bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and genetic analysis of benign familial infantile epilepsy caused by PRRT2 gene variant
Authors: Gu Yu , Mei Daoqi , Wang Xiaona , Ma Ang , Kong Jinghui , Zhang Yaodong 
Published: May 2023

ObjectiveThis study presents the clinical phenotypes and genetic analysis of seven patients with benign familial infantile epilepsy (BFIE) diagnosed by whole-exome sequencing.MethodsThe clinical data of seven children with BFIE diagnosed at the Department of Neurology, Children’s Hospital Affiliated to Zhengzhou University between December 2017 and April 2022 were retrospectively analyzed. Whole-exome sequencing was used to identify the genetic causes, and the variants were verified by Sanger sequencing in other family members.ResultsThe seven patients with BFIE included two males and five females ranging in age between 3 and 7 months old. The main clinical phenotype of the seven affected children was the presence of focal or generalized tonic–clonic seizures, which was well controlled by anti-seizure medication. Cases 1 and 5 exhibited predominantly generalized tonic–clonic seizures accompanied by focal seizures while cases 2, 3, and 7 displayed generalized tonic–clonic seizures, and cases 4 and 6 had focal seizures. The grandmother and father of cases 2, 6, and 7 had histories of seizures. However, there was no family history of seizures in the remaining cases. Case 1 carried a de novo frameshift variant c.397delG (p.E133Nfs*43) in the proline-rich transmembrane protein 2 (PRRT2) gene while case 2 had a nonsense variant c.46G &gt; T (p.Glu16*) inherited from the father, and cases 3–7 carried a heterozygous frameshift variant c.649dup (p.R217Pfs*8) in the same gene. In cases 3 and 4, the frameshift variant was de novo, while in cases 5–7, the variant was paternally inherited. The c.397delG (p.E133Nfs*43) variant is previously unreported.ConclusionThis study demonstrated the effectiveness of whole-exome sequencing in the diagnosis of BFIE. Moreover, our findings revealed a novel pathogenic variant c.397delG (p.E133Nfs*43) in the PRRT2 gene that causes BFIE, expanding the mutation spectrum of PRRT2.
Deep-learning segmentation of fascicles from microCT of the human vagus nerve
Authors: Buyukcelik Ozge N. , Lapierre-Landry Maryse , Kolluru Chaitanya , Upadhye Aniruddha R. , Marshall Daniel P. , Pelot Nicole A. , Ludwig Kip A. , Gustafson Kenneth J. , Wilson David L. , Jenkins Michael W. , Shoffstall Andrew J. 
Published: May 2023

IntroductionMicroCT of the three-dimensional fascicular organization of the human vagus nerve provides essential data to inform basic anatomy as well as the development and optimization of neuromodulation therapies. To process the images into usable formats for subsequent analysis and computational modeling, the fascicles must be segmented. Prior segmentations were completed manually due to the complex nature of the images, including variable contrast between tissue types and staining artifacts.MethodsHere, we developed a U-Net convolutional neural network (CNN) to automate segmentation of fascicles in microCT of human vagus nerve.ResultsThe U-Net segmentation of ~500 images spanning one cervical vagus nerve was completed in 24 s, versus ~40 h for manual segmentation, i.e., nearly four orders of magnitude faster. The automated segmentations had a Dice coefficient of 0.87, a measure of pixel-wise accuracy, thus suggesting a rapid and accurate segmentation. While Dice coefficients are a commonly used metric to assess segmentation performance, we also adapted a metric to assess fascicle-wise detection accuracy, which showed that our network accurately detects the majority of fascicles, but may under-detect smaller fascicles.DiscussionThis network and the associated performance metrics set a benchmark, using a standard U-Net CNN, for the application of deep-learning algorithms to segment fascicles from microCT images. The process may be further optimized by refining tissue staining methods, modifying network architecture, and expanding the ground-truth training data. The resulting three-dimensional segmentations of the human vagus nerve will provide unprecedented accuracy to define nerve morphology in computational models for the analysis and design of neuromodulation therapies.
Inflammatory biomarkers as predictors of immune activation to different irradiated sites and short-term efficacy in advanced squamous cell esophageal carcinoma received radioimmunotherapy
Authors: Li Mengying , Cai Guoxin , Gao Zhenhua , Meng Xue , Han Xiao 
Published: May 2023

PurposeThe present study aimed to compare immune activation among different irradiated sites and identify potential short-term efficacy prognostic factors in patients with advanced squamous cell esophageal carcinoma (ESCC) who received radiotherapy (RT) and immunotherapy.Patients and methodsWe recorded the clinical characteristics, blood cell counts, and derived blood index ratios, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), at three time points (before, during, and after RT) in 121 patients with advanced ESCC who had received RT and immunotherapy. Chi-square test and univariate and multivariate logistic regression analyses were used to calculate the relationships among inflammatory biomarkers (IBs), irradiated sites, and short-term efficacy.ResultsDelta-IBs were calculated as (medio-IBs - pre-IBs) ÷ pre-IBs. The medians of delta-LMR, and delta-ALC were the highest, whereas the median of delta-SII was the lowest in patients with brain radiation. Treatment responses were observed within 3 months after RT or until the beginning of the next line therapy, and the disease control rate (DCR) was 75.2%. The areas under the receiver operating characteristic curve (AUCs) for delta-NLR and delta-SII were 0.723 (p = 0.001) and 0.725 (p &lt; 0.001), respectively. Multivariate logistic regression analysis showed that the treatment lines of immunotherapy (odds ratio [OR], 4.852; 95% confidence interval [CI], 1.595-14.759; p = 0.005) and delta-SII (OR, 5.252; 95% CI, 1.048-26.320; p = 0.044) were independent indicators of short-term efficacy.ConclusionIn this study, we found that RT to the brain had a stronger immune activation effect than RT to extracranial organs. We also found that earlier-line immunotherapy plus RT and a decrease in SII during RT may generate better short-term efficacy in advanced ESCC.
Ondansetron: recommended antiemetics for patients with acute pancreatitis? a population-based study
Authors: Wu Ge , Ma Yifei , Wei Wanzhen , Zeng Jiahui , Han Yimin , Song Yiqun , Wang Zheng , Qian Weikun 
Published: May 2023

Objective: Ondansetron administration is a common antemetic of acute pancreatitis therapy in the intensive care unit (ICU), but its actual association with patients’ outcomes has not been confirmed. The study is aimed to determine whether the multiple outcomes of ICU patients with acute pancreatitis could benefit from ondansetron.Methods: 1,030 acute pancreatitis patients diagnosed in 2008–2019 were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database as our study cohort. The primary outcome we considered is the 90-day prognosis, and secondary outcomes included in-hospital survival and overall prognosis.Results: In MIMIC-IV, 663 acute pancreatitis patients received ondansetron administration (OND group) during their hospitalization, while 367 patients did not (non-OND group). Patients in the OND group presented better in-hospital, 90-day, and overall survival curves than the non-OND group (log-rank test: in-hospital: p &lt; 0.001, 90-day: p = 0.002, overall: p = 0.009). After including covariates, ondansetron was associated with better survival in patients with multiple outcomes (in-hospital: HR = 0.50, 90-day: HR = 0.63, overall: HR = 0.66), and the optimal dose inflection points were 7.8 mg, 4.9 mg, and 4.6 mg, respectively. The survival benefit of ondansetron was unique and stable in the multivariate analyses after consideration of metoclopramide, diphenhydramine, and prochlorperazine, which may also be used as antiemetics.Conclusion: In ICU acute pancreatitis patients, ondansetron administration was associated with better 90-day outcomes, while results were similar in terms of in-hospital and overall outcomes, and the recommended minimum total dose might be suggested to be 4–8 mg.
Nanosecond pulse effectively ablated hepatocellular carcinoma with alterations in the gut microbiome and serum metabolites
Authors: Zou Yawen , Sun Ying , Chen Xinhua , Hong Liangjie , Dong Gang , Bai Xiwen , Wang Haiyu , Rao Benchen , Ren Zhigang , Yu Zujiang 
Published: May 2023

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world. Nanosecond pulsed electric fields (nsPEFs) have emerged as a new treatment for cancer. This study aims to identify the effectiveness of nsPEFs in the treatment of HCC and analyze the alterations in the gut microbiome and serum metabonomics after ablation.Methods: C57BL/6 mice were randomly divided into three groups: healthy control mice (n = 10), HCC mice (n = 10), and nsPEF-treated HCC mice (n = 23). Hep1-6 cell lines were used to establish the HCC model in situ. Histopathological staining was performed on tumor tissues. The gut microbiome was analyzed by 16S rRNA sequencing. Serum metabolites were analyzed by liquid chromatography–mass spectrometry (LC-MS) metabolomic analysis. Spearman’s correlation analysis was carried out to analyze the correlation between the gut microbiome and serum metabonomics.Results: The fluorescence image showed that nsPEFs were significantly effective. Histopathological staining identified nuclear pyknosis and cell necrosis in the nsPEF group. The expression of CD34, PCNA, and VEGF decreased significantly in the nsPEF group. Compared with normal mice, the gut microbiome diversity of HCC mice was increased. Eight genera including Alistipes and Muribaculaceae were enriched in the HCC group. Inversely, these genera decreased in the nsPEF group. LC-MS analysis confirmed that there were significant differences in serum metabolism among the three groups. Correlation analysis showed crucial relationships between the gut microbiome and serum metabolites that are involved in nsPEF ablation of HCC.Conclusion: As a new minimally invasive treatment for tumor ablation, nsPEFs have an excellent ablation effect. The alterations in the gut microbiome and serum metabolites may participate in the prognosis of HCC ablation.
Characterization of pharmacogenomic variants in a Brazilian admixed cohort of elderly individuals based on whole-genome sequencing data
Authors: Bertholim-Nasciben Luciana , Scliar Marilia O. , Debortoli Guilherme , Thiruvahindrapuram Bhooma , Scherer Stephen W. , Duarte Yeda A. O. , Zatz Mayana , Suarez-Kurtz Guilherme , Parra Esteban J. , Naslavsky Michel S. 
Published: May 2023

Introduction: Research in the field of pharmacogenomics (PGx) aims to identify genetic variants that modulate response to drugs, through alterations in their pharmacokinetics (PK) or pharmacodynamics (PD). The distribution of PGx variants differs considerably among populations, and whole-genome sequencing (WGS) plays a major role as a comprehensive approach to detect both common and rare variants. This study evaluated the frequency of PGx markers in the context of the Brazilian population, using data from a population-based admixed cohort from Sao Paulo, Brazil, which includes variants from WGS of 1,171 unrelated, elderly individuals.Methods: The Stargazer tool was used to call star alleles and structural variants (SVs) from 38 pharmacogenes. Clinically relevant variants were investigated, and the predicted drug response phenotype was analyzed in combination with the medication record to assess individuals potentially at high-risk of gene-drug interaction.Results: In total, 352 unique star alleles or haplotypes were observed, of which 255 and 199 had a frequency &lt; 0.05 and &lt; 0.01, respectively. For star alleles with frequency &gt; 5% (n = 97), decreased, loss-of-function and unknown function accounted for 13.4%, 8.2% and 27.8% of alleles or haplotypes, respectively. Structural variants (SVs) were identified in 35 genes for at least one individual, and occurred with frequencies &gt;5% for CYP2D6, CYP2A6, GSTM1, and UGT2B17. Overall 98.0% of the individuals carried at least one high risk genotype-predicted phenotype in pharmacogenes with PharmGKB level of evidence 1A for drug interaction. The Electronic Health Record (EHR) Priority Result Notation and the cohort medication registry were combined to assess high-risk gene-drug interactions. In general, 42.0% of the cohort used at least one PharmGKB evidence level 1A drug, and 18.9% of individuals who used PharmGKB evidence level 1A drugs had a genotype-predicted phenotype of high-risk gene-drug interaction.Conclusion: This study described the applicability of next-generation sequencing (NGS) techniques for translating PGx variants into clinically relevant phenotypes on a large scale in the Brazilian population and explores the feasibility of systematic adoption of PGx testing in Brazil.
Long-term cold, freezing and drought: overlapping and specific regulatory mechanisms and signal transduction in tea plant (Camellia sinensis (L.) Kuntze)
Authors: Samarina Lidiia , Wang Songbo , Malyukova Lyudmila , Bobrovskikh Alexandr , Doroshkov Alexey , Koninskaya Natalia , Shkhalakhova Ruset , Matskiv Alexandra , Fedorina Jaroslava , Fizikova Anastasia , Manakhova Karina , Loshkaryova Svetlana , Tutberidze Tsiala , Ryndin Alexey , Khlestkina Elena 
Published: May 2023

IntroductionLow temperatures and drought are two main environmental constraints reducing the yield and geographical distribution of horticultural crops worldwide. Understanding the genetic crosstalk between stress responses has potential importance for crop improvement.MethodsIn this study, Illumina RNA-seq and Pac-Bio genome resequencing were used to annotate genes and analyze transcriptome dynamics in tea plants under long-term cold, freezing, and drought.ResultsThe highest number of differentially expressed genes (DEGs) was identified under long-term cold (7,896) and freezing (7,915), with 3,532 and 3,780 upregulated genes, respectively. The lowest number of DEGs was observed under 3-day drought (47) and 9-day drought (220), with five and 112 genes upregulated, respectively. The recovery after the cold had 6.5 times greater DEG numbers as compared to the drought recovery. Only 17.9% of cold-induced genes were upregulated by drought. In total, 1,492 transcription factor genes related to 57 families were identified. However, only 20 transcription factor genes were commonly upregulated by cold, freezing, and drought. Among the 232 common upregulated DEGs, most were related to signal transduction, cell wall remodeling, and lipid metabolism. Co-expression analysis and network reconstruction showed 19 genes with the highest co-expression connectivity: seven genes are related to cell wall remodeling (GATL7, UXS4, PRP-F1, 4CL, UEL-1, UDP-Arap, and TBL32), four genes are related to calcium-signaling (PXL1, Strap, CRT, and CIPK6), three genes are related to photo-perception (GIL1, CHUP1, and DnaJ11), two genes are related to hormone signaling (TTL3 and GID1C-like), two genes are involved in ROS signaling (ERO1 and CXE11), and one gene is related to the phenylpropanoid pathway (GALT6).DiscussionBased on our results, several important overlapping mechanisms of long-term stress responses include cell wall remodeling through lignin biosynthesis, o-acetylation of polysaccharides, pectin biosynthesis and branching, and xyloglucan and arabinogalactan biosynthesis. This study provides new insight into long-term stress responses in woody crops, and a set of new target candidate genes were identified for molecular breeding aimed at tolerance to abiotic stresses.
Spatial genetic patterns and distribution dynamics of Begonia grandis (Begoniaceae), a widespread herbaceous species in China
Authors: Xiao Yan , Li Xing-Juan , Jiang Xiao-Long , Li Chun , Li Xiang-Peng , Li Wei-Ping , Tian Dai-Ke 
Published: May 2023

IntroductionBegonia L., one of the 10 largest plant genera, contains over 2,100 species, most of which have a very limited distribution range. Understanding the spatial genetic structure and distribution dynamics of a widespread species in this genus will contribute to clarifying the mechanism responsible for Begonia speciation.MethodsIn this study, we used three chloroplast DNA markers (ndhF-rpl32, atpI-atpH, and ndhA intron), coupled with species distribution modeling (SDM), to investigate the population genetic structure and distribution dynamics of Begonia grandis Dryand., the species of Begonia with the widest distribution in China.ResultsThirty-five haplotypes from 44 populations clustered into two groups, and haplotype divergence began in the Pleistocene (1.75 Mya). High genetic diversity (Hd = 0.894, HT = 0.910), strong genetic differentiation (FST = 0.835), and significant phylogeographical structure (GST/NST = 0.848/0.917, P &lt; 0.05) were observed. The distribution range of B. grandis migrated northwards after the last glacial maximum, but its core distribution area remained stable.DiscussionCombined, the observed spatial genetic patterns and SDM results identified the Yunnan-Guizhou Plateau, the Three Gorges region, and the Daba Mountains as potential refugia of B. grandis. BEAST-derived chronogram and haplotype network analysis do not support the Flora Reipublicae Popularis Sinicae and Flora of China for subspecies classification based on morphological characteristics. Our results support the hypothesis that population-level allopatric differentiation may be an important speciation process for the Begonia genus and a key contributor to its rich diversity.
Abnormal dynamic functional connectivity of thalamic subregions in patients with first-episode, drug-naïve major depressive disorder
Authors: Zheng Yanting , Wu Yujie , Liu Yujie , Li Danian , Liang Xinyu , Chen Yaoping , Zhang Hanyue , Guo Yan , Lu Ruoxi , Wang Jinhui , Qiu Shijun 
Published: May 2023

BackgroundRecent studies have shown that major depressive disorder (MDD) is associated with altered intrinsic functional connectivity (FC) of the thalamus; however, investigations of these alterations at a finer time scale and the level of thalamic subregions are still lacking.MethodsWe collected resting-state functional MRI data from 100 treatment-naïve, first-episode MDD patients and 99 age-, gender- and education-matched healthy controls (HCs). Seed-based whole-brain sliding window-based dFC analyses were performed for 16 thalamic subregions. Between-group differences in the mean and variance of dFC were determined using threshold-free cluster enhancement algorithm. For significant alterations, there relationships with clinical and neuropsychological variables were further examined via bivariate and multivariate correlation analyses.ResultsOf all thalamic subregions, only the left sensory thalamus (Stha) showed altered variance of dFC in the patients characterized by increases with the left inferior parietal lobule, left superior frontal gyrus, left inferior temporal gyrus, and left precuneus, and decreases with multiple frontal, temporal, parietal, and subcortical regions. These alterations accounted for, to a great extent, clinical, and neuropsychological characteristics of the patients as revealed by the multivariate correlation analysis. In addition, the bivariate correlation analysis revealed a positive correlation between the variance of dFC between the left Stha and right inferior temporal gurus/fusiform and childhood trauma questionnaires scores (r = 0.562, P &lt; 0.001).ConclusionThese findings suggest that the left Stha is the most vulnerable thalamic subregion to MDD, whose dFC alterations may serve as potential biomarkers for the diagnosis of the disease.
Stevioside Improves Antioxidant Capacity and Intestinal Barrier Function while Attenuating Inflammation and Apoptosis by Regulating the NF-κB/MAPK Pathways in Diquat-Induced Oxidative Stress of IPEC-J2 Cells
Authors: Xu Qinglei , Liu Mingzheng , Chao Xiaohuan , Zhang Chunlei , Yang Huan , Chen Jiahao , Zhou Bo 
Published: May 2023

As a natural sweetener, stevioside is extracted from Stevia rebaudiana Bertoni and possesses potent antioxidant activity. However, little information is known about its protective role in maintaining the intestinal epithelial cells health under oxidative stress. The aim of this study was to investigate the protective effects and underlying mechanisms of stevioside on alleviating inflammation, apoptosis, and improving antioxidant capacity in intestinal porcine epithelial cells (IPEC-J2) under oxidative stress by diquat. The results demonstrated that the pretreatment with stevioside (250 μM) for 6 h increased cell viability and proliferation and prevented apoptosis induced by diquat at 1000 μM for 6 h in IPEC-J2 cells, compared with the diquat alone-treated cells. Importantly, stevioside pretreatment significantly reduced ROS and MDA production as well as upregulated T-SOD, CAT, and GSH-Px activity. Moreover, it also decreased cell permeability and improved intestinal barrier functions by significantly upregulating the tight junction protein abundances of claudin-1, occludin, and ZO-1. At the same time, stevioside significantly down-regulated the secretion and gene expression of IL-6, IL-8, and TNF-α and decreased the phosphorylation levels of NF-κB, IκB, and ERK1/2 compared with the diquat alone group. Taken together, this study demonstrated that stevioside alleviated diquat-stimulated cytotoxicity, inflammation, and apoptosis in IPEC-J2 cells, protecting cellular barrier integrity and mitigating oxidative stress by interfering with the NF-κB and MAPK signaling pathways.
Entreprendre au Sénégal après la dévaluation
Authors: Galand Patrice 
Published: May 2023

Business in Senegal after the devaluation.
The devaluation of the CFA franc modifies the entrepreneurs’ financing networks as well as the pressures they come under from their social environment. To make up for the gaps of the banking system and the surge of interest rates, investment committees based on pre-established ties are created. The change in parity reduces the profitability of firms when the community pressures are increasing. The rise in imports encourages manufacturers to equip themselves with second hand technologies. Devaluation can be synonymous with euthanasia for the business world or on the contrary with revitalization.
Zaïre : l’officiel contredit par le réel
Authors: Kuyu mwissa Camille 
Published: May 2023

In Zaire reality is in contradiction with the state.
Today in Zaire , real life takes place out of the State and its institutions. This grassroot social regulation has made possible the development of new positions of power out of State’ control or substitution of monopoly. These positions of power which correspond to the actual needs of the population are mushrooming in the streets of the country’s main towns. It is the case of the open currency markets and the new communities of prayers.