bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and the influence of rs1800470 in patients with Camurati-Engelmann disease
Authors: Liang Hanting , Jiajue Ruizhi , Qi Wenting , Liu Wei , Chi Yue , Jiang Yan , Wang Ou , Li Mei , Xing Xiaoping , Xia Weibo 
Published: October 2022

BackgroundCamurati-Engelmann disease (CED) is a sclerosing bone dysplasia caused by transforming growth factor β1 (TGFB1) gene variants.ObjectiveWe aim to summarize the clinical characteristics and the efficacy of glucocorticoids in 14 individuals with CED, and explore the correlation between the phenotype and the SNP of rs1800470 (c.29C&gt;T).MethodsClinical, biochemical, radiological, and therapeutic data were collected from 14 patients. DNA was extracted for TGFB1 variants detection by Sanger sequencing.ResultsThe median onset and record age were 3.0 and 16.1 years, respectively. All patients manifested bone pain and decreased subcutaneous fat tissue. Inflammatory markers increased in over 60% of patients, and the median erythrocyte sedimentation rate (ESR) was 1.40 (0.50~3.67) of the upper limit of normal (ULN), and the median high sensitivity C reactive protein (hsCRP) was 1.71 (0.48~12.56) of ULN. There was a positive correlation between ESR and hsCRP (rs=0.806, p=0.003). Both ESR and hsCRP were negatively correlated with the levels of hemoglobin (HGB), calcium, and creatinine, but positively correlated with the level of alkaline phosphatase. Four known variants of TGFB1 were identified, including p.Tyr171Cys, p.Arg218Cys, p.Arg218His, and p.Cys225Arg. Moreover, 35.7% and 28.6% of them carried the heterozygous and homozygous SNP of c.29C&gt;T, called C/T and T/T groups, respectively, but 35.7% of them were without c.29C&gt;T (C/C group). The onset age, anthropometric data, percentages of different clinical manifestations, and biochemical parameters were comparable among the three groups. But there were increasing trends in levels of HGB and calcium and decreasing trends in ESR and hsCRP among C/C, C/T, and T/T groups in turn. Glucocorticoid improves the two inflammatory markers among CED patients.ConclusionThe phenotype of CED is highly heterogeneous. There is no clear genotype-phenotype correlation, but it seems to have better trends of biochemical parameters in patients with CED carrying the T allele of rs1800470.
Case report: A late-onset cobalamin C defect first presenting as a depression in a teenager
Authors: Cheng Siqi , Chen Weihong , Zhao Mingmin , Xing Xing , Zhao Lei , Ren Bowen , Li Na 
Published: October 2022

Background: The cobalamin C (cblC) defect, a common inborn disorder of cobalamin metabolism due to a genetic mutation in MMACHC, can cause combined methylmalonic acid and homocysteine accumulation in blood, urine, or both. In this article, a late-onset case was reported, and the patient first presented with depression identified with the MMACHC gene. We summarized the clinical features of the cblC defect, the relationship between genotype and phenotype, and the clinical experience concerning the diagnosis and treatment of the cblC defect.Case presentation: Initially presented with depression, the 16-year-old female patient showed progressive abnormal gait and bilateral lower limb weakness after 3 months. Blood routine examination suggested severe hyperhomocysteinemia, and screening for urine organic acids found elevated methylmalonic acid. Family gene sequencing showed mutations detected in MMACHC. She had a compound heterozygous mutation, while the c.271dupA (p.R91Kfs∗14) was only detected in her father and the c.482 G&gt;A (p.R161Q) was only detected in her mother. Hence, she was diagnosed with a cblC defect and treated with B vitamin supplements. The muscle strength of both lower limbs improved notably.Conclusion: This case indicated that depression could be a presenting sign of cblC-type methylmalonic aciduria and homocysteinemia, and enhanced the genotype–phenotype relationship of the cblC defect, which will contribute to further understanding of this emerging disease.
Chromatin regulators-related lncRNA signature predicting the prognosis of kidney renal clear cell carcinoma and its relationship with immune microenvironment: A study based on bioinformatics and experimental validation
Authors: Zhang Xinyu , Qin Xinyue , Yu Tiannan , Wang Kexin , Chen Yinhao , Xing Qianwei 
Published: October 2022

Background: Kidney Renal Clear cell carcinoma (KIRC) is a major concern in the urinary system. A lot of researches were focused on Chromatin Regulators (CRs) in tumors. In this study, CRs-related lncRNAs (CRlncRNAs) were investigated for their potential impact on the prognosis of KIRC and the immune microenvironment.Methods: The TCGA database was used to obtain transcriptome and related clinical information. CRs were obtained from previous studies, whereas CRlncRNAs were obtained by differential and correlation analysis. We screened the lncRNAs for the signature construction using regression analysis and LASSO regression analysis. The effectiveness of the signature was evaluated using the Kaplan-Meier (K-M) curve and Receiver Operating Characteristic curve (ROC). Additionally, we examined the associations between the signature and Tumor Microenvironment (TME), and the efficacy of drug therapy. Finally, we further verified whether these lncRNAs could affect the biological function of KIRC cells by functional experiments such as CCK8 and transwell assay.Results: A signature consisting of 8 CRlncRNAs was constructed to predict the prognosis of KIRC. Quantitative Real-Time PCR verified the expression of 8 lncRNAs at the cell line and tissue level. The signature was found to be an independent prognostic indicator for KIRC in regression analysis. This signature was found to predict Overall Survival (OS) better for patients in the subgroups of age, gender, grade, stage, M, N0, and T. Furthermore, a significant correlation was found between riskScore and immune cell infiltration and immune checkpoint. Finally, we discovered several drugs with different IC50 values in different risk groups using drug sensitivity analysis. And functional experiments showed that Z97200.1 could affect the proliferation, migration and invasion of KIRC cells.Conclusion: Overall, the signature comprised of these 8 lncRNAs were reliable prognostic biomarkers for KIRC. Moreover, the signature had significant potential for assessing the immunological landscape of tumors and providing individualized treatment.
Identification and validation of a novel tumor driver gene signature for diagnosis and prognosis of head and neck squamous cell carcinoma
Authors: Liu Shixian , Liu Weiwei , Ding Zhao , Yang Xue , Jiang Yuan , Wu Yu , Liu Yehai , Wu Jing 
Published: October 2022

Objective: Head and neck squamous cell carcinoma (HNSCC) is a common heterogeneous cancer with complex carcinogenic factors. However, the current TNM staging criteria to judge its severity to formulate treatment plans and evaluate the prognosis are particularly weak. Therefore, a robust diagnostic model capable of accurately diagnosing and predicting HNSCC should be established.Methods: Gene expression and clinical data were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Key prognostic genes associated with HNSCC were screened with the weighted gene co-expression network analysis and least absolute shrinkage and selection operator (LASSO) Cox regression model analysis. We used the timeROC and survival R packages to conduct time-dependent receiver operating characteristic curve analyses and calculated the area under the curve at different time points of model prediction. Patients in the training and validation groups were divided into high- and low-risk subgroups, and Kaplan-Meier (K-M) survival curves were plotted for all subgroups. Subsequently, LASSO and support vector machine algorithms were used to screen genes to construct diagnostic model. Furthermore, we used the Wilcoxon signed-rank test to compare the half-maximal inhibitory concentrations of common chemotherapy drugs among patients in different risk groups. Finally, the expression levels of eight genes were measured using quantitative real-time polymerase chain reaction and immunohistochemistry.Results: Ten genes (SSB, PFKP, NAT10, PCDH9, SHANK2, PAX8, CELSR3, DCLRE1C, MAP2K7, and ODF4) with prognostic potential were identified, and a risk score was derived accordingly. Patients were divided into high- and low-risk groups based on the median risk score. The K-M survival curves confirmed that patients with high scores had significantly worse overall survival. Receiver operating characteristic curves proved that the prognostic signature had good sensitivity and specificity for predicting the prognosis of patients with HNSCC. Univariate and multivariate Cox regression analyses confirmed that the gene signature was an independent prognostic risk factor for HNSCC. Diagnostic model was built by identifying eight genes (SSB, PFKP, NAT10, PCDH9, CELSR3, DCLRE1C, MAP2K7, and ODF4). The high-risk group showed higher sensitivity to various common chemotherapeutic drugs. DCLRE1C expression was higher in normal tissues than in HNSCC tissues.Conclusion: Our study identified the important role of tumor-driver genes in HNSCC and their potential clinical diagnostic and prognostic values to facilitate individualized management of patients with HNSCC.
Preoperative hyperglycemia is associated with elevated risk of perioperative ischemic stroke in type 2 diabetic patients undergoing non-cardiovascular surgery: A retrospective cohort study
Authors: Liu Siyuan , Shi Likai , Wang Binbin , Lou Jingsheng , Sun Miao , Yang Huikai , Zhang Faqiang , Liu Min , Song Yuxiang , Mi Weidong , Ma Yulong 
Published: October 2022

BackgroundDiabetes mellitus (DM) has been reported to be associated with perioperative stroke, but the effects of preoperative hyperglycemia on the risk of perioperative stroke in diabetic patients undergoing non-cardiovascular surgery remain unclear. This study investigated the association between preoperative hyperglycemia and the risk of perioperative ischemic stroke in type 2 diabetic patients undergoing non-cardiovascular surgery.MethodsThis retrospective cohort study screened 27,002 patients with type 2 DM undergoing non-cardiovascular surgery with general anesthesia between January 2008 and August 2019 at The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital. The exposure of interest was preoperative hyperglycemia, defined as a fasting plasma glucose (FPG) ≥ 7 mmol/L. The outcome of interest was a new diagnosis of perioperative ischemic stroke within 30 days after surgery. Residual confounding was minimized by controlling for observable patient and intraoperative factors. Logistic regression was conducted in the total and propensity score matched cohorts. In addition, we stratified patients into six subgroups to investigate whether the association between preoperative hyperglycemia and perioperative ischemic stroke differs in these subgroups.ResultsThe overall incidence of perioperative ischemic stroke was 0.53% (n = 144) in the current cohort. The odds of perioperative ischemic stroke were significantly increased for patients with preoperative hyperglycemia after adjusting for patient- related variables (OR: 1.95; 95% CI: 1.39–2.75; p &lt; 0.001), surgery-related variables (OR: 2.1; 95% CI: 1.51–2.94; p &lt; 0.001), and all confounding variables (OR: 1.78; 95% CI: 1.26–2.53; p &lt; 0.001). The risk of perioperative stroke was significantly increased in patients with preoperative hyperglycemia (OR: 2.51; 95% CI: 1.66–3.9; p &lt; 0.001) in the propensity score matched cohort. Preoperative hyperglycemia was associated with the outcome for all the subgroups except for patients undergoing neurosurgery.ConclusionPreoperative hyperglycemia is associated with an elevated risk of perioperative stroke in patients with type 2 DM undergoing non-cardiovascular surgery. The effect could be eliminated for patients undergoing neurosurgery, during which specific risk factors should be considered.
Progression of kidney injury with the combination of vancomycin and piperacillin-tazobactam or cefepime in sepsis-associated acute kidney injury
Authors: Whitenack Kaylee , Behal Michael L. , Thompson Bastin Melissa L. , Aycinena Juan C. , Adams Paul M. , Flannery Alexander H. 
Published: October 2022

IntroductionThe combination of vancomycin/piperacillin-tazobactam is associated with increases in serum creatinine compared to other antibiotic combinations in the treatment of infections for hospitalized patients. However, the available literature is limited to the study of incident acute kidney injury (AKI). The combination has not been evaluated in patients with AKI already present and the degree to which the trajectory of AKI is influenced by this combination is unknown.MethodsThis was a single center, retrospective cohort study of adult patients with sepsis and AKI present on admission prescribed a combination of vancomycin with either piperacillin-tazobactam or cefepime within the first 3 days of admission. The primary outcome was maximum serum creatinine observed within days 2-7 of the hospital stay. Subsequent kidney outcomes were evaluated at one week and hospital discharge.ResultsOf 480 patients with sepsis and AKI who met inclusion criteria, 288 (60%) received vancomycin/piperacillin-tazobactam, and 192 (40%) received vancomycin/cefepime. Patients were well-matched on clinical factors, including severity of illness, stage of AKI, exposure to other nephrotoxins, and durations of antimicrobial therapy. There were no differences in AKI trajectory during the first week as assessed by maximum serum creatinine (2.1 (1.4-3.5) mg/dl vs. 2.1 (1.4-3.0) mg/dl; p=0.459) and AKI progression (24.0% vs. 23.4%; p=0.895). No differences were observed with other kidney related outcomes, including the need for dialysis (14.6% vs. 13.0%; p=0.628) or major adverse kidney events at hospital discharge (48.3% vs. 47.9%; p=0.941).ConclusionsIn patients with sepsis and AKI, the combination of vancomycin/piperacillin-tazobactam compared to vancomycin/cefepime was not associated with higher serum creatinine values or AKI progression in the week following ICU admission.
Development of a core set of gait features and their potential underlying impairments to assist gait data interpretation in children with cerebral palsy
Authors: van der Krogt Marjolein M. , Houdijk Han , Wishaupt Koen , van Hutten Kim , Dekker Sarah , Buizer Annemieke I. 
Published: October 2022

BackgroundThe interpretation of clinical gait data in children with cerebral palsy (CP) is time-consuming, requires extensive expertise and often lacks transparency. Here we aimed to develop a set of look-up tables to support this process, linking typical gait features as present in CP to their potential underlying impairments.MethodsWe developed an initial core set of gait features and their potential underlying impairments based on biomechanical reasoning, literature and clinical experience. This core set was further specified through a Delphi process in a multidisciplinary group of experts in gait analysis of children with CP and evaluated on 20 patient cases. The likelihood of the listed gait feature–impairment relationships was scored by the expert panel on a five-point scale.ResultsThe final core set included 120 relevant gait feature–impairment relations including likelihood scores. This set was presented in the form of look-up tables in both directions, i.e., sorted by gait features with potential underlying impairment, and sorted by impairments with potential related gait features. The average likelihood score for the relations was 3.5 ± 0.6 (range 2.1–4.6).ConclusionThe developed set of look-up tables linking gait features and impairments, can assist gait analysts and clinicians in standardized biomechanical reasoning, to support treatment decision-making for gait impairments in children with CP.
Identification of CFHR4 associated with poor prognosis of hepatocellular carcinoma
Authors: Ding Qinglin , Li Hanluo , Xu Zhigao , Hu Kanghong , Ye Qifa 
Published: October 2022

BackgroundHepatocellular carcinoma (HCC) is one of the most leading causes of cancer death worldwide. The 5-year survival rate of HCC patients remains low due to the lack of early-stage symptoms. Human complement factor H-related protein 4 (CFHR4) is a critical gene that belongs to the factor H family of plasma glycoproteins, which has not been linked to HCC development. The correlations between CFHR4 and prognosis and tumor-infiltrating lymphocytes in HCC are yet unknown. The present study demonstrated the involvement of CFHR4 in HCC via data mining approaches.ResultsA total of 18 upregulated and 67 down-regulated differentially expressed genes (DEGs) were identified. Importantly, CFHR4, which was screened from DEGs, was shown to express at a lower level in HCC tumor tissue than normal tissues. Western blotting (WB), immunohistochemical (IHC) and quantitative reverse transcription PCR (qRT-PCR) experiments of clinical samples further validated CFHR4 was aberrantly expressed in HCC patients; Data from TCGA showed that CFHR4 was inversely correlated with a cancer family history, histological grade, tumor node metastasis (TNM) stage, and serum AFP level of HCC patients; Univariate and multivariate analyses revealed that low expression of CFHR4 was an independent predictive marker in patients with HCC; Kaplan-Meier analysis showed that the lower expression of CFHR4 was significantly associated with the progression of HCC and poor prognosis rates. Furthermore, TIMER analysis indicated that CFHR4 expression levels had correlations with infiltrating levels of immune cells in HCC.ConclusionCFHR4 expression was low in HCC and was significantly related to the poor prognosis of HCC and the level of immune infiltration. CFHR4 played important roles in regulating the initiation and progression of HCC and could be a potential biomarker for the diagnosis and prognosis of HCC.MethodsThe expression of CFHR4 was analyzed by GEO and TCGA-LIHC database and verified by WB and IHC assay. The biological function of CFHR4 was performed by GO and KEGG enrichment analysis, and the genomic alteration of CFHR4 was investigated by cBioPortal database.The correlation between CFHR4 expression and clinical relevance was evaluated through Cox proportional hazards model, and the correlation between CFHR4 expression and tumor immune infiltrates were studied by TIMER database.
Population-level and individual-level explainers for propensity score matching in observational studies
Authors: Ghosh Debashis , Amini Arya , Jones Bernard L. , Karam Sana D. 
Published: October 2022

PrecisThe exclusion of unmatched observations in propensity score matching has implications for the generalizability of causal effects. Machine learning methods can help to identify how the study population differs from the unmatched subpopulation.BackgroundThere has been widespread use of propensity scores in evaluating the effect of cancer treatments on survival, particularly in administrative databases and cancer registries. A byproduct of certain matching schemes is the exclusion of observations. Borrowing an analogy from clinical trials, one can view these exclusions as subjects that do not satisfy eligibility criteria.MethodsDeveloping identification rules for these “data-driven eligibility criteria” in observational studies on both population and individual levels helps to ascertain the population on which causal effects are being made. This article presents a machine learning method to determine the representativeness of causal effects in two different datasets from the National Cancer Database.ResultsDecision trees reveal that groups with certain features have a higher probability of inclusion in the study population than older patients. In the first dataset, younger age categories had an inclusion probability of at least 0.90 in all models, while the probability for the older category ranged from 0.47 to 0.65. Most trees split once more on an even higher age at a lower node, suggesting that the oldest patients are the least likely to be matched. In the second set of data, both age and surgery status were associated with inclusion.ConclusionThe methodology presented in this paper underscores the need to consider exclusions in propensity score matching procedures as well as complementing matching with other propensity score adjustments.
Deciphering the action mechanism of paeoniflorin in suppressing pancreatic cancer: A network pharmacology study and experimental validation
Authors: Cao Chunhao , Zhao Wenting , Chen Xianglin , Shen Bin , Wang Teng , Wu Chaoxu , Rong Xiaofeng 
Published: October 2022

Background: Paeoniflorin (PF) is the main active component of Chinese herbaceous peony that has been shown to have an anti-tumor effect. However, there are few studies on the prevention and treatment of pancreatic cancer with PF.Methods: We gathered Microarray data pertaining to paeoniflorin intervention in pancreatic cancer by utilizing the GEO database (GSE97124). Then, the DEGs were filtered by the 33R program. RNA-seq data of pancreatic cancer and normal tissue samples were taken from the TCGA and GTEx databases, respectively, and the WGCNA technique was utilized to examine the pancreatic cancer-specific genes. Paeoniflorin target genes for the treatment of pancreatic cancer were determined based on the overlap between DEGs and WGCNA. GO and KEGG enrichment analyses were then performed on paeoniflorin target genes to discover which biological processes were impacted. Using the 3 hierarchical methods included in the Cytohubba plugin, we re-screened the hub genes in the target genes to find the genes most relevant to paeoniflorin treatment. The overall survival effects of hub genes were confirmed using the TCGA database. Finally, the paeoniflorin targets identified by the network pharmacology analysis were validated using PANC-1 and Capan-2 cells.Results: We identified 148 main potential PF targets, and gene enrichment analysis suggested that the aforementioned targets play a crucial role in the regulation of MAPK, PI3K-AKT, and other pathways. The further screening of the prospective targets resulted in the identification of 39 hub genes. Using the TCGA database, it was determined that around 33.33% of the hub gene’s high expression was linked with a bad prognosis. Finally, we demonstrated that PF inhibits IL-6 and IL-10 expression and p38 phosphorylation in pancreatic cancer cells, thereby reducing inflammation.Conclusion: PF may regulate inflammatory factors mainly through the p38 MAPK signal pathway. These findings provide theoretical and experimental evidence suggesting the PF as a promising natural source of anti-tumor compounds for pancreatic cancer.