bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation
Authors: Wang Huiwen , Zhang Jian , Liu Jinqing , Jiang Yongfang , Fu Lei , Peng Shifang 
Published: February 2023

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that eventually progresses to cirrhosis and hepatocellular carcinoma (HCC) in the absence of proper treatment. However, Gene expression and molecular mechanisms involved in the pathogenesis of PBC have not been completely elucidated.Methods: Microarray expression profiling dataset GSE61260 was downloaded from the Gene Expression Omnibus (GEO) database. Data were normalized to screen differentially expressed genes (DEGs) using the limma package in R. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. A protein–protein interaction (PPI) network was constructed to identify hub genes and an integrative regulatory network of transcriptional factor–DEG–microRNA was established. Gene Set Enrichment Analysis (GSEA) was used to analyze differences in biological states for groups with different expressions of aldo-keto reductase family 1 member B10 (AKR1B10). Immunohistochemistry (IHC) analysis was performed to validate the expression of hepatic AKR1B10 in patients with PBC. The association of hepatic AKR1B10 levels with clinical parameters was evaluated using one-way analysis of variance (ANOVA) and Pearson’s correlation analysis.Results: This study identified 22 upregulated and 12 downregulated DEGs between patients with PBC and healthy controls. GO and KEGG analysis revealed that DEGs were mainly enriched in immune reactions. AKR1B10 was identified as a key gene and was further analyzed by screening out hub genes from the PPI network. GSEA analysis indicated that high expression of AKR1B10 might promote PBC to develop into HCC. Immunohistochemistry results verified the increased expression of hepatic AKR1B10 in patients with PBC and demonstrated its positive correlation with the severity of PBC.Conclusion: AKR1B10 was identified as a hub gene in PBC by integrated bioinformatics analysis and clinical validation. The increase of AKR1B10 expression in patients with PBC was associated with disease severity and might promote the progression of PBC to HCC.
Genetic and clinical analysis of TP73 gene in amyotrophic lateral sclerosis patients from Chinese mainland
Authors: Tang Xuxiong , Yuan Yanchun , Liu Zhen , Bu Yue , Tang Linxin , Zhao Qianqian , Jiao Bin , Guo Jifeng , Shen Lu , Jiang Hong , Tang Beisha , Wang Junling 
Published: February 2023

IntroductionTP73 was recently identified as a novel causative gene for amyotrophic lateral sclerosis (ALS). We aimed to determine the contribution of variations in TP73 in the Chinese ALS population and to further explore the genotype-phenotype correlations.MethodsWe screened rare, putative pathogenic TP73 mutations in a large Chinese ALS cohort and performed association analysis of both rare and common TP73 variations between cases and controls.ResultsOf the 985 ALS patients studied, six rare, heterozygous putative pathogenic variants in TP73 were identified among six unrelated sALS patients. Exon 14 of TP73 might be a mutant hotspot in our cohort. Patients with ALS with only rare, putative pathogenic TP73 mutations exhibited a characteristic clinical profile. Patients harboring multiple mutations in TP73 and other ALS-related genes displayed a significantly earlier onset of ALS. Association analysis revealed that rare TP73 variants in the untranslated regions (UTRs) were enriched among ALS patients; meanwhile, two common variants in the exon-intron boundary were discovered to be associated with ALS.DiscussionWe demonstrate that TP73 variations also have contributed to ALS in the Asian population and broaden the genotypic and phenotypic spectrum of TP73 variants in the ALS-frontotemporal dementia (FTD) spectrum. Furthermore, our findings first suggest that TP73 is not only a causative gene, but also exerts a disease-modifying effect. These results may contribute to a better understanding of the molecular mechanism of ALS.
Research on steel rail surface defects detection based on improved YOLOv4 network
Authors: Mi Zengzhen , Chen Ren , Zhao Shanshan 
Published: February 2023

IntroductionThe surface images of steel rails are extremely difficult to detect and recognize due to the presence of interference such as light changes and texture background clutter during the acquisition process.MethodsTo improve the accuracy of railway defects detection, a deep learning algorithm is proposed to detect the rail defects. Aiming at the problems of inconspicuous rail defects edges, small size and background texture interference, the rail region extraction, improved Retinex image enhancement, background modeling difference, and threshold segmentation are performed sequentially to obtain the segmentation map of defects. For the classification of defects, Res2Net and CBAM attention mechanism are introduced to improve the receptive field and small target position weights. The bottom-up path enhancement structure is removed from the PANet structure to reduce the parameter redundancy and enhance the feature extraction of small targets.ResultsThe results show the average accuracy of rail defects detection reaches 92.68%, the recall rate reaches 92.33%, and the average detection time reaches an average of 0.068 s per image, which can meet the real-time of rail defects detection.DiscussionComparing the improved method with the mainstream target detection algorithms such as Faster RCNN, SSD, YOLOv3 and other algorithms, the improved YOLOv4 has excellent comprehensive performance for rail defects detection, the improved YOLOv4 model obviously better than several others in Pr, Rc, and F1 value, and can be well-applied to rail defect detection projects.
Optimal CT perfusion thresholds for core and penumbra in acute posterior circulation infarction
Authors: Edwards Leon Stephen , Cappelen-Smith Cecilia , Cordato Dennis , Bivard Andrew , Churilov Leonid , Lin Longting , Chen Chushuang , Garcia-Esperon Carlos , Butcher Kenneth , Kleinig Tim , Choi Phillip M. C. , Cheng Xin , Dong Qiang , Aviv Richard I. , Parsons Mark William 
Published: February 2023

BackgroundAt least 20% of strokes involve the posterior circulation (PC). Compared to the anterior circulation, posterior circulation infarction (POCI) are frequently misdiagnosed. CT perfusion (CTP) has advanced stroke care by improving diagnostic accuracy and expanding eligibility for acute therapies. Clinical decisions are predicated upon precise estimates of the ischaemic penumbra and infarct core. Current thresholds for defining core and penumbra are based upon studies of anterior circulation stroke. We aimed to define the optimal CTP thresholds for core and penumbra in POCI.MethodsData were analyzed from 331-patients diagnosed with acute POCI enrolled in the International-stroke-perfusion-registry (INSPIRE). Thirty-nine patients with baseline multimodal-CT with occlusion of a large PC-artery and follow up diffusion weighted MRI at 24–48 h were included. Patients were divided into two-groups based on artery-recanalization on follow-up imaging. Patients with no or complete recanalisation were used for penumbral and infarct-core analysis, respectively. A Receiver operating curve (ROC) analysis was used for voxel-based analysis. Optimality was defined as the CTP parameter and threshold which maximized the area-under-the-curve. Linear regression was used for volume based analysis determining the CTP threshold which resulted in the smallest mean volume difference between the acute perfusion lesion and follow up MRI. Subanalysis of PC-regions was performed.ResultsMean transit time (MTT) and delay time (DT) were the best CTP parameters to characterize ischaemic penumbra (AUC = 0.73). Optimal thresholds for penumbra were a DT &gt;1 s and MTT&gt;145%. Delay time (DT) best estimated the infarct core (AUC = 0.74). The optimal core threshold was a DT &gt;1.5 s. The voxel-based analyses indicated CTP was most accurate in the calcarine (Penumbra-AUC = 0.75, Core-AUC = 0.79) and cerebellar regions (Penumbra-AUC = 0.65, Core-AUC = 0.79). For the volume-based analyses, MTT &gt;160% demonstrated best correlation and smallest mean-volume difference between the penumbral estimate and follow-up MRI (R2 = 0.71). MTT &gt;170% resulted in the smallest mean-volume difference between the core estimate and follow-up MRI, but with poor correlation (R2 = 0.11).ConclusionCTP has promising diagnostic utility in POCI. Accuracy of CTP varies by brain region. Optimal thresholds to define penumbra were DT &gt;1 s and MTT &gt;145%. The optimal threshold for core was a DT &gt;1.5 s. However, CTP core volume estimates should be interpreted with caution.
Novel variant c.92T > G (p.Val31Gly) in the PFN1 gene (ALS18) responsible for a specific phenotype in a large Bulgarian amyotrophic lateral sclerosis pedigree
Authors: Angelov Teodor , Chamova Teodora , Atemin Slavena , Todorov Tihomir , Ormandzhiev Slavko , Tourtourikov Ivan , Todorova Albena , Devos David , Tournev Ivailo 
Published: February 2023

ObjectivesAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of motor function, disability, and death. Variants in the PFN1 gene, encoding the Profilin-1 protein, are related to ALS18.MethodsWe present a pedigree consisting of 3 generations and 4 affected individuals, 3 of which carry a novel heterozygous variant: c.92T &gt; G (p.Val31Gly) in the PFN1 gene. This variant was discovered through means of whole exome sequencing (WES) and targeted analysis of ALS-related genes.ResultsThe mean age of onset in our pedigree was 59.75 (±10.11 SD) years with a significant difference between the first two generations (females) and the third (male) of 22.33 (±3.4 SD) years. For this ALS form, we observed a longer disease progression of 4 (±1.87 SD) years (three of four affected are still alive). Clinical manifestations displayed predominant impairment of the lower motor neuron (LMN) in one limb, with gradual involvement of other limbs. A novel heterozygous missense variant c.92T &gt; G, p. Val31Gly (NM_005022.4) in exon 1 in the PFN1 gene was discovered through means of whole exome sequencing (WES). Segregation analysis in the family showed that the detected variant was inherited from the affected mother, and the affected aunt also turned out to be a variant carrier.ConclusionsALS18 is a very rare form of the disease. We report here a relatively large pedigree with a novel variant, leading to late onset (after 50 years), initial involvement of the lower limbs and relatively slow progression.
Antiplatelet therapy adjustment improved the radiomic characteristics of acute silent cerebral infarction after stent-assisted coiling in patients with high on-treatment platelet reactivity: A prospective study
Authors: Li Wenqiang , Wang Anxin , Ma Chao , Wang Yanmin , Zhao Yapeng , Zhang Yisen , Wang Kun , Zhang Ying , Wang Yang , Yang Xinjian , Liu Jian , Liu Xianzhi 
Published: February 2023

BackgroundWe aimed to investigate the effects of high on-treatment platelet reactivity (HPR) and antiplatelet therapy adjustment on high-risk radiomic features in patients with antiplatelet therapy adjustment on acute silent cerebral infarction (ASCI) who had unruptured intracranial aneurysms (UIA) after stent placement.MethodsThis single-institution study prospectively included 230 UIA patients who had ACSI after stent placement in our hospital between January 2015 and July 2020. All patients underwent magnetic resonance imaging with diffusion-weighted imaging (MRI-DWI) after stent placement and 1,485 radiomic features were extracted from each patient. The least absolute shrinkage and selection operator regression methods were used for selection of high-risk radiomic features associated with clinical symptoms. In addition, 199 patients with ASCI were classified into three groups: controls without HPR (n = 113), HPR patients with standard antiplatelet therapy (n = 63) and HPR patients with antiplatelet therapy adjustment (n = 23). We compared high-risk radiomic features between three groups.ResultsOf the patients who had acute infarction after MRI-DWI, 31 (13.5%) exhibited clinical symptoms. Eight risk radiomic features associated with clinical symptoms were selected, and the radiomics signature exhibited good performance. In ASCI patients, compared with controls, the radiomic characteristics of ischemic lesion in HPR patients were consistent with the following high-risk radiomic features associated with clinical symptoms: higher gray-level values, greater variance in intensity values, and greater homogeneity. However, the adjustment of antiplatelet therapy in HPR patients modified the high-risk radiomic features, which showed lower gray-level values, less variance in intensity values, and more heterogeneous texture. The radiomic shape feature of elongation showed no notable difference between three groups.ConclusionAdjustment of antiplatelet therapy might reduce the high-risk radiomic features of UIA patients with HPR after stent placement.
Marked paper: Type 2 diabetes mellitus indicates increased postoperative complications and poor prognosis in colorectal cancer patients receiving curative surgery
Authors: Liu Daoli , Zhang Xubing , Zhou Hong , Zhu Zhiqiang , He Yiren , Wan Xiao , Zhang Bo , Liu Shaojun , Liu Liu 
Published: February 2023

PurposeThis study aimed to evaluate the impact of type 2 diabetes mellitus (T2DM) on the short-term outcomes and long-term survival of patients with colorectal cancer (CRC) who underwent curative resection.MethodsThis study retrospectively included 136 patients (T2DM group) with resectable CRC and T2DM from Jan 2013 to Dec 2017. Propensity score-matched control group consisting of 136 patients (non-T2DM group) were selected from 1143 CRC patients without T2DM. The short-term outcomes and prognosis were compared between the T2DM and non-T2DM group.ResultsA total of 272 patients (136 patients for each group) were included in this study. Patients in T2DM group had higher body mass index (BMI), higher proportion of hypertension and cerebrovascular diseases (P&lt;0.05). T2DM group had more overall complications (P=0.001), more major complications (P=0.003) and higher risk of reoperation (P=0.007) when compared with non-T2DM patients. T2DM patients had longer hospitalization time than non-T2DM (20.7 ± 10.2 vs. 17.5 ± 6.2, P=0.002). As for the prognosis, T2DM patients had worse 5-year overall survival (OS) (P=0.024) and 5-year disease-free survival (DFS) (P=0.019) in all stage. Moreover, T2DM and TNM stage were the independent predictors of OS and DFS for CRC patients.ConclusionsT2DM increases overall complications and major complications, and prolongs the hospitalization time after CRC surgery. In addition, T2DM indicates the poor prognosis of CRC patients. A prospective study with large sample size is required to confirm our findings.
Clinical features and gene variation analysis of COQ8B nephropathy: Report of seven cases
Authors: Liang Rui , Chen Xuelan , Zhang Ying , Law Chak-Fun , Yu Sijie , Jiao Jia , Yang Qin , Wu Daoqi , Zhang Gaofu , Chen Han , Wang Mo , Yang Haiping , Wang Anshuo 
Published: February 2023

ObjectiveCOQ8B nephropathy is a relatively rare autosomal recessive kidney disease characterized by proteinuria and a progressive deterioration of renal function, eventually leading to end-stage renal disease (ESRD). The objective is to study the characteristics and correlation between the genotype and the clinical phenotype of COQ8B nephropathy.MethodsThis is a retrospective study focusing on the clinical characteristics of seven COQ8B nephropathy patients diagnosed by gene sequencing. Basic clinical information, clinical manifestations, examinations, imaging, genomes, pathology, treatments, and prognosis of the patients were reviewed.ResultsOf the seven patients, two were male children and five were female children. The median age at the disease onset was 5 years and 3 months. The initial main clinical manifestations were proteinuria and renal insufficiency. Four patients had severe proteinuria, four had focal segmental glomerulosclerosis (FSGS) diagnosed by a renal biopsy, and two had nephrocalcinosis after an ultrasound was performed on them. There were no other clinical manifestations such as neuropathy, muscle atrophy, and so on in all of them. Their gene mutations were all exon variants, which were classified as heterozygous or homozygous variants by performing family verification analysis. Compound heterozygous variants were predominant in all, and all gene variants were inherited from their parents. One novel mutation, c.1465c&gt;t, was found in this study. This gene mutation resulted from changes in the amino acid sequence, thus leading to an abnormal protein structure. Two patients with early diagnosis of COQ8B nephropathy presented with no renal insufficiency and were treated with oral coenzyme Q10 (CoQ10), and they maintained normal renal function. For the remaining five who were treated with CoQ10 following renal insufficiency, the deterioration of renal function could not be reversed, and they progressed to ESRD within a short time (median time: 7 months). A follow-up of these patients showed normal renal function with a CoQ10 supplement.ConclusionFor unexplained proteinuria, renal insufficiency, or steroid-resistant nephrotic syndrome, gene sequencing should be considered, in addition to renal biopsy, as early as possible. Timely diagnosis of COQ8B nephropathy and early supplementation of sufficient CoQ10 can help control the progression of the disease and significantly improve the prognosis.
Understanding transitions in exploration profiles of students opting for higher education
Authors: Demulder Lien , Verschueren Karine , Donche Vincent 
Published: February 2023

IntroductionSince previous research on educational career exploration has mainly been cross-sectional and therefore has been unsuccessful in explaining how this process can change during the final year in secondary education before students make the transition to higher education, this study aimed to examine changes over time in the exploration process. A person-centered research perspective was taken to further deepen the understanding of how different exploration tasks jointly combine into meaningful profiles. In this way, this study tried to gain more insight into why some students go through this process successfully and others do not. Four goals guided this study: identifying exploration profiles of students in Fall and Spring of the final year in secondary school based on four decisional tasks (orientation, self-, broad and in-depth exploration), investigating transitions between exploration profiles across these two timepoints, and examining the role which different antecedents (i.e., academic self-efficacy, academic self-concept, motivation, test anxiety, gender, educational track, socio-economic status) play in explaining both profile membership and transitions between profiles.MethodsUsing self-report questionnaires to measure the exploration tasks and the antecedents in final year students, two cross-sectional samples collected in Fall (n = 9,567) and Spring (n = 7,254), and one longitudinal sample (n = 672) were examined.ResultsLatent profile analyses identified three exploration profiles at both timepoints: passive, moderately active, and highly active explorers. Latent transition analysis showed the moderately active explorers profile to be the most stable profile, while the passive profile was the most variable profile. Academic self-concept, motivation, test anxiety, and gender had an effect on the initial states, while motivation and test anxiety affected the transition probabilities. For both academic self-concept and motivation, students scoring higher were found to be less present in the passive or the moderately active than in the highly active profile. Furthermore, compared to students who remained in the passive profile, higher levels of motivation were associated with a higher probability to transition to the moderately active profile. Next to that, compared to students who remained in the highly active profile, higher levels of motivation were associated with a lower probability to transition to the moderately active profile. Results on anxiety were inconsistent.DiscussionBased on substantial cross-sectional as well as longitudinal data, our findings contribute to a more comprehensive understanding of the explanatory base of important differences in the study choice making process of students opting for higher education. This may ultimately lead to more timely and fitting support for students with different exploration profiles.
Cross sectional association between cognitive frailty and disability among community-dwelling older adults: Focus on the role of social factors
Authors: Choi Kyungwon , Ko Young 
Published: February 2023

BackgroundThis study aimed to investigate the prevalence of cognitive frailty and the influence of social factors on the association between different levels of cognitive frailty and disability.MethodsA nationally representative survey of non-institutionalized community-dwelling older adults in Korea was used. A total, 9,894 older adults were included in the analysis. We assessed the effects of social factors using social activities, social contacts, living arrangements, emotional support, and satisfaction with friends and neighbors.ResultsThe prevalence of cognitive frailty was 1.6%, which was consistent with other population-based studies. Hierarchical logistic analysis demonstrated that the association between different levels of cognitive frailty and disability was attenuated when social participation, social contact, and satisfaction with friends and community were included in the model, and the magnitude of these effects differed across the levels of cognitive frailty.DiscussionConsidering the influence of social factors, interventions to enhance social relationships can help slow down the progression of cognitive frailty to disability.