bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of EGFR-TKIs combined with craniocerebral radiotherapy on the prognosis of EGFR-mutant lung adenocarcinoma patients with brain metastasis: A propensity-score matched analysis
Authors: Deng Guangchuan , Tan Xiaojing , Li Yankang , Zhang Yingyun , Wang Qi , Li Jianbin , Li Zhenxiang 
Published: February 2023

Background and PurposeEpidermal growth factor receptor (EGFR)-mutant lung cancers are associated with a high risk of developing brain metastases (BM). Craniocerebral radiotherapy is a cornerstone for the treatment of BM, and EGFR-TKIs act on craniocerebral metastases”. However, whether EGFR-TKIs combined with craniocerebral radiotherapy can further increase the efficacy and improve the prognosis of patients is unclear. This study aimed to evaluate the difference in efficacy between targeted-therapy alone and targeted-therapy combined with radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM.Materials and MethodsA total of 291 patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutations were enrolled in this retrospective cohort study. Propensity score matching (PSM) was conducted using a nearest-neighbor algorithm (1:1) to adjust for demographic and clinical covariates. Patients were divided into two groups: EGFR-TKIs alone and EGFR-TKIs combined with craniocerebral radiotherapy. Intracranial progression-free survival (iPFS) and overall survival (OS) were calculated. Kaplan–Meier analysis was used to compare iPFS and OS between the two groups. Brain radiotherapy included WBRT, local radiotherapy, and WBRT+Boost.ResultsThe median age at diagnosis was 54 years (range: 28–81 years). Most patients were female (55.9%) and non-smokers (75.5%). Fifty-one pairs of patients were matched using PSM. The median iPFS for EGFR-TKIs alone (n=37) and EGFR-TKIs+craniocerebral radiotherapy (n=24) was 8.9 and 14.7 months, respectively. The median OS for EGFR-TKIs alone (n=52) and EGFR-TKIs+craniocerebral radiotherapy (n=52) was 32.1 and 45.3 months, respectively.ConclusionIn EGFR-mutant lung adenocarcinoma patients with BM, targeted therapy combined with craniocerebral radiotherapy is an optimal treatment.
RNF6 activates TGF-β1/c-Myb pathway to promote EMT in esophageal squamous cell carcinoma
Authors: Cheng Jingge , Wu Kun , Yang Qian , Zhu Ziming , Zhao Hongye 
Published: February 2023

ObjectiveThis study aimed to investigate RING-Finger Protein 6 (RNF6) expression in esophageal squamous cell carcinoma (ESCC) cells and whether it affects cell proliferation, invasion, and migration by regulating the TGF-β1/c-Myb pathway.MethodsTCGA database was used to analyze RNF6 expression in normal tissues and esophageal cancer tissues. Kaplan–Meier method was used to examine the correlation between RNF6 expression and patient prognosis. SiRNA interference vector and RNF6 overexpression plasmid were constructed, and RNF6 was transfected into Eca-109 and KYSE-150 esophageal cancer cell line. In vitro scratch assay and Transwell assay were conducted to investigate the effects of RNF6 on the migration and invasion of Eca-109 and KYSE-150 cells. RT-PCR detected the expression of Snail, E-cadherin, and N-cadherin, and TUNEL detected the apoptosis of cells.ResultsRNF6 up-regulation promoted the progression of esophageal cancer and predicted poor prognosis. RNF6 also enhanced the migration and invasion of ESCC cells in vitro. RNF6 silencing inhibited the migration and invasion of ESCC cells. TGF-β inhibitors reversed the oncogenic effects of RNF6. RNF6 regulated the migration and invasion of ESCC cells by activating the TGF-β pathway. RNF6/TGF-β1 promoted esophageal cancer progression through c-Myb.ConclusionRNF6 promotes the proliferation, invasion, and migration of ESCC cells possibly by activating the TGF-β1/c-Myb pathway and affects the progression of ESCC.
High-risk multiple myeloma predicted by circulating plasma cells and its genetic characteristics
Authors: Xia Yuan , Shen Na , Zhang Run , Wu Yujie , Shi Qinglin , Li Jianyong , Chen Lijuan , Xu Min , Jin Yuanyuan 
Published: February 2023

IntroductionCirculating plasma cells (CPC) have been reported to be one of the indicators of high-risk multiple myeloma (MM), yet the prognostic significance of CPC in Chinese population and the genetic mechanisms underlying CPC formation have not been fully elucidated.MethodsPatients with newly diagnosed MM were included in this study. We used multi-parameter flow cytometry (MFC) for CPC quantification and next-generation sequencing (NGS) technology for mutational landscape mapping to identify the correlation of CPC level with clinical characteristics and the mutations.ResultsA total of 301 patients were enrolled in this investigation. We demonstrated that CPC quantification could effectively mirror the tumor load, and CPC ≥ 0.105% at diagnosis or detectable CPC after therapy indicates poor treatment response and adverse outcome, and the introduction of CPC into the R-ISS enables a more accurate risk stratification. Interestingly, we noticed an elevated percentage of light-chain MM in patients with higher CPC. Mutational landscape revealed that patients harboring mutations in TP53, BRAF, DNMT3A, TENT5C, and IL-6/JAK/STAT3 pathway-related genes tended to have higher CPC levels. Gene enrichment analysis demonstrated that pathways involving chromosome regulation and adhesion may be potential mechanisms accounting for CPC formation.DiscussionAccordingly, quantification of CPC may provide a less-invasive and reliable approach for identifying high-risk MM in Chinese population.
Prognostic significance of ING3 expression in patients with cancer: A systematic review and meta-analysis
Authors: Li Zehan , Xu Shengchao , Chen Lin , Huang Shuqi , Kuerban Xieyida , Li Tianyu 
Published: February 2023

BackgroundIt has been reported that ING3 inhibits the progression of various cancers. However, some studies have shown that it promotes the development of prostate cancer. The purpose of this study was to investigate whether ING3 expression is associated with the prognosis of patients with cancer.Materials and methodsPubMed, Cochrane Database, Embase, Medline, ScienceDirect, Scopus and Web of Science were searched until September 2022. The hazard ratio (HR)/odds ratio (OR) and 95% confidence interval (95% CI) were calculated using Stata 17 software. We used the Newcastle-Ottawa Scale (NOS) to assess the risk of bias.ResultSeven studies involving 2371 patients with five types of cancer were included. The results showed that high expression of ING3 was negatively associated with a more advanced TNM stage (III-IV vs. I-II) (OR=0.61, 95% CI: 0.43-0.86), lymph node metastasis (OR=0.67, 95% CI: 0.49-0.90) and disease-free survival (HR=0.63, 95% CI: 0.37-0.88). However, ING3 expression was not associated with overall survival (HR=0.77, 95% CI: 0.41-1.12), tumor size (OR=0.67, 95% CI: 0.33-1.37), tumor differentiation (OR=0.86, 95% CI: 0.36-2.09) and gender (OR=1.14, 95% CI: 0.78-1.66).ConclusionThis study showed that the expression of ING3 was associated with better prognosis, suggesting that ING3 may be a potential biomarker for cancer prognosis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier (CRD42022306354).
Neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable BRAF-mutated and wild-type melanoma: NEO-TIM, a phase II randomized non-comparative study
Authors: Ascierto Paolo A. , Cioli Eleonora , Chiarion-Sileni Vanna , Quaglino Pietro , Spagnolo Francesco , Guidoboni Massimo , Del Vecchio Michele , Peris Ketty , Queirolo Paola , Fioretto Luisa , Caracò Corrado , Paone Miriam , Sorrentino Antonio , Capone Mariaelena , Giannarelli Diana , Ferrara Gerardo , Massi Daniela , Trojaniello Claudia 
Published: February 2023

BackgroundFollowing the increased survival of patients with metastatic melanoma thanks to immunotherapy and targeted therapy, neoadjuvant approaches are being investigated to address the unmet needs of unresponsive and intolerant patients. We aim to investigate the efficacy of neoadjuvant plus adjuvant combined or sequenced vemurafenib, cobimetinib and atezolizumab in patients with high-risk, resectable BRAF-mutated and wild-type melanoma.MethodsThe study is a phase II, open-label, randomized non-comparative trial in patients with stage IIIB/C/D surgically resectable, BRAF-mutated and wild-type melanoma, with three possible treatments: (1) vemurafenib 960 mg twice daily from day 1 to 42; (2) vemurafenib 720 mg twice daily from day 1 to 42; (3) cobimetinib 60 mg once daily from day 1 to 21 and from day 29 to 42; and (4) atezolizumab 840 mg for two cycles (day 22 and day 43).Patients will be randomized to three different arms: A) BRAF-mutated patients will receive over 6 weeks (1) + (3); B) BRAF-mutated patients will receive over 6 weeks (2) + (3) + (4); C) BRAF wild-type patients will receive over 6 weeks (3) + (4). All patients will also receive atezolizumab 1200 mg every 3 weeks for 17 cycles after surgery and after a second screening period (up to 6 weeks).DiscussionNeoadjuvant therapy for regional metastases may improve operability and outcomes and facilitate the identification of biomarkers that can guide further lines of treatment. Patients with clinical stage III melanoma may especially benefit from neoadjuvant treatment, as the outcomes of surgery alone are very poor. It is expected that the combination of neoadjuvant and adjuvant treatment may reduce the incidence of relapse and improve survival.Clinical trial registrationeudract.ema.europa.eu/protocol.htm, identifier 2018-004841-17.
Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis
Authors: Zhang Yunyun , Huang Chengrong , Zhang Hao , Duan Zhi , Liu Qian , Li Jianfei , Zong Qiyin , Wei Yu , Liu Futing , Duan Wanlu , Chen Liwen , Zhou Qiang , Wang Qin 
Published: February 2023

Backgrounds &amp; aimsEpstein-Barr virus (EBV) infection occurs commonly in children and may cause acute infectious mononucleosis (AIM) and various malignant diseases. Host immune responses are key players in the resistance to EBV infection. We here assessed the immunological events and laboratory indicators of EBV infection, as well as determined the clinical usefulness of evaluating the severity and efficacy of antiviral therapy in AIM patients.MethodsWe enrolled 88 children with EBV infection. The immune environment was defined by immunological events such as frequencies of lymphocyte subsets, phenotypes of T cells, and their ability to secrete cytokines, and so on. This environment was analyzed in EBV-infected children with different viral loads and in children in different phases of infectious mononucleosis (IM) from disease onset to convalescence.ResultsChildren with AIM had higher frequencies of CD3+ T and CD8+ T cells, but lower frequencies of CD4+ T cells and CD19+ B cells. In these children, the expression of CD62L was lower and that of CTLA-4 and PD-1 was higher on T cells. EBV exposure induced granzyme B expression, but reduced IFN-γ secretion, by CD8+ T cells, whereas NK cells exhibited reduced granzyme B expression and increased IFN-γ secretion. The frequency of CD8+ T cells was positively correlated with the EBV DNA load, whereas the frequencies of CD4+ T cells and B cells were negatively correlated. During the convalescent phase of IM, CD8+ T cell frequency and CD62L expression on T cells were restored. Moreover, patient serum levels of IL-4, IL-6, IL-10, and IFN-γ were considerably lower throughout the convalescent phase than throughout the acute phase.ConclusionRobust expansion of CD8+ T cells, accompanied by CD62L downregulation, PD-1 and CTLA-4 upregulation on T cells, enhanced granzyme B production, and impaired IFN-γ secretion, is a typical characteristic of immunological events in children with AIM. Noncytolytic and cytolytic effector functions of CD8+ T cells are regulated in an oscillatory manner. Furthermore, the AST level, number of CD8+ T cells, and CD62L expression on T cells may act as markers related to IM severity and the effectiveness of antiviral treatment.
Methodological, reporting, and evidence quality of systematic reviews of traditional Chinese medicine for ischemic stroke
Authors: Sun Shouyuan , Zhao Liang , Zhou Xiaoli , Liu Xuewu , Xie Zongzhi , Ren Jun , Zhou Baoyuan , Pan Yawen 
Published: February 2023

Objective: The aim of this study is to critically appraise whether published systematic reviews/meta-analyses of traditional Chinese medicine for adults with ischemic stroke are of sufficient quality and to rate the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Method: A literature search was performed in the Cochrane Library, PubMed, Chinese National Knowledge Infrastructure, and SinoMed databases by March 2022. The inclusion criteria were systematic reviews/meta-analyses of traditional Chinese medicine in adults who suffered from ischemic stroke. A Measurement Tool to Access Systematic Reviews 2 (AMSTAR-2) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Abstract (PRISMA-A) statements were used to assess the methodological and reporting quality of the included reviews. The Grading of Recommendations, Assessment, Development, and Evaluation system was utilized to assess each report’s evidence level.Results: Of the 1,908 titles and abstracts, 83 reviews met the inclusion criteria. These studies were published between 2005 and 2022. The results of AMSTAR-2 showed that 51.4% of the items were reported, but the registration, reasons for the inclusion of study design, the list of excluded studies, and funding information were ignored in the majority of the reviews. The results of PRISMA-A showed that 33.9% of items were reported, and the information on registration, limitation, and funding was not available in many publications. The assessment of the evidence with the Grading of Recommendations, Assessment, Development, and Evaluation showed that more than half (52/83) of the included studies had either low or very low levels of evidence.Conclusion: The reporting quality in the abstract of systematic reviews/meta-analyses on traditional Chinese medicine for ischemic stroke is poor and does not facilitate timely access to valid information for clinical practitioners. Although the methodological quality is of a medium level, this evidence lacks certainty, especially with a high risk of bias in individual studies.
Exposure to artificial light at night mediates the locomotion activity and oviposition capacity of Dastarcus helophoroides (Fairmaire)
Authors: Jiang Xiang-lan , Ren Zhe , Hai Xiao-xia , Zhang Ling , Wang Zhi-gang , Lyu Fei 
Published: February 2023

Light entrains the endogenous circadian clocks of organisms to synchronize their behavioral and physiological rhythms with the natural photoperiod. The presence of artificial light at night disrupts these photoperiodic cues and is currently considered to be a major threat to key fitness-related behaviors, including sleep disruption and physiological stress. Research on the ecological influence of forest pest and their natural enemies is lacking. The wood-boring insects significantly damage forest and urban forest ecosystem functions. The parasitic beetles, Dastarcus helophoroides is an important natural enemy of wood-boring insects, especially those in the Cerambycidae family. However, the effect of artificial light at night on the locomotor rhythms and oviposition capacity of D. helophoroides has received little attention. To address this gap, diel changes in the locomotor activity and number of eggs laid by female D. helophoroides was analyzed under different light-dark (LD) cycles and temperatures. The results showed that the 24-h rhythmic of locomotor activity in these beetles was elevated in darkness and reduced under illumination, indicating that they are nocturnal insects. This activity has two major peaks, the evening (1–8 h after lights off) and morning (3.5–12.5 h after lights off) components, reflecting that light mediate regular changes in locomotor activity. Moreover, the circadian rhythms and active percentage were influenced by the illumination duration and temperature, especially constant light and 40°C. Females laid more eggs under the 16 L: 8 D cycles at 30°C than under the other combinations of photoperiod (including constant light and darkness) and temperature. Finally, the potential influence of exposure to four ecologically relevant intensities of artificial light at night (0, 1, 10 or 100 lx) on oviposition capacity was studied. The results showed that lifetime exposure to bright artificial light (1–100 lx) at night decreased the number of eggs laid relative to those laid with no lighting at night. These results demonstrate that chronic exposure to bright artificial light at night may influence the locomotor activity and oviposition capacity of this parasitic beetle.
Uncovering the genetic links of diabetic erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome
Authors: Yuan Penghui , Sun Taotao , Han Zhengyang , Chen Yinwei , Meng Qingjun 
Published: February 2023

Background: Clinical associations between erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been noticed, but the common pathogenic mechanisms between them remain elusive. The aim of the study was to mine shared genetic alterations between ED and chronic prostatitis/chronic pelvic pain syndrome.Method: Transcriptome data of ED and chronic prostatitis/chronic pelvic pain syndrome-related genes (CPRGs) were retrieved from relevant databases and differentially expressed analysis was used to obtain significant CPRGs. Then function enrichment and interaction analyses were performed to show shared transcriptional signature, including gene ontology and pathway enrichment, the construction of protein-protein interaction (PPI) network, cluster analysis, and co-expression analysis. Hub CPRGs and key cross-link were selected by validating these genes in clinical samples, chronic prostatitis/chronic pelvic pain syndrome and ED-related datasets. Then the miRNA-OSRGs co-regulatory network was predicted and validated. Subpopulation distribution and disease association of hub CPRGs were further identified.Result: Differentially expressed analysis revealed 363 significant CPRGs between ED and chronic prostatitis/chronic pelvic pain syndrome, functioning in inflammatory reaction, oxidative stress, apoptosis, smooth muscle cell proliferation, and extracellular matrix organization. A PPI network containing 245 nodes and 504 interactions was constructed. Module analysis depicted that multicellular organismal process and immune metabolic process were enriched. 17 genes were screened in PPI via topological algorithms, and reactive oxygen species as well as interleukin-1 metabolism were regarded as the bridging interactive mechanism. After screening and validation, a hub-CPRG signature consisting of COL1A1, MAPK6, LPL, NFE2L2 and NQO1 were identified and associated miRNA were verified. These miRNAs played an important role in immune and inflammatory response likewise. Finally, NQO1 was identified as a key genetic link between ED and chronic prostatitis/chronic pelvic pain syndrome. It was predominately enriched in corpus cavernosum endothelial cell, and correlated with other male urogenital and immune system diseases tightly.Conclusion: We identified the genetic profiles as well as corresponding regulatory network underlying interaction between ED and chronic prostatitis/chronic pelvic pain syndrome via multi-omics analysis. These findings expanded a new understanding for the molecular mechanism of ED with chronic prostatitis/chronic pelvic pain syndrome.
Heart rate variability as a predictor of stroke course, functional outcome, and medical complications: A systematic review
Authors: Aftyka Joanna , Staszewski Jacek , Dębiec Aleksander , Pogoda-Wesołowska Aleksandra , Żebrowski Jan 
Published: February 2023

Background: Heart rate variability (HRV) is a non-invasive marker of autonomic nervous system function that is based on the analysis of length differences between subsequent RR intervals of the electrocardiogram. The aim of this systematic review was to assess the current knowledge gap in the utility of HRV parameters and their value as predictors of the acute stroke course.Methods: A systematic review was performed in accordance with the PRISMA guidelines. Relevant articles published between 1 January 2016 and 1 November 2022 available in the PubMed, Web of Science, Scopus, and Cochrane Library databases were obtained using a systematic search strategy. The following keywords were used to screen the publications: “heart rate variability” AND/OR “HRV” AND “stroke.” The eligibility criteria that clearly identified and described outcomes and outlined restrictions on HRV measurement were pre-established by the authors. Articles assessing the relationship between HRV measured in the acute phase of stroke and at least one stroke outcome were considered. The observation period did not exceed 12 months. Studies that included patients with medical conditions influencing HRV with no established stroke etiology and non-human subjects were excluded from the analysis. To minimize the risk of bias, disagreements throughout the search and analysis were resolved by two independent supervisors.Results: Of the 1,305 records obtained from the systematic search based on keywords, 36 were included in the final review. These publications provided insight into the usability of linear and non-linear HRV analysis in predicting the course, complications, and mortality of stroke. Furthermore, some modern techniques, such as HRV biofeedback, for the improvement of cognition performance after a stroke are discussed.Discussion: The present study showed that HRV could be considered a promising biomarker of a stroke outcome and its complications. However, further research is needed to establish a methodology for appropriate quantification and interpretation of HRV-derived parameters.
Uncovering the role of wheat magnesium transporter family genes in abiotic responses
Authors: Tang Yanhong , Yang Xiaoyue , Li Han , Shuai Yating , Chen Wang , Ma Dongfang , Lü Zhichuang 
Published: February 2023

BackgroundThe CorA / MGT / MRS2 family proteins are an important group of magnesium transporter proteins that maintain magnesium ion homeostasis in plant cells. However, little is known about the MGT functions in wheat.MethodsThe known MGT sequences were used as queries to BlastP against wheat genome IWGSC RefSeq v2.1 assembly (E-value &lt;10–5). Chromosome localization information for each TaMGT gene was obtained from the GFF3 file of the wheat genome data (IWGSCv2.1).The sequence of 1500 bp upstream of the TaMGT genes was extracted from the wheat genome data. The cis-elements were analyzed using PlantCARE online tool.ResultA total of 24 MGT genes were identified on 18 chromosomes of wheat. After functional domain analysis, only TaMGT1A, TaMGT1B, and TaMGT1D had GMN mutations to AMN, while all the other genes had conserved GMN tripeptide motifs. Expression profiling showed that the TaMGT genes were differentially expressed under different stresses and at different growth and development stages. The expression levels of TaMGT4B and TaMGT4A were significantly up-regulated in cold damage. In addition, qRT-PCR results also confirmed that these TaMGT genes are involved in the wheat abiotic stress responses.ConclusionIn conclusion, The results of our research provide a theoretical basis for further research on the function of TaMGT gene family in wheat.