bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel ALK Gene Mutation and Its Response to Second-Generation TKIs: a Case Report and Literature Review
Authors: Cheng Xiaqin , Liu Jia , Hu Qiongxia , Gao Yingchun , Zhou Lin 
Published: June 2023

Abstract
Background
Adenocarcinoma with positive echinoderm microtubule-associated protein-like 4 gene and anaplastic lymphoma kinase (EML4-ALK) gene fusion accounts for 3–7% of lung cancer cases and can be targeted with ALK tyrosine kinase inhibitors (TKIs). Second-generation TKIs are the standard of care for targeted populations, especially those with central nervous system (CNS) metastasis. However, most patients eventually experience disease progression because of drug resistance caused by multiple mechanisms, predominantly secondary mutations.
Case description
: We present a female advanced non-small cell lung cancer (NSCLC) case with positive EML4-ALK gene fusion, in which disease progression occurred in only 3 months after first-line treatment with alectinib. Two secondary mutations were detected by next-generation sequencing; one was V1180l located in exon 23, and the other was E803Q located in exon 14, which was a novel mutation that had never been reported. Ensartinib and ceritinib were administered as second-line and third-line treatments. However, the response to these TKIs was poor, and her overall survival was only 7 months.
Conclusion
The secondary mutation E803Q located in exon 14 seems resistant to most second-generation ALK-TKIs. If there is an opportunity, the efficacy of the third-generation ALK-TKI loratinib should be tested.
Contribution of an Asian-prevalent HLA haplotype to the risk of HBV-related hepatocellular carcinoma
Authors: Kawamura Atsushi , Matsuda Koichi , Murakami Yoshinori , Saruta Masayuki , Kohno Takashi , Shiraishi Kouya 
Published: June 2023

Abstract
Liver cancer, especially HBV (Hepatitis B Virus)-related hepatocellular carcinoma (HCC), is more common in Asian than Caucasian. Regional difference in prevalence of exogenous factors, such as HBV, partially accounts for the fact, however, endogenous factors specific to Asian might also be responsible. HLA (Human Leukocyte Antigen) genes are considered as a candidate due to their high racial diversity. To address this issue, we performed a pan-cancer association study of 147 alleles of HLA class I/II genes (HLA-A, B, and C/DRB1, DQA1, DQB1, DPA1, and DPB1) between 31,727 cases of 12 cancer types, including 1,684 liver cancer cases, and 107,103 controls. HLA alleles consisting a haplotype prevalent in Asian were significantly associated with pan-cancer risk (e.g. odds ratio [OR] for a DRB1*15:02 allele=1.12, p=2.7 x 10-15) and the associations were evidently strong in HBV-related HCC (OR=1.95, p=2.8 x 10-5). In silico prediction suggested that DRB1*15:02 molecule encoded by the haplotype does not efficiently bind HBV-derived peptides. RNA sequencing indicated that HBV-related HCC of the haplotype carriers have low infiltrations of NK cells. These results indicate that Asian-prevalent the HLA haplotype confers HBV-related liver cancer risk by attenuating immune activity against HBV infection and by decreasing NK cell infiltration.
Reliability Analysis of Subsea Control System Using FMEA and FFTA
Authors: Xiao Wen-sheng , Liu Chao , Li Guang-xin , Liu Jian 
Published: June 2023

Abstract

Reliability technology has significant importance to ensure the safe operation of the system. To address the problems of complex system structure and lack of reliability data, a combination of Failure Mode and Effects Analysis (FMEA) and Fuzzy Fault Tree Approach (FFTA) is introduced. Firstly, the FMEA method is used to complete the qualitative analysis of the system reliability from the perspective of multi-factor failure modes, analyze the potential failure modes and failure causes of the system. And the risk matrix diagram is used to determine the degree of harm of different failure modes to the system function. Then, the system reliability is quantitatively analyzed by FFTA, and a fault tree model is established by dividing the system into "system-subsystem-component" and solving for the minimum cut set. In addition, by introducing fuzzy set theory to blur the failure probability of each bottom event and introducing triangular fuzzy function to quantitatively calculate the failure probability of the top event and the probabilistic importance of the bottom event, the weak points of each subsystem are identified. Finally, a qualitative and quantitative reliability analysis is conducted by using FMEA-FFTA method for subsea control system. Measures should be taken to focus on preventive protection and regular testing for the high risk, medium-high risk and medium risk modes of the subsea control system.
Genetic evidence causally linking gastroesophageal reflux disease to cholecystitis：A two- sample Mendelian randomization study
Authors: Wang Chao , Wang Jia , Fang Ming , Fei Bojian 
Published: June 2023

Abstract

Background and aims: Overlapping symptoms of gastroesophageal reflux disease (GERD) and cholecystitis include belching, acid reflux, and heartburn. Nevertheless, the causal relationship between these two conditions remains uncertain. The study aimed to investigate the causal relationship between GERD and cholecystitis via the Mendelian randomization (MR) approach.Methods A two-sample MR analysis utilizing the inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods was conducted to assess the causal effects of GERD on the risk of cholecystitis. The genome-wide association studies (GWASs) for GERD (n = 602604) and cholecystitis (n = 361194) were obtained from the MR-base platform. The pleiotropy and heterogeneity were assessed using various techniques.Results A total of 77 single nucleotide polymorphisms from GWASs with GERD were selected as instrumental variables (IVs). The primary IVW method demonstrated a significant association between GERD and an elevated risk of cholecystitis [odds ratio (OR) = 1.004; 95% CI 1.003–1.005, p = 2.68×10− 9]. The absence of heterogeneity and pleiotropy in the data suggested that the results were dependable.Conclusion Our study demonstrated a positive correlation between GERD and the likelihood of developing cholecystitis. These findings may serve as a fundamental basis for comprehending the intricate interplay between GERD and cholecystitis. However, additional investigations are warranted to elucidate the precise underlying mechanisms of this plausible causal relationship.
Identification of potential therapeutic targets from bioinformatic analysis of necroptosis and immune infiltration in acute myocardial infarction
Authors: Ma Likang , Chen Keyuan , Li Jiakang , Zhang Zhaofeng , Zarif Mohammad , Chai Tianci , Wu Qingsong , Chen Liangwan , Qiu Zhihuang 
Published: June 2023

Abstract
Background
Acute myocardial infarction (AMI) is a serious, deadly disease with a high incidence. However, it remains unclear how necroptosis affects the pathophysiology of AMI. Using bioinformatic analyses, this study investigated necroptosis in AMI.
Methods
Using the Gene Expression Omnibus (GEO) database, we obtained the GSE66360 dataset related to AMI. Venn diagrams were used to identify necroptosis-related differential genes (NRDEGs). The genes with differential expression in AMI were analyzed using gene set enrichment analysis (GSEA), and a protein-protein interaction (PPI) network was established. A transcription factor prediction and enrichment analysis was conducted for the NRDEGs, and the relationships between AMI, NRDEGs, and immune cells were determined. Finally, in the additional dataset (GSE61145), NRDEG expression levels and immune infiltration were confirmed, and gene expression levels were further verified experimentally.
Results
GSEA revealed that necroptosis pathways were significantly enriched in AMI. We identified 10 NRDEGs, including TNF, TLR4, FTH1 and so on. Enrichment analysis indicated that the NOD-like receptor and TNF signaling pathways were significantly enriched. Four NRDEGs, FTH1, IFNGR1, STAT3, and TLR4, were identified; however, additional datasets and further experimental validation are required to confirm their roles. In addition, we determined that a high abundance of monocytes, macrophages, neutrophils, induced Tregs, and Th2 cells prompted AMI development.
Conclusions
In this study, four genes with potential to affect the development of AMI through necroptosis (FTH1, IFNGR1, STAT3, and TLR4) were identified. In addition, we found that a high abundance of monocytes, macrophages, neutrophils, and Th2 cells affected AMI. This helps determine the pathological mechanism of necroptosis and immune cells that influence AMI and provides a novel strategy for targeted therapy.
Unveiling the Link: Examining the Relationship between Nonverbal Communication and Affectivity in Relation to Gender, Age, and Education
Authors: Abbas Mariyam , Fatima Mahvish 
Published: June 2023

Abstract
The current study examined the relationship between nonverbal communication and affectivity in relation to gender, age, and educational level. A sample of 200 participants, including 129 males and 71 females with a mean age of 34.93, was gathered with their consent. The sample was divided into different age groups, including 18–21 years, 22–25 years, 26–29 years, and 30 years and above. The educational levels of the participants varied, with 115 holding post-graduate degrees or higher, 16 being semi-literate, and 69 being undergraduates. The Nonverbal Communication and Affectivity (NCVA) scale developed by Abbas & Khan (2022) was used to collect data. Results indicated a significant positive correlation between nonverbal communication and affectivity. Furthermore, males reported higher levels of nonverbal communication and affectivity than females. Additionally, significant differences in nonverbal communication means were found between the 18–25 years and 26–29 years age groups, and between the 22–25 years and 26–29 years age groups. However, no significant differences were found in affectivity means based on age. There were also no significant differences in nonverbal communication or affectivity based on educational level.
A potent formula against Triple-negative Breast Cancer - Sorafenib-Carbon Nanotubes- Folic Acid: Targeting, Apoptosis triggering, and bioavailability enhancing
Authors: Nabawi Hossam M. S. , Abdelazem Ahmed Z. , Rouby Waleed M.A. El , El-Shahawy Ahmed A. G. 
Published: June 2023

Abstract
Triple-negative breast cancer (TNBC) has short survival rates, a high recurrence rate, aggressive clinical behavior, a high risk of metastasis and it is difficult to be targeted by ordinary medicines. This study aimed to (i) prepare a novel formula of sorafenib, carbon nanotubes, and folic acid to be tested as a drug delivery system targeting TNBC with higher safety and efficacy compared with free sorafenib and to (ii) evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, carbon nanotube pegylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using XRD, FTIR, 1HNMR, UV, HR-TEM, FESEM, Zeta sizer and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT anti-proliferative assay revealed that the formula was 3-fold more cytotoxic towards TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. Moreover, in vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients.
Prognostic and clinicopathological value of SOX10 protein expression in breast cancer: a systematic review and meta- analysis
Authors: Lin Xia , Qu Li 
Published: June 2023

Abstract
Background
Recently, many studies were conducted to explore the role of SRY-box transcription factor 10 (SOX10) expression in clinical progression and prognosis of breast cancer, but the results remained controversial. In order to clarify the association between SOX10 expression and breast cancer, we conducted the meta-analysis.
Methods
The eligible studies were obtained by conducting a thorough search of various databases, including Embase, PubMed, Wan Fang, Chinese Biomedical Literature, Medline, Science Direct, Scopus, and China National Knowledge Infrastructure (CNKI). Odd ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the associations between SOX10 expression and clinical features as well as overall survival time of breast cancer. The meta-analysis was conducted using STATA 14.0 software.
Results
The meta-analysis included 19 eligible studies, which involved 4,899 breast cancer patients. The results showed that SOX10 overexpression in breast cancer tissues was significantly associated with a shorter overall survival time (OR = 1.63, 95%CI = 1.25-2.00, P < 0.05), with no significant heterogeneity found (I2 = 41.7%, P = 0.13). In terms of clinical characteristics, SOX10 overexpression was significantly associated with TNM-stage (OR = 2.61, 95%CI = 1.72–3.95, P < 0.05) and grade (OR = 5.16, 95%CI = 2.62–10.17, P < 0.05) of breast cancer. Furthermore, SOX10 overexpression was found to predict a higher incidence rate of triple negative breast cancer (TNBC) (OR = 34.46, 95%CI = 11.70-101.48, P < 0.05) and lower expression of human epidermal growth factor receptor-2 (HER2) (OR = 0.20, 95%CI = 0.12–0.34, P < 0.05), estrogen receptor (ER) (OR = 0.11, 95%CI = 0.02–0.57, P < 0.05), and progesterone receptor (PR) (OR = 0.12, 95%CI = 0.08–0.19, P < 0.05).
Conclusion
The study found that higher expression of the SOX10 was significantly associated with advanced progression and worse prognosis of breast cancer, particularly in TNBC. Therefore, SOX10 expression could be a promising predictor for evaluating the clinical progression and prognosis of breast cancer.
Assessment of non-proliferative diabetic retinopathy severity level using ultra-widefield Clarus versus conventional five-field and ultra-widefield Optos fundus imaging
Authors: Xiao Yuanyuan , Dan Handong , Du Xiaofeng , Michaelide michel , Nie. Xiaodong , Wang Wanxiao , Zheng Miao , Wang Dongdong , Zixu Huang , Song Zongming 
Published: June 2023

Abstract
Purpose
To compare diabetic retinopathy (DR) severity level and the abilities in detecting early DR lesions among conventional five-field, ultrawide-field (UWF) Optos, and UWF Clarus fundus imaging methods.
Methods
This was a single-center, prospective, clinic-based, and comparative study. In total, 157 consecutive patients with diabetes mellitus were enrolled in this study. All patients underwent comprehensive ophthalmological examinations. Following induction of mydriasis, each eye was examined by conventional five-field, UWF Optos, and UWF Clarus fundus imaging methods. All images were graded using the International Clinical DR severity scale. DR grades were compared and analyzed by weighted kappa statistics among the three fundus imaging methods.
Results
In total, 157 consecutive patients with diabetes (302 eyes) were enrolled in this study. Weighted kappa statistics for agreement were 0.471 (five-field vs. covered optimized Optos), 0.809 (five-field vs. covered Clarus), 0.396 (covered optimized Optos vs. covered Clarus), 0.463 (five-field vs. optimized Optos), 0.521 (five-field vs. Clarus 133°), 0.500 (five-field vs. Clarus 200°), 0.323 (optimized Optos vs. Clarus 133°), 0.349 (optimized Optos vs. Clarus 200°),0.976 (Clarus 133° vs. Clarus 200°), and 0.491(optimized Optos vs. red-free channel Optos). The area under curve of covered Clarus images was higher than that of conventional five-field images at three different thresholds.
Conclusion
Compared with conventional five-field and optimized Optos fundus imaging methods, Clarus fundus imaging methods exhibited excellent performance in assessing NPDR severity. Compared with optimized Optos, red-free channel Optos can detect more small lesions. Thus, Clarus and red-free channel Optos fundus imaging methods were superior for early detection of DR.
Volatile organic compounds produced by Pseudomonas chlororaphis subsp. aurantiaca ST-TJ4 antagonize the cherry blossom crown gall pathogen Agrobacterium tumefaciens
Authors: Zhang Qiao-Qiao , Kong Wei-Liang , Lu Lan-Xiang , Ni Hang , Wu Xiao-Qin 
Published: June 2023

Abstract
Background Plant crown gall disease caused by Agrobacterium tumefaciens causes significant losses in the cultivation of various ornamental and fruit trees. The emission of volatile organic compounds (VOCs) by biocontrol agents (BCAs) has garnered considerable attention due to their notable antagonistic effects. This study evaluated the biocontrol effects of VOCs produced by Pseudomonas chlororaphis subsp. aurantiaca ST-TJ4 against A. tumefaciens PX-1, the causal agent of cherry blossom crown gall.Results The VOCs released by P. chlororaphis subsp. aurantiaca ST-TJ4 significantly inhibited the colony size, cell viability, and swimming motility of A. tumefaciens PX-1, consequently impairing chemotaxis. Moreover, transmission and scanning electron microscopy revealed substantial severe morphological and ultrastructural changes in A. tumefaciens PX-1 cells, accompanied by a significant reduction in their ability to attach to plant roots. Furthermore, VOCs decreased the transcriptional expression levels of virulence-related genes (VirA, VirG, VirD2, VirE3) and three chemotaxis-related genes (CheW1, CheW2, CheA), which play pivotal roles in the pathogenicity of the bacteria. The observed downregulation of the superoxide dismutase (sod) gene indicated oxidative damage to A. tumefaciens PX-1 cells. These gene expression changes explained why A. tumefaciens PX-1 lost its early pathogenicity when inoculated on rose. In the antibacterial substance test, the VOCs of P. chlororaphis subsp. aurantiaca ST-TJ4 exhibited antagonistic effects on A. tumefaciens PX-1, with 2-undecone, 1-nonanol and 2-heptanone identified as the active compounds; among them, 1-nonanol and 2-heptanone exhibited the strongest antibacterial effect.Conclusions The VOCs produced by P. chlororaphis subsp. aurantiaca ST-TJ4 exhibited biocontrol potential against the tree crown gall pathogen A. tumefaciens.
Comprehensive analysis based on machine learning algorithm: Hspb1 and Lgals3 in neurons after spinal cord injury are closely related to autophagy
Authors: Yan Lei , Li Zihao , Li Chuanbo , Chen Jingyu , Zhou Xun , Cui Jiaming , Chen Chu , Hong Hongxiang , Wu Chunshuai , Xu Guanhua , Cui Zhiming 
Published: June 2023

Abstract
Spinal cord injury (SCI) refers to the dysfunction of sensorimotor and autonomic nerves caused by extensive and permanent loss of neurons after different degrees of damage to the spinal cord or cauda equina. The mechanism of spinal cord neuron injury after SCI has not been fully elucidated so far, although some opinions have been put forward. In this study, we extracted primary spinal neurons from neonatal rats, constructed a neuron injury model using glutamate stimulation, and performed full transcriptome sequencing analysis. We used machine learning algorithm (WGCNA, RF, and LASSO) to comprehensively and in-depth explore the important genes of spinal cord neuron injury and screen out the key genes Anxa2, Ccng1, Hspb1, Lgals3, Timp1 and S100a10, which are accompanied by the up-regulation of six expression levels of spinal cord neuron injury. Importantly, Hspb1 and Lgals3 are closely related to autophagy. To improve the reliability of our results, we downloaded the corresponding expression levels of six key genes of GSE2599, GSE20907, GSE45006, and GSE174549 to make ROC curve for verification, and then conducted RT-PCR verification of six key genes in vitro and in vivo, respectively. These findings will help us to further understand the pathogenesis of SCI, and may contribute to the screening of key targets for future clinical treatment.
Associations of cognitive impairment and longitudinal change in cognitive function with the risk of stroke events in middle-aged to older Chinese
Authors: Li Jun-xiao , Zhong Qiong-qiong , Zhu Tong , Jin Ya-li , Pan Jing , Yuan Shi-xiang , Zhu Feng 
Published: June 2023

Abstract
Background
Associations of cognitive impairment and longitudinal change in cognition with the risk of stroke events are unclear in older populations.
Method
Study data was obtained from the Guangzhou Biobank Cohort Study; 200 participants with a stroke history and an equal volume of participants who were age- and sex-matched, were respectively selected as the cases and the controls; a total of 26,064 participants at baseline and all with fatal stroke in a mean follow-up of 14.3 (standard deviation = 3.2) years, were included in a prospective cohort study. Conditional logistic regression and the Cox proportional hazard regression were used.
Results
Cognitive impairment was not associated with the risk of nonfatal stroke, with adjusted odd ratio (aOR) = 0.87 (95% confidence intervals (CI) 0.44–1.74, P = 0.70), when median cognition was taken as the reference. Cognitive impairment was respectively associated with an increased risk of fatal all strokes (adjusted hazard ratio (aHR) = 1.38, 95% CI 1.16–1.64, P < 0.001) and fatal ischaemic stroke (aHR = 1.39, 95% CI 1.10–1.77, P = 0.007), compared to median cognition; the Delayed Word Recall Test (DWRT) score was associated with a decreasing trend for the risk of fatal all strokes in a restricted cubic spline analysis; longitudinal DWRT score decline was associated with the increased risks of fatal all strokes (aHR = 1.42, 95% CI 1.11–1.82, P = 0.006) and fatal haemorrhagic stroke (aHR = 1.75, 95% CI 1.10–2.78, P = 0.02), compared to longitudinal DWRT score rise.
Conclusions
Cognitive impairment and longitudinal change in the DWRT score decline were associated with the increased risks of fatal strokes in middle-aged to older Chinese.
Effect of Social Media Sentiment on Donations Received by Npos
Authors: Gandía Juan L. , Huguet David 
Published: June 2023

Abstract
Previous literature has analyzed the effect of internet disclosure on NPO donations, specifically, through website disclosure, showing a positive relation between internet disclosure and NPO income. Nonetheless, there is a lack of studies examining the association between sentiment on social media and NPO donations. Therefore, the aim of this study is to examine the effect that sentiment in Twitter messages has on the donations received by NPOs. Using a sample of NPOs listed on the Non-Profit Times 100, we examine whether the sentiment transmitted by the NPOs through Twitter affects their donations. The results show that the sentiment associated with certain specific categories of messages (community messages and information messages about matters not directly related to the NPO) has a significant effect on the amount of donations received.