bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and genetic characterization of pediatric patients with Wilson’s disease from Yunnan province where ethnic minorities gather
Authors: Wang Yanjun , Fang Jiahui , Li Bin , Li Chongyang , Liu Shan , He Juan , Tao Lvyan , Li Cuifen , Yang Ya , Li Li , Xiao Shufang 
Published: March 2023

Background: Wilson’s disease (WD) is an autosomal recessive disease that is caused by mutations in the ATP7B (a copper-transporting P-type ATPase) gene. The disease has a low prevalence and is characterized by a copper metabolism disorder. However, various characteristics of the disease are determined by race and geographic region. We aimed to discover novel ATP7B mutations in pediatric patients with WD from Yunnan province, where there is a high proportion of ethnic minorities. We also performed a comprehensive analysis of ATP7B mutations in the different ethnic groups found in Southwest China.Methods: We recruited 45 patients who had been clinically diagnosed with WD, from 44 unrelated families. Routine clinical examinations and laboratory evaluations were performed and details of age, gender, ethnic group and symptoms at onset were collected. Direct sequencing of the ATP7B gene was performed in 39 of the 45 patients and their families.Results: In this study, participants came from seven different ethnic groups in China: Han, Bai, Dai, Zhuang, Yi, Hui and Jingpo. Three out of ten patients from ethnic minorities presented with elevated transaminases, when compared to the majority of the Han patients. Forty distinct mutations (28 missense, six splicing, three non-sense, two frameshift and one mutation of uncertain significance) were identified in the 39 patients with WD. Four of the mutations were novel and the most frequent mutation was c.2333G &gt; T (p.R778L, allelic frequency: 15.38%). Using the phenotype-genotype correlation analysis, patients from ethnic minorities were shown to be more likely to have homozygous mutations (p = 0.035) than Han patients. The patients who carried the c.2310C &gt; G mutation had lower serum ceruloplasmin levels (p = 0.012). In patients with heterozygous mutations, c.3809A &gt; G was significantly associated with ethnic minorities (p = 0.042). The frequency of a protein-truncating variant (PTV) in Han patients was 34.38% (11/32), while we did not find PTV in patients from ethnic minorities.Conclusion: This study revealed genetic defects in 39 pediatric patients with WD from Yunnan province. Four novel mutations were identified and have enriched the WD database. We characterized the genotypes and phenotypes in different minorities, which will enhance the current knowledge on the population genetics of WD in China.
Nrf2−/− regulated lung DNA demethylation and CYP2E1 DNA methylation under PM2.5 exposure
Authors: Wu Mengjie , Jiang Menghui , Ding Hao , Tang Siying , Li Daochuan , Pi Jingbo , Zhang Rong , Chen Wen , Chen Rui , Zheng Yuxin , Piao Jinmei 
Published: March 2023

Cytochrome P450 (CYP450) can mediate fine particulate matter (PM2.5) exposure leading to lung injury. Nuclear factor E2-related factor 2 (Nrf2) can regulate CYP450 expression; however, the mechanism by which Nrf2−/− (KO) regulates CYP450 expression via methylation of its promoter after PM2.5 exposure remains unclear. Here, Nrf2−/− (KO) mice and wild-type (WT) were placed in a PM2.5 exposure chamber (PM) or a filtered air chamber (FA) for 12 weeks using the real-ambient exposure system. The CYP2E1 expression trends were opposite between the WT and KO mice following PM2.5 exposure. After exposure to PM2.5,CYP2E1 mRNA and protein levels were increased in WT mice but decreased in KO mice, and CYP1A1 expression was increased after exposure to PM2.5 in both WT and KO mice. CYP2S1 expression decreased after exposure to PM2.5 in both the WT and KO groups. We studied the effect of PM2.5 exposure on CYP450 promoter methylation and global methylation levels in WT and KO mice. In WT and KO mice in the PM2.5 exposure chamber, among the methylation sites examined in the CYP2E1 promoter, the CpG2 methylation level showed an opposite trend with CYP2E1 mRNA expression. The same relationship was evident between CpG3 unit methylation in the CYP1A1 promoter and CYP1A1 mRNA expression, and between CpG1 unit methylation in the CYP2S1 promoter and CYP2S1 mRNA expression. This data suggests that methylation of these CpG units regulates the expression of the corresponding gene. After exposure to PM2.5, the expression of the DNA methylation markers ten-eleven translocation 3 (TET3) and 5-hydroxymethylcytosine (5hmC) was decreased in the WT group but significantly increased in the KO group. In summary, the changes in CYP2E1, CYP1A1, and CYP2S1 expression in the PM2.5 exposure chamber of WT and Nrf2−/− mice might be related to the specific methylation patterns in their promoter CpG units. After exposure to PM2.5, Nrf2 might regulate CYP2E1 expression by affecting CpG2 unit methylation and induce DNA demethylation via TET3 expression. Our study revealed the underlying mechanism for Nrf2 to regulate epigenetics after lung exposure to PM2.5.
Rodent models of postherpetic neuralgia: How far have we reached?
Authors: Ou Mingxi , Chen Jiamin , Yang Shaomin , Xiao Lizu , Xiong Donglin , Wu Songbin 
Published: March 2023

BackgroundInduced by varicella zoster virus (VZV), postherpetic neuralgia (PHN) is one of the common complications of herpes zoster (HZ) with refractory pain. Animal models play pivotal roles in disclosing the pain mechanisms and developing effective treatments. However, only a few rodent models focus on the VZV-associated pain and PHN.ObjectiveTo summarize the establishment and characteristics of popular PHN rodent models, thus offer bases for the selection and improvement of PHN models.DesignIn this review, we retrospect two promising PHN rodent models, VZV-induced PHN model and HSV1-induced PHN model in terms of pain-related evaluations, their contributions to PHN pathogenesis and pharmacology.ResultsSignificant difference of two PHN models is the probability of virus proliferation; 2) Most commonly used pain evaluation of PHN model is mechanical allodynia, but pain-induced anxiety and other behaviours are worth noting; 3) From current PHN models, pain mechanisms involve changes in virus gene and host gene expression, neuroimmune–glia interactions and ion channels; 4) antiviral drugs and classical analgesics serve more on the acute stage of herpetic pain.ConclusionsDifferent PHN models assessed by various pain evaluations combine to fulfil more comprehensive understanding of PHN.
Exploration of the common genetic landscape of COVID-19 and male infertility
Authors: Chen Yinwei , Sun Taotao , Liu Kang , Yuan Penghui , Liu Chang 
Published: March 2023

BackgroundCOVID-19 has spread widely across continents since 2019, causing serious damage to human health. Accumulative research uncovered that SARS-CoV-2 poses a great threat to male fertility, and male infertility (MI) is a common comorbidity for the COVID-19 pandemic. The aim of the study was to explore the cross-talk molecular mechanisms between COVID-19 and MI.Materials and methodsA total of four transcriptome data regarding COVID-19 and MI were downloaded from the Gene Expression Omnibus (GEO) repository, and were divided for two purposes (initial analysis and external validation). Differentially expressed genes (DEGs) analysis, GO and pathway annotation, protein-protein interaction (PPI) network, connectivity ranking, ROC analysis, immune infiltration, and translational and post-translational interaction were performed to gain hub COVID-19-related DEGs (CORGs). Moreover, we recorded medical information of COVID-19 patients with MI and matched healthy controls, and harvested their sperm samples in the university hospital. Expressions of hub CORGs were detected through the qRT-PCR technique.ResultsWe identified 460 overlapped CORGs in both the COVID-19 DEGs and MI DEGs. CORGs were significantly enriched in DNA damage and repair-associated, cell cycle-associated, ubiquitination-associated, and coronavirus-associated signaling. Module assessment of PPI network revealed that enriched GO functions were closely related to cell cycle and DNA metabolism processes. Pharmacologic agent prediction displayed protein-drug interactions of ascorbic acid, biotin, caffeine, and L-cysteine with CORGs. After connectivity ranking and external validation, three hub CORGs (ENTPD6, CIB1, and EIF3B) showed good diagnostic performance (area under the curve &gt; 0.75). Subsequently, three types of immune cells (CD8+ T cells, monocytes, and macrophages M0) were dominantly enriched, and 24 transcription factor-CORGs interactions and 13 miRNA-CORGs interactions were constructed in the network. Finally, qRT-PCR analysis confirmed that there were significant differences in the expression of hub CORGs (CIB1 and EIF3B) between the patient and control groups.ConclusionThe present study identified and validated hub CORGs in COVID-19 and MI, and systematically explored molecular interactions and regulatory features in various biological processes. Our data provide new insights into the novel biomarkers and potential therapeutic targets of COVID-19-associated MI.
Abscopal effect triggered by radiation sequential mono-immunotherapy resulted in a complete remission of PMMR sigmoid colon cancer
Authors: Zhou Pu , Wang Yan , Qin Si , Han Yan , Yang Yumeng , Zhao Liang , Zhou Quan , Zhuo Wenlei 
Published: March 2023

BackgroundRadiation therapy combined with immune checkpoint inhibitors (ICIs) has recently turned into an appealing and promising approach to enhance the anti-tumor immunity and efficacy of immunological drugs in many tumors. Abscopal effect induced by radiation is a phenomenon that often leads to an efficient immunity response. In this study, we investigated whether the combination of the immunogenic effects derived from radiotherapy sequential ICIs-based therapy could increase the incidence of abscopal effects, and improve the survival rates.Case presentationWe described a clinical case regarding a 35-year-old male patient who was admitted to our hospital with a diagnosis of adenocarcinoma of the sigmoid colon and synchronous multiple liver metastases following a surgical resection. The molecular pathological examination showed immune-desert phenotype and proficient mismatch repair (pMMR). The patient was treated with adjuvant chemotherapy after surgery, however, after 7 months, multiple metastasis in the pelvic lymph nodes were diagnosed. Unfortunately, the tumor progressed despite multiple cycles of chemotherapy combined with cetuximab or bevacizumab. Within the follow-up treatment, the patient was administered with only 50Gy/25F of radiation dose to treat the anastomotic lesions. Subsequently, mono-sindilizumab was used as systemic therapy, leading to a rapid reduction of all pelvic lesions and complete clinical remission. So far, the patient survived for more than 20 months under continuous mono-sindilizumab treatment and is still in complete remission.ConclusionA localized radiotherapy combined with a sindilizumab-based systemic therapy may overcome the immune resistance of pMMR metastatic colorectal cancer (mCRC), thus obtaining greater efficacy of the therapy. Its mechanism may be related to the abscopal effect obtained by the synergistic use of radiation and sindilizumab, which should be further investigated in the future.
Improving dengue diagnosis and case confirmation in children by combining rapid diagnostic tests, clinical, and laboratory variables
Authors: Coronel-Ruiz Carolina , Velandia-Romero Myriam L. , Calvo Eliana , Camacho-Ortega Sigrid , Parra-Alvarez Shirly , Beltrán Edgar O. , Calderón-Pelaez María Angélica , Porras-Ramírez Alexandra , Cortés-Muñoz Fabián , Rojas-Hernandez Juan Pablo , Velasco-Alvarez Syrley , Pinzón-Junca Alfredo , Castellanos Jaime E. 
Published: March 2023

BackgroundDengue is the most widely distributed arboviral disease in tropical and subtropical countries. Most suspected cases are diagnosed according to the clinical criteria, and early diagnosis is difficult. Moreover, in underdeveloped countries, several factors continue to challenge the diagnosis and surveillance of dengue cases. This study aimed to design a diagnostic algorithm using rapid diagnostic tests (RDTs), ELISA tests, and clinical and hematological variables to confirm dengue cases in febrile patients in Colombia.MethodsAltogether, 505 samples were collected. Serum samples were evaluated by RDTs (IgM and IgG antibodies and NS1 antigen), capture IgM and IgG ELISAs, and endpoint hemi-nested RT-PCR assay (qualitative). We statistically analyzed the performance of individual tests to determine the most useful ones to confirm dengue cases accurately.ResultsIndividual results for IgM, IgG, and NS1 RDTs yielded lower sensitivity and specificity values than the reference standard. High sensitivity and specificity were obtained after combining IgM and NS1 ELISA results (96.3% and 96.4%) and NS1 RDT plus IgM ELISA results (90.3% and 96.2%), respectively. Adjusted odds ratios (aORs) were calculated for clinical variables and laboratory tests to differentiate dengue from other febrile illnesses (OFI). This approach showed that myalgia, abdominal tenderness, and platelet count were identified with higher sensitivity to confirm dengue cases. IgM RDT and NS1 RDT differentiated dengue cases from OFI. A positive IgM RDT or a positive NS1 RDT combined with specific signs or symptoms confirmed 81.6% of dengue cases. A combination of clinical findings and a positive NS1 RDT or positive ELISA IgM confirmed 90.6% of the cases.ConclusionOur findings showed that clinical diagnoses in pediatric population alone cannot confirm true dengue cases and needs to be complemented by laboratory diagnostic tests. We also demonstrate the usefulness of combining clinical criteria with RDTs, suggesting that their implementation with the IgM ELISA test improves dengue case confirmation.
EREG is a risk factor for the prognosis of patients with cervical cancer
Authors: Li Tianye , Feng Ruijing , Chen Bingxin , Zhou Jianwei 
Published: March 2023

BackgroundCervical cancer continues to threaten women's health worldwide. Identifying critical oncogenic molecules is important to drug development and prognosis prediction for patients with cervical cancer. Recent studies have demonstrated that epiregulin (EREG) is upregulated in various cancer types, which contributes to cancer progression by triggering the EGFR signaling pathway. However, the role of EREG is still unclear.MethodsIn this study, we first conducted a comprehensive biological analysis to investigate the expression of EREG in cervical cancer. Then, we investigated the correlations between EREG expression level and clinicopathological features. In addition, we validated the effects of EREG expression on the proliferation and apoptosis of cervical cancer cells.ResultsBased on the public database, we found that the expression of EREG was higher in advanced cervical cancer samples. Survival analysis showed that EREG was a risk factor for the prognosis of cervical cancer. In vitro experiments demonstrated that EREG knockdown undermined proliferation and promoted apoptosis in cancer cells.ConclusionEREG plays a vital role in the progression of cervical cancer, which contributes to hyperactive cell proliferation and decreased cell apoptosis. It might be a valuable target for prognosis prediction and drug development for cervical cancer in the future.
Optical character recognition on engineering drawings to achieve automation in production quality control
Authors: Villena Toro Javier , Wiberg Anton , Tarkian Mehdi 
Published: March 2023

Introduction: Digitization is a crucial step towards achieving automation in production quality control for mechanical products. Engineering drawings are essential carriers of information for production, but their complexity poses a challenge for computer vision. To enable automated quality control, seamless data transfer between analog drawings and CAD/CAM software is necessary.Methods: This paper focuses on autonomous text detection and recognition in engineering drawings. The methodology is divided into five stages. First, image processing techniques are used to classify and identify key elements in the drawing. The output is divided into three elements: information blocks and tables, feature control frames, and the rest of the image. For each element, an OCR pipeline is proposed. The last stage is output generation of the information in table format.Results: The proposed tool, called eDOCr, achieved a precision and recall of 90% in detection, an F1-score of 94% in recognition, and a character error rate of 8%. The tool enables seamless integration between engineering drawings and quality control.Discussion: Most OCR algorithms have limitations when applied to mechanical drawings due to their inherent complexity, including measurements, orientation, tolerances, and special symbols such as geometric dimensioning and tolerancing (GD&amp;T). The eDOCr tool overcomes these limitations and provides a solution for automated quality control.Conclusion: The eDOCr tool provides an effective solution for automated text detection and recognition in engineering drawings. The tool's success demonstrates that automated quality control for mechanical products can be achieved through digitization. The tool is shared with the research community through Github.
Modularity and neuronal heterogeneity: Two properties that influence in vitro neuropharmacological experiments
Authors: Brofiga Martina , Poggio Fabio , Callegari Francesca , Tedesco Mariateresa , Massobrio Paolo 
Published: March 2023

IntroductionThe goal of this work is to prove the relevance of the experimental model (in vitro neuronal networks in this study) when drug-delivery testing is performed.MethodsWe used dissociated cortical and hippocampal neurons coupled to Micro-Electrode Arrays (MEAs) arranged in different configurations characterized by modularity (i.e., the presence of interconnected sub-networks) and heterogeneity (i.e., the co-existence of neurons coming from brain districts). We delivered increasing concentrations of bicuculline (BIC), a neuromodulator acting on the GABAergic system, and we extracted the IC50 values (i.e., the effective concentration yielding a reduction in the response by 50%) of the mean firing rate for each configuration.ResultsWe found significant lower values of the IC50 computed for modular cortical-hippocampal ensembles than isolated cortical or hippocampal ones.DiscussionAlthough tested with a specific neuromodulator, this work aims at proving the relevance of ad hoc experimental models to perform neuropharmacological experiments to avoid errors of overestimation/underestimation leading to biased information in the characterization of the effects of a drug on neuronal networks.
MCP-1 levels in astrocyte-derived exosomes are changed in preclinical stage of Alzheimer's disease
Authors: Wang Ting , Yao Yunxia , Han Chao , Li Taoran , Du Wenying , Xue Jinhua , Han Ying , Cai Yanning 
Published: March 2023

BackgroundAlzheimer's disease (AD) is the most common form of dementia in older adults. There is accumulating evidence that inflammatory processes play a critical role in AD pathogenesis. In this study, we investigated whether inflammatory factors in plasma and astrocyte-derived exosomes (ADEs) from plasma are differentially expressed in the early stages of AD and their potential role in pathological processes in the AD continuum.MethodWe included 39 normal controls (NCs), 43 participants with subjective cognitive decline (SCD), and 43 participants with amnestic mild cognitive impairment (aMCI)/AD. IL-6, IL-8, and MCP-1 in plasma and ADEs from plasma were evaluated using a commercial multiplex Luminex-based kit.ResultsPairwise comparisons between the groups showed no significant differences in plasma levels of IL-6, IL-8, or MCP-1. However, ADEs in the SCD group showed an increase in MCP-1 levels compared to the NC group. To differentiate the preclinical group, discriminant analysis was performed using sex, age, years of education, and genotype. This revealed a difference between the SCD and NC groups (area under the curve: 0.664). A Spearman correlation analysis of MCP-1 in plasma and ADEs showed no or weak correlation in the SCD (R = 0.150, p = 0.350) and aMCI/AD (R = 0.310, p = 0.041) groups, while a positive correlation in the NC group (R = 0.360, p = 0.026).ConclusionPlasma IL-6, IL-8, and MCP-1 levels were not significantly different. However, the concentration of MCP-1 in ADEs is slightly altered during the preclinical phase of AD, which could be a potential role of the central neuron system (CNS) immune response in the AD continuum.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT03370744.
Absence of susceptibility vessel sign and hyperdense vessel sign in patients with cancer-related stroke
Authors: Beyeler Morin , Grunder Lorenz , Göcmen Jayan , Steinauer Fabienne , Belachew Nebiyat F. , Kielkopf Moritz , Clénin Leander , Mueller Madlaine , Silimon Norbert , Kurmann Christoph , Meinel Thomas , Bücke Philipp , Seiffge David , Dobrocky Tomas , Piechowiak Eike I. , Pilgram-Pastor Sara , Mattle Heinrich P. , Navi Babak B. , Arnold Marcel , Fischer Urs , Pabst Thomas , Gralla Jan , Berger Martin D. , Jung Simon , Kaesmacher Johannes 
Published: March 2023

Background and aimIdentification of paraneoplastic hypercoagulability in stroke patients helps to guide investigations and prevent stroke recurrence. A previous study demonstrated an association between the absence of the susceptibility vessel sign (SVS) on brain MRI and active cancer in patients treated with mechanical thrombectomy. The present study aimed to confirm this finding and assess an association between the absence of the hyperdense vessel sign (HVS) on head CT and active cancer in all stroke patients.MethodsSVS and HVS status on baseline imaging were retrospectively assessed in all consecutive stroke patients treated at a comprehensive stroke center between 2015 and 2020. Active cancer, known at the time of stroke or diagnosed within 1 year after stroke (occult cancer), was identified. Adjusted odds ratios (aOR) and their 95% confidence interval (CI) for the association between the thrombus imaging characteristics and cancer were calculated using multivariable logistic regression.ResultsOf the 2,256 patients with thrombus imaging characteristics available at baseline, 161 had an active cancer (7.1%), of which 36 were occult at the time of index stroke (1.6% of the total). The absence of SVS was associated with active cancer (aOR 3.14, 95% CI 1.45–6.80). No significance was reached for the subgroup of occult cancer (aOR 3.20, 95% CI 0.73–13.94). No association was found between the absence of HVS and active cancer (aOR 1.07, 95% CI 0.54–2.11).ConclusionThe absence of SVS but not HVS could help to identify paraneoplastic hypercoagulability in stroke patients with active cancer and guide patient care.