risk of venous thromboembolism in lung cancer.
Urinary Angiotensinogen-Melatonin Ratio in Gestational Diabetes and Preeclampsia
Authors: Valias Gabriela Ribeiro , Gomes Patricia Rodrigues Lourenço , Amaral Fernanda G. , Alnuaimi Saif , Monteiro Daniela , O'Sullivan Siobhán , Zangaro Renato , Cipolla-Neto José , Acuna Juan , Baltatu Ovidiu Constantin , Campos Luciana Aparecida 
Published: March 2022

Background: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our study’s primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications.Methods: This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort.Results: Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups.Conclusion: These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.
Transcranial Direct-Current Stimulation as an Adjunct to Verb Network Strengthening Treatment in Post-stroke Chronic Aphasia: A Double-Blinded Randomized Feasibility Study
Authors: Matar Shereen J. , Newton Caroline , Sorinola Isaac O. , Pavlou Marousa 
Published: March 2022

BackgroundDifficulties in discourse production are common in post-stroke chronic aphasia. Previous studies have found that speech and language therapy combined with transcranial direct-current stimulation (tDCS) may improve language skills like naming and enhance aphasia treatment outcomes. However, very few studies have investigated the effect of tDCS when combined with interventions for improving higher level language skills such as the Verb Network Strengthening Treatment (VNeST).AimsThis study aimed to determine the feasibility of anodal tDCS as an adjunct to VNeST to improve discourse production in post-stroke chronic aphasia.MethodsSix people with post-stroke chronic aphasia took part in this double-blinded randomized feasibility study. Participants were randomly allocated to either the experimental group receiving a 6-week block of once weekly VNeST sessions combined with active tDCS over the left inferior frontal gyrus (LIFG) or a control group that received VNeST with sham stimulation. Feasibility outcomes included screening, eligibility, retention, and completion rates, and adverse events. Preliminary response to intervention was also examined using discourse production, functional communication, quality of life, psychological state, and cognition outcomes.ResultsOverall 19 individuals were screened and ten met the inclusion criteria. Six individuals provided consent and participated in the study giving a consent rate of 60%. Participant retention and completion rates were 100% and no adverse effects were reported. Exploratory analyses revealed promising changes (i.e., estimated large effect size) in discourse production measures across discourse language tasks and functional communication for the active tDCS group.ConclusionsOur results support the feasibility of tDCS as an adjunct to VNeST. Preliminary findings provide motivation for future large-scale studies to better understand the potential of tDCS as a safe and economical tool for enhancing rehabilitation in chronic aphasia.
Identification of Stroke and TIA in Patients With Acute Dizziness, Vertigo or Imbalance in Emergency Departments of Primary Care Hospitals: Early Experiences With a Network-Based Telemedical Approach
Authors: Müller-Barna Peter , Leinweber Christina , Pfaffenrath Julia , Schütt-Becker Nina , von Martial Rascha , Greck Susanne , Hubert Nikolai , Rambold Holger , Haberl Roman , Hubert Gordian Jan 
Published: March 2022

BackgroundAcute dizziness, vertigo, and imbalance are frequent and difficult to interpret symptoms in the emergency department (ED). Primary care hospitals often lack the expertise to identify stroke or TIA as underlying causes. A telemedical approach based on telestroke networks may offer adequate diagnostics and treatment.AimThe aim of this study is to evaluate the accuracy of a novel ED algorithm in differentiating between peripheral and central vestibular causes.MethodsWithin the Telemedical Project for Integrative Stroke Care (TEMPiS), a telemedical application including a videooculography (VOG) system was introduced in 2018 in 19 primary care spoke hospitals. An ED triage algorithm was established for all patients with acute dizziness, vertigo, or imbalance of unknown cause (ADVIUC) as a leading complaint. In three predefined months, all ADVIUC cases were prospectively registered and discharge letters analyzed. Accuracy of the ED triage algorithm in differentiation between central and peripheral vestibular cases was analyzed by comparison of ED diagnoses to final discharge diagnoses. The rate of missed strokes was calculated in relation to all cases with a suitable brain imaging. Acceptance of teleconsultants and physicians in spoke hospitals was assessed by surveys.ResultsA total number of 388 ADVIUC cases were collected, with a median of 12 cases per months and hospital (IQR 8–14.5). The most frequent hospital discharge diagnoses are vestibular neuritis (22%), stroke/TIA (18%), benign paroxysmal positioning vertigo (18%), and dizziness due to internal medicine causes (15%). Detection of a central vestibular cause by the ED triage algorithm has a high sensitivity (98.6%), albeit poor specificity (45.9%). One stroke out of 32 verified by brain scan was missed (3.1%). User satisfaction, helpfulness of the project, improvement of care, personal competence, and satisfaction about handling of the VOG systems were rated consistently positive.DiscussionThe concept shows good acceptance for a telemedical and network-based approach to manage ADVIUC cases in the ED of primary care hospitals. Identification of stroke cases is accurate, while specificity needs further improvement. The concept could be a major step toward a broadly available state of the art diagnostics and therapy for patients with ADVIUC in primary care hospitals.
Diffusion Tensor Imaging Revealed Microstructural Changes in Normal-Appearing White Matter Regions in Relapsing–Remitting Multiple Sclerosis
Authors: Bao Jianfeng , Tu Hui , Li Yijia , Sun Jubao , Hu Zhigang , Zhang Fengshou , Li Jinghua 
Published: March 2022

BackgroundAxons and myelin sheaths are the physical foundation for white matter (WM) to perform normal functions. Our previous study found the metabolite abnormalities in frontal, parietal, and occipital normal-appearing white matter (NAWM) regions in relapsing–remitting multiple sclerosis (RRMS) patients by applying a 2D 1H magnetic resonance spectroscopic imaging method. Since the metabolite changes may associate with the microstructure changes, we used the diffusion tensor imaging (DTI) method to assess the integrity of NAWM in this study.MethodDiffusion tensor imaging scan was performed on 17 clinically definite RRMS patients and 21 age-matched healthy controls on a 3.0-T scanner. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 19 predefined regions of interest (ROIs), which were generated by removing a mask of manually drawn probabilistic lesion map from the Johns Hopkins University white-matter atlas. The mean values of FA, MD, AD, and RD were compared between different groups in the same ROIs.ResultsA probabilistic lesion map was successfully generated, and the lesion regions were eliminated from the WM atlas. We found that the RRMS patients had significantly lower FA in the entire corpus callosum (CC), bilateral of anterior corona radiata, and right posterior thalamic radiation (PTR). At the same time, RRMS patients showed significantly higher MD in the bilateral anterior corona radiata and superior corona radiata. Moreover, all AD values increased, and the bilateral external capsule, PTR, and left tapetum NAWM show statistical significance. What is more, all NAWM tracts showed increasing RD values in RRMS patients, and the bilateral superior corona radiata, the anterior corona radiata, right PTR, and the genu CC reach statistical significance.ConclusionOur study revealed widespread microstructure changes in NAWM in RRMS patients through a ready-made WM atlas and probabilistic lesion map. These findings support the hypothesis of demyelination, accumulation of inflammatory cells, and axonal injury in NAWM for RRMS. The DTI-based metrics could be considered as potential non-invasive biomarkers of disease severity.
Altered Intra- and Inter-Network Functional Connectivity in Patients With Crohn’s Disease: An Independent Component Analysis-Based Resting-State Functional Magnetic Resonance Imaging Study
Authors: Li Lu , Ma Jie , Hua Xuyun , Zhou Yan , Qiu Yage , Zhu Zhen , Zheng Yanling , Xie Qian , Liang Zonghui , Xu Jianguang 
Published: March 2022

BackgroundMany studies have reported changes in the structure and function of several brain areas in patients with Crohn’s disease (CD). However, little is known about whether the possible functional connectivity of resting-state networks (RSNs) is altered in CD patients.PurposeAim to investigate the intra- and inter-network alterations between related RSNs in patients with CD and the potential relationships between altered neuroimaging and CD clinical indices.Materials and MethodsIn this study, 20 CD patients and 22 age- and sex-matched healthy controls were included. All participants underwent functional magnetic resonance imaging examination. We used independent component analysis (ICA) to explore the changes in RSNs and evaluated functional connectivity between different RSNs using functional network connectivity (FNC) analysis, and Pearson correlation analysis was performed between altered intra- and inter-network functional connectivity and CD clinical index.ResultsSix CD-related RSNs were identified via ICA, namely the high visual, prime visual, language, dorsal default mode, posterior insula, and precuneus networks. Compared to healthy controls, patients with CD showed significant changes in prime visual and language networks. Additionally, the functional connectivity (FC) values of the left calcarine within the prime visual network were negatively correlated with CD duration. The inter-alterations showed that a significantly increased FNC existed between the language and dorsal default mode networks.ConclusionThe results showed CD-related changes in brain functional networks. This evidence provides more insights into the pathophysiological mechanisms of brain plasticity in CD.
Identifying Changes of Brain Regional Homogeneity and Cingulo-Opercular Network Connectivity in First-Episode, Drug-Naïve Depressive Patients With Suicidal Ideation
Authors: He Mengxin , Ping Liangliang , Chu Zhaosong , Zeng Chunqiang , Shen Zonglin , Xu Xiufeng 
Published: March 2022

ObjectiveAdult patients with major depressive disorder (MDD) may not actively reveal their suicidal ideation (SI). Therefore, this study is committed to finding the alterations in the cingulo-opercular network (CON) that are closely related to SI with multi-imaging methods, thus providing neuroimaging basis for SI.MethodA total of 198 participants (129 MDD patients and 69 healthy controls) were recruited and evaluated with the Montgomery–Asberg Depression Rating Scale (MADRS). The healthy individuals formed the HC group, while the MDD patients were subdivided into no SI MDD (NSI, n = 32), mild SI MDD (MSI, n = 64), and severe SI MDD (SSI, n = 33) according to their MADRS item 10. We obtained MRI data of all participants and applied regional homogeneity (ReHo) analysis to verify a previous finding that links CON abnormality to SI. In addition, we employed the structural covariance network (SCN) analysis to investigate the correlation between abnormal structural connectivity of CON and SI severity.ResultsCompared to those of the HC group, MDD ReHo values and gray matter volume (GMV) were consistently found abnormal in CON. ReHo values and GMV of the right orbital inferior frontal gyrus (ORBinf.R) in the MDD group decreased with the increase of SI. Compared to the HC group, the MDD patients showed enhanced structural connectivity of three pairs of brain regions in CON [ACC.L–left superior frontal gyrus (SFG.L), SFG.L–left middle temporal gyrus (MTG.L), and the SFG.L–left post-central gyrus (PoCG.L)]. Compared with that of the NSI and MSI groups, the structural connectivity of three pairs of brain regions in CON is enhanced in the SSI groups [ORBinf.L–right ventral posterior cingulate gyrus (VPCC.R), VPCC.R–SFG.R, and SFG.R–PoCG.R].ConclusionOur findings showed the distinctive ReHo, GMV, and SCN pattern of CON in MDD patients with SI; and with the severity of suicide, abnormal brain regions increased. Our finding suggested that MDD patients with different severity of SI have different neuroimaging changes.
Significance of Postprandial Insulin and Triglycerides to Evaluate the Metabolic Response of Composite Meals Differing in Nutrient Composition – A Randomized Cross-Over Trial
Authors: Thota Rohith N. , Moughan Paul J. , Singh Harjinder , Garg Manohar L. 
Published: March 2022

Background and aimsGlucoTRIG, based on postprandial plasma insulin and triglyceride concentrations, has been recently developed as a novel index to determine the postprandial metabolic response to the meals. This study aimed to test GlucoTRIG as a measure for ranking composite meals for their metabolic effects.MethodsIn a randomized cross-over trial, healthy adult volunteers (both males and females; n = 10 for each meal) consumed three is caloric (2000 kj) test meals (meal 1, meal 2, meal 3) of varying macronutrient composition. Postmeal consumption, venous blood samples were collected to determine plasma insulin and plasma triglycerides for estimating the GlucoTRIG value using (Triglycerides180min × Insulin180min) - (Triglycerides0min × Insulin0min).ResultsThe GlucoTRIG values differed significantly (p = 0.0085) across meals. The statistical significance remains even after adjusting for confounding variables such as baseline diet, insulin, and triglycerides. The meal (M3) with a high fiber, low total fat content and containing less refined foods (fruits, beans, vegetables, plain yogurt) exhibited a significantly (p = 0.007) lower GlucoTRIG value (10 ± 7.7) compared to the other two meals, M1 (77 ± 19.8) and M2 (38 ± 12.1) which contained low processed foods, and were relatively high in fat and low in fiber meals. No statistically significant differences were observed between M1 and M2 meal.ConclusionsGlucoTRIG is a physiologically based index that may be useful to rank composite meals for reducing the risk of metabolic diseases. Further research focusing on the application of GlucoTRIG to foods, meals, and diets is warranted.ACTRN12619000973112 (Australian New Zealand Clinical Trials Registry, ANZCTR).
A Classifier for Improving Early Lung Cancer Diagnosis Incorporating Artificial Intelligence and Liquid Biopsy
Authors: Ye Maosong , Tong Lin , Zheng Xiaoxuan , Wang Hui , Zhou Haining , Zhu Xiaoli , Zhou Chengzhi , Zhao Peige , Wang Yan , Wang Qi , Bai Li , Cai Zhigang , Kong Feng-Ming (Spring) , Wang Yuehong , Li Yafei , Feng Mingxiang , Ye Xin , Yang Dawei , Liu Zilong , Zhang Quncheng , Wang Ziqi , Han Shuhua , Sun Lihong , Zhao Ningning , Yu Zubin , Zhang Juncheng , Zhang Xiaoju , Katz Ruth L. , Sun Jiayuan , Bai Chunxue 
Published: March 2022

Lung cancer is the leading cause of cancer-related deaths worldwide and in China. Screening for lung cancer by low dose computed tomography (LDCT) can reduce mortality but has resulted in a dramatic rise in the incidence of indeterminate pulmonary nodules, which presents a major diagnostic challenge for clinicians regarding their underlying pathology and can lead to overdiagnosis. To address the significant gap in evaluating pulmonary nodules, we conducted a prospective study to develop a prediction model for individuals at intermediate to high risk of developing lung cancer. Univariate and multivariate logistic analyses were applied to the training cohort (n = 560) to develop an early lung cancer prediction model. The results indicated that a model integrating clinical characteristics (age and smoking history), radiological characteristics of pulmonary nodules (nodule diameter, nodule count, upper lobe location, malignant sign at the nodule edge, subsolid status), artificial intelligence analysis of LDCT data, and liquid biopsy achieved the best diagnostic performance in the training cohort (sensitivity 89.53%, specificity 81.31%, area under the curve [AUC] = 0.880). In the independent validation cohort (n = 168), this model had an AUC of 0.895, which was greater than that of the Mayo Clinic Model (AUC = 0.772) and Veterans’ Affairs Model (AUC = 0.740). These results were significantly better for predicting the presence of cancer than radiological features and artificial intelligence risk scores alone. Applying this classifier prospectively may lead to improved early lung cancer diagnosis and early treatment for patients with malignant nodules while sparing patients with benign entities from unnecessary and potentially harmful surgery.Clinical Trial Registration NumberChiCTR1900026233, URL: http://www.chictr.org.cn/showproj.aspx?proj=43370.