bluuebunny/crossref_metadata_2025_split huggingface dataset:
Babao Dan decreases hepatocarcinogenesis by inhibiting hepatic progenitor cells malignant transformation via down-regulating toll-like receptor 4
Authors: Liang Lei , Zhang Lu-Yao , Liu Wen-Ting , Zong Chen , Gao Lu , Li Rong , Zhao Qiu-Dong , Zhao Na-Ping , Wei Li-Xin , Zhang Li , Han Zhi-Peng 
Published: May 2023

BackgroundBabao Dan (BBD) is a traditional Chinese medicine that has been widely used as a complementary and alternative medicine to treat chronic liver diseases. In this study, we aimed to observe the effect of BBD on the incidence of diethylnitrosamine (DEN)-initiated hepatocellular carcinoma formation in rats and explored its possible mechanism.MethodsTo verify this hypothesis, BBD was administrated to rats at a dose of 0.5g/kg body weight per two days from the 9th to 12th week in HCC-induced by DEN. Liver injury biomarkers and hepatic inflammatory parameters were evaluated by histopathology as well as serum and hepatic content analysis. We applied immunohistochemical analysis to investigate the expression of CK-19 and SOX-9 in liver tissues. The expression of TLR4 was determined by immunohistochemical, RT-PCR, and western blot analysis. Furthermore, we also detected the efficacy of BBD against primary HPCs neoplastic transformation induced by LPS.ResultsWe observed that DEN could induce hepatocarcinogenesis, and BBD could obviously decrease the incidence. The biochemical and histopathological examination results confirmed that BBD could protect against liver injury and decrease inflammatory infiltration. Immunohistochemistry staining results showed that BBD could effectively inhibit the ductal reaction and the expression of TLR4. The results showed that BBD-serumcould obviously inhibit primary HPCs neoplastic transformation induced by regulating the TLR4/Ras/ERK signaling pathway.ConclusionIn summary, our results indicate that BBD has potential applications in the prevention and treatment of HCC, which may be related to its effect on hepatic progenitor cells malignant transformation via inhibiting the TLR4/Ras/ERK signaling pathway.
Metabolic syndrome is independently associated with improved overall survival to first-line therapy with immune checkpoint inhibitors in non-small cell lung cancer
Authors: Bou Zerdan Maroun , Ashok Kumar Prashanth , Barrios Dulce M. , Glidden Alanna , Nasr Dayana , Niforatos Stephanie , Ghelani Ghanshyam , Leibovitch Jennifer , Nasr Sandy , KC Binod , Ombada Mulham , Khokhar Farzam , Poudyal Bhavya , Bhandari Jenish , Shahnawaz Myera , Graziano Stephen , Lim Seah H. 
Published: May 2023

BackgroundMany co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC).MethodsWe carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC.ResultsOne hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival.ConclusionsOur results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.
Xerna™ TME Panel is a machine learning-based transcriptomic biomarker designed to predict therapeutic response in multiple cancers
Authors: Uhlik Mark , Pointing Daniel , Iyer Seema , Ausec Luka , Štajdohar Miha , Cvitkovič Robert , Žganec Matjaž , Culm Kerry , Santos Valerie Chamberlain , Pytowski Bronislaw , Malafa Mokenge , Liu Hong , Krieg Arthur M. , Lee Jeeyun , Rosengarten Rafael , Benjamin Laura 
Published: May 2023

IntroductionMost predictive biomarkers approved for clinical use measure single analytes such as genetic alteration or protein overexpression. We developed and validated a novel biomarker with the aim of achieving broad clinical utility. The Xerna™ TME Panel is a pan-tumor, RNA expression-based classifier, designed to predict response to multiple tumor microenvironment (TME)-targeted therapies, including immunotherapies and anti-angiogenic agents.MethodsThe Panel algorithm is an artificial neural network (ANN) trained with an input signature of 124 genes that was optimized across various solid tumors. From the 298-patient training data, the model learned to discriminate four TME subtypes: Angiogenic (A), Immune Active (IA), Immune Desert (ID), and Immune Suppressed (IS). The final classifier was evaluated in four independent clinical cohorts to test whether TME subtype could predict response to anti-angiogenic agents and immunotherapies across gastric, ovarian, and melanoma datasets.ResultsThe TME subtypes represent stromal phenotypes defined by angiogenesis and immune biological axes. The model yields clear boundaries between biomarker-positive and -negative and showed 1.6-to-7-fold enrichment of clinical benefit for multiple therapeutic hypotheses. The Panel performed better across all criteria compared to a null model for gastric and ovarian anti-angiogenic datasets. It also outperformed PD-L1 combined positive score (&gt;1) in accuracy, specificity, and positive predictive value (PPV), and microsatellite-instability high (MSI-H) in sensitivity and negative predictive value (NPV) for the gastric immunotherapy cohort.DiscussionThe TME Panel’s strong performance on diverse datasets suggests it may be amenable for use as a clinical diagnostic for varied cancer types and therapeutic modalities.
EGFR p.V774M/p.L833V compound mutations in lung adenocarcinoma responded well to almonertinib: a case report
Authors: Pan Hai , Zhang Linlin , Meng Fanlu , Guan Shasha , Zhong Diansheng 
Published: May 2023

BackgroundThere are about 10-15% of uncommon EGFR mutations found in NSCLC patients, and their sensitivity to EGFR TKIs still lack sufficient clinical evidence, especially for rare compound mutations. Almonertinib is the third generation of EGFR-TKI that has demonstrated excellent efficacy in classical mutations, however, effects in rare mutations have also been rarely reported.Case presentationIn this case report, we present a patient with advanced lung adenocarcinoma with a rare EGFR p.V774M/p.L833V compound mutations, who achieved long-lasting and stable disease control after first-line Almonertinib targeted therapy. This case report could provide more information for therapeutic strategy selecting of NSCLC patients harboring rare EGFR mutations.ConclusionWe report for the first time the long-lasting and stable disease control with Almonertinib for EGFR p.V774M/p.L833V compound mutations treatment, hoping to provide more clinical case references for the treatment of rare compound mutations.
Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer
Authors: Shi Demin , Li Yan , Liang Xueyan , Chen Lingyuan 
Published: May 2023

BackgroundThe efficiency and safety of sacituzumab govitecan (SG) for the therapy of hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) metastatic breast cancer (BC) has been demonstrated. The aim of this study is to evaluate its cost-effectiveness on HR+/HER2- metastatic BC from the third-party payer perspective in the United States.MethodsWe performed the cost-effectiveness of SG and chemotherapy using a partitioned survival model. TROPiCS-02 provided clinical patients for this study. We evaluated the robustness of this study by one-way and probabilistic sensitivity analyses. Subgroup analyses were also conducted. The outcomes were costs, life-years, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB).ResultsSG treatment was related to an increase of 0.284 life years and 0.217 QALYs over chemotherapy, as well as a cost increase of $132,689, reaching an ICER of $612,772/QALY. The INHB was -0.668 QALYs, and the INMB was -$100,208. SG was not cost-effective at the willingness to pay (WTP) threshold of $150,000/QALY. The outcomes were sensitive to patient body weight and cost of SG. SG may be cost-effective at the WTP threshold of $150,000/QALY if the price is less than $3.997/mg or the weight of patients is under 19.88 kg. Based on the subgroup analysis, SG did not prove cost-effective in all subgroups at the WTP threshold of $150,000/QALY.ConclusionFrom a third-party payer standpoint in the United States, SG was not cost-effective, even though it had a clinically significant advantage over chemotherapy for the treatment of HR+/HER2- metastatic BC. The cost-effectiveness of SG can be improved if the price is substantially reduced.
Comprehensive analysis and molecular map of Hippo signaling pathway in lower grade glioma: the perspective toward immune microenvironment and prognosis
Authors: Guo Yu-Duo , Sun Jie , Zhao Chao , Han Le , Yu Chun-Jiang , Zhang Hong-Wei 
Published: May 2023

BackgroundThe activation of YAP/TAZ transcriptional co-activators, downstream effectors of the Hippo/YAP pathway, is commonly observed in human cancers, promoting tumor growth and invasion. The aim of this study was to use machine learning models and molecular map based on the Hippo/YAP pathway to explore the prognosis, immune microenvironment and therapeutic regimen of patients with lower grade glioma (LGG).MethodsSW1783 and SW1088 cell lines were used as in vitro models for LGG, and the cell viability of the XMU-MP-1 (a small molecule inhibitor of the Hippo signaling pathway) treated group was evaluated using a Cell Counting Kit-8 (CCK-8). Univariate Cox analysis on 19 Hippo/YAP pathway related genes (HPRGs) was performed to identify 16 HPRGs that exhibited significant prognostic value in meta cohort. Consensus clustering algorithm was used to classify the meta cohort into three molecular subtypes associated with Hippo/YAP Pathway activation profiles. The Hippo/YAP pathway’s potential for guiding therapeutic interventions was also investigated by evaluating the efficacy of small molecule inhibitors. Finally, a composite machine learning models was used to predict individual patients’ survival risk profiles and the Hippo/YAP pathway status.ResultsThe findings showed that XMU-MP-1 significantly enhanced the proliferation of LGG cells. Different Hippo/YAP Pathway activation profiles were associated with different prognostic and clinical features. The immune scores of subtype B were dominated by MDSC and Treg cells, which are known to have immunosuppressive effects. Gene Set Variation Analysis (GSVA) indicated that subtypes B with a poor prognosis exhibited decreased propanoate metabolic activity and suppressed Hippo pathway signaling. Subtype B had the lowest IC50 value, indicating sensitivity to drugs that target the Hippo/YAP pathway. Finally, the random forest tree model predicted the Hippo/YAP pathway status in patients with different survival risk profiles.ConclusionsThis study demonstrates the significance of the Hippo/YAP pathway in predicting the prognosis of patients with LGG. The different Hippo/YAP Pathway activation profiles associated with different prognostic and clinical features suggest the potential for personalized treatments.
A senescence-associated signature refines the classification of different modification patterns and characterization of tumor immune microenvironment infiltration in triple-negative breast cancer
Authors: Huang Renhong , Wang Han , Hong Jin , Wang Zheng , Wu Jiayi , Huang Ou , He Jianrong , Chen Weiguo , Li Yafen , Chen Xiaosong , Shen Kunwei 
Published: May 2023

Background: Recent studies have found that senescence-associated genes play a significant role in cancer biological processes. We aimed to analyze the characteristics and role of senescence-associated genes in triple-negative breast cancer (TNBC).Methods: We systematically screened senescence-associated secretory phenotype (SASP) genes based on the gene expression information in the TCGA database. According to the expression levels of senescence-associated genes, TNBC was classified into two subtypes, namely, TNBCSASP1 and TNBCSASP2, using an unsupervised cluster algorithm. We then performed gene expression, enrichment pathway, immune infiltration, mutational profile characterization, drug sensitivity and prognostic value analyses for the two subtypes. The reliability and prognostic predictive utility of this classification model were validated. The most prognostically relevant gene, FAM3B, was comprehensively identified and validated by tissue microarray in TNBC.Results: TNBC was classified into two senescence-associated subtypes, TNBCSASP1 and TNBCSASP2, based on the set of senescence-associated secretory phenotype genes, among which the TNBCSASP1 subtype had a poor prognosis. The TNBCSASP1 subtype was immunosuppressed, with suppressed immune-related signaling pathways and low immune cell infiltration. The effect of the mutation on the TP53 and TGF-β pathways could be related to the poor prognosis of the TNBCSASP1 subtype. Drug sensitivity analysis showed that AMG.706, CCT007093, and CHIR.99021 were potential targeted drugs for the TNBCSASP1 subtype. Finally, FAM3B was a key biomarker affecting the prognosis of patients with triple-negative breast cancer. Compared to normal breast tissue, the expression of FAM3B was reduced in triple-negative breast cancer. Survival analysis showed that overall survival was significantly shorter in triple-negative breast cancer patients with high FAM3B expression.Conclusion: A senescence-associated signature with different modification patterns has critical potential for providing a better understanding of TNBC biological processes, and FAM3B might serve as an applicable target for TNBC therapy.
The manufacture and reliability analysis of the all-rigid Fabry–Perot resonator for fiber-optic acoustic sensors
Authors: Zheng Yongqiu , Chen Jiamin , Bai Jiandong , Li Zonghao , Zhao Xinyu , Xue Chenyang 
Published: May 2023

By the continuous development of aerospace, petroleum exploration, and other industrial fields, the fiber-optic acoustic sensor (FOAS) with high reliability is a desideration sensor, which can be used for noise monitoring in the extremely harsh environment. The FOAS based on the all-rigid Fabry–Perot resonator (FPR) relies on the new acoustic sensitive principle, where the change in the air refractive index is induced by sound waves and gets rid of the distortion caused by the mechanical characteristics of the acoustic sensor based on the movable parts. So, the FPR-based FOAS is very suitable for acoustic sensing in the harsh environment. In this paper, the reliability of this kind of FOASs is simulated and analyzed. The modal and anti-vibration simulation results of FPR with different sizes show that the FPR has a high natural frequency, and the external vibration environment does not affect the acoustic sensitivity of the FPR. The micro and small-batch all-rigid FPR can be manufactured by the optical contact. Moreover, the FPR can withstand the high temperature of 500°C that is verified by rapid heat treatment equipment. In order to improve the reliability of the FOAS, the metal packing shell is designed and fabricated. Moreover, the vibration and high-temperature tests of the packaged sensor are carried out. The two groups of tests show that the sensor can work normally under 10 g of acceleration vibration and 200°C high temperature, respectively. Therefore, the FOAS based on the FPR has high reliability and is very suitable for noise monitoring in the extreme harsh environment of various industrial fields. Furthermore, the research results of this paper will enhance the competitiveness and influence of the commercialized FOAS.
Drying temperatures affect the qualitative–quantitative variation of aromatic profiling in Anethum graveolens L. ecotypes as an industrial–medicinal–vegetable plant
Authors: Farmanpour Kalalagh Karim , Mohebodini Mehdi , Fattahi Reza , Beyraghdar Kashkooli Arman , Davarpanah Dizaj Sanaz , Salehifar Fatemeh , Mokhtari Amir Mohammad 
Published: May 2023

IntroductionThere are several factors that affect the quality and quantity of active ingredients and essential oil (EO) content, including pre and postharvest practices such as drying conditions. One of the most important factors in drying is temperature and then selective drying temperature (DT). In general, DT has a direct effect on the aromatic properties of Anethum graveolens.MethodsOn this basis, the present study was conducted to evaluate the effects of different DTs on the aroma profile of A. graveolens ecotypes.Results and discussionThe results showed that different DTs, ecotypes, and their interaction significantly affect EO content and composition. The highest EO yield was obtained from the Parsabad ecotype (1.86%) followed by the Ardabil ecotype (1.4%), both at 40° C. More than 60 EO compounds were identified, mainly monoterpenes and sesquiterpenes, highlighting α-Phellandrene, Germacrene D, and Dill apiole as major components in all treatments. Besides α-Phellandrene, the major EO compounds at shad drying (ShD) were β-Phellandrene and p-Cymene, while plant parts dried at 40° C showed l-Limonene and Limonene as the main constituents, and Dill apiole was detected in greater amounts in the samples dried at 60 °C. To determine the appropriate DT, simple and factorial based-ANOVA together multivariate analysis demonstrated significant differences in the compounds produced under different DTs. The results indicated that more EO compounds, mainly monoterpenes, were extracted at ShD than other DTs. On the other hand, the content and composition of sesquiterpenes increased significantly when DT was increased to 60 °C. From the genetic backgrounds point of view, the Parsabad ecotype (with 12 similar compounds) and Esfahan ecotype (with 10 similar compounds) were the most suitable ecotypes under all DTs in terms of EO compounds. Accordingly, the present study would help various industries to optimize specific DT(s) to obtain special EO compound(s) from different A. graveolens ecotypes based on commercial requirements.
A model of teacher enthusiasm, teacher self-efficacy, grit, and teacher well-being among English as a foreign language teachers
Authors: Shao Guohua 
Published: May 2023

IntroductionThis study aimed to investigate the relationship among teacher enthusiasm and teacher self-efficacy, grit, and teacher psychological well-being among Chinese English as a foreign language (EFL) teachers.MethodsA sample of 553 Chinese EFL teachers completed self-report measures of teacher enthusiasm, teacher self-efficacy, grit, and teacher psychological well-being. Confirmatory factor analysis was used to confirm the validity of the scales, and structural equation modeling was used to test the hypothesized model.ResultsThe results indicated that teacher self-efficacy and grit were positively associated with teacher psychological well-being, providing support for the importance of these teacher characteristics in promoting teacher well-being. Furthermore, teacher enthusiasm was found to have an indirect effect on teacher psychological well-being through the mediation of teacher grit, providing evidence for the importance of teacher motivation and engagement in promoting teacher well-being. The partial mediation model was found to be the best fitting model.DiscussionThese findings have important implications for the development of interventions and programs aimed at promoting teacher well-being in the context of EFL teaching.
Students with learning disabilities/attention-deficit/hyperactivity disorder in higher education dealing with remote learning: lessons learned from COVID-19 era
Authors: Sarid Miriam , Lipka Orly 
Published: May 2023

IntroductionThe current study aimed to examine how students with learning disabilities (LD) and/or attention-deficit/hyperactivity disorder (ADHD) adjusted to higher education during the transition to remote learning (RL) in Israel during the COVID-19 pandemic.MethodsThe study involved 621 undergraduate students, 330 of whom participated during the COVID-19 pandemic and 291 before the pandemic. Among these students, 198 had been diagnosed with LD and/or ADHD, while 423 had no reported disabilities (control group).ResultsStudents with LD/ADHD generally had lower adjustment scores during face-to-face learning and RL than the control group. In-depth analyses of four subgroups revealed that students with LD + ADHD reported lower academic, emotional, and institutional adjustments as well as reported lower satisfaction with life during RL than the control group members. ADHD was found to directly predict low satisfaction with life through the mediation of adjustment scores.DiscussionIn conclusion, it is recommended that support be provided to high-risk LD/ADHD populations during a crisis. Furthermore, the implication of this study can inform intervention during emergency times.