bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-22-3p as a potential biomarker for coronary artery disease based on integrated bioinformatics analysis
Authors: Zhang Minghua , Hu Yan , Li Haoda , Guo Xiaozi , Zhong Junhui , He Sha 
Published: August 2022

Background: Coronary artery disease (CAD) is a common cardiovascular disease that has attracted attention worldwide due to its high morbidity and mortality. Recent studies have shown that abnormal microRNA (miRNA) expression is effective in CAD diagnoses and processes. However, the potential relationship between miRNAs and CAD remains unclear.Methods: Microarray datasets GSE105449 and GSE28858 were downloaded directly from the Gene Expression Omnibus (GEO) to identify miRNAs involved in CAD. Target gene prediction and enrichment analyses were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Results: There were nine differentially expressed miRNAs in CAD patients compared to the controls. A total of 352 genes were predicted and subjected to GO analysis, which showed that differentially expressed genes (DEGs) were mainly associated with axon guidance, neuron projection guidance, neuron-to-neuron synapses, and postsynaptic density. According to the KEGG pathway analysis, the most enriched pathways were those involved in transcriptional misregulation in cancer, growth hormone synthesis, secretion and action, endocrine resistance, axon guidance, and Cushing syndrome. Pathway analysis was mainly involved in the HIPPO and prion disease signaling pathways. Furthermore, a competing endogenous RNA (ceRNA) interaction network centered on miR-22-3p revealed eight related transcription factors in the cardiovascular system. The receiver operating characteristic (ROC) curve analysis suggested that miR-22-3p may be a better CAD predictor.Conclusion: The results indicate that miR-22-3p may function in pathophysiological CAD processes. Our study potentiates miR-22-3p as a specific biomarker for diagnosing CAD.
Hierarchical identification of a transcriptional panel for the histological diagnosis of lung neuroendocrine tumors
Authors: Zhang Juxuan , Deng Jiaxing , Feng Xiao , Tan Yilong , Li Xin , Liu Yixin , Li Mengyue , Qi Haitao , Tang Lefan , Meng Qingwei , Yan Haidan , Qi Lishuang 
Published: August 2022

Background: Lung cancer is a complex disease composed of neuroendocrine (NE) and non-NE tumors. Accurate diagnosis of lung cancer is essential in guiding therapeutic management. Several transcriptional signatures have been reported to distinguish between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) belonging to non-NE tumors. This study aims to identify a transcriptional panel that could distinguish the histological subtypes of NE tumors to complement the morphology-based classification of an individual.Methods: A public dataset with NE subtypes, including 21 small-cell lung cancer (SCLC), 56 large-cell NE carcinomas (LCNECs), and 24 carcinoids (CARCIs), and non-NE subtypes, including 85 ADC and 61 SCC, was used as a training set. In the training set, consensus clustering was first used to filter out the samples whose expression patterns disagreed with their histological subtypes. Then, a rank-based method was proposed to develop a panel of transcriptional signatures for determining the NE subtype for an individual, based on the within-sample relative gene expression orderings of gene pairs. Twenty-three public datasets with a total of 3,454 samples, which were derived from fresh-frozen, formalin-fixed paraffin-embedded, biopsies, and single cells, were used for validation. Clinical feasibility was tested in 10 SCLC biopsy specimens collected from cancer hospitals via bronchoscopy.Results: The NEsubtype-panel was composed of three signatures that could distinguish NE from non-NE, CARCI from non-CARCI, and SCLC from LCNEC step by step and ultimately determine the histological subtype for each NE sample. The three signatures achieved high average concordance rates with 97.31%, 98.11%, and 90.63%, respectively, in the 23 public validation datasets. It is worth noting that the 10 clinic-derived SCLC samples diagnosed via immunohistochemical staining were also accurately predicted by the NEsubtype-panel. Furthermore, the subtype-specific gene expression patterns and survival analyses provided evidence for the rationality of the reclassification by the NEsubtype-panel.Conclusion: The rank-based NEsubtype-panel could accurately distinguish lung NE from non-NE tumors and determine NE subtypes even in clinically challenging samples (such as biopsy). The panel together with our previously reported signature (KRT5-AGR2) for SCC and ADC would be an auxiliary test for the histological diagnosis of lung cancer.
Case report: Cystic hygroma accompanied with campomelic dysplasia in the first trimester caused by haploinsufficiency with SOX9 deletion
Authors: Liu Xijing , Wang Jianmin , Yang Mei , Tian Tian , Hu Ting 
Published: August 2022

Introduction: Campomelic dysplasia (CD) is a rare autosomal dominant skeletal malformation syndrome characterized by shortness and bowing of the lower extremities with or without XY sex reversal. Diagnosis using ultrasonography is most often made in the latter half of pregnancy. Intragenic heterozygous mutations in SOX9 are responsible for most cases of CD. CD caused by SOX9 deletion is a rare condition.Case presentation: We present a single case report of an individual with cystic hygroma accompanied by CD, which was detected by ultrasound in the first trimester. Chromosomal microarray analysis (CMA) was performed to determine copy number variants, whereas whole exome sequencing (WES) was performed to elucidate single-nucleotide variants. Chorionic villus sampling was performed to enable such analyses. Ultimately, CMA detected a 606 kb deletion in the 17q24.3 region with only one protein-coding gene (SOX9). However, no mutation in the SOX9 protein-coding sequence was detected by WES.Conclusion: When cystic hygroma is detected, prenatal diagnoses for skeletal dysplasia by ultrasound are likely to be confirmed in the first trimester. We propose a comprehensive prenatal diagnostic strategy that combines CMA and WES to diagnose fetuses with cystic hygroma accompanied by skeletal dysplasia.
An integrative analysis of DNA methylation and gene expression to predict lung adenocarcinoma prognosis
Authors: Xu Liexi , Huang Zhengrong , Zeng Zihang , Li Jiali , Xie Hongxin , Xie Conghua 
Published: August 2022

Background: Abnormal DNA methylation of gene promoters is an important feature in lung adenocarcinoma (LUAD). However, the prognostic value of DNA methylation remains to be further explored. Objectives. We sought to explore DNA methylation characteristics and develop a quantifiable criterion related to DNA methylation to improve survival prediction for LUAD patients.Methods: Illumina Human Methylation450K array data, level 3 RNA-seq data and corresponding clinical information were obtained from TCGA. Cox regression analysis and the Akaike information criterion were used to construct the best-prognosis methylation signature. Receiver operating characteristic curve analysis was used to validate the prognostic ability of the DNA methylation-related feature score. qPCR was used to measure the transcription levels of the identified genes upon methylation.Results: We identified a set of DNA methylation features composed of 11 genes (MYEOV, KCNU1, SLC27A6, NEUROD4, HMGB4, TACR3, GABRA5, TRPM8, NLRP13, EDN3 and SLC34A1). The feature score, calculated based on DNA methylation features, was independent of tumor recurrence and TNM stage in predicting overall survival. Of note, the combination of this feature score and TNM stage provided a better overall survival prediction than either of them individually. The transcription levels of all the hypermethylated genes were significantly increased after demethylation, and the expression levels of 3 hypomethylated proteins were significantly higher in tumor tissues than in normal tissues, as indicated by immunohistochemistry data from the Human Protein Atlas. Our results suggested that these identified genes with prognostic features were regulated by DNA methylation of their promoters.Conclusion: Our studies demonstrated the potential application of DNA methylation markers in the prognosis of LUAD.
Efficacy of umbilical cord mesenchymal stromal cells for COVID-19: A systematic review and meta-analysis
Authors: Yang Cong-wen , Chen Ru-dong , Zhu Qing-run , Han Shi-jie , Kuang Ming-jie 
Published: August 2022

ObjectivesA major challenge for COVID-19 therapy is dysregulated immune response associated with the disease. Umbilical cord mesenchymal stromal cells (UC-MSCs) may be a promising candidate for COVID-19 treatment owing to their immunomodulatory and anti-inflammatory functions. Therefore, this study aimed to evaluate the effectiveness of UC-MSCs inpatients with COVID-19.MethodMedline, Embase, PubMed, Cochrane Library, and Web of Science databases were searched to collect clinical trials concerning UC-MSCs for the treatment of COVID-19. After literature screening, quality assessment, and data extraction, a systematic review and meta-analysis of the included study were performed.ResultsThis systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022304061. After screening, 10 studies involving 293 patients with COVID-19 were eventually included. Our meta-analysis results showed that UC-MSCs can reduce mortality (relative risk [RR] =0.60, 95% confidence interval [CI]: [0.38, 0.95], P=0.03) in COVID-19 patients. No significant correlation was observed between adverse events and UC-MSC treatment (RR=0.85, 95% CI: [0.65, 1.10], P=0.22; RR=1.00, 95%CI: [0.64, 1.58], P=1.00). In addition, treatment with UC-MSCs was found to suppress inflammation and improve pulmonary symptoms.ConclusionsUC-MSCs hold promise as a safe and effective treatment for COVID-19.Systematic Review RegistartionPROSPERO, identifier CRD42022304061
Nomogram based on circulating lymphocyte subsets for predicting radiation pneumonia in esophageal squamous cell carcinoma
Authors: Zhang Xiao-zhen , Tao Su-ping , Liang Shi-xiong , Chen Shu-bin , Liu Fu-shuang , Jiang Wei , Chen Mao-jian 
Published: August 2022

PurposeCurrently, the relationship between radiation pneumonia (RP) and circulating immune cell in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to explore the relationship between RP and circulating lymphocyte subsets in patients with ESCC receiving chemoradiotherapy (CRT), and develop a nomogram model to predict RP. Since we should implement clinical intervention to ≥ grade 2 RP, a nomogram model for ≥ grade 2 RP was also established to provide an early warning.Patients and methodsThis study retrospectively included 121 patients with ESCC receiving CRT from Guangxi Medical University Cancer Hospital from 2013 to 2021. Independent factors associated with occurrence of RP and ≥ grade 2 RP were identified by univariate and multivariate logistic regression analysis in the training cohort, and incorporated into nomograms. The predictive accuracy and discrimination of the model was assessed using Concordance Index (C-index), calibration curve and decision curve analysis (DCA). And each model was internally validated. Additionally, to verify the optimized predictive performance of the nomograms, the area under the ROC curve (AUC) of each nomogram was compared to that of single independent risk factors, lung V10 and lung V20, respectively. Moreover, each model was further evaluated for risk stratification to identify populations at high risk of RP and ≥ grade 2 RP.ResultsMultivariate analysis suggested that TNM stage, post-RT percentage of CD8+ T cell, and lung V15 were independent predictive factors of RP. Besides, pre- and post-RT percentage of CD8+ T cell, and V15 were independent factors of ≥ grade 2 RP. The C-indexes of RP and ≥ grade 2 RP nomograms were 0.809 (95% CI: 0.715-0.903) and 0.787 (95% CI: 0.685-0.889) in the training cohort, respectively. And the C-indexes of RP and ≥ grade 2 RP nomograms were 0.718 (95% CI: 0.544-0.892) and 0.621 (95% CI: 0.404-0.837) in the validation cohort, respectively. The calibration curves showed that the predicted values of model agreed well with actual observations. Moreover, DCA results indicated the applicability and accuracy of the models to predict RP and ≥ grade 2 RP. After stratification, the incidence of the high-risk group was significantly higher than that of the low-risk group with respect to either RP or ≥ grade 2 RP.ConclusionTNM stage, post-RT percentage of CD8+ T cell, and lung V15 were the independent predictors of RP toxicity. Pre- and post-RT percentage of CD8+ T cell, and lung V15 were the independent factors of ≥ grade 2 RP toxicity. The nomograms based on circulating lymphocyte subsets can robustly predict RP and ≥ grade 2 RP, guiding clinicians in risk stratification and early intervention.
Cancer cell membrane-wrapped nanoparticles for cancer immunotherapy: A review of current developments
Authors: Jiang Qi , Xie Mixue , Chen Ruyin , Yan Feifei , Ye Chanqi , Li Qiong , Xu Shuaishuai , Wu Wei , Jia Yunlu , Shen Peng , Ruan Jian 
Published: August 2022

BackgroundAs the forefront of nanomedicine, bionic nanotechnology has been widely used for drug delivery in order to obtain better efficacy but less toxicity for cancer treatments. With the rise of immunotherapy, the combination of nanotechnology and immunotherapy will play a greater potential of anti-tumor therapy. Due to its advantage of homologous targeting and antigen library from source cells, cancer cell membrane (CCM)-wrapped nanoparticles (CCNPs) has become an emerging topic in the field of immunotherapy.Key scientific concepts of reviewCCNP strategies include targeting or modulating the tumor immune microenvironment and combination therapy with immune checkpoint inhibitors and cancer vaccines. This review summarizes the current developments in CCNPs for cancer immunotherapy and provides insight into the challenges of transferring this technology from the laboratory to the clinic as well as the potential future of this technology.ConclusionThis review described CCNPs have enormous potential in cancer immunotherapy, but there are still challenges in terms of translating their effects in vitro to the clinical setting. We believe that these challenges can be addressed in the future with a focus on individualized treatment with CCNPs as well as CCNPs combined with other effective treatments.
Safety and immunogenicity of BK-SE36 in a blinded, randomized, controlled, age de-escalating phase Ib clinical trial in Burkinabe children
Authors: Bougouma Edith Christiane , Palacpac Nirianne Marie Q. , Tiono Alfred B. , Nebie Issa , Ouédraogo Alphonse , Houard Sophie , Yagi Masanori , Coulibaly Sam Aboubacar , Diarra Amidou , Tougan Takahiro , Ouedraogo Amidou Z. , Soulama Issiaka , Arisue Nobuko , Yaro Jean Baptiste , D’Alessio Flavia , Leroy Odile , Cousens Simon , Horii Toshihiro , Sirima Sodiomon B. 
Published: August 2022

BackgroundA blood-stage vaccine targeting the erythrocytic-stages of the malaria parasite Plasmodium falciparum could play a role to protect against clinical disease. Antibodies against the P. falciparum serine repeat antigen 5 (SE47 and SE36 domains) correlate well with the absence of clinical symptoms in sero-epidemiological studies. A previous phase Ib trial of the recombinant SE36 antigen formulated with aluminum hydroxyl gel (BK-SE36) was promising. This is the first time the vaccine candidate was evaluated in young children below 5 years using two vaccination routes.MethodsSafety and immunogenicity of BK-SE36 was assessed in a double-blind, randomized, controlled, age de-escalating phase Ib trial. Fifty-four Burkinabe children in each age cohort, 25–60 or 12–24 months, were randomized in a 1:1:1 ratio to receive three doses of BK-SE36 either by intramuscular (BK IM) or subcutaneous (BK SC) route on Day 0, Week 4, and 26; or the control vaccine, Synflorix®via IM route on Day 0, Week 26 (and physiological saline on Week 4). Safety data and samples for immunogenicity analyses were collected at various time-points.ResultsOf 108 subjects, 104 subjects (96.3%) (Cohort 1: 94.4%; Cohort 2: 98.1%) received all three scheduled vaccine doses. Local reactions, mostly mild or of moderate severity, occurred in 99 subjects (91.7%). The proportion of subjects that received three doses without experiencing Grade 3 adverse events was similar across BK-SE36 vaccines and control arms (Cohort 1: 100%, 89%, and 89%; and Cohort 2: 83%, 82%, and 83% for BK IM, BK SC, and control, respectively). BK-SE36 vaccine was immunogenic, inducing more than 2-fold change in antibody titers from pre-vaccination, with no difference between the two vaccination routes. Titers waned before the third dose but in both cohorts titers were boosted 6 months after the first vaccination. The younger cohort had 2-fold and 4-fold higher geometric mean titers compared to the 25- to 60-month-old cohort after 2 and 3 doses of BK-SE36, respectively.ConclusionBK-SE36 was well tolerated and immunogenic using either intramuscular or subcutaneous routes, with higher immune response in the younger cohort.Clinical Trial Registrationhttps://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=934, identifier PACTR201411000934120.
Habitat value of subsea wells and pipelines for fishery target species in Australia
Authors: McLean Dianne , Speed Conrad W. , Birt Matthew Jon , Colquhoun Jamie , Case Mark , Stowar Marcus , Bond Todd , Ierodiaconou Daniel , Whitmarsh Sasha K. , Taylor Michael D. , Wines Sam , Booth David John , Fowler Ashley M. , Vaughan Brigit I. 
Published: August 2022

Subsea pipelines and wells installed to support the oil and gas industry represent some of the most extensive and numerous anthropogenic structures throughout global marine ecosystems. There remains a paucity of information on the habitat value of these structures for fishery target species and, as a result, little understanding of how decommissioning should be conducted to minimise impacts to populations of these economically and socially important species. We assess the diversity and abundance of species that are targets of recreational and commercial fisheries on 33 subsea wells and 17 pipelines across the tropical northwest and temperate southeast marine regions of Australia. We examine relationships between fish identity and abundance and a range of environmental (e.g., depth, location), infrastructure-specific (e.g., pipeline position, diameter, age, length of pipeline, height of well, position on well), and biological (% cover of epibiota) variables using video filmed by remotely operated vehicles during their routine offshore inspection and maintenance campaigns. A total of 100 fishery target species were observed across subsea well and pipeline infrastructure, 56 species uniquely observed on pipelines and nine unique to wells. The families Lutjanidae (snapper), Serranidae (rock cods, groupers, perch), and Carangidae (trevallies) were most common and abundant on both wells and pipelines. In the northwest, lutjanids were most abundant around the base of wells, in shallow depths, on shorter wells, and where pipelines spanned the seafloor. A greater number of fishery target species and abundance of ocean perch (Helicolenus spp.) were also associated with pipelines that spanned the seafloor in temperate southeast Australia. The combined biomass of three species of snapper on wells in the northwest was 1,270 kg, with production levels for these species on each well estimated to be 105.2 g m2 year-1. The present study serves as an important reference point for informing decommissioning decisions for pipeline and well infrastructure and demonstrates the utility of industry-held data for science. We suggest that key predictor variables identified here be incorporated into comprehensive before-after-control-impact scientific studies for specific fields/assets to enable the prediction of potential impacts of decommissioning scenarios on marine communities present and quantification of such impacts after the decommissioning activity has occurred.
Acute oxalate nephropathy: A potential cause of acute kidney injury in diabetes mellitus—A case series from a single center
Authors: Bao Daorina , Wang Yu , Yu Xiaojuan , Zhao Minghui 
Published: August 2022

BackgroundAcute oxalate nephropathy (AON) is an uncommon condition that causes acute kidney injury (AKI), characterized by the massive deposition of calcium oxalate crystals in the renal parenchyma. In previous studies, urinary oxalate excretion has been found to be increased in patients with diabetes mellitus (DM). Here, we report a case series of diabetic patients with AKI with biopsy-proven AON, aiming to alert physicians to the potential of AON as a trigger of AKI in diabetic patients in clinical practice.Materials and methodsCases with pathological diagnosis of AON who presented with AKI clinically and had DM between January 2016 and December 2020 were retrospectively enrolled. Their clinical and pathological manifestations, treatment, and prognosis were collected.ResultsSix male patients with biopsy-proven AON out of a total of 5,883 native kidney biopsies were identified, aged 58.3 ± 9.1 years at the time of kidney biopsy. Only one patient who had received Roux-en-Y gastric bypass surgery took oxalate-rich food before the onset of the disease. None of them had clinical features of enteric malabsorption. Three patients were currently on renin-angiotensin system inhibitor treatment for hypertension, and 5 of them received non-steroidal anti-inflammatory drugs. Three patients presented with oliguria and 4 patients needed dialysis at the beginning with none requiring dialysis at discharge. Four patients received a course of corticosteroid treatment empirically. Among them, two patients had estimated glomerular filtration rate (eGFR) recovered to over 60 ml/min/1.73 m2, while the other two patients remained with kidney dysfunction at the last follow-up. In two patients without corticosteroid treatment, one patient fully recovered with eGFR over 90 ml/min/1.73 m2 and the other patient remained with kidney dysfunction at the last follow-up.ConclusionAON might be a rare but potentially trigger of AKI in patients with DM. A kidney biopsy could help physicians to make the correct diagnosis. The proper treatment to alleviate oxalate-induced injury needs to be further studied.