bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and experimental validation of mitochondria-related genes biomarkers associated with immune infiltration for sepsis
Authors: Shu Qi , She Han , Chen Xi , Zhong Like , Zhu Junfeng , Fang Luo 
Published: May 2023

BackgroundSepsis remains a complex condition with incomplete understanding of its pathogenesis. Further research is needed to identify prognostic factors, risk stratification tools, and effective diagnostic and therapeutic targets.MethodsThree GEO datasets (GSE54514, GSE65682, and GSE95233) were used to explore the potential role of mitochondria-related genes (MiRGs) in sepsis. WGCNA and two machine learning algorithms (RF and LASSO) were used to identify the feature of MiRGs. Consensus clustering was subsequently carried out to determine the molecular subtypes for sepsis. CIBERSORT algorithm was conducted to assess the immune cell infiltration of samples. A nomogram was also established to evaluate the diagnostic ability of feature biomarkers via “rms” package. ResultsThree different expressed MiRGs (DE-MiRGs) were identified as sepsis biomarkers. A significant difference in the immune microenvironment landscape was observed between healthy controls and sepsis patients. Among the DE-MiRGs, NDUFB3 was selected to be a potential therapeutic target and its significant elevated expression level was confirmed in sepsis using in vitro experiments and confocal microscopy, indicating its significant contribution to the mitochondrial quality imbalance in the LPS-simulated sepsis model. ConclusionBy digging the role of these pivotal genes in immune cell infiltration, we gained a better understanding of the molecular immune mechanism in sepsis and identified potential intervention and treatment strategies.
The applicability of transperceptual and deep learning approaches to the study and mimicry of complex cartilaginous tissues
Authors: Waghorne J. , Howard C. , Hu H. , Pang J. , Peveler W. J. , Harris L. , Barrera O. 
Published: May 2023

Introduction: Complex soft tissues, such as knee meniscus, play a crucial role in mobility and joint health but are incredibly difficult to repair and replace when damaged. This difficulty is due to the highly hierarchical and porous nature of the tissues, which, in turn, leads to their unique mechanical properties that provide joint stability, load redistribution, and friction reduction. To design tissue substitutes, the internal architecture of the native tissue needs to be understood and replicated.Methods: We explore a combined audiovisual approach, a so-called transperceptual approach, to generate artificial architectures mimicking the native architectures. The proposed methodology uses both traditional imagery and sound generated from each image to rapidly compare and contrast the porosity and pore size within the samples. We have trained and tested a generative adversarial network (GAN) on 2D image stacks of a knee meniscus. To understand how the resolution of the set of training images impacts the similarity of the artificial dataset to the original, we have trained the GAN with two datasets. The first consists of 478 pairs of audio and image files for which the images were downsampled to 64 × 64 pixels. The second dataset contains 7,640 pairs of audio and image files for which the full resolution of 256 × 256 pixels is retained, but each image is divided into 16 square sections to maintain the limit of 64 × 64 pixels required by the GAN.Results: We reconstructed the 2D stacks of artificially generated datasets into 3D objects and ran image analysis algorithms to characterize the architectural parameters statistically (pore size, tortuosity, and pore connectivity). Comparison with the original dataset showed that the artificially generated dataset based on the downsampled images performs best in terms of parameter matching, achieving between 4% and 8% of the mean of grayscale values of the pixels, mean porosity, and pore size of the native dataset.Discussion: Our audiovisual approach has the potential to be extended to larger datasets to explore how similarities and differences can be audibly recognized across multiple samples.
Uncovering transcriptomic landscape alterations of CAN-2409 in in vitro and in vivo glioma models
Authors: Koch Marilin S. , Zdioruk Mykola , Nowicki Michal O. , Hoetker Michael S. , Herbert Zachary T. , Barone Francesca , Tak Paul P. , Chiocca E. Antonio , Tabatabai Ghazaleh , Lawler Sean E. 
Published: May 2023

RationaleCAN-2409 is a locally delivered oncolytic therapy, which results in vaccination against the injected tumor. CAN-2409 consists of a non-replicating adenovirus armed with the Herpes virus thymidine kinase, which metabolizes ganciclovir into a phosphorylated nucleotide that is incorporated into the tumor cell’s genome, thereby inflicting immunogenic cancer cell death. While CAN-2409’s immunological impact has been well characterized, its effects on the tumor cells transcriptome remains unknown. We compared the transcriptomic landscape after treatment of glioblastoma models with CAN-2409 in vitro and in vivo to assess how the interplay with the tumor microenvironment influences CAN-2409-mediated transcriptome alterations.MethodsWe performed RNA-Seq with CAN-2409 treated patient-derived glioma stem-like cells and tumors of C57/BL6 mice and compared KEGG pathway usage and differential gene expression focusing on immune cell and cytokine profiles. T-cell -killing assays were performed to assess candidate effectors.ResultsPCA analysis showed distinct clustering of control and CAN-2409 samples under both conditions. KEGG pathway analysis revealed significant enrichment for p53 signaling and cell cycle pathway, with similar dynamics for key regulators of both pathways in vitro and in vivo, including MYC, CCNB1, PLK1 and CDC20. Selected alterations (PLK1 and CCNB1) were validated at the protein level. Cytokine expression analysis revealed upregulation of pro-inflammatory IL12a under both conditions; immune cell gene profiling showed reduction of myeloid associated genes. T-cell-killing assays showed increased killing in the presence of IL-12.ConclusionCAN-2409 significantly alters the transcriptome both in vitro and in vivo. Comparison of pathway enrichment revealed mutual and differential utilization of pathways under both conditions, suggesting a modulating influence on the cell cycle in tumor cells, and of the tumor microenvironment on the transcriptome in vivo. IL-12 synthesis likely depends on interactions with the tumor microenvironment, and it facilitates CAN-2409 cell killing. This dataset provides potential to understand resistance mechanisms and identify potential biomarkers for future studies.
“Huoling Shengji granule” for amyotrophic lateral sclerosis: protocol for a multicenter, randomized, double-blind, riluzole parallel controlled clinical trial
Authors: Liu Xiaolu , Qin Tingting , Li Tao , Shan Lei , Lei Xiang , Xu Xin , Wen Bin , Feng Yi , Yin Ping , Fan Dongsheng 
Published: May 2023

BackgroundThere is still a large demand for effective treatments to delay disease deterioration in amyotrophic lateral sclerosis (ALS). Typical symptoms of ALS are considered “flaccidity syndrome” in traditional Chinese medicine (TCM). Huoling Shengji Granule (HLSJ) is a TCM formula used to treat flaccidity syndrome. Results of preclinical tests and a previous clinical study support HLSJ as a novel drug for ALS patients. This trial proposed to examine whether a 48-week course of HLSJ is effective and safe for ALS patients diagnosed with the Chinese medicine syndrome of spleen qi insufficiency and kidney yang deficiency.Methods and analysisIn this phase II, multicenter, randomized, double-blind, riluzole parallel-controlled, superiority-design study, eligible participants had the equal opportunity to be assigned to receive either HLSJ or riluzole randomly. Eleven specialized ALS centers in Mainland China will recruit 144 patients for this trial. The primary and secondary outcomes included the change in the ALSFRS-R score and the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) from baseline to Week 48.DiscussionHere, we endeavored to evaluate TCM for ALS using a standard evidence-based approach for the first time. In addition, the ROADS, a self-report linear-weighted questionnaire, was selected as a secondary outcome measure. We expect to offer a new reference for the outcome evaluation of ALS trials.Clinical trial registration:http://www.Chictr.org.cn, identifier ChiCTR2100044085.
APOE as potential biomarkers of moyamoya disease
Authors: Wu Haibin , Xu Jiang , Sun Jiarong , Duan Jian , Xiao Jinlin , Ren Quan , Zhou Pengfei , Yan Jian , Li Youping , Xiong Xiaoxing , Zeng Erming 
Published: May 2023

ObjectiveThe mechanisms underpinning Moyamoya disease (MMD) remain unclear, and effective biomarkers remain unknown. The purpose of this study was to identify novel serum biomarkers of MMD.MethodsSerum samples were collected from 23 patients with MMD and 30 healthy controls (HCs). Serum proteins were identified using tandem tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) in the serum samples were identified using the SwissProt database. The DEPs were assessed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Gene Ontology (GO), and protein-protein interaction (PPI) networks, and hub genes were identified and visualized using Cytoscape software. Microarray datasets GSE157628, GSE189993, and GSE100488 from the Gene Expression Omnibus (GEO) database were collected. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified, and miRNA targets of DEGs were predicted using the miRWalk3.0 database. Serum apolipoprotein E (APOE) levels were compared in 33 MMD patients and 28 Moyamoya syndrome (MMS) patients to investigate the potential of APOE to be as an MMD biomarker.ResultsWe identified 85 DEPs, of which 34 were up- and 51 down-regulated. Bioinformatics analysis showed that some DEPs were significantly enriched in cholesterol metabolism. A total of 1105 DEGs were identified in the GSE157628 dataset (842 up- and 263 down-regulated), whereas 1290 were identified in the GSE189993 dataset (200 up- and 1,090 down-regulated). The APOE only overlaps with the upregulated gene expression in Proteomic Profiling and in GEO databases. Functional enrichment analysis demonstrated that APOE was associated with cholesterol metabolism. Moreover, 149 miRNAs of APOE were predicted in the miRWalk3.0 database, and hsa-miR-718 was the only DE-miRNA overlap identified in MMD samples. Serum APOE levels were significantly higher in patients with MMD than in those without. The performance of APOE as an individual biomarker to diagnose MMD was remarkable.ConclusionsWe present the first description of the protein profile of patients with MMD. APOE was identified as a potential biomarker for MMD. Cholesterol metabolism was found to potentially be related to MMD, which may provide helpful diagnostic and therapeutic insights for MMD.
Effects of transcutaneous neuromuscular electrical stimulation on post-stroke dysphagia: a systematic review and meta-analysis
Authors: Wang Yuhan , Xu Lu , Wang Linjia , Jiang Minjiao , Zhao Ling 
Published: May 2023

BackgroundDysphagia is one of the common complications after stroke. It is closely related to lung infection and malnutrition. Neuromuscular electrical stimulation (NMES) is widely used in the treatment of post-stroke dysphagia, but the evidence-based medical evidence of NMES is limited. Therefore, this study aimed to evaluate the clinical efficacy of NMES in patients with post-stroke dysphagia by systematic review and meta-analysis.MethodsWe searched the CNKI, Wanfang, VIP, SinoMed, PubMed, Embase, Cochrane Library, and Web of Science databases for all randomized controlled trials (RCTs) of NMES in the treatment of post-stroke dysphagia from the establishment of the database to 9 June 2022. The risk of bias assessment tool recommended by Cochrane and the GRADE method was used to assess the risk of bias and the quality of evidence. RevMan 5.3 was used for statistical analysis. Sensitivity and subgroup analyses were performed to evaluate the intervention effect more specifically.ResultsA total of 46 RCTs and 3,346 patients with post-stroke dysphagia were included in this study. Our meta-analysis showed that NMES combined with routine swallowing therapy (ST) could effectively improve swallowing function in Penetration-Aspiration Scale (MD = −0.63, 95% CI [−1.15, −0.12], P = 0.01), Functional Oral Intake Scale (MD = 1.32, 95% CI [0.81, 1.83], P &lt; 0.00001), Functional Dysphagia Scale (MD = − 8.81, 95% CI [−16.48, −1.15], P = 0.02), the Standardized Swallowing Assessment (MD = −6.39, 95% CI [−6.56, −6.22], P &lt; 0.00001), the Videofluoroscopic Swallow Study (MD = 1.42, 95% CI [1.28, 1.57], P &lt; 0.00001) and the Water swallow test (MD = −0.78, 95% CI [−0.84, −0.73], P &lt; 0.00001). Furthermore, it could improve the quality of life (MD = 11.90, 95% CI [11.10, 12.70], P &lt; 0.00001), increase the upward movement distance of hyoid bone (MD = 2.84, 95% CI [2.28, 3.40], P &lt; 0.00001) and the forward movement distance of hyoid bone (MD = 4.28, 95% CI [3.93, 4.64], P &lt; 0.00001), reduce the rate of complications (OR = 0.37, 95%CI [0.24, 0.57], P &lt; 0.00001). Subgroup analyses showed that NMES+ST was more effective at 25 Hz, 7 mA or 0–15 mA, and at courses ( ≤ 4 weeks). Moreover, patients with an onset of fewer than 20 days and those older than 60 years appear to have more positive effects after treatment.ConclusionNMES combined with ST could effectively increase the forward and upward movement distance of the hyoid bone, improve the quality of life, reduce the rate of complications, and improve the swallowing function of patients with post-stroke dysphagia. However, its safety needs to be further confirmed.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022368416.
Association of predicted fat mass and lean body mass with diabetes: a longitudinal cohort study in an Asian population
Authors: Kuang Maobin , Lu Song , Yang Ruijuan , Chen Huaigang , Zhang Shuhua , Sheng Guotai , Zou Yang 
Published: May 2023

ObjectiveThe relationship between body composition fat mass (FM) and lean body mass (LBM) and diabetes risk is currently debated, and the purpose of this study was to examine the association of predicted FM and LBM with diabetes in both sexes.MethodsThe current study was a secondary analysis of data from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) cohort study of 15,463 baseline normoglycemic participants. Predicted LBM and FM were calculated for each participant using anthropometric prediction equations developed and validated for different sexes based on the National Health and Nutrition Examination Survey (NHANES) database, and the outcome of interest was diabetes (types not distinguished) onset. Multivariate Cox regression analyses were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of predicted FM and LBM with diabetes risk and further visualized their associations using a restricted cubic spline function.ResultsThe incidence density of diabetes was 3.93/1000 person-years over a mean observation period of 6.13 years. In women, predicted LBM and FM were linearly associated with diabetes risk, with each kilogram increase in predicted LBM reducing the diabetes risk by 65% (HR 0.35, 95%CI 0.17, 0.71; P &lt; 0.05), whereas each kilogram increase in predicted FM increased the diabetes risk by 84% (HR 1.84, 95%CI 1.26, 2.69; P &lt; 0.05). In contrast, predicted LBM and FM were non-linearly associated with diabetes risk in men (all P for non-linearity &lt; 0.05), with an L-shaped association between predicted LBM and diabetes risk and a saturation point that minimized the risk of diabetes was 45.4 kg, while predicted FM was associated with diabetes risk in a U-shape pattern and a threshold point with the lowest predicted FM-related diabetes risk was 13.76 kg.ConclusionIn this Asian population cohort, we found that high LBM and low FM were associated with lower diabetes risk according to anthropometric equations. Based on the results of the non-linear analysis, we believed that it may be appropriate for Asian men to keep their LBM above 45.4 kg and their FM around 13.76 kg.
Analysis of predictors of malnutrition in adult hospitalized patients: social determinants and food security
Authors: Ouaijan Krystel , Hwalla Nahla , Kandala Ngianga-Bakwin , Abi Kharma Joelle , Kabengele Mpinga Emmanuel 
Published: May 2023

BackgroundMalnutrition in hospitalized patients is becoming a priority during the patient care process due to its implications for worsening health outcomes. It can be the result of numerous social factors beyond clinical ones. This study aimed to evaluate the link between these various risk factors considered social determinants of health, food security levels, and malnutrition and to identify potential predictors.MethodsA cross-sectional observational study was conducted on a random sample of adult patients in five different hospitals in Lebanon. Malnutrition was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Patients were interviewed to collect social and economic characteristics and were categorized into four criteria: (1) area of residence (urbanization level), (2) level of education, (3) employment status, and (4) source of health coverage. The food security level was screened by a validated two-question tool, adapted from the US Department of Agriculture Household Food Security Survey, targeting both quantity and quality.ResultsIn a random sample of 343 patients, the prevalence of malnutrition according to the GLIM criteria was 35.6%. Patients with low levels of food security, mainly low quality of food, had higher odds of being malnourished (OR = 2.93). Unemployed or retired patients and those who have only completed only elementary school had higher odds of being diagnosed with malnutrition as compared to those who were employed or had university degrees, respectively (OR = 4.11 and OR = 2.33, respectively). Employment status, education level, and type of health coverage were identified as predictors of malnutrition in the multiple regression model. Household location (urban vs. rural) was not associated with malnutrition.ConclusionThe social determinants of health identified in our study, mainly the level of education and income level, in addition to food security, were identified as predictors of malnutrition in hospitalized patients. These findings should guide healthcare professionals and national policies to adopt a broader perspective in targeting malnutrition by including social determinants in their nutrition care.
Gene mutation landscape of a rare patient with acute megakaryoblastic leukemia after treatment of intracranial germ cell tumor
Authors: Wang Li-Xin , Liao Wei-Jie , Jiang Yu-Hua , Chen Chao , Lu Wang-Sheng , Yin Feng , Ning Hao-Yong 
Published: May 2023

IntroductionIt was first reported that germ cell tumor patients suffer from hematologic malignancies 37 years ago. Since then, the number of relevant reports has increased each year, with most cases being mediastinal germ cell tumor. Theories have been proposed to explain this phenomenon, including a shared origin of progenitor cells, the effects of treatment, and independent development. However, up to now, no widely accepted explanation exists. The case with acute megakaryoblastic leukemia and intracranial germ cell tumor has never been reported before and the association is far less known.MethodsWe used whole exome sequencing and gene mutation analysis to study the relationship between intracranial germ cell tumor and acute megakaryoblastic leukemia of our patient.ResultsWe report a patient who developed acute megakaryoblastic leukemia after treatment for an intracranial germ cell tumor. Through whole exome sequencing and gene mutation analysis, we identified that both tumors shared the same mutation genes and mutation sites, suggesting they originated from the same progenitor cells and differentiated in the later stage.DiscussionOur findings provide the first evidence supporting the theory that acute megakaryoblastic leukemia and intracranial germ cell tumor has the same progenitor cells.
Survival and complications after neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for locally advanced gastric cancer: a systematic review and meta-analysis
Authors: Zhu Youqi , Chen Jiuzhou , Sun Xueqing , Lou Yufei , Fang Miao , Zhou Fengjuan , Zhang Lei , Xin Yong 
Published: May 2023

BackgroundThere is increasing evidence that neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. However, a number of studies have come to the opposite conclusion. Therefore, our meta-analysis is to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer.MethodsWe searched Wanfang Database, China National Knowledge Network database, VIP database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library. The searched terms included’Stomach Neoplasms’, ‘Neoadjuvant Therapy’ and ‘Chemoradiotherapy’. The retrieval time was from the establishment of the corresponding database to September 2022, and our meta-analysis was performed using RevMan (version 5.3) and Stata (version 17) software.ResultsA total of 17 literatures were included, which involved 7 randomized controlled trials and 10 retrospective studies, with a total of 6831 patients. The results of meta-analysis showed that compared with NACT group, the complete response rate(RR=1.95, 95%CI 1.39-2.73, p=0.0001), the partial response rate(RR=1.44, 95%CI 1.22-1.71, p=0.0001), the objective response rate(RR=1.37, 95%CI 1.27-1.54, p=0.00001), the pathologic complete response rate(RR=3.39, 95%CI 2.17-5.30, p=0.00001), the R0 resection rate(RR=1.18, 95%CI 1.09-1.29, p=0.0001) and 3-year overall survival rate(HR=0.89, 95%CI 0.82-0.96, p=0.002) of neoadjuvant chemoradiotherapy group were significantly improved. The results of subgroup analyses of gastric cancer subgroup and gastroesophageal junction cancer subgroup were consistent with the overall results. Meanwhile, the stable disease(RR=0.59, 95%CI:0.44-0.81, P=0.0010) of neoadjuvant chemoradiotherapy group was lower than that of neoadjuvant chemotherapy group, and there were no statistical significance in the progressive disease rate(RR=0.57, 95%CI:0.31-1.03, P=0.06), five-year overall survival rate(HR=1.03, 95%CI:0.99-1.07, P=0.839), postoperative complications and adverse reactions between the neoadjuvant chemoradiotherapy group and neoadjuvant chemotherapy group.ConclusionCompared with neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy might bring more survival benefits without significantly increasing adverse reactions. neoadjuvant chemoradiotherapy may be a recommended treatment for patients with locally advanced gastric cancer.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-12-0068/, identifier INPLASY202212068.