bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteoglycan-4 predicts good prognosis in patients with hepatocellular carcinoma receiving transcatheter arterial chemoembolization and inhibits cancer cell migration in vitro
Authors: Guo Yuan , Hu Hong Tao , Xu Shi Jun , Xia Wei Li , Zhao Yan , Zhao Xiao Hui , Zhu Wen Bo , Li Fang Ting , Li Hai Liang 
Published: November 2022

PurposeTo search for adaptive response molecules that affect the efficacy of transcatheter arterial chemoembolization (TACE), analyze their clinical correlation with and prognostic value for hepatocellular carcinoma (HCC), and explore their impact on cell biological behavior and their mechanisms of action.MethodsHCC tissue gene sequencing was used to identify differentially expressed genes. The expression of proteoglycan 4 (PRG4) in the serum of 117 patients with HCC who received TACE was detected by enzyme-linked immunosorbent assay. Serum-free medium mimicked TACE-induced nutrient deprivation. Cells with stable knockdown of PRG4 (shPRG4) were constructed to verify the effect and mechanism of PRG4 on the biological behavior of HCC cells in vitro.ResultsThe expression of PRG4 was significantly elevated under TACE-induced starvation conditions. Low PRG4 expression was associated with worse response to TACE treatment, shorter survival time, and stronger HCC migration ability. Furthermore, in vitro experiments showed that knockdown of PRG4 promoted HCC cell migration by enhancing epithelial–mesenchymal transition (EMT) while did not affect proliferation. When PRG4 expression was low, starvation treatment impaired the migratory ability of HCC cells and reduced the chemosensitivity of HCC cells to epirubicin.ConclusionsPRG4 expression predicts survival and TACE treatment response in patients with HCC. Furthermore, knockdown of PRG4 enhanced EMT, leading to HCC cell migration. PRG4 may serve as a biomarker for HCC patients receiving TACE.
Stage IV non-small cell lung cancer among young individuals: Incidence, presentations, and survival outcomes of conventional therapies
Authors: Cai Jing-Sheng , Qiu Man-Tang , Yang Fan , Wang Xun 
Published: November 2022

BackgroundThere is a paucity of data published on the clinicopathological features and prognosis of stage IV non-small cell lung cancer (NSCLC) patients aged ≤45 years. Herein, we evaluated a large clinical series in an effort to provide a clearer picture of this population.MethodsThe least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to identify prognostic factors for NSCLC among individuals aged ≤45 years. The Kaplan–Meier method with log-rank test was used to compare overall survival (OS) differences between groups. Competing risk analysis with the Fine–Gray test was used to analyze cancer-specific survival (CSS) differences. Propensity score matching (PSM) was used to minimize selection bias.ResultsIncidence-rate analyses, including 588,680 NSCLC cases (stage IV, 233,881; age ≤ 45 years stage IV, 5,483; and age &gt; 45 years stage IV, 228,398) from 2004 to 2015, showed that the incidence of stage IV NSCLC among young individuals decreased over the years. In comparative analyses of clinical features and survival outcomes, a total of 48,607 eligible stage IV cases (age ≤ 45 years stage IV, 1,390; age &gt; 45 years stage IV, 47,217) were included. The results showed that although patients in the young cohort were more likely to be diagnosed at advanced stages, they were also more likely to receive aggressive treatments. In addition, the survival rates of the young patients were superior to those of the older patients both before and after PSM.ConclusionsStage IV NSCLC patients aged ≤45 years comprise a relatively small but special NSCLC subgroup. Although this population had better survival outcomes than older patients, these patients deserve more attention due to their young age and the significant socioeconomic implications.
Characterization of genomic alterations and neoantigens and analysis of immune infiltration identified therapeutic and prognostic biomarkers in adenocarcinoma at the gastroesophageal junction
Authors: Lao Yueqiong , Wang Yuqian , Yang Jie , Liu Tianyuan , Ma Yuling , Luo Yingying , Sun Yanxia , Li Kai , Zhao Xuan , Niu Xiangjie , Xi Yiyi , Zhong Ce 
Published: November 2022

ObjectivesAdenocarcinoma at the gastroesophageal junction (ACGEJ) refers to a malignant tumor that occurs at the esophagogastric junction. Despite some progress in targeted therapies for HER2, FGFR2, EGFR, MET, Claudin 18.2 and immune checkpoints in ACGEJ tumors, the 5-year survival rate of patients remains poor. Thus, it is urgent to explore genomic alterations and neoantigen characteristics of tumors and identify CD8+ T-cell infiltration-associated genes to find potential therapeutic targets and develop a risk model to predict ACGEJ patients’ overall survival (OS).MethodsWhole-exome sequencing (WES) was performed on 55 paired samples from Chinese ACGEJ patients. Somatic mutations and copy number variations were detected by Strelka2 and FACETS, respectively. SigProfiler and SciClone were employed to decipher the mutation signature and clonal structure of each sample, respectively. Neoantigens were predicted using the MuPeXI pipeline. RNA sequencing (RNA-seq) data of ACGEJ samples from our previous studies and The Cancer Genome Atlas (TCGA) were used to identify genes significantly associated with CD8+ T-cell infiltration by weighted gene coexpression network analysis (WGCNA). To construct a risk model, we conducted LASSO and univariate and multivariate Cox regression analyses.ResultsRecurrent MAP2K7, RNF43 and RHOA mutations were found in ACGEJ tumors. The COSMIC signature SBS17 was associated with ACGEJ progression. CCNE1 and VEGFA were identified as putative CNV driver genes. PI3KCA and TP53 mutations conferred selective advantages to cancer cells. The Chinese ACGEJ patient neoantigen landscape was revealed for the first time, and 58 potential neoantigens common to TSNAdb and IEDB were identified. Compared with Siewert type II samples, Siewert type III samples had significant enrichment of the SBS17 signature, a lower TNFRSF14 copy number, a higher proportion of samples with complex clonal architecture and a higher neoantigen load. We identified 10 important CD8+ T-cell infiltration-related Hub genes (CCL5, CD2, CST7, GVINP1, GZMK, IL2RB, IKZF3, PLA2G2D, P2RY10 and ZAP70) as potential therapeutic targets from the RNA-seq data. Seven CD8+ T-cell infiltration-related genes (ADAM28, ASPH, CAMK2N1, F2R, STAP1, TP53INP2, ZC3H3) were selected to construct a prognostic model. Patients classified as high risk based on this model had significantly worse OS than low-risk patients, which was replicated in the TCGA-ACGEJ cohort.ConclusionsThis study provides new neoantigen-based immunotherapeutic targets for ACGEJ treatment and effective disease prognosis biomarkers.
Methylation-based reclassification and risk stratification of skull-base chordomas
Authors: Huo Xulei , Guo Tengxian , Wang Ke , Yao Bohan , Li Da , Li Huan , Chen Wei , Wang Liang , Wu Zhen 
Published: November 2022

BackgroundSkull-base chordomas are rare malignant bone cancers originating from the remnant of the notochord. Survival is variable, and clinical or molecular factors cannot reliably predict their outcomes. This study therefore identified epigenetic subtypes that defined new chordoma epigenetic profiles and their corresponding characteristics.MethodsMethylation profiles of 46 chordoma-resected neoplasms between 2008 and 2014, along with clinical information, were collected. K-means consensus clustering and principal component analysis were used to identify and validate the clusters. Single-sample gene set enrichment analysis, methylCIBERSORT algorithm, and copy number analysis were used to identify the characteristics of the clusters.ResultsUnsupervised clustering analysis confirmed two clusters with a progression-free survival difference. Gene set enrichment analysis indicated that the early and late estrogen response pathways and the hypoxia pathway were activated whereas the inflammatory and interferon gamma responses were suppressed. Forty-six potential therapeutic targets corresponding to differentially methylated sites were identified from chordoma patients. Subgroups with a worse outcome were characterized by low immune cell infiltration, higher tumor purity, and higher stemness indices. Moreover, copy number amplifications mostly occurred in cluster 1 tumors and the high-risk group. Additionally, the presence of a CCNE1 deletion was exclusively found in the group of chordoma patients with better outcome, whereas RB1 and CDKN2A/2B deletions were mainly found in the group of chordoma patients with worse outcome.ConclusionsChordoma prognostic epigenetic subtypes were identified, and their corresponding characteristics were found to be variable.
Osteofibrous dysplasia-like adamantinoma: A case report and literature review
Authors: Li Jian-Wei , Miao Lei , Zhao Zhen-Guo , Yang Lin , Shi Zhuo , Li Meng 
Published: November 2022

Abstract backgroundOsteofibrous dysplasia-like adamantinoma (OFD-like adamantinoma), classical adamantinoma and dedifferentiated adamantinoma were previously considered to be three subtypes of adamantinoma of long bones. In the 5th edition of the World Health Organization (WHO) classification of bone tumors in 2020, OFD-like adamantinoma was newly proposed and classified as an intermediate-locally aggressive tumor in other mesenchymal tumors of bone. OFD-like adamantinoma is rare, accounting for only 0.4% of all primary bone tumors. OFD-like adamantinoma is often misdiagnosed due to the insufficient understanding of it. Here we report a case of OFD-like adamantinoma treated in our hospital with a literature review.Case presentationThe patient, a 14-year-old male, had swelling in his right leg with intermittent pain for one year. Plain radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. Based on the radiological and histological examinations, a diagnosis of OFD-like adamantinoma was suspected. After admission, the patient underwent tumor resection of the right tibia, free transplantation of the left fibula and internal fixation. After resection of the tumor, the wound recovered well, the vital signs were stable, and activity was normal. The patient has been followed up for more than a year with no recurrence or distant metastasis.ConclusionOFD-like adamantinoma is a rare primary bone tumor with nonspecific clinical features. Imaging examination can demonstrate the lesion and help diagnosis. The pathological discovery of epithelioid tissue is the key evidence for diagnosis.
Carrier frequency and incidence estimation of familial hemophagocytic lymphohistiocytosis in East Asian populations by genome aggregation database (gnomAD) based analysis
Authors: Park Jong Eun , Lee Taeheon , Ha Kyeongsu , Cho Eun Hye , Ki Chang-Seok 
Published: November 2022

ObjectivesHemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome characterized by a life-threatening condition caused by severe hypercytokinemia. The hereditary forms of HLH, also called familial HLH (fHLH), have 4 different genes (PRF1, UNC13D, STX11, and STXBP2) and have been identified as being causative for fHLH. This study aimed to analyze the carrier frequency and expected incidence of fHLH in East Asians and Koreans using exome data from the Genome Aggregation Database (gnomAD).MethodsWe analyzed 9,197 exomes for East Asian populations from gnomAD with 1,909 Korean for four fHLH genes. All identified variants were classified according to 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline.Results19 pathogenic variant/likely pathogenic variants (PV/LPVs) were identified in 30 East Asian individuals (0.33%). Among them, 7 PV/LPVs were identified in 17 Korean individuals (0.63%). The estimated incidence of fHLH was 1 in 1,105,652 for East Asians and l in 235,128 for Koreans.ConclusionsThis study is the first to identify carrier frequencies in East Asian and Korean populations for fHLH using gnomAD. It was confirmed that the carrier frequency of fHLH patients was high in Koreans among East Asians and the incidence was also predicted to be higher than that of other East Asians. The variant spectrum of fHLH genes in East Asian and Korean populations differed greatly from those of other ethnic groups.
Clinical application of artificial intelligence in longitudinal image analysis of bone age among GHD patients
Authors: Zhang Lina , Chen Jia , Hou Lele , Xu Yingying , Liu Zulin , Huang Siqi , Ou Hui , Meng Zhe , Liang Liyang 
Published: November 2022

ObjectiveThis study aims to explore the clinical value of artificial intelligence (AI)-assisted bone age assessment (BAA) among children with growth hormone deficiency (GHD).MethodsA total of 290 bone age (BA) radiographs were collected from 52 children who participated in the study at Sun Yat-sen Memorial Hospital between January 2016 and August 2017. Senior pediatric endocrinologists independently evaluated BA according to the China 05 (CH05) method, and their consistent results were regarded as the gold standard (GS). Meanwhile, two junior pediatric endocrinologists were asked to assessed BA both with and without assistance from the AI-based BA evaluation system. Six months later, around 20% of the images assessed by the junior pediatric endocrinologists were randomly selected to be re-evaluated with the same procedure half a year later. Root mean square error (RMSE), mean absolute error (MAE), accuracy, and Bland-Altman plots were used to compare differences in BA. The intra-class correlation coefficient (ICC) and one-way repeated ANOVA were used to assess inter- and intra-observer variabilities in BAA. A boxplot of BA evaluated by different raters during the course of treatment and a mixed linear model were used to illustrate inter-rater effect over time.ResultsA total of 52 children with GHD were included, with mean chronological age and BA by GS of 6.64 ± 2.49 and 5.85 ± 2.30 years at baseline, respectively. After incorporating AI assistance, the performance of the junior pediatric endocrinologists improved (P &lt; 0.001), with MAE and RMSE both decreased by more than 1.65 years (Rater 1: ΔMAE = 1.780, ΔRMSE = 1.655; Rater 2: ΔMAE = 1.794, ΔRMSE = 1.719), and accuracy increasing from approximately 10% to over 91%. The ICC also increased from 0.951 to 0.990. During GHD treatment (at baseline, 6-, 12-, 18-, and 24-months), the difference decreased sharply when AI was applied. Furthermore, a significant inter-rater effect (P = 0.002) also vanished upon AI involvement.ConclusionAI-assisted interpretation of BA can improve accuracy and decrease variability in results among junior pediatric endocrinologists in longitudinal cohort studies, which shows potential for further clinical application.
Acute hepatitis of unknown origin in children: A combination of factors
Authors: Gong Kai , Xu Xianbin , Yao Junjie , Ye Shaoheng , Yu Xia , Tu Huilan , Lan Yan , Fan Yu-chen , Shi Yu 
Published: November 2022

On 5 April 2022, the World Health Organization was notified of 10 cases of severe acute hepatitis of unknown etiology in children under 10 years of age in the United Kingdom. Although the exact cause of a proportion of pediatric acute hepatitis and acute liver failure cases was unclear, the above event has caused widespread concern worldwide. As of 14 September 2022, approximately 1,296 probable cases of acute hepatitis of unknown etiology have been reported from 37 countries/regions, of which approximately 55 required or received liver transplantation and 29 died. Although the etiology of acute hepatitis of unknown origin in children remains unclear, many hypotheses have been proposed about the disease. Instead of individual factors such as “adenovirus infection,” “SARS-CoV-2 related,” and “Adeno-associated virus 2 with helper virus coinfection,” it is more likely due to a combination of factors. Accordingly, there is an urgent need for more data and research to clarify the disease etiology. This review aims to provide a historical perspective of acute hepatitis of unknown etiology in children in the past decades and summarize the current hypothesis and evidence on this emerging disease.
A survey of health status of healthcare providers in a square cabin hospital during the new corona omicron outbreak: A cross-sectional study
Authors: Pei Haoyu , Gan Xiaoqin , Guo Fei , Wu Qiuping , Liu Ding , Li Zhouzhou , Lan Ping , Zhang Lili , Yan Hong 
Published: November 2022

BackgroundThe coronavirus omicron variant outbroke in early 2022 in Shanghai. Although previous studies indicated that long working hours in a square cabin hospital might increase the risk of mental health among frontline healthcare providers, few studies have investigated whether the mental health risk could be reduced among well-trained professionals following the new guidelines.ObjectiveThis study aimed to investigate the health situation of frontline healthcare providers in Shanghai square cabin during the omicron variant circulation.MethodsAn online survey was used to evaluate those healthcare providers working in the square cabin hospitals from March 1, 2022, to May 31, 2022. The first online survey was conducted and emailed to the health providers on April 1. The second survey was conducted and sent to the nonrespondents on May 31. Overall, 142 frontline healthcare providers completed the online survey. Their mental health was assessed by the Insomnia Severity Index Scale, the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire-9, and the Psychological Resilience Scale. We estimated multiple clinical systems and identified factors associated with those symptoms among participants. Multivariable logistic regression models were used to assess the risk factors of these symptoms.ResultsOverall, 66.20%, 45.07%, and 27.46% of frontline healthcare providers in Shanghai City reported symptoms of insomnia, depression, and anxiety, respectively. In addition, the most common symptoms included dry eyes (57.75%), lumbar muscle strain (47.18%), dry mouth (35.92%), itching (31.69%), headache (29.58%), and sore throat (28.87%) among the frontline healthcare providers. There was no statistical difference in symptoms by gender, age, personnel category, or job position (p &gt; 0.05).ConclusionIn the case of an unexpected pandemic, the mental health of healthcare providers is not optimistic. This situation still exists more than 2 years after the global outbreak of the COVID-19 pandemic. Therefore, the physical and mental health of long-term healthcare providers working in a square cabin hospital still needs monitoring.
The Swedish version of the multidimensional inventory for religious/spiritual well-being – Part II: Development of a four-field typology
Authors: Podolin-Danner Nikita , Wenzl Magdalena , Knorr Anna , Fuchshuber Jürgen , Silani Giorgia , Unterrainer Human-Friedrich 
Published: November 2022

BackgroundIn the field of mental health, religiosity and spirituality have gained particular attention in recent decades. However, only a few studies to date have investigated the effects of different types of religiosity and spirituality. In association with the recent introduction of a Swedish version of the multidimensional inventory of religious/spiritual well-being (MI-RSWB-S), the present study aimed to identify possible types of Religious/Spiritual Well-Being by using cluster analyses and to examine the extracted groups for differences in the sense of coherence (SOC), the Big Five personality factors, and central aspects of religiosity. Additionally, the study design was intended to further contribute to the validation of the MI-RSWB-S.MethodsBased on a convenience sample of Swedish students (N = 1,011), initially obtained for the development of the MI-RSWB-S, the study included the MI-RSWB-S, the 13-items sense of coherence scale, the 10-item personality inventory, and the centrality of religiosity scale. For the statistical analysis, cluster analyses and one-way analyses of variance (ANOVAs) were conducted.ResultsThe cluster analyses yielded the following four groups: Religiosity and spirituality high (n = 124), religiously oriented (n = 200), spiritually oriented (n = 149), and religiosity and spirituality low (n = 538). The groups differed in most aspects of well-being, in the personality dimensions agreeableness and openness to experience, as well as in central aspects of religiosity. In contrast, no differences were found for SOC, extraversion, conscientiousness, and emotional instability.ConclusionOur results suggest that different types of religious/spiritual well-being are associated with mental health and personality dimensions in substantially different ways, thus offering an interesting potential for future research.
Alexithymia and post-traumatic stress disorder symptoms in Chinese undergraduate students during the COVID-19 national lockdown: The mediating role of sleep problems and the moderating role of self-esteem
Authors: Zhang Yi , Zhao Yijin , Ni Ting , Chen Jing , Tang Wanjie 
Published: November 2022

ObjectiveThis study examined whether sleep disturbance was a mediator between alexithymic traits and post-traumatic stress disorder (PTSD) COVID-19 pandemic-related stress symptoms, and explored whether self-esteem moderated the alexithymic contribution to poor sleep and PTSD symptoms.MethodA representative sample of young adults (N = 2,485) from six universities in Southwest China completed online self-report surveys on alexithymia, sleep, PTSD, self-esteem, sociodemographic information, and health-related behaviors.ResultsHigh alexithymic young adults were found to be more likely to have higher sleep problems and higher PTSD symptoms. The moderated mediation model showed that sleep problems mediated the associations between alexithymia and PTSD symptoms. Alexithymic people with lower self-esteem were more likely to have elevated PTSD symptoms and sleep problems than those with higher self-esteem.ConclusionTargeted psychological interventions for young people who have difficulty expressing and identifying emotions are recommended as these could assist in reducing their post-traumatic psychophysical and psychological problems. Improving self-esteem could also offer some protection for trauma-exposed individuals.