bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between serologic parameters and disease activity of IgG4-related disease: Differences between patients with normal and elevated serum IgG4 concentrations
Authors: Kwon Oh Chan , Park Min-Chan , Kim Yong-Gil 
Published: October 2022

ObjectiveWe aimed to identify serologic parameters that correlate with the disease activity of IgG4-related disease (IgG4-RD) in patients with normal and elevated serum IgG4 concentrations, respectively.MethodsThis retrospective cohort study included 148 patients with IgG4-RD. Patients were categorized into normal (≤201 mg/dL) and elevated (&gt;201 mg/dL) serum IgG4 concentration groups. Disease activity was assessed using the IgG4-RD responder index (RI). The correlations between IgG4-RD RI and serologic parameters (erythrocyte sedimentation rate [ESR], C-reactive protein, C3, C4, IgG4 concentration, IgG concentration, and IgG4/IgG ratio) were evaluated in each group, using Spearman’s correlation coefficient.ResultsOf the 148 patients with IgG4-RD, 38 (25.7%) and 110 (74.3%) patients were categorized into the normal and elevated serum IgG4 concentration groups, respectively. In the normal serum IgG4 concentration group, IgG concentration was the only serologic parameter that showed a significant correlation with IgG4-RD RI (rho=0.411, p=0.013). However, in the elevated serum IgG4 concentration group, ESR (rho=0.196, p=0.041), C3 (rho=-0.432, p&lt;0.001), C4 (rho=-0.363, p=0.001), IgG4 concentration (rho=0.423, p&lt;0.001), IgG concentration (rho=0.224, p=0.020), and IgG4/IgG ratio (rho=0.328, p=0.001) correlated with IgG4-RD RI. The combination of C3 and IgG4 concentration (rho=0.509, p&lt;0.001) had the strongest correlation with IgG4-RD RI in this group.ConclusionAmong the serologic parameters tested, IgG concentration was the only parameter that correlated with IgG4-RD RI in patients with normal serum IgG4 concentrations, whereas multiple parameters correlated with IgG4-RD RI in those with elevated serum IgG4 concentrations. The combination of C3 and IgG4 concentration had the strongest correlation coefficient in the latter group.
Altered transcription factor targeting is associated with differential peripheral blood mononuclear cell proportions in sarcoidosis
Authors: Ascoli Christian , Schott Cody A. , Huang Yue , Turturice Benjamin A. , Wang Wangfei , Ecanow Naomi , Sweiss Nadera J. , Perkins David L. , Finn Patricia W. 
Published: October 2022

IntroductionIn sarcoidosis, peripheral lymphopenia and anergy have been associated with increased inflammation and maladaptive immune activity, likely promoting development of chronic and progressive disease. However, the molecular mechanisms that lead to reduced lymphocyte proportions, particularly CD4+ T-cells, have not been fully elucidated. We posit that paradoxical peripheral lymphopenia is characterized by a dysregulated transcriptomic network associated with cell function and fate that results from altered transcription factor targeting activity.MethodsMessenger RNA-sequencing (mRNA-seq) was performed on peripheral blood mononuclear cells (PBMCs) from ACCESS study subjects with sarcoidosis and matched controls and findings validated on a sarcoidosis case-control cohort and a sarcoidosis case series. Preserved PBMC transcriptomic networks between case-control cohorts were assessed to establish cellular associations with gene modules and define regulatory targeting involved in sarcoidosis immune dysregulation utilizing weighted gene co-expression network analysis and differential transcription factor involvement analysis. Network centrality measures identified master transcriptional regulators of subnetworks related to cell proliferation and death. Predictive models of differential PBMC proportions constructed from ACCESS target gene expression corroborated the relationship between aberrant transcription factor regulatory activity and imputed and clinical PBMC populations in the validation cohorts.ResultsWe identified two unique and preserved gene modules significantly associated with sarcoidosis immune dysregulation. Strikingly, increased expression of a monocyte-driven, and not a lymphocyte-driven, gene module related to innate immunity and cell death was the best predictor of peripheral CD4+ T-cell proportions. Within the gene network of this monocyte-driven module, TLE3 and CBX8 were determined to be master regulators of the cell death subnetwork. A core gene signature of differentially over-expressed target genes of TLE3 and CBX8 involved in cellular communication and immune response regulation accurately predicted imputed and clinical monocyte expansion and CD4+ T-cell depletion.ConclusionsAltered transcriptional regulation associated with aberrant gene expression of a monocyte-driven transcriptional network likely influences lymphocyte function and survival. Although further investigation is warranted, this indicates that crosstalk between hyperactive monocytes and lymphocytes may instigate peripheral lymphopenia and underlie sarcoidosis immune dysregulation and pathogenesis. Future therapies selectively targeting master regulators, or their targets, may mitigate dysregulated immune processes in sarcoidosis and disease progression.
Circular RNA hsa-circ-0005238 enhances trophoblast migration, invasion and suppresses apoptosis via the miR-370-3p/CDC25B axis
Authors: Huang Zhuomin , Zhu Litong , Zhang Quanfu , Zhao Depeng , Yao Jilong 
Published: October 2022

BackgroundFetal growth restriction (FGR) is attributed to various maternal, fetal, and placental factors. Trophoblasts participate in the establishment and maintenance of pregnancy from implantation and placentation to providing nutrition to fetus. Studies have reported that impaired trophoblast invasion and proliferation are among factors driving development of FGR. Circular RNAs (circRNAs) can regulate trophoblast function. We assessed the significance of circRNAs underlying FGR development.Materials and methodsNext generation sequencing (NGS) was carried out to quantify levels of circRNAs in placenta tissues with and without FGR. In vitro experiments including transfection, (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium) (MTS) assays, flow cytometry analyses, Transwell assays, wound healing assays, western blotting, qRT-PCR, dual-luciferase assays, immunofluorescence staining, and RIP assay were performed.ResultsThere were 18 differentially expressed circRNAs between FGR placentas and uncomplicated pregnancies, while levels of hsa-circ-0005238 were markedly low in FGR placentas. Our in vitro experiments further revealed that hsa-circ-0005238 suppressed apoptosis and enhanced proliferation, migration, invasion of trophoblast cell lines. The hsa-miR-370-3p was identified as a direct target of hsa-circ-0005238. Mechanistically, hsa-miR-370-3p prevents invasion as well as migration of trophoblast cells by downregulating CDC25B.ConclusionThe hsa-circ-0005238 modulates FGR pathogenesis by inhibiting trophoblast cell invasion and migration through sponging hsa-miR-370-3p. Hence, targeting this circRNA may be an attractive strategy for FGR treatment.
Radiomics analysis of contrast-enhanced CT scans can distinguish between clear cell and non-clear cell renal cell carcinoma in different imaging protocols
Authors: Budai Bettina Katalin , Stollmayer Róbert , Rónaszéki Aladár Dávid , Körmendy Borbála , Zsombor Zita , Palotás Lõrinc , Fejér Bence , Szendrõi Attila , Székely Eszter , Maurovich-Horvat Pál , Kaposi Pál Novák 
Published: October 2022

IntroductionThis study aimed to construct a radiomics-based machine learning (ML) model for differentiation between non-clear cell and clear cell renal cell carcinomas (ccRCC) that is robust against institutional imaging protocols and scanners.Materials and methodsPreoperative unenhanced (UN), corticomedullary (CM), and excretory (EX) phase CT scans from 209 patients diagnosed with RCCs were retrospectively collected. After the three-dimensional segmentation, 107 radiomics features (RFs) were extracted from the tumor volumes in each contrast phase. For the ML analysis, the cases were randomly split into training and test sets with a 3:1 ratio. Highly correlated RFs were filtered out based on Pearson’s correlation coefficient (r &gt; 0.95). Intraclass correlation coefficient analysis was used to select RFs with excellent reproducibility (ICC ≥ 0.90). The most predictive RFs were selected by the least absolute shrinkage and selection operator (LASSO). A support vector machine algorithm-based binary classifier (SVC) was constructed to predict tumor types and its performance was evaluated based-on receiver operating characteristic curve (ROC) analysis. The “Kidney Tumor Segmentation 2019” (KiTS19) publicly available dataset was used during external validation of the model. The performance of the SVC was also compared with an expert radiologist’s.ResultsThe training set consisted of 121 ccRCCs and 38 non-ccRCCs, while the independent internal test set contained 40 ccRCCs and 13 non-ccRCCs. For external validation, 50 ccRCCs and 23 non-ccRCCs were identified from the KiTS19 dataset with the available UN, CM, and EX phase CTs. After filtering out the highly correlated and poorly reproducible features, the LASSO algorithm selected 10 CM phase RFs that were then used for model construction. During external validation, the SVC achieved an area under the ROC curve (AUC) value, accuracy, sensitivity, and specificity of 0.83, 0.78, 0.80, and 0.74, respectively. UN and/or EX phase RFs did not further increase the model’s performance. Meanwhile, in the same comparison, the expert radiologist achieved similar performance with an AUC of 0.77, an accuracy of 0.79, a sensitivity of 0.84, and a specificity of 0.69.ConclusionRadiomics analysis of CM phase CT scans combined with ML can achieve comparable performance with an expert radiologist in differentiating ccRCCs from non-ccRCCs.
Manual acupuncture benignly regulates blood-brain barrier disruption and reduces lipopolysaccharide loading and systemic inflammation, possibly by adjusting the gut microbiota
Authors: Zhang Yue , Ding Ning , Hao Xin , Zhao Jun , Zhao Yali , Li Yiran , Li Zhigang 
Published: October 2022

BackgroundBlood-brain barrier (BBB) disruption and gut microbiota dysbiosis play crucial roles in Alzheimer’s disease (AD). Lipopolysaccharide (LPS) stimulation triggered by gut microbial dysbiosis is an important factor in BBB disruption and systemic inflammation, but the mechanism of acupuncture regulation of BBB disruption via the gut microbiota in AD is not clear.ObjectiveThe current study evaluated the effect of manual acupuncture (MA) on BBB dysfunction in APP/PS1 mice and examined the mechanism of gut microbiota by acupuncture in AD.MethodsAcupoints were applied to Baihui (GV20), Yintang (GV29), and Zusanli (ST36) in the MA group. Mice in the manual acupuncture plus antibiotics (MAa) group received antibiotics and acupuncture, while mice in the probiotics (P) group received probiotics. Alterations in spatial learning and memory, the gut microbiota, tightly connected structure and permeability of BBB, and the expression of LPS and inflammatory factors in each group were assessed.ResultsCompared to the normal (N) group, cognitive ability was significantly impaired, the gut microbiota composition was markedly altered, the BBB was significantly disrupted, and the expression of LPS in serum and brain, serum TNF-α, and IL-1β were significantly increased in the AD group (p &lt; 0.01). These changes were inhibited in the MA and P groups (p &lt; 0.01 or p &lt; 0.05), and antibiotics reversed the benign regulatory effects of MA (p &lt; 0.01 or p &lt; 0.05).ConclusionManual acupuncture benignly modulated the gut microbiota and BBB dysfunction, reduced LPS, TNF-α, and IL-1β. These effects were comparable to probiotics. The decrease in LPS load and systemic inflammation may play important roles in the regulation of BBB dysfunction by acupuncture, and the gut microbiota may be a potential target for the benign regulation of BBB disruption by acupuncture.
Analysis of macular microvasculature with optical coherence tomography angiography for migraine: A systematic review and meta-analysis
Authors: Ke Weishaer , Yu Naiji , Liu Xin , Gu Yuxiang , Qin Qiyu , Ye Zifan , Li Yuhang , Wang Kaijun , Chen Min 
Published: October 2022

ObjectiveThis study aimed to evaluate the features of macular microvasculature with optical coherence tomography angiography (OCTA) among migraine patients.MethodsWe systematically searched PubMed, Web of Science, Embase, and Cochrane Library for studies that evaluated the macular microvasculature of migraine patients. The weighted mean differences (WMDs) of the foveal avascular zone (FAZ), foveal superficial capillary plexus (SCP) vessel density (VD), parafoveal SCP VD, foveal deep capillary plexus (DCP) VD, and parafoveal DCP VD with 95% confidence intervals (CIs) among migraine with aura (MA) group, migraine without aura (MO) group, and healthy controls (HC) group were analyzed using a random-effect model. P &lt; 0.05 was considered significant in statistical analyses. Publication bias was assessed using funnel plots and statistical tests (Egger's test and Begg's test).ResultsNine studies covering 675 individuals were enrolled in this meta-analysis ultimately. The FAZ of MA patients was not significantly different from HC (WMD = 0.04, 95% CI −0.00 to 0.09). However, the FAZ of MA was significantly larger than that of HC after correction of publication bias by trim and fill method (WMD = 1.03, 95% CI 0.99 to 1.08). The FAZ of MO patients was similar to that of HC (WMD = 0.03, 95% CI −0.00 to 0.07), while smaller than that of MA patients (WMD = 0.05, 95% CI 0.01 to 0.09). VD of the SCP, either in the foveal or parafoveal area, was not significantly different among the three groups. As for DCP, VD in MA patients was lower when compared with HC in the parafovea (WMD = −1.20, 95% CI −1.88 to −0.51).ConclusionsWe found that there was a larger FAZ in MA compared with HC after adjusting for publication bias. The FAZ in MO was not significantly different from that in HC, but significantly lower than that in MA. There was no significant difference in either foveal or parafoveal VD of SCP among MA, MO, and HC participants, while the parafoveal VD of the DCP in MA was lower than that of the HC.
A multicenter retrospective controlled study of the Pipeline™ and Tubridge™ Flow Diverter devices for intracranial wide-necked aneurysms
Authors: Cai Heng , Yang Fangyu , Xu Yousong , Geng Yu , Li Jinwei , Li Yugang , Fu Kailei , Liu Chang , Wang Meiyan , Li Zhiqing 
Published: October 2022

PurposeTo compare the safety and efficacy of PipelineTM and TubridgeTM Flow Diverter devices (FDs) in the treatment of intracranial wide-necked aneurysms.MethodsWe retrospectively analyzed the clinical data of 92 patients with intracranial wide-necked aneurysms who were treated with those two flow-diverter devices (FDs) at four participating centers between July 2012 and December 2020.ResultsThis study included 92 patients who underwent endovascular therapy using either Pipeline™ (n = 39) or TubridgeTM (n = 53) for treating intracranial wide-necked aneurysms. The periprocedural complication developed in 2.56% (1/39) patients of Pipeline group and 3.77% (2/53) patients of the TubridgeTM group. During perioperative period, one patient in Pipeline™ group showed subarachnoid hemorrhage (2.56%, 1/39) and two ischemic complications in the Tubridge™ group (3.77%, 2/53). Follow-up assessments were conducted on 31 patients (79.49%) in the Pipeline™ group (the mean follow-up period was 9.7 ± 3.3 months). The rate of complete aneurysm occlusion at the final angiographic follow-up was 77.42%. Patients with a modified Rankin scale (mRS) score of 0.44 ± 0.31. Follow-up assessments were conducted on 42 patients (79.25%) in the TubridgeTM group (the mean follow-up period was 9.1 ± 4.4 months). The rate of complete aneurysm occlusion at the final angiographic follow-up was 85.71%. Patients with mRS score of 0.52 ± 0.28. Three patients showed parent artery stenosis, and one showed parent artery occlusion.ConclusionBoth the PipelineTM and TubridgeTM are safe and effective for the treatment of intracranial wide-necked aneurysms, with no significant difference in the rate of complete aneurysm occlusion and perioperative complications between the two FDs.
Devastating delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
Authors: Koopman Inez , van Wijngaarden Philippine B. , Rinkel Gabriel J. E. , Vergouwen Mervyn D. I. 
Published: October 2022

BackgroundWe investigated the proportion of patients in an initial good clinical condition who developed devastating DCI, and aimed to characterize these patients by aneurysm location, blood pressure instability prior to DCI, and the extent of cerebral ischemia.MethodsWe included aSAH patients admitted between 2010 and 2021 with a Glasgow Coma Scale of 11 or higher 24 h after aneurysm treatment, who developed devastating DCI, defined as DCI leading to coma for at least 48 h with cerebral infarction on the subsequent scan. Blood pressure instability was defined as nimodipine-induced blood pressure drops, dosage adjustments, or the use of blood pressure drugs before onset of DCI. Descriptive statistics were used to summarize the data.ResultsOut of 1,211 consecutive aSAH patients, 617 patients had a good clinical condition after aneurysm treatment of whom 16 (3%) patients [14 (88%) women] were included in this study. Thirteen (81%) patients had an aneurysm in the anterior circulation. Thirteen patients (81%) had blood pressure instability: twelve (75%) had nimodipine-induced blood pressure drops, eleven (69%) received antihypertensive drugs, and 7 (44%) received hypertension induction before onset of DCI. Thirteen (81%) patients had bilateral ischemia, mainly in the anterior circulation (56%).ConclusionsThe proportion of aSAH patients with a good clinical condition after aneurysm treatment who develop devastating DCI is small. The vast majority of these patients had blood pressure instability. Future studies are needed to investigate if a reduction in the number and extent of blood pressure fluctuations decreases the incidence of devastating DCI.
Radiomic features of amygdala nuclei and hippocampus subfields help to predict subthalamic deep brain stimulation motor outcomes for Parkinson‘s disease patients
Authors: Saudargiene Ausra , Radziunas Andrius , Dainauskas Justinas J. , Kucinskas Vytautas , Vaitkiene Paulina , Pranckeviciene Aiste , Laucius Ovidijus , Tamasauskas Arimantas , Deltuva Vytenis 
Published: October 2022

Background and purposeThe aim of the study is to predict the subthalamic nucleus (STN) deep brain stimulation (DBS) outcomes for Parkinson’s disease (PD) patients using the radiomic features extracted from pre-operative magnetic resonance images (MRI).MethodsThe study included 34 PD patients who underwent DBS implantation in the STN. Five patients (15%) showed poor DBS motor outcome. All together 9 amygdalar nuclei and 12 hippocampus subfields were segmented using Freesurfer 7.0 pipeline from pre-operative MRI images. Furthermore, PyRadiomics platform was used to extract 120 radiomic features for each nuclei and subfield resulting in 5,040 features. Minimum Redundancy Maximum Relevance (mRMR) feature selection method was employed to reduce the number of features to 20, and 8 machine learning methods (regularized binary logistic regression (LR), decision tree classifier (DT), linear discriminant analysis (LDA), naive Bayes classifier (NB), kernel support vector machine (SVM), deep feed-forward neural network (DNN), one-class support vector machine (OC-SVM), feed-forward neural network-based autoencoder for anomaly detection (DNN-A)) were applied to build the models for poor vs. good and very good STN-DBS motor outcome prediction.ResultsThe highest mean prediction accuracy was obtained using regularized LR (96.65 ± 7.24%, AUC 0.98 ± 0.06) and DNN (87.25 ± 14.80%, AUC 0.87 ± 0.18).ConclusionThe results show the potential power of the radiomic features extracted from hippocampus and amygdala MRI in the prediction of STN-DBS motor outcomes for PD patients.
Effects of the Mediterranean Diet during pregnancy on the onset of allergy in at risk children: A study protocol of a multi-center, randomized- controlled, parallel groups, prospective trial (the PREMEDI study)
Authors: Coppola Serena , Paparo Lorella , Chiariotti Lorenzo , Ercolini Danilo , Nocerino Rita , de Giovanni di Santa Severina Anna Fiorenza , Carucci Laura , De Filippis Francesca , Agangi Annalisa , Napolitano Marcello , Passariello Annalisa , Messina Francesco , Berni Canani Roberto 
Published: October 2022

IntroductionMaternal diet during pregnancy has been linked to offspring allergy risk and it could represent a potential target for allergy prevention. The Mediterranean Diet (MD) is considered one of the healthiest dietary models. Randomized-controlled trials on the effect of MD in preventing pediatric allergic diseases are still needed.Methods and analysisThe Mediterranean Diet during Pregnancy study (PREMEDI) will be a 9-month multi-center, randomized-controlled, parallel groups, prospective trial. Healthy women (20–35 years) at their first trimester of pregnancy at risk for atopy baby, will be randomly allocated to Group 1 (standard obstetrical and gynecological follow-up and nutritional counseling to promote MD) or Group 2 (standard obstetrical and gynecological follow-up alone). 138 mother-child pair per group will be needed to detect a reduction in cumulative incidence of ≥1 allergic disease at 24 months of age. The primary study aim will be the evaluation of the occurrence of allergic disorders in the first 24 months of life. The secondary aims will be the evaluation of maternal weight gain, pregnancy/perinatal complications, growth indices and occurrence of other chronic disorders, mother-child pair adherence to MD and gut microbiome features, breastfeeding duration and breast milk composition, epigenetic modulation of genes involved in immune system, and metabolic pathways in the offspring.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the University of Naples Federico II (number 283/21) and it will be conducted in accordance with the Helsinki Declaration (Fortaleza revision, 2013), the Good Clinical Practice Standards (CPMP/ICH/135/95), the Italian Decree-Law 196/2003 regarding personal data and the European regulations on this subject. The study has been registered in the Clinical Trials Protocol Registration System.Clinical trial registration[http://clinicaltrials.gov], identifier [NCT05119868].