bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe pediatric acute encephalopathy syndromes related to SARS-CoV-2
Authors: Sakuma Hiroshi , Takanashi Jun-ichi , Muramatsu Kazuhiro , Kondo Hidehito , Shiihara Takashi , Suzuki Motomasa , Okanari Kazuo , Kasai Mariko , Mitani Osamu , Nakazawa Tomoyuki , Omata Taku , Shimoda Konomi , Abe Yuichi , Maegaki Yoshihiro , Murayama Kei , Murofushi Yuka , Nagase Hiroaki , Okumura Akihisa , Sakai Yasunari , Tada Hiroko , Mizuguchi Masashi ,   Japanese Pediatric Neuro-COVID-19 Study Group
Published: March 2023

Background and objectivesTo clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes.MethodsA nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged &lt; 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting &gt; 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge.ResultsOf the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group (P &lt; 0.01).DiscussionAcute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes.
Triose-phosphate isomerase deficiency is associated with a dysregulation of synaptic vesicle recycling in Drosophila melanogaster
Authors: Stone Aelfwin , Cujic Oliver , Rowlett Angel , Aderhold Sophia , Savage Emma , Graham Bruce , Steinert Joern R. 
Published: March 2023

IntroductionNumerous neurodegenerative diseases are associated with neuronal dysfunction caused by increased redox stress, often linked to aberrant production of redox-active molecules such as nitric oxide (NO) or oxygen free radicals. One such protein affected by redox-mediated changes is the glycolytic enzyme triose-phosphate isomerase (TPI), which has been shown to undergo 3-nitrotyrosination (a NO-mediated post-translational modification) rendering it inactive. The resulting neuronal changes caused by this modification are not well understood. However, associated glycation-induced cytotoxicity has been reported, thus potentially causing neuronal and synaptic dysfunction via compromising synaptic vesicle recycling.MethodsThis work uses Drosophila melanogaster to identify the impacts of altered TPI activity on neuronal physiology, linking aberrant TPI function and redox stress to neuronal defects. We used Drosophila mutants expressing a missense allele of the TPI protein, M81T, identified in a previous screen and resulting in an inactive mutant of the TPI protein (TPIM81T, wstd1). We assessed synaptic physiology at the glutamatergic Drosophila neuromuscular junction (NMJ), synapse morphology and behavioural phenotypes, as well as impacts on longevity.ResultsElectrophysiological recordings of evoked and spontaneous excitatory junctional currents, alongside high frequency train stimulations and recovery protocols, were applied to investigate synaptic depletion and subsequent recovery. Single synaptic currents were unaltered in the presence of the wstd1 mutation, but frequencies of spontaneous events were reduced. Wstd1 larvae also showed enhanced vesicle depletion rates at higher frequency stimulation, and subsequent recovery times for evoked synaptic responses were prolonged. A computational model showed that TPI mutant larvae exhibited a significant decline in activity-dependent vesicle recycling, which manifests itself as increased recovery times for the readily-releasable vesicle pool. Confocal images of NMJs showed no morphological or developmental differences between wild-type and wstd1 but TPI mutants exhibited learning impairments as assessed by olfactory associative learning assays.DiscussionOur data suggests that the wstd1 phenotype is partially due to altered vesicle dynamics, involving a reduced vesicle pool replenishment, and altered endo/exocytosis processes. This may result in learning and memory impairments and neuronal dysfunction potentially also presenting a contributing factor to other reported neuronal phenotypes.
Bi-directional causal effect between vitamin B12 and non-alcoholic fatty liver disease: Inferring from large population data
Authors: Fu Liwan , Wang Yuquan , Hu Yue-Qing 
Published: March 2023

ObjectivesMany observational studies evaluate the association between vitamin B12 and non-alcoholic fatty liver disease (NAFLD). However, the causality of this association remains uncertain, especially in European populations. We conducted a bidirectional Mendelian randomization study to explore the association between vitamin B12 and NAFLD.MethodsTwo-sample Mendelian randomization study was conducted. Summary statistics for vitamin B12 were acquired from a genome-wide association studies (GWAS) meta-analysis including 45,576 subjects. Summary-level data for NAFLD was obtained from a GWAS meta-analysis of 8,434 cases and 770,180 non-cases and another GWAS meta-analysis of 1,483 cases and 17,781 non-cases. Summary-level data for 4 enzymes including alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GGT), was available from the UK Biobank. Inverse variance weighting (as main analysis), weighted median estimate, robust adjusted profile score, MR-Egger, and MR-PRESSO (sensitivity analyses) were performed to calculate causal estimates.ResultsGenetically predicted higher vitamin B12 concentrations were consistently associated with an increased NAFLD in two sources. The combined odds ratio (OR) of NAFLD was 1.30 (95% confidence interval (CI), 1.13 to 1.48; p &lt; 0.001) per SD-increase in vitamin B12 concentrations. Genetic liability to NAFLD was also positively associated with vitamin B12 concentrations (Beta 0.08, 95%CI, 0.01 to 0.16; p = 0.034). Sensitivity analyses also revealed consistent results. Genetically predicted vitamin B12 concentrations showed no significant association with liver enzymes.ConclusionThe present study indicates that increased serum vitamin B12 concentrations may play a role in NAFLD risk. NAFLD also has a causal impact on elevated vitamin B12 concentrations in the circulation. Notably, vitamin B12 concentrations imply the levels of vitamin B12 in the circulation, and higher intake of vitamin B12 may not directly lead to higher levels of serum vitamin B12, instead the higher levels of vitamin B12 in the circulation may be caused by the dysregulation of the metabolism of this vitamin in this study. There exist bidirectional causal effects between serum vitamin B12 concentrations and risk of NAFLD in European individuals.
Metabolic classification of non-small cell lung cancer patient-derived xenografts by a digital pathology approach: A pilot study
Authors: Ferrarini Federica , Zulato Elisabetta , Moro Massimo , Del Bianco Paola , Borzi Cristina , Esposito Giovanni , Zanin Tiziana , Sozzi Gabriella , Indraccolo Stefano 
Published: March 2023

IntroductionGenetically characterized patient-derived tumor xenografts (PDX) are a valuable resource to understand the biological complexity of cancer and to investigate new therapeutic approaches. Previous studies, however, lack information about metabolic features of PDXs, which may limit testing of metabolism targeting drugs.MethodsIn this pilot study, we investigated by immunohistochemistry (IHC) expression of five essential metabolism-associated markers in a set of lung adenocarcinoma PDX samples previously established and characterized. We exploited digital pathology to quantify expression of the markers and correlated results with tumor cell proliferation, angiogenesis and time of PDX growth in mice.ResultsOur results indicate that the majority of the analyzed PDX models rely on oxidative phosphorylation (OXPHOS) metabolism, either alone or in combination with glucose metabolism. Double IHC enabled us to describe spatial expression of the glycolysis-associated monocarboxylate transporter 4 (MCT4) marker and the OXPHOS-associated glutaminase (GLS) marker. GLS expression was associated with cell proliferation and with expression of liver-kinase B1 (LKB1), a tumor suppressor involved in the regulation of multiple metabolic pathways. Acetyl CoA carboxylase (ACC) was associated with the kinetics of PDX growth.ConclusionAlbeit limited by the small number of samples and markers analyzed, metabolic classification of existing collections of PDX by this mini panel will be useful to inform pre-clinical testing of metabolism-targeting drugs.
Prognostic and immunological characteristics of CDK1 in lung adenocarcinoma: A systematic analysis
Authors: Du Qingwu , Liu Wenting , Mei Ting , Wang Jingya , Qin Tingting , Huang Dingzhi 
Published: March 2023

BackgroundCyclin-dependent kinases (CDKs) play a key role in cell proliferation in lung adenocarcinoma (LUAD). Comprehensive analysis of CDKs to elucidate their clinical significance and interactions with the tumor immune microenvironment is needed.MethodsRNA expression, somatic mutation, copy number variation, and single-cell RNA sequencing data were downloaded from public datasets. First, we comprehensively evaluated the expression profile and prognostic characteristics of 26 CDKs in LUAD, and CDK1 was selected as a candidate for further analysis. Then, a systematic analysis was performed to explore the relationships of CDK1 with clinical characteristics and tumor immune microenvironment factors in LUAD.ResultsCDK1 was markedly upregulated at both the mRNA and protein level in LUAD. Moreover, overexpression of CDK1 was related to poor clinical outcomes. CDK1 coexpressed genes were mainly involved in the cell cycle, the DNA repair process, and the p53 signaling pathway. In addition, CDK1 expression was found to be correlated with the expression of multiple immunomodulators and chemokines, which participate in activating and suppressing the immune microenvironment. CDK1 expression was also correlated with increased infiltration of numerous immune cells, including CD4+ T cells and M1 macrophages. Patients with high CDK1 expression tended to have a poor response to immunotherapy but were sensitive to multiple chemotherapies and targeted drugs. The MDK-NCL and SPP1-CD44 ligand−receptor pairs were markedly activated in the intercellular communication network. CDK1 was an independent prognostic factor for LUAD and improved the ability to predict overall survival when combined with tumor stage.ConclusionCDK1 plays an essential role in reshaping the tumor immune microenvironment and might be a prognostic and treatment biomarker in LUAD.
Mapping trends and hotspot regarding testicular torsion: A bibliometric analysis of global research (2000–2022)
Authors: Hu Shaowen , Guo Mingjie , Xiao Yafei , Li Yang , Luo Qingyang , Li Zun , Zhu Chaoyang 
Published: March 2023

BackgroundTesticular torsion is an acute scrotal disorder requiring immediate emergency treatment. Ischemic injury and reperfusion injury are important causes of oxidative stress and irreversible oxidative damage after testicular torsion. Although a large number of literatures have discussed the causes and treatment of testicular torsion, there is currently a lack of systematic exploration of the historical evolution of testicular torsion and the construction of a knowledge framework.MethodThe Web of Science Core Collection was searched for studies on testicular torsion published between 2000 and 2022. The basic data of the literature were analyzed by using Excel and CiteSpace software.ResultA total of 1,007 publications on testicular torsion published were found in 64 countries between 2000 and 2022, with an increasing annual publication level. Early detection, early diagnosis and early treatment of testicular torsion had always been at the core of clinical practice, and the pathological cascade reaction of ischemic injury and ischemia-reperfusion injury after testicular torsion were also at the core of basic research. Emphasis had been placed on the development of protective drugs for ischemia and reperfusion after testicular torsion in various countries, regions and institutions.ConclusionOver the past 20 years, the research on testicular torsion had been widely concerned. Hot topics in testicular torsion in recent years were ischemia-reperfusion injury, oxidative stress, rat, doppler ultrasonography, diagnosis and orchiectomy. This article may provide a useful resource for clinicians and basic researchers regarding testicular torsion.
Detection of enterovirus in cerebrospinal fluids without pleocytosis in febrile infants under 3 months old reduces antibiotherapy duration
Authors: Blachez Marion , Boussier Jeremy , Mariani Patricia , Caula Caroline , Gaschignard Jean , Lefèvre-Utile Alain 
Published: March 2023

BackgroundInfants under 3 months old with fever often receive empirical antibiotic treatment. Enterovirus is one of the leading causes of infection and aseptic meningitis but is not systematically screened. We aimed to evaluate enterovirus positive RT-PCR proportion in cerebrospinal fluid (CSF) with no pleocytosis and its impact on antibiotic treatment duration.MethodsDuring the enterovirus endemic season, from 2015 to 2018, we retrospectively studied infants under 3 months old, consulting for fever without cause, with normal CSF analysis, and receiving empirical antibiotic treatment. Clinical and biological data were analyzed, notably enterovirus RT-PCR results. The primary outcome was the duration of antibiotic therapy.Results92 patients were recruited. When tested, 41% of infants were positive for enterovirus, median antibiotic duration was reduced in enterovirus positive in comparison to negative patients with respectively 1.9 [interquartile range (IQR), 1.7–2] vs. 4.1 [IQR, 2–6], p &lt; 0.001. No clinical nor biological features differed according to the enterovirus status.ConclusionIn this population, enterovirus positive CSF are frequent despite the absence of pleocytosis. However, its research was not guided by clinical or biological presentations. Systematic and routine use of enterovirus RT-PCR during enterovirus season, regardless of CSF cell count, could reduce the prescription of antibiotics in febrile infants under 3 months old without clinical orientation.
The efficacy and safety of Chinese herbal medicine in the treatment of painful diabetic neuropathy: A systematic review and meta-analysis
Authors: Song Min , Huai Baogeng , Shi Zhenpeng , Li Wenyi , Xi Yutan , Liu Zhenguo , Zhang Jihang , Zhou Junyu , Qiao Yun , Liu Deshan 
Published: March 2023

Objective: The objective of this systematic review and meta-analysis is to assess the effectiveness and security of Chinese herbal medicine (CHM) in the therapy of painful diabetic neuropathy (PDN).Methods: We searched databases for randomized controlled trials (RCTs) of CHM in the treatment of PDN. Outcome indicators included nerve conduction velocity, clinical efficiency, pain score, TCM syndrome score, and adverse events. Stata 16.0 was used to carry out the Meta-analysis.Results: A total of 21 RCTs with 1,737 participants were included. This meta-analysis found that using CHM as adjuvant treatment or as monotherapy for PDN can improve SCV of median nerve [mean difference (MD) = 3.56, 95% Confidence interval (CI) (2.19, 4.92) ], MCV of median nerve [ MD = 3.82, 95% CI (2.51, 5.12) ], SCV of common peroneal nerve [ MD = 4.16, 95% CI (1.62, 6.70) ], MCV of common peroneal nerve [ MD = 4.37, 95% CI (1.82, 6.93) ], SCV of gastrocnemius nerve [ MD = 4.95, 95% CI (3.52, 6.37) ], SCV of tibial nerve [ MD = 3.17, 95% CI (−2.64, 8.99) ], MCV of tibial nerve [MD = 6.30, 95%CI (5.00, 7.60)] and clinical effective rate [ odds ratio (OR) = 4.00, 95% CI (2.89, 5.52) ] and reduce pain score [standardized mean difference (SMD) = -2.23, 95% CI (-3.04, -1.41) ], TCM syndrome score [ MD = -4.70, 95% CI (-6.61, -2.80) ]. In addition, compared to the control group, adverse events of Chinese medicine intervention occurred less.Conclusion: CHM as adjuvant therapy or single treatment has a good curative effect and is safe for patients with PDN, which is worthy of clinical promotion and use, however; higher quality clinical studies are still needed to prove.Systematic Review Registration:https://www.crd.york.ac.uk/, identifier CRD42022327967
Ethyl-acetate fraction from a cinnamon-cortex extract protects pancreatic β-cells from oxidative stress damage
Authors: Li Weiling , Qiao Jialu , Lin Kuan , Sun Ping , Wang Yuansong , Peng Qian , Ye Xiansheng , Liu Wei , Sun Binlian 
Published: March 2023

Background: The pathogenesis of diabetes mellitus is mediated mainly by oxidative stress produced by damaged pancreatic β-cells. We identified that an ethyl-acetate fraction (EA) from a cinnamon-cortex extract (CCE) is rich in flavonoid, and showed no toxicity to β cells.Objective: In this study, we evaluated the pharmacologic activities of EA on pancreatic β cells using a model of oxidative stress induced by H2O2 or alloxan.Results: The results showed that EA could significantly reduce reactive oxygen (ROS) accumulation to improve the survival of cells. Western blot showed that EA treatment upregulated expression of nuclear factor erythroid 2 related factor 2, heme oxygenase-1, and gamma glutamylcysteine synthetase. The same model study found that EA also can protect β cells against the apoptosis induced by oxidative stress. Furthermore, EA can enhance insulin secretion in rat and mouse β cell lines treated or not with alloxan or H2O2. The expression of the insulin transcription factor PDX-1 increased in an EA concentration-dependent manner. At last, the major functional compounds of EA analysis showed that three compounds, cinnamyl alcohol, coumarin, and cinnamic acid, had similar effects as EA.Conclusions: In sum, our data suggested that EA fraction from CCE can protect β cells from oxidative stress, and increase insulin secretion to improve the function of β cells. This function might be due to these three compounds found in EA. Our findings provide a theoretical basis and functional molecules for the use of CCE against diabetes mellitus.
A new molecular subclassification and in silico predictions for diagnosis and prognosis of papillary thyroid cancer by alternative splicing profile
Authors: Li Haiyan , Lan Hao , Li Menglong , Pu Xuemei , Guo Yanzhi 
Published: March 2023

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. However, different PTC variants reveal high heterogeneity at histological, cytological, molecular and clinicopathological levels, which complicates the precise diagnosis and management of PTC. Alternative splicing (AS) has been reported to be potential cancer biomarkers and therapeutic targets.Method: Here, we aim to find a more sophisticated molecular subclassification and characterization for PTC by integrating AS profiling. Based on six differentially expressed alternative splicing (DEAS) events, a new molecular subclassification was proposed to reclassify PTC into three new groups named as Cluster0, Cluster1 and Cluster2 respectively.Results: An in silico prediction was performed for accurate recognition of new groups with the average accuracy of 91.2%. Moreover, series of analyses were implemented to explore the differences of clinicopathology, molecular and immune characteristics across them. It suggests that there are remarkable differences among them, but Cluster2 was characterized by poor prognosis, higher immune heterogeneity and more sensitive to anti-PD1 therapy. The splicing correlation networks proved the complicated regulation relationships between AS events and splicing factors (SFs). An independent prognostic indicator for PTC overall survival (OS) was established. Finally, three compounds (orantinib, tyrphostin-AG-1295 and AG-370) were discovered to be the potential therapeutic agents.Discussion: Overall, the six DEAS events are not only potential biomarkers for precise diagnosis of PTC, but also the probable prognostic predictors. This research would be expected to highlight the effect of AS events on PTC characterization and also provide new insights into refining precise subclassification and improving medical therapy for PTC patients.
Construction of anoikis-related lncRNAs risk model: Predicts prognosis and immunotherapy response for gastric adenocarcinoma patients
Authors: Li Qinglin , Zhang Huangjie , Hu Jinguo , Zhang Lizhuo , Zhao Aiguang , Feng He 
Published: March 2023

Background: Anoikis acts as a programmed cell death that is activated during carcinogenesis to remove undetected cells isolated from ECM. Further anoikis based risk stratification is expected to provide a deeper understanding of stomach adenocarcinoma (STAD) carcinogenesis.Methods: The information of STAD patients were acquired from TCGA dataset. Anoikis-related genes were obtained from the Molecular Signatures Database and Pearson correlation analysis was performed to identify the anoikis-related lncRNAs (ARLs). We performed machine learning algorithms, including Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (Lasso) analyses on the ARLs to build the OS-score and OS-signature. Clinical subgroup analysis, tumor mutation burden (TMB) detection, drug susceptibility analysis, immune infiltration and pathway enrichment analysis were further performed to comprehensive explore the clinical significance.Results: We established a STAD prognostic model based on five ARLs and its prognostic value was verified. Survival analysis showed that the overall survival of high-risk score patients was significantly shorter than that of low-risk score patients. The column diagrams show satisfactory discrimination and calibration. The calibration curve verifies the good agreement between the prediction of the line graph and the actual observation. TIDE analysis and drug sensitivity analysis showed significant differences between different risk groups.Conclusion: The novel prognostic model based on anoikis-related lncRNAs we identified could be used for prognosis prediction and precise therapy in gastric adenocarcinoma.