bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiotherapy interruption due to holidays adversely affects the survival of patients with nasopharyngeal carcinoma: a joint analysis based on large-scale retrospective data and clinical trials
Authors: Xu Cheng , Yang Kai-Bin , Feng Rui-Jia , Chen Lei , Du Xiao-Jing , Mao Yan-Ping , Li Wen-Fei , Liu Qing , Sun Ying , Ma Jun 
Published: February 2022

Abstract
Background
The impact of radiotherapy interruption due to the Spring Festival holidays in China on the survival of patients with nasopharyngeal carcinoma (NPC) is unclear.

Methods
Nontrial patients with locoregionally advanced NPC receiving radiotherapy plus induction chemotherapy (IC) and/or concurrent chemotherapy (CC) were included (N = 5035) and divided into two groups based on the Spring Festival-induced radiotherapy interruption. Kaplan–Meier curves for overall survival (OS) and failure-free survival (FFS) were compared between rival groups. Impact of the timing of radiotherapy interruption (during or outside the Spring Festival) on survival was investigated in a propensity score-matched dataset. We adopted ordination correspondence analysis to determine the cut-off of radiotherapy prolongation for prognostic prediction, and accordingly performed subgroup analysis based on delayed days and chemotherapy details. Individual patient data of three phase III NPC trials (NCT00677118, NCT01245959, NCT01872962) were used for validation (N = 1465).

Results
Radiotherapy interruption was most frequently observed between December to January of the following year. Significantly lower OS and FFS were associated with the Spring Festival-induced interruption of radiotherapy (P = 0.009 and 0.033, respectively), but not that interruption of IC. In two matched comparison groups, the timing of radiotherapy interruption during the Spring Festival was more likely to lead to a decrease in FFS than outside the Spring Festival (P = 0.046), which was not observed in the validation using clinical trial data or in the subgroup analysis based on the 5-day delayed time. The absence of CC and the accumulated dose of cisplatin < 200 mg were related to the negative influences of the Spring Festival-induced radiotherapy interruption on FFS (P = 0.002) and OS (P = 0.010), respectively.

Conclusions
The poor survival of patients with NPC is associated with the Spring Festival-induced interruption of radiotherapy. We recommend that these patients receive adequate doses of cisplatin concurrently with radiotherapy.
Knockdown of PDX1 enhances the osteogenic differentiation of ADSCs partly via activation of the PI3K/Akt signaling pathway
Authors: Liu Fan , Chen Guang-Dong , Fan Long-Kun 
Published: February 2022

Abstract
Background
Osteoporosis (OP) is a systemic bone disease manifested as low bone mass, destruction of bone microstructure, increased bone fragility and fracture risk. The purpose of this study was to explore the role and mechanism of PDX1 for osteogenic differentiation of adipose derived stem cells (ADSCs).

Methods
GSE37329 dataset was retrieved from NCBI Gene Expression Omnibus (GEO) database and performed bioinformatic analyses. ADSCs were incubated with normal medium, osteogenic induction medium (OIM) and OIM+si-PDX1. Then, alkaline phosphatase (ALP) staining and Alizarin Red Staining (ARS) were performed to assess the role of PDX1 for osteogenesis of ADSCs. PI3K inhibitor, LY294002 was then added to further explore the mechanism of PDX1 for osteogenic differentiation of ADSCs. Western blot assay was used to assess the osteogenic-related markers. Graphpad software was used to perform statistically analysis.

Results
A total of 285 DEGs were obtained from analysis of the dataset GSE37329, of which 145 were upregulated and 140 were downregulated genes. These differentially expressed genes mainly enriched in cell differentiation and PI3K/Akt signaling pathway. Moreover, PDX1 was decreased in osteogenic induced ADSCs. Knockdown of PDX1 significantly increased osteogenic differentiation capacity and p-PI3K and p-Akt protein levels. Administration with LY294002 could partially reversed the promotion effects of si-PDX1.

Conclusion
In conclusion, knockdown of PDX1 promotes osteogenic differentiation of ADSCs through the PI3K/Akt signaling pathway.
Epidemiological characterization of tibial plateau fractures
Authors: Reátiga Aguilar Juan , Rios Ximena , González Edery Eduardo , De La Rosa Alfredo , Arzuza Ortega Laura 
Published: February 2022

Abstract
Background
Tibial plateau fractures are traumatic injuries with severities ranging from nondisplaced to complicated fractures. This study describes the epidemiological characteristics of patients with tibial plateau fractures treated in five trauma clinics.

Methods
This retrospective, cross-sectional study included 1165 patients with tibial plateau fractures treated between December 2015 and May 2017. Subjects were selected from the medical records of five institutions based on the inclusion and exclusion criteria. Age, sex, laterality, fracture type, trauma mechanism, vehicle type, classification, and associated injuries were assessed via univariate and bivariate analyses.

Results
In total, 23.3% of patients with tibial fractures treated during the study period had tibial plateau fractures. Of those affected, 73% were men and 50% were younger than 40 years. Furthermore, 95.7% of fractures were caused by traffic accidents, 82.6% of which involved motorcycles. Fractures were closed in 93.1% of cases, and 78% of subjects had associated injuries. The most common fractures, according to Schatzker classification, were type VI (23%) and V (19.1%) fractures.

Conclusions
Tibial plateau fractures are frequent injuries in our setting and mostly occur in men in their 30 s and 40 s. These fractures are typically caused by motorcycle traffic accidents.
Level of Evidence.
IV.
Cucurbitacin B inhibits TGF-β1-induced epithelial–mesenchymal transition (EMT) in NSCLC through regulating ROS and PI3K/Akt/mTOR pathways
Authors: Yuan Renyikun , Fan Qiumei , Liang Xiaowei , Han Shan , He Jia , Wang Qin-Qin , Gao Hongwei , Feng Yulin , Yang Shilin 
Published: February 2022

Abstract
Background
Lung cancer is the leading cause of cancer mortality worldwide, and most of the patients after treatment with EGF-TKIs develop drug resistance, which is closely correlated with EMT. Cucurbitacin B (CuB) is a natural product of the Chinese herb Cucurbitaceae plant, which has a favorable role in anti-inflammation and anti-cancer activities. However, the effect of CuB on EMT is still far from fully explored. In this study, the inhibition effect of CuB on EMT was investigated.

Methods
In this study, TGF-β1 was used to induce EMT in A549 cells. MTS assay was used to detect the cell viability of CuB co-treated with TGF-β1. Wound healing assay and transwell assay were used to determine the migration and invasion capacity of cells. Flow cytometry and fluorescence microscope were used to detect the ROS level in cells. Western blotting assay and immunofluorescence assay were used to detect the proteins expression. Gefitinib was used to establish EGF-TKI resistant NSCLC cells. B16-F10 intravenous injection mice model was used to evaluate the effect of CuB on lung cancer metastasis in vivo. Caliper IVIS Lumina and HE staining were used to detect the lung cancer metastasis of mice.

Results
In this study, the results indicated that CuB inhibited TGF-β1-induced EMT in A549 cells through reversing the cell morphology changes of EMT, increasing the protein expression of E-cadherin, decreasing the proteins expression of N-cadherin and Vimentin, suppressing the migration and invasion ability. CuB also decreased the ROS production and p-PI3K, p-Akt and p-mTOR expression in TGF-β1-induced EMT in A549 cells. Furthermore, Gefitinib resistant A549 cells (A549-GR) were well established, which has the EMT characteristics, and CuB could inhibit the EMT in A549-GR cells through ROS and PI3K/Akt/mTOR pathways. In vivo study showed that CuB inhibited the lung cancer metastasis effectively through intratracheal administration.

Conclusion
CuB inhibits EMT in TGF-β1-induced A549 cells and Gefitinib resistant A549 cells through decreasing ROS production and PI3K/Akt/mTOR signaling pathway. In vivo study validated that CuB inhibits lung cancer metastasis in mice. The study may be supporting CuB as a promising therapeutic agent for NSCLC and Gefitinib resistant NSCLC.
Diagnostic yield of next-generation sequencing in 87 families with neurodevelopmental disorders
Authors: Álvarez-Mora María Isabel , Sánchez Aurora , Rodríguez-Revenga Laia , Corominas Jordi , Rabionet Raquel , Puig Susana , Madrigal Irene 
Published: February 2022

Abstract
Background
Neurodevelopmental disorders (NDDs) are a group of heterogeneous conditions, which include mainly intellectual disability, developmental delay (DD) and autism spectrum disorder (ASD), among others. These diseases are highly heterogeneous and both genetic and environmental factors play an important role in many of them. The introduction of next generation sequencing (NGS) has lead to the detection of genetic variants in several genetic diseases. The main aim of this report is to discuss the impact and advantages of the implementation of NGS in the diagnosis of NDDs. Herein, we report diagnostic yields of applying whole exome sequencing in 87 families affected by NDDs and additional data of whole genome sequencing (WGS) from 12 of these families.

Results
The use of NGS technologies allowed identifying the causative gene alteration in approximately 36% (31/87) of the families. Among them, de novo mutation represented the most common cause of genetic alteration found in 48% (15/31) of the patients with diagnostic mutations. The majority of variants were located in known neurodevelopmental disorders genes. Nevertheless, some of the diagnoses were made after the use of GeneMatcher tools which allow the identification of additional patients carrying mutations in THOC2, SETD1B and CHD9 genes. Finally the use of WGS only allowed the identification of disease causing variants in 8% (1/12) of the patients in which previous WES failed to identify a genetic aetiology.

Conclusion
NGS is more powerful in identifying causative pathogenic variant than conventional algorithms based on chromosomal microarray as first-tier test. Our results reinforce the implementation of NGS as a first-test in genetic diagnosis of NDDs.
Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families
Authors: Banerjee Indraneel , Raskin Julie , Arnoux Jean-Baptiste , De Leon Diva D. , Weinzimer Stuart A. , Hammer Mette , Kendall David M. , Thornton Paul S. 
Published: February 2022

Abstract
Background
Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children, and carries a considerable risk of neurological damage and developmental delays if diagnosis and treatment are delayed. Despite rapid advances in diagnosis and management, long-term developmental outcomes have not significantly improved in the past years. CHI remains a disease that is associated with significant morbidity, and psychosocial and financial burden for affected families, especially concerning the need for constant blood glucose monitoring throughout patients’ lives.

Results
In this review, we discuss the key clinical challenges and unmet needs, and present insights on patients’ and families’ perspective on their daily life with CHI. Prevention of neurocognitive impairment and successful management of patients with CHI largely depend on early diagnosis and effective treatment by a multidisciplinary team of specialists with experience in the disease.

Conclusions
To ensure the best outcomes for patients and their families, improvements in effective screening and treatment, and accelerated referral to specialized centers need to be implemented. There is a need to develop a wider range of centers of excellence and networks of specialized care to optimize the best outcomes both for patients and for clinicians. Awareness of the presentation and the risks of CHI has to be raised across all professions involved in the care of newborns and infants. For many patients, the limited treatment options currently available are insufficient to manage the disease effectively, and they are associated with a range of adverse events. New therapies would benefit all patients, even those that are relatively stable on current treatments, by reducing the need for constant blood glucose monitoring and facilitating a personalized approach to treatment.
The adaptor protein PICK1 targets the sorting receptor SorLA
Authors: Binkle Lars , Klein Marcel , Borgmeyer Uwe , Kuhl Dietmar , Hermey Guido 
Published: February 2022

AbstractSorLA is a member of the Vps10p-domain (Vps10p-D) receptor family of type-I transmembrane proteins conveying neuronal endosomal sorting. The extracellular/luminal moiety of SorLA has a unique mosaic domain composition and interacts with a large number of different and partially unrelated ligands, including the amyloid precursor protein as well as amyloid-β. Several studies support a strong association of SorLA with sporadic and familial forms of Alzheimer’s disease (AD). Although SorLA seems to be an important factor in AD, the large number of different ligands suggests a role as a neuronal multifunctional receptor with additional intracellular sorting capacities. Therefore, understanding the determinants of SorLA’s subcellular targeting might be pertinent for understanding neuronal endosomal sorting mechanisms in general. A number of cytosolic adaptor proteins have already been demonstrated to determine intracellular trafficking of SorLA. Most of these adaptors and several ligands of the extracellular/luminal moiety are shared with the Vps10p-D receptor Sortilin. Although SorLA and Sortilin show both a predominant intracellular and endosomal localization, they are targeted to different endosomal compartments. Thus, independent adaptor proteins may convey their differential endosomal targeting. Here, we hypothesized that Sortilin and SorLA interact with the cytosolic adaptors PSD95 and PICK1 which have been shown to bind the Vps10p-D receptor SorCS3. We observed only an interaction for SorLA and PICK1 in mammalian-two-hybrid, pull-down and cellular recruitment experiments. We demonstrate by mutational analysis that the C-terminal minimal PDZ domain binding motif VIA of SorLA mediates the interaction. Moreover, we show co-localization of SorLA and PICK1 at vesicular structures in primary neurons. Although the physiological role of the interaction between PICK1 and SorLA remains unsolved, our study suggests that PICK1 partakes in regulating SorLA’s intracellular itinerary.
Decreased in vivo glutamate/GABA ratio correlates with the social behavior deficit in a mouse model of autism spectrum disorder
Authors: Park Gaeun , Jeon Se Jin , Ko In Ok , Park Ji Hwan , Lee Kyo Chul , Kim Min-Sik , Shin Chan Young , Kim Hyeonjin , Lee Yong-Seok 
Published: February 2022

AbstractTo diagnose autism spectrum disorder (ASD), researchers have sought biomarkers whose alterations correlate with the susceptibility to ASD. However, biomarkers closely related to the pathophysiology of ASD are lacking. Even though excitation/inhibition (E/I) imbalance has been suggested as an underlying mechanism of ASD, few studies have investigated the actual ratio of glutamate (Glu) to γ-aminobutyric acid (GABA) concentration in vivo. Moreover, there are controversies in the directions of E/I ratio alterations even in extensively studied ASD animal models. Here, using proton magnetic resonance spectroscopy (1H-MRS) at 9.4T, we found significant differences in the levels of different metabolites or their ratios in the prefrontal cortex and hippocampus of Cntnap2−/− mice compared to their wild-type littermates. The Glu/GABA ratio, N-acetylaspartate (NAA)/total creatine (tCr) ratio, and tCr level in the prefrontal cortex were significantly different in Cntnap2−/− mice compared to those in wild-type mice, and they significantly correlated with the sociability of mice. Moreover, receiver operating characteristic (ROC) analyses indicated high specificity and selectivity of these metabolites in discriminating genotypes. These results suggest that the lowered Glu/GABA ratio in the prefrontal cortex along with the changes in the other metabolites might contribute to the social behavior deficit in Cntnap2−/− mice. Our results also demonstrate the utility of 1H-MRS in investigating the underlying mechanisms or the diagnosis of ASD.
FOXQ1-mediated SIRT1 upregulation enhances stemness and radio-resistance of colorectal cancer cells and restores intestinal microbiota function by promoting β-catenin nuclear translocation
Authors: Yang Mei , Liu Qian , Dai Maolin , Peng Renqun , Li Xinghui , Zuo Wei , Gou Juhua , Zhou Feixue , Yu Shuangjiang , Liu Hao , Huang Min 
Published: February 2022

Abstract
Background
Resistance of colorectal cancer (CRC) cells to radiotherapy considerably contributes to poor clinical outcomes of CRC patients. Microarray profiling in this study revealed the differentially expressed forkhead box Q1 (FOXQ1) in CRC, and thus we aimed to illustrate the role of FOXQ1 in CRC by modulating stemness and radio-resistance of CRC cells.

Methods
CRC and adjacent normal tissues were collected from CRC patients, and the correlation between FOXQ1 expression and CRC prognosis was analyzed. Subsequently, we determined the expression of FOXQ1, sirtuin 1 (SIRT1) and β-catenin in CRC tissues and cell lines. The binding affinity between FOXQ1 and SIRT1 and that between SIRT1 and β-catenin were validated with luciferase reporter gene, Co-IP and ChIP assays. Following a metagenomics analysis of CRC intestinal microbiota, the effects of the FOXQ1/SIRT1/β-catenin axis on CRC stem cell phenotypes and radio-resistance was evaluated in vitro and in vivo through manipulation of gene expression. Besides, mouse feces were collected to examine changes in intestinal microbiota.

Results
FOXQ1 was highly expressed in CRC tissues and cells and positively correlated with poor prognosis of CRC patients. FOXQ1 overexpression contributed to resistance of CRC cells to radiation. Knockdown of FOXQ1 inhibited the stemness of CRC cells and reversed their radio-resistance. FOXQ1 enhanced the transcriptional expression of SIRT1, and SIRT1 enhanced the expression and nuclear translocation of β-catenin. Knockdown of FOXQ1 repressed SIRT1 expression, thus reducing the stemness and radio-resistance of CRC cells. Moreover, FOXQ1 knockdown suppressed CRC xenograft formation in xenograft-bearing nude mice through inhibiting SIRT1 and β-catenin to reduce the content of pathological bacteria that were up-regulated in CRC.

Conclusion
FOXQ1-mediated SIRT1 upregulation augments expression and nuclear translocation of β-catenin and benefits CRC-related intestinal pathological bacterial, thereby enhancing the stemness and radio-resistance of CRC cells.
A reciprocal feedback between N6-methyladenosine reader YTHDF3 and lncRNA DICER1-AS1 promotes glycolysis of pancreatic cancer through inhibiting maturation of miR-5586-5p
Authors: Hu Yuhang , Tang Jiang , Xu Fengyu , Chen Jinhuang , Zeng Zhu , Han Shengbo , Wang Fan , Wang Decai , Huang Mengqi , Zhao Yong , Huang Yan , Zhuo Wenfeng , Zhao Gang 
Published: February 2022

Abstract
Background
Glycolysis is a pivotal process in metabolic reprogramming of tumorigenesis. Previous research has indicated that lncRNAs might play crucial roles in glycolysis of various tumors. However, the function of lncRNAs in glycolysis of pancreatic cancer has not been fully elucidated.

Methods
Bio-information analyses were applied to reveal the potential glycolysis-associated lncRNA. RT-PCR and fluorescence in situ hybridization (FISH) assays were applied to detect the expression of antisense RNA1 of DICER1 (DICER1-AS1) in pancreatic cancer tissues and cell lines. Gain- and loss-of-function experiments were performed to evaluate the roles of DICER1-AS1 in glycolysis and tumorigenesis of PC. Mechanistic experiments including luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) were employed to uncover the downstream targets and regulatory mechanism of DICER1-AS1 in glycolysis of PC.

Results
Bio-information analysis indicated that DICER1-AS1 was downregulated in PC and negatively correlated with glycolytic genes expression. Meanwhile, overexpression of DICER1-AS1 inhibited glycolysis, proliferation, and metastasis of PC cells both in vitro and in vivo. Mechanistically, DICER1-AS1 promoted transcription of its sense gene DICER1 by recruiting transcriptional factor YY1 to the DICER1 promoter. Meanwhile, DICER1 promoted maturation of miR-5586-5p which consequently inhibited glycolytic gene expression including LDHA, HK2, PGK1, and SLC2A1. Notably, enhanced interaction between N6-methyladenosine (m6A) reader YTHDF3 and DICER1-AS1 led to degradation of DICER1-AS1 in response to glucose depletion. Moreover, our data revealed that YTHDF3 was a critical target for miR-5586-5p, by which forming a negative feedback with DICER1-AS1 to regulate glycolysis of PC.

Conclusion
Our results implicate a negative feedback of m6A reader YTHDF3 and glycolytic lncRNA DICER1-AS1 is involved in glycolysis and tumorigenesis of PC.
Detection of plasma exosomal miRNA-205 as a biomarker for early diagnosis and an adjuvant indicator of ovarian cancer staging
Authors: Zhu Zehua , Chen Zhaojun , Wang Mingxing , Zhang Min , Chen Yiwen , Yang Xiao , Zhou Changjun , Liu Yuhua , Hong Liquan , Zhang Lahong 
Published: February 2022

Abstract
Background
Ovarian cancer (OC) is one of the serious threats to the health of women worldwide, and accurate biomarkers are urgently demanded for early diagnosis of OC. We have previously confirmed that miR-205 promotes the invasion and metastasis of OC cells by inhibiting the expression of the tumor suppressor gene TCF21. In this study, we used liquid biopsy technology to detect the expression levels of the four genes, miR-205, CA125, HE4 and TCF21, in the exosomes of plasma of OC patients. Combined with analysis of clinicopathological parameters of OC patients, we aimed to provide efficient and non-invasive laboratory biomarkers for early diagnosis of OC.

Methods
36 OC patients who were diagnosed in local hospitals from September 2020 to July 2021 were selected as OC group, 31 cases of surgically diagnosed with ovarian benign lesions were selected as benign group, and 32 healthy people who underwent physical examination during the same period were selected as a control group. We employed transmission electron microscope (TEM), Western blotting (WB), and nanoparticle tracking analysis (NTA) to identify biomarkers in the exosomes extracted from plasma of the three groups. The RNA levels of miR-205, CA125, HE4 and TCF21 genes in plasma exosomes were detected by real-time quantitative PCR (qRT-PCR) method. We used clinical pathological parameters and the Receiver Operating Characteristic (ROC) curves to evaluate the diagnostic efficacy for the genes detected in plasma exosomes.

Results
We found that the expression level of miR-205 in plasma exosomes of the OC group was significantly higher than that of the benign and control groups (P <  0.05), and the level of miR-205 was elevated during the III-IV periods of OC and lymph node metastasis.

Conclusion
The level of miR-205 in plasma exosomes is a valuable tumor biomarker to improve OC diagnosis.