bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of sweating responses in patients with systemic connective tissue disorders using the quantitative sudomotor axon reflex test
Authors: Ashida Miwa , Morimoto Shimpei , Yozaki Mariko , Ehara Daisuke , Koike Yuta , Murota Hiroyuki
Published: April 2022

In systemic connective tissue disorders (SCTDs), eccrine sweat glands are frequently attacked by immune cells, as evidenced by pathological observations. Sweating reflects vascular activity through the autonomic nervous system, while few studies have reported sweating ability in SCTDs or the relationship between sweating ability and Raynaud's phenomenon caused by sympathetic hyperreactivity. We performed the quantitative sudomotor axon reflex test on 85 patients diagnosed with systemic sclerosis, mixed connective tissue disease, systemic lupus erythematosus, Sjogren’s syndrome, and dermatomyositis. Evaluations were performed once in summer and once in winter. We investigated the relationship of the axon reflex sweat volume and the reaction time to Raynaud's phenomenon, skin symptoms, and patient background. Most patients did not show a decrease in sweating compared to healthy participants, but patients with systemic sclerosis who were positive for anti-RNA polymerase III antibodies showed little or no sweating. One in three patients showed less sweating in summer than in winter, which is the opposite of the normal seasonal variation. Although no relationship was observed between the sweat volume and the total Raynaud’s condition scores, patients with pain had more sweating than those without pain. These results suggested the possible utility of measuring sweating on autonomic peripheral circulatory disorders.
A Novel PD-L1-Containing MSLN Targeting Vaccine Elicits Therapeutic Antitumor Immunity in Mice
Authors: Zeng Wuyi , Pan Jiayi , Huang Maoping , Fang Zixuan , Jia Jiangtao , Dong Jun , Zhang Rong , He Menghua , Zhong Hanyu , He Jiashan , Yang Xinyu , Shi Yi , Wang Danni , Zeng Jun , Fu Bishi , Zhong Bei , Liu Hui
Published: April 2022

Therapeutic tumor vaccines have become an important breakthrough in the treatment of various solid tumors including lung cancer. Dendritic cells (DCs)-based tumor vaccines targeting tumor-associated antigens (TAAs) play a key role in immunotherapy and immunoprevention. However, the weak immunogenicity of TAAs and low immune response rates are a major challenge faced in the application of therapeutic tumor vaccines. Here, we tested whether targeting an attractive target Mesothelin (MSLN) and PD-L1 immune checkpoint molecule to DCs in vivo would elicit therapeutic antitumor cytotoxic T lymphocyte (CTL) response. We generated specific MSLN fragment combined with PD-L1 and GM-CSF peptide immunogen (MSLN-PDL1-GMCSF) based on the novel anti-PD-L1 vaccination strategy we recently developed for the cancer treatment and prevention. We found that DCs loaded with MSLN-PDL1-GMCSF vaccine elicited much stronger endogenous anti-PD-L1 antibody and T cell responses in immunized mice and that antigen specific CTLs had cytolytic activities against tumor cells expressing both MSLN and PD-L1. We demonstrated that vaccination with MSLN-PDL1-GMCSF potently inhibited the tumor growth of MSLN+ and PD-L1+ lung cancer cells, exhibiting a significant therapeutic anti-tumor potential. Furthermore, PD-1 blockade further improved the synergistic antitumor therapeutic efficacy of MSLN-PDL1-GMCSF vaccine in immunized mice. In summary, our data demonstrated for the first time that this PD-L1-containing MSLN therapeutic vaccine can induce persistent anti-PD-L1 antibody and CTL responses, providing an effective immunotherapeutic strategy for lung cancer immunotherapy by combining MSLN-PDL1-GMCSF vaccine and PD-1 blockade.
PBX1-SIRT1 positive feedback loop attenuates ROS-mediated HF- MSC senescence and apoptosis
Authors: Wang Yuan , Sui Yutong , Niu Ye , Liu Dan , Xu Qi , Liu Feilin , Zuo Kuiyang , Liu mingsheng , Sun Wei , Wang Ziyu , Liu Zinan , Zou Fei , Shi Jiahong , Liu Xiao mei , Liu Jinyu
Published: April 2022

Background: Stem cell senescence and depletion are major causes of organismal aging and aging-related diseases. The NAD–SIRT1–PARP1 axis has garnered remarkable interest owing to its significant role in regulating stem cell senescence and organismal aging. Event though our recent study showes that PBX1 overexpression attenuates hair follicle-derived mesenchymal stem cell (HF-MSC) senescence and apoptosis by regulating ROS-mediated DNA damage via downregulation of PARP1 expression, suggesting PARP1 downregulation is a common manifestation of the roles of both PBX1 and SIRT1 in the attenuation of HF-MSC senescence, and implying a potential link between PBX1 and SIRT1 via PARP1. Methods: HF-MSCs overexpressing PBX1, overexpressing both PBX1 and PARP1, downregulating SIRT1, and overexpressing PBX1 and downregulating SIRT1 were generated, and biomarkers related to cell senescence, apoptosis, DNA damage, and repair were detected at the cellular and protein levels. Results: (1) PBX1 overexpression alleviated HF-MSC senescence and apoptosis accompanied by upregulation of SIRT1 expression, downregulation of PARP1 expression, and increased intracellular NAD and ATP levels. (2) SIRT1 knockdown or PARP1 overexpression enhanced cellular senescence and apoptosis, accompanied by increased ROS accumulation and DNA damage aggravation and decreased intracellular NAD and ATP levels. (3) PBX1 overexpression rescued HF-MSC senescence and apoptosis induced by SIRT1 knockdown or PARP1 overexpression. (4) Dual luciferase reporter showed PBX1 enhanced SIRT1 expression by activating SIRT1 promoter. Conclusions: Our results reveal that a positive interaction feedback loop exists between PBX1 and SIRT1, that PBX1 is the upstream of SIRT1. To the best of our knowledge we are the first to report that there is a PBX1-SIRT1-PARP1 axis and this axis plays a critical role in alleviation of HF-MSC senescence and apoptosis. The results provide a new perspective on the mechanism of stem cell senescence and age-related disease prevention and treatment.
ERK 1 and ERK 2 gene polymorhisms has a role in PCOS pathogenesis
Authors: Guney Gurhan , Taşkın Mine Islimye , Sener Nazli , Tolu Ezgi , Dodurga Yavuz , Elmas Levent , Cetin Orkun , Sarigul Cengiz
Published: April 2022

Background: Ovulation is regulated by extracellular signal-regulated kinase-1 (ERK-1) and ERK-2 signaling mechanisms, and ERK-1/2 kinases modulates the function of most of the LH-regulated genes. Defective ERK kinase signaling that is secondary to a genetic problem contributes to both ovulatory dysfunction and metabolic problems in polycystic ovary syndrome (PCOS). We planned to investigate ERK-1 and ERK-2 gene polymorphisms in PCOS for the first time in the Turkish population.Methods: 102 PCOS patients and 102 healthy controls were recruited for this patient control study. HOMA-IR, Ferriman-Gallwey score (FGS), waist-to-hip ratio (WHR), and body mass index (BMI) were assessed. Lipid profile levels, CRP, and total testosterone were determined. ERK-2 rs2276008 (G > C) and ERK-1 rs11865228 (G > A) SNPs were analyzed with a real-time PCR system.Results: ERK-1 and ERK-2 genotypes were found to differ between the PCOS and control groups. In patients with PCOS, ERK-1 GA and ERK-2 GC genotypes were different in terms of BMI, FGS, HOMA-IR, CRP, total testosterone, and total cholesterol levels.Conclusions: ERK-1 and ERK-2 genes are involved in PCOS pathogenesis. BMI, FGS, HOMA-IR, and CRP levels are related to the heterozygote polymorphic types of ERK-1 and ERK-2 genes.
Novel probiotic Brazilian strains of Lactiplantibacillus plantarum protect intestinal mucositis in experimental mice
Authors: Coelho-Rocha Nina Dias , de Jesus Luís Cláudio Lima , Barroso Fernanda Alvarenga Lima , Silva Tales Fernando da , Ferreira Enio , Gonçalves José Eduardo , Martins Flaviano dos Santos , Carvalho Rodrigo Dias de Oliveira , Barh Debmalya , Azevedo Vasco Ariston de Carvalho
Published: April 2022

Several studies have shown the probiotic potential of Lactiplantibacillus plantarum strains. However, the efficacy of this strain in treating intestinal mucositis is little explored. Here, we investigated the gastrointestinal protective effects of nine novel L. plantarum strains isolated from Bahia, Brazil. The probiotic functionality was first evaluated, in vitro, by characterization of bile salt and low pH tolerance, antibacterial activity, and adhesion to Caco-2 cells. Antibiotic resistance profile, mucin degradation, and haemolytic activity assays were also carried out to evaluate safety features. In vivo analyses were conducted to investigate the anti-inflammatory effects of the strains using a mouse model of 5-FU-induced mucositis. Our results suggest that the used L. plantarum strains have good tolerance to bile salts and low pH and are able to inhibit commonly gastrointestinal pathogens. Additionally, Lp11 and Lpl2 strains exhibit high adhesion rates to Caco-2 cells (9.05 and 13.64% respectively) and no strain show haemolytic or mucolytic activity. Phenotypical resistance to aminoglycosides, vancomycin, and tetracycline is observed for most strains. Seven strains can protect against histopathological damage in a mouse model of mucositis. Gene expression analysis of immune response markers shows that five strains upregulate Il10, while four downregulate both Il6 and Il1b to inhibit mucositis. Additionally, all strains were found to reduce eosinophilic and neutrophilic infiltration; however, they are not able to prevent weight loss or reduced liquid/ food intake. Taken together, our study suggests these Brazilian L. plantarum strains are safe for human use and are potential alternatives to treat intestinal mucositis.
Integrated analysis on m6A-related prognostic lncRNA signatures associated with prognosis and tumor immunotherapy in renal papillary cell carcinoma
Authors: Dai Xinglong , Zeng Menghua , Huang Zhen , Zhang Jun , Wei Zhengqiang , Wang Ziwei
Published: April 2022

Background
To elucidate the prognostic patterns of m6A-related lncRNAs and construct a prognostic model of m6A-related lncRNAs in Kidney renal papillary cell carcinoma (KIRP).
Methods
We downloaded KIRP-related RNA-seq and clinical data from the TCGA dataset. Potential m6A-related prognostic lncRNAs in KIRP patients were selected by Pearson correlation test and univariate Cox analysis. KIRP patients were divided into two clusters using consensus clustering. The prognostic model of m6A-related lncRNAs was constructed to explore the relationship between m6A-related lncRNAs and clinical features and survival data using LASSO regression analysis. We also determined the relationship of risk models to tumor microenvironment (TME) and drug sensitivity.
Results
We first identified two m6A-related lncRNA pattern clusters by consensus clustering based on 32 m6A-related prognostic lncRNAs. Patients from cluster 2 were dramatically associated with poor prognosis, worse clinical grades, etc. Cluster 2 not only had higher immuneScore, ESTIMATEScore, and stromalScore but was also associated with higher levels of immune cell infiltration and expression of immune checkpoint molecules. Then, 14 m6A-related prognostic lncRNAs were selected and validated as independent and robust predictors of KIRP prognosis. Two nomograms based on age, tumor grade, clinical stage, and m6A-related lncRNAs expression were generated, showing high accuracy and reliability in predicting overall survival in KIRP patients. KIRP patients in the high-risk group had higher pN stage, pT stage, pM stage, advanced clinical stage, and higher tumor grade than the low-risk group. Importantly, cluster 2 with worse overall survival had a higher risk score than cluster 1, thus indicating consistency between the two methods for predicting survival in KIRP. Furthermore, some tumor-infiltrating immune cells, immune checkpoint molecules, and drugs sensitivity were closely related to the risk score of the prognostic model in KIRP patients.
Conclusion
We not only established a model of novel m6A-related prognostic lncRNAs with favorable prognostic value in KIRP patients, but also could provide new insights into tumorigenesis and predict treatment response in KIRP patients.
How public and private health insurance coverage mitigates catastrophic health expenditures in South Korea
Authors: Jung Hyun Woo , Kwon Young Dae , Noh Jin-Won
Published: April 2022

Background: Korea has instituted a private health insurance (PHI) scheme that covers the remaining expenses uncovered by the National Health Insurance (NHI). No study has yet estimated the extent to which PHI coverage lowers the economic burden of household access to health care. The current study intends to evaluate the design of Korea's PHI system in terms of coverage using a catastrophic health expenditure (CHE) indicator and compare it with NHI. Methods: This study determined the difference between the number of households subscribed to PHI and the number of households that paid benefits. Also, it compared the effects of reduced CHE through NHI benefits with those of PHI. Furthermore, it compared PHI benefit rates by income class. Finally, it analyzed the benefit contribution of NHI and PHI to CHE reduction through a two-part model with hierarchical regression. Results: Results indicated that of the 5,644 households studied, 3,769 subscribed to PHI, but only 246 households received benefits. The NHI reduced CHE incidence by 15.17%, whereas PHI only reduced CHE by 1.22%. The NHI scheme indicated reduced inequality as it provided more benefits to the low-income class, whereas the PHI paid more to the high-income class. The NHI coverage has protected households from CHE and improved equality to some extent; however, PHI coverage has had little effect on relieving CHE and has deteriorated equality. Conclusions: Korean private insurance companies, which are mostly subsidiaries of for-profit conglomerates, only pay for pre-contracted diseases, therefore, most patients do not receive benefits. Thus, Korea's private insurance system needs to improve to provide benefits to patients more generously and alleviate the financial burden of medical use.
Barriers and facilitators to shared decision-making for frail and elderly patients within the perioperative setting: A scoping review protocol
Authors: Vogel Amyn , Guinemer Camille , Fürstenau Daniel
Published: April 2022

BACKGROUND: Shared decision-making (SDM) is an approach to enable patient-centeredness and tailored treatment pathways, within the perioperative setting. This could benefit frail and elderly patients, who suffer from multiple health issues and increased surgical vulnerability and postoperative complications, requiring individualized healthcare. However, little is known about facilitators and barriers to implementing SDM into clinical practice for the specific requirements of frail and elderly patients.The objective is to gain a comprehensive overview of original studies on facilitators and barriers to SDM perceived by clinical healthcare personnel and patients to SDM within the perioperative setting. Our aim is twofold: First, we aim at collecting and understanding facilitators and barriers regarding SDM addressed by elderly and frail patients and clinical healthcare personnel. Second, we aim at understanding the underlying approaches and methods employed in respective studies.METHODS: We conduct a scoping literature review, based on the databases MEDLINE, Embase, CINAHL, and Web of Science and report results with PRISMA-ScR. We follow the methodological framework developed by Arksey and O'Malley and the recommendations by the Joanna Briggs Institute. Restrictions relate to language: only English, French, and German language articles are considered. We developed a data charting template to organize the data extraction. We decided to conduct a scoping review to better understand key concepts and the implementation of SDM and to identify the evidence for barriers and facilitators of SDM as perceived by patients and clinical healthcare personnel.DISCUSSION: To our knowledge, this is the first scoping review to address SDM for elderly and frail patients within the perioperative setting. A preliminary search has been conducted. After removing all duplicates, we found 984 results. We assessed that a sufficient body of literature exists to conduct this scoping review.The scoping review will provide a map of the research on facilitators and barriers perceived by clinical healthcare personnel and patients regarding SDM for perioperative care. The results are meant to support researchers and clinical healthcare personnel, in determining further research initiatives and the implementation of SDM within perioperative care for elderly and frail patients. Research gaps and future directions will be addressed in the forthcoming review.Registration: https://osf.io/8fjnb/
Evaluation of cow’s and goat’s fresh cheese preservation under hyperbaric storage at room temperature up to 60 days versus refrigeration regarding nutritional and physicochemical parameters
Authors: Duarte Ricardo V. , Casal Susana , Gomes Ana M. , Delgadillo Ivonne , Saraiva Jorge A.
Published: April 2022

Two highly perishable dairy products (cow’s and goat’s fresh cheese (FC)), were stored under hyperbaric storage at room temperature (HS/RT, 50-100MPa) and compared with RF (4ºC), for 60 days. HS/RT (≥75MPa) lead to a more stable volatile organic and fatty acid profiles, reducing lipid oxidation rate, particularly for cow’s FC, resembling more to FC prior storage, contrarily to refrigerated cheeses. No variation was observed for total protein, while free amino acids increased over time after 60 days at 75/RT of 13- and 16-fold, and at 100/RT of 14- and 8-fold, respectively in cow’s and goat’s FC, which may have contributed to increased protein digestibility (5.2%) observed for goat’s FC after 60 days at 100/RT.These results indicate the overall increased preservation performance achieved by HS/RT for cow’s and goat’s FC when compared with RF, slowing down FC matrix degradation, possibly leading to considerable shelf-life extension.
Prognostic impact of the Controlling Nutritional Status score in patients with esophageal cancer treated with immune checkpoint inhibitor
Authors: Chang Lele , Cheng Qian , Ma Qian , He Lei , Li Qingwei , Tao Ji
Published: April 2022

Background: In recent years, a growing number of clinical studies have shown that immune checkpoint inhibitor (ICI) can increase the remission rate and improve the prognosis of patients with esophageal cancer. The Controlling Nutritional Status (CONUT) score is a novel nutritional indicator that can predict the prognosis of certain malignancies. However, no one has yet pointed to its role in ICI treatment in patients with esophageal cancer. The aim of this study was to investigate the clinical significance of CONUT score in patients with esophageal cancer receiving immune checkpoint inhibitor treatment.Methods: We retrospectively analyzed the clinical data of 69 patients with advanced esophageal cancer treated with ICI. Based on the receiver operating characteristic (ROC) curve, we chose 1 as the optimal cut-off value (AUC; 0.619, 95%CI: 0.477-0.762; sensitivity 0.565; specificity 0.696), and divided 69 patients into the low CONUT and the high CONUT groups. We assessed the relationship between clinicopathological factors including CONUT score, systemic immune-inflammatory index (SII), and neutrophil-to-lymphocyte ratio (NLR) and the prognosis.Results: In univariate analysis, we found that the CONUT score, NLR could predict progression-free survival (PFS) and overall survival (OS) (P<0.05); in multivariate analysis, the CONUT score and SII, NLR were an independent prognostic factor for OS (P<0.05). Furthermore, among patients treated with ICI, a high CONUT score was associated with a significantly worse PFS and OS compared with a low CONUT group.Conclusion: The CONUT can be used to predict the efficacy and prognosis of ICI therapy in patients with esophageal cancer. Our studies have shown that the CONUT score can be used as an effective indicator for the prognosis of patients with esophageal cancer receiving ICI.
MMP9 is a prognostic marker for bladder cancer and relates to the Immune Cell Infiltration in the Tumor Microenvironment
Authors: Lin HanSheng , Liu WanWan , Feng NengZhuo , He JingWei , Liang Jian , Zhong ShuangZe , Chen ShangJin
Published: April 2022

Background:
Bladder cancer (BLCA) is one of the most common human cancers while its incidence is on the rise, especially in female. The tumor microenvironment (TME) acts a significant part in the development and progression of the tumor. We surveyed the expression profiles of BLCA in the Cancer Genome Atlas Program database and investigated genes that might affect the composition of tumor microenvironment (TME). We then analyzed the relationship between genes and tumor prognosis, looking for immune prognostic markers which might lead to new styles for the diagnosis and treatment of BLCA.
Methods
We got the RNA-seq data of BLCA from The Cancer Genome Atlas (TCGA); utilized the Estimation of Stromal and Immune Cells in the Malignant Tissues Expression (ESTIMATE) data algorithm to compute the immune and stromal score. The differentially expressed genes were performed to COX regression analysis and used to construct a protein-protein interaction (PPI) network.
Results
Intersection analysis demonstrated that Matrix Metalloproteinase-9 (MMP9) is the only crossover gene. We computed the percent of tumor infiltrating immune cells (TICs) in BLCA through the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. The differences in the high and low expression group of MMP9 in TICs were established. The expression levels of MMP9 in each kind of TICs were then correlated. Via survival, clinical, and enrichment analyses, MMP9 was found to be an immune prognostic factor for BLCA and act a significant part in the tumor microenvironment. Ultimately, the correlation analysis between MMP9 and the immune checkpoint genes indicated that MMP9 can forecast the effect of immunotherapy on BLCA.
Conclusion
MMP9 is an immune prognostic marker gene. MMP9 is involved in regulating the immunological process of BLCA through multiple pathways and is closely related to PD-1 and CTLA4 immune targets. The expression of MMP9 may impact the prognosis of BLCA, indicating that it may be a prognostic-related marker of BLCA.
Comparison of Two Validated Instruments to Measure Financial Hardship in Cancer Survivors: Comprehensive Score for Financial Toxicity (COST) versus Personal Financial Wellness (PFW) Scale
Authors: D'Rummo Kevin A. , Nganga David , Chollet-Hinton Lynn , Shen Xinglei
Published: April 2022

PurposeFinancial distress and financial toxicity are recognized challenges in cancer survivorship. There is currently no universally accepted instrument to quantify patient-reported financial hardship. We hypothesized that financial distress is correlated to financial toxicity. We compared two widely accepted instruments to measure financial distress and financial toxicity. MethodsPatients in the follow-up phase of care at a single institution were surveyed regarding demographic and economic status. Financial toxicity was measured using the Comprehensive Score for Financial Toxicity – Functional Assessment of Chronic Illness (COST-FACIT) and financial distress using the Personal Financial Wellness (PFW) Scale. Surveys were analyzed for correlation and internal consistency. Patient score distributions were compared. Associations between survey scores and patient factors were assessed using multivariable linear regression models.ResultsA total of 116 patients were included. Scores from the COST-FACIT showed a strong correlation with PFW scores (r =0.90, p <0.0001). Scale reliability was high for both the COST-FACIT (α =0.92) and PFW (α =0.97) surveys. Score distributions exhibited left skew for both surveys, with 9.5% of patient scores falling in the worst quartile of possible scores on each respective survey. The strongest predictors of financial distress and financial toxicity included young age, lower monetary savings, lower household income, and less perceived social support during cancer treatment. ConclusionsThe COST-FACIT measure of financial toxicity correlated strongly with PFW measure of financial distress. Although these instruments were designed to assess different concepts (financial distress vs financial toxicity), they gave strikingly similar results. Either instrument may be used as a meaningful patient-reported outcome for study of financial hardship in cancer survivors.
Fatty Acid Metabolism-Related Genes Are Potential Biomarkers for Prognostic Prediction and Clinical Guidance in Patients with Hepatocellular Carcinoma
Authors: Yang Jingze , Yang Xin , Guo Jinlu , Liu Shi
Published: April 2022

Background: Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors with high mortality. Fatty acid metabolism is associated with the development and treatment of HCC. This study aimed to build a fatty acid metabolism-related gene model to evaluate the prognosis of HCC patients and provide guidance for individualized treatment.Methods: RNA-sequencing data of HCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were extracted as the training set and validation set. Fatty acid metabolism-related genes predictive signature was built using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The predictive value of prognostic model was evaluated by Kaplan-Meier (K-M) curves, ROC curves, univariate and multivariate Cox regression. In addition, the immune infiltration and drug sensitivity were also explored.Results: A twelve-gene fatty acid metabolism-related risk signature was constructed. Patients were divided into low-risk and high-risk groups according to risk scores. High-risk patients with the higher risk scores had a poor prognosis. Then, univariate and multivariate Cox regression showed that risk score was an independent risk factor for the overall survival of HCC. K-M and ROC curves further verified the predictive value of the signature. Besides, nomograms were drawn and exhibited the good performance in the prognostic prediction. Finally, the immune cell infiltration and sensitivity to chemotherapy drugs exhibited a correlation with different risk levels.Conclusion: This novel fatty acid metabolism-related gene predictive signature may be useful for improving prognosis evaluation and individualized treatment for HCC patients.
Sulforaphane Enhances the Anticancer Properties of Paclitaxel in Two Human Derived Prostate Cancer Cell Lines
Authors: Habib Tito N. , Altonsy Mohamed O. , Ghanem Salah A. , Salama Mohammed S. , Hosny Mai A.
Published: April 2022

Background
In cancer therapy, combined treatment results in synergistic or additive outcomes and reduces the development of drug resistance in response to anticancer agents compared with monotherapy. We propose that when Paclitaxel (Taxol, PTX) is combined with sulforaphane (SFN), may result in better treatment outcomes in prostate cancer.
Methods
We measured apoptosis, cell cycle, and expression of Bax and Bcl2 in response to the PTX and SFN individual and combined treatments. Cell lines (PC-3) and (LNCaP), were individually treated with different concentrations of PTX, SFN, and its combination. Annexin V/PI positivity and data analysis were conducted using a flow cytometer and guava data acquisition and analysis software. Graph-Pad Prism 6, and Microsoft Excel software were used for statistical analyses and graphs generation. Student’s t-tests or one-way analysis of variance with Tukey’s correction were used to determine the significant difference between treatments.
Results
The effect of the PTX or SNF treatments on reducing cell viability increased in a dose-dependent manner. Combined treatment enhanced PTX’s effects and reduced the EC50 values of both drugs compared to individual treatments. Flow cytometry analysis revealed that PTX or SFN treatments redistributed cell-cycle phases by inducing S-phase arrest and increasing apoptotic cell population in PC-3 cells. Such effects were enhanced in the PTX + SFN combination group. Interestingly, the necrotic cells’ numbers were not affected by the combination treatments. Caspase-3 cleavage and morphological deformations of the cell nuclei are signs of apoptotic cell death; such parameters were examined by western blot and fluorescent microscopy in response to individual and combination treatments.
Conclusion
The PTX or SNF differentially modulated the expression of Bax and Bcl2 in PC-3 and LNCaP cell lines, and the combined treatment enhanced these effects in favor of cell apoptosis versus survival. These findings will help develop new biomarkers and guide therapy choices.
Tribological, Oxidation and Thermal Conductivity Studies of Microwave Synthesised Molybdenum Disulfide (MoS 2 ) Nanoparticles as Nano-Additives in Diesel Based Engine Oil
Authors: Nagarajan Thachnatharen , Khalid Mohammad , Srid Nanthini , Jagadish Priyanka , Shahabuddin Syed , Muthoosamy Kasturi , Walvekar Rashmi
Published: April 2022

In this research, Molybdenum disulfide (MoS2) nanoparticle was synthesised via microwave synthesis. Later, the nanoparticles were dispersed in SAE 20W50 diesel engine oil to formulate the nanolubricant. The results show that nanolubricant with 0.01 wt.% MoS2 concentration showed the coefficient of friction (COF), average wear scar diameter (WSD) decreased by 19.24%, 19.52%, respectively, compared to the base oil. The nanolubricant with 0.01 wt.% concentration of MoS2 nanoparticle showed the enhancement of 61.15% in Oxidation Induction Time (OIT) in comparison to the base oil. Furthermore, MoS2 addition within the base oil demonstrates a ~ 10% improvement in thermal conductivity compared to the base oil.
Recurrence Risk Factors of Intravitreal Ranibizumab Monotherapy in Retinopathy of Prematurity: A Retrospective Study at One Center
Authors: Wu Fengyue , Yu Wenting , Zhao Daixin , Pu Wei , Zhang Xue , Gai Chunliu
Published: April 2022

Purpose: The risk factors for retinopathy of prematurity (ROP) recurrence in patients with intravitreal ranibizumab (IVR) treatments after long-term follow-up are unclear, so we aimed to identify risk factors of recurrence of this disorder after IVR monotherapy.Methods: We retrospectively reviewed 33 eyes of 19 patients who underwent initial IVR treatments for type 1 ROP at our center between April 1, 2016 and December 31, 2017. Patient demographics, the side of ROP, multiple gestations, Apgar scores, zone, stage, plus disease, postmenstrual age at injection, surfactant therapy, blood transfusion therapy, hemorrhage before IVR, hemorrhage after IVR, gestational diabetes mellitus, pregnancy-induced hypertension, anemia, intraventricular hemorrhage, sepsis, respiratory distress syndrome, carbohemia, and congenital heart defects were recorded. Adjusted hazard ratios (HRs) and 95% confidence intervals were determined after adjusting for potential confounders using multivariate proportional Cox regression. Results: Of the 33 eyes, 12 (36.4%) had ROP recurrences 45.3 (5.1, 50.9) months after initial IVR treatments. The independent risk factors for ROP recurrences were zone [Ⅱ vs. Ⅰ, hazard ratio (HR): 0.056, P = 0.003] and gestational diabetes mellitus (no vs. yes, HR: 0.095, P < 0.001). The mean uncorrected visual acuity for four recurrence eyes was 0.46 logMAR (0.13, 0.70) at 55.0 (51.0, 58.9) months after the initial IVR treatment. The mean uncorrected visual acuity for 10 eyes without recurrence was 0.46 logMAR (0.19, 0.63) at 48.0 (43.8, 58.4) months after the initial IVR treatment.Conclusions: We identified two independent risk factors for type 1 ROP recurrence after IVR treatment involving zone Ⅰ and gestational diabetes mellitus, and the mean uncorrected visual acuity was 0.46 logMAR at 51.0 (44.0, 58.9) months. The findings of this study are important for follow-up management and for improving the visual function of ROP patients.
Predictive Effect of Spatial Protein Signature in Advanced Non-small Cell Lung Cancer Patients Treated with Bispecific Antibody (KN046) Immunotherapy
Authors: Song Xinyu , Xiong Anwen , Jiang Tao , Chen Peixin , Li Xuefei , Wu Fengying , Zhang Xiaoshen , Zhao Zhikai , Cheng Lei , Zhao Chao , Wang Zhehai , Chen Dawei , Wu Xiaoqian , Xu Shengqiang , Xu Ting , Su Xiaofan , Zhou Caicun
Published: April 2022

Background
Immunotherapy, targeting programmed death ligand-1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4, has shown significant antitumor activity and favourable safety profile in patients with advanced non-small cell lung cancer (NSCLC), while predictive biomarkers remain largely unknown. Here, we investigated the predictive effect of spatial protein expression signature of KN046, a bispecific antibody (bsAb), as a treatment in advanced NSCLC patients.
Methods
Digital spatial profiling was used to investigate protein expression in both tumor and stroma areas of formalin-fixed paraffin-embedded sections at baseline. Regions of interests (ROIs) were recorded after tricolor fluorescence labeling. The geometric means of different protein expression of different response groups were combined to construct the tumor signature, the stroma signature and the tumor + stroma signature. The accurate score was determined by receiver operating characteristic curve and the area under the curve (AUC).
Results
Eight patients with partial response (PR) and nine with progressive disease (PD) were enrolled in the study. Among 133 ROIs, 14 proteins expressed differently between PR and PD groups (both P < 0.05). Among tumor areas, tumor necrosis factor superfamily member 4, CD276, B-cell lymphoma-2 and CD45RO were highly expressed in PR group, while transmembrane protein 173 was highly expressed in PD group (both P < 0.05). Among stroma areas, PR group exhibited a greater expression of T cell immunoglobulin and mucin domain 3 (Tim-3), PD-L1, complement component 3 receptor 4 subunit (CD11c) and Beta-2-microglobulin (B2M) than those in PD group (P < 0.05). The stroma signature showed a superior predictive performance (AUC = 0.840, P < 0.05) to the tumor + stroma signature (AUC = 0.732, P < 0.05) and the tumor signature (AUC = 0.670, P < 0.05). The predictive effect of the stroma signature was much better than that of PD-L1 expression or tumor mutation burden.
Conclusions
In NSCLC, we firstly found that there are differences in the expression of immune-related proteins in different spatial regions. And we successfully developed a stroma signature with Tim-3/PD-L1/CD11c/B2M which could better predict the response to KN046. This signature might potentially complement the limitations of PD-L1 and TMB measurements and be useful in clinical practice about bsAbs.
Pyrotinib in patients with HER2-positive advanced breast cancer: A multicenter, retrospective, real-world study
Authors: Zhang Xiaoling , Li Zhaohui , Han Linlin , Lv Zheng , Teng Yuee , Cui Xiujie , Zhou Caiyun , Wu Hongwei , Fang Wei , Xu Lingzhi , Zhao Shanshan , Song Chen , Zheng Yuanyuan , Gao Tianqi , Li Man
Published: April 2022

Purpose: Pyrotinib, a novel human epidermal growth factor receptor 2 (HER2)-targeted tyrosine kinase inhibitor (TKI), was approved for second-line standards of treatment for HER2-positive advanced breast cancer (ABC) in China. This real-world study aimed to assess the actual efficacy and safety of pyrotinib in HER2+ ABC.Methods: In this multicenter, retrospective, observational real-world study, we analyzed 171 patients with HER2+ ABC, who received pyrotinib-based treatment from November 2017 to November 2020. The primary end point was progression-free survival (PFS). Results: Up to November 30, 2021, the median PFS (mPFS) was 12.0 months (95% CI, 10.4-13.6) for all patients. When compared with Eastern Cooperative Oncology Group performance status (ECOG-PS) of 2-4, patients with the ECOG-PS of 0-1 had significant longer PFS (12.9 months vs. 6.7 months, p<0.0001). Patients receiving pyrotinib as first-line treatment demonstrated a significantly longer PFS than those who received pyrotinib as second-line or beyond treatment (13.0 months vs. 10.7 months, p=0.020). Furthermore, lapatinib-naive patients exhibited a significant longer mPFS compared to lapatinib-treated patients (12.2 months vs. 8.1 months, p=0.021). One hundred and sixty-two patients (94.7%) with measurable lesions had been included in efficacy assessment, and objective response rate (ORR) was 45.1%. The most common adverse event (AE) was diarrhea (86.5%). Conclusion: Pyrotinib dramatically improved the clinical outcomes of HER2+ ABC with imaginable toxicities, especially for patients who received first-line treatment and had the ECOG-PS of 0-1, as well as those who were lapatinib-naive.Trial registration: ChiCTR2100051632, Sep 28, 2021
Compressive Test of Concrete With Teak Wood Attached Waste Iron Lathe as a Replacement of Coarse Aggregate
Authors: TRIASTUTI NUSA SETIANI , Sutanto Muhammad Restu , indriasari
Published: April 2022

The research team thought about the sustainability of concrete material because the stone used every year will be exhausted for the next generation. Innovation material renewable, sustainable, and waste materials required. This is pre-research teak wood used as a mixture to reduce coarse aggregate stone, added containing lathe waste to give friction to the wood. Objective: find an alternative coarse aggregate, with renewable and sustainable materials. Experimental methods in laboratories with relatively high quality are widely used in construction projects in Indonesia.Standard quality plan of concrete fc29.05 MPa, variation t 1 coarse aggregate teak wood 10%, variation t 2 teak 9.5%, lathe waste 5%. Test results of standard concrete 28.87 MPa, 13.70 MPa Variation 1 drop 52.75.. % and 14.24 MPa variation 2 drops 49.18 % The failure of standard concrete experienced large cracks, while variations 1 and 2 were smaller, which means it is not brittle and light, which is advantageous in applying the concrete structure for buildings. The conclusion. alternative use of teak wood waste material, especially attached iron lathe filler waste, is very useful for the sustainability of the use of concrete. However, mixed concrete design requires a higher concrete quality to achieve applied concrete
Identification of circRNA-miRNA-mRNA Networks to investigate lung adenocarcinoma pathogenesis based on whole-transcriptome analysis
Authors: JUAN YANG JUAN , Li Qian , Gu Yi lu , Bian Ting ting , Shi Jiahai , Liu Yi fei
Published: April 2022

Background
The progression of lymph node metastasis has been elucidated in lung adenocarcinoma (LUAD), whist which and how transcripts worked in this process remains unclear. We aimed to investigate the markers and potential mechanism of lymph node metastasis in LUAD.
Methods
The whole-transcriptome sequencing was performed on the whole blood from the non-nodal metastasis (LUAD_low), lymph node metastasis (LUAD_high) lung adenocarcinoma patients and healthy people (Control). Subsequently, differential expression analysis among three groups was performed, followed by functional interaction prediction analysis to investigate gene-regulatory circuits in LUAD development. Then, following the rigorous selection, the competing endogenous RNAs (ceRNAs) networks mainly involved in ferroptosis were discovered, and a few of the miRNAs (such as hsa-miR-6509-3p, hsa-miR-6511a-3p, hsa-miR-6803-3p) and their central target gene (IREB2) were validated in clinical specimens through qRT-PCR assays.
Results
Our results identified 75 differentially expressed messenger RNAs (dif-mRNAs), 125 differentially expressed microRNAs (dif-miRNAs), and 880 differentially expressed circular RNAs (dif-circRNAs) in non-nodal metastasis LUAD samples compared with Control; similarly, 352 dif-mRNAs, 3 dif-miRNAs, and 270 dif-circRNAs were found in advanced-stage LUAD compared with Control samples. Then the most comprehensive circRNA-associated ceRNA networks were constructed in the pathogenesis and metastasis of LUAD, respectively. Additionally, ferroptosis-associated miRNAs (such as hsa-miR-6509-3p, hsa-miR-6511a-3p, hsa-miR-6803-3p) were both significantly upregulated, whilst their central target gene (IREB2) were obviously downregulated in LUAD tissues.
Conclusion
In summary, this study systematically demonstrated circRNA-associated ceRNA profiles in the development of LUAD, which could provide insights that facilitate LUAD diagnosis and therapy in the future.
Teachers’ willingness to pay for social health insurance and its determinant factors at Harar region, Ethiopia, 2021
Authors: Hailu Sintayehu Girma , Firde Gizachew Abebe , Debele Aklilu Tamire , Zakaria Hamdi Fekredin , Merga Bedasa Taye
Published: April 2022

Background
Most developing countries are characterized by low health cost protection system for the poor and lack of risk pooling and cost sharing methods. This study aims to assess the participants’ willingness to pay for social health insurance.
Methods
Cross-sectional study was conducted. Stratified and simple random sampling techniques were used to select schools and teachers respectively. Data were collected from 323 participants. Multivariate logistic regressions was done to determine the determinants of willingness to pay for social health insurance.
Results
About 59.2% and 54% of teachers had positive attitude and good knowledge toward health insurance respectively. Of all, 89.5% had willingness to pay for social health insurance. Willingness to pay was more likely among those taught in primary school AOR = 1.85, 95%CI= [1.023, 3.45] and those had good knowledge AOR = 2.785, 95CI= [1.509, 5.142]
Conclusion
Near to three-fourths of the teachers had willingness to pay for social health insurance.
Moral Distress and Dilemmas Experienced by Healthcare Professionals during Care of Patients with COVID-19
Authors: Rashidi Kobra , Goudarzi Fateme , Fadavi Mohsen , Akrami Forouzan
Published: April 2022

Background
Emerging COVID-19 pandemic has posed numerous ethical challenges to the healthcare. This study aimed to explain ethical challenges experienced by healthcare professionals giving care for COVID-19 patients during early phases of the pandemic.
Method
This qualitative study was conducted by content analysis approach. 22 semi-structured in-depth interviews were done with 18 healthcare professionals working in medical centers and hospitals of public or private sectors, in Tehran, capital of Iran, from July to October 2020.
Results
The ethical challenges categorized into 4 categories (and 11 sub-categories) including: poor professional care, preference of public interests over individual care, difficult decision-making, and moral distress.
Conclusion
The findings indicate on the attenuation of professional care, need to developing evidence-based clinical guidelines with regard to the resulted insights. In addition, devising appropriate interventions is recommended to psycho-emotional support of frontline healthcare workers, especially the nurses.
Virtuelle Realität: Immersion als Erlebnisdimension beim Lernen mit visuellen Informationen
Authors: Kerres Michael , Mulders Miriam , Buchner Josef
Published: April 2022

Der Begriff der Immersion wird häufig als Merkmal von Technik verwendet. Doch Immersion wird nicht durch eine bestimmte Technologie (etwa eine VR- oder AR-Brille) erzeugt, sondern ist die Leistung des psychischen Systems und eine Dimension des Erlebens einer visuell dargebotenen Information. Eine solche Klärung lenkt den Blick auf die Determinanten des Immersionserlebens und die Frage, wie die mediendidaktische Gestaltung von Lernanwendungen Immersion nutzen kann, um den Lernprozess zu fördern. Der Artikel setzt das Erleben von Immersion in Beziehung zu anderen Dimensionen der visuellen Wahrnehmung (Raum-, Realitäts-, Bewegungs-, Präsenzerleben), um die Besonderheiten des Immersionserlebens herauszuarbeiten. Vorgestellt wird ein Modell des Erlebens visueller Information beim Lernen, das Merkmale der Technik, des Erlebens, des Lernprozesses und des Lernergebnisses separiert und in ihrer Relation verdeutlicht. Das Modell zeigt auf, wie sich Forschungsfragen zu Implikationen des Immersionserlebens anlegen lassen. Für mediendidaktische Konzepte wird deutlich, dass Immersion nicht durch eine bestimmte Technologie eingelöst wird und nicht automatisch zum Lernerfolg beiträgt. Die verschiedenen Dimensionen des Erlebens visueller Information sind im Hinblick auf den Lernprozess und die Lernergebnisse sehr genau zu prüfen und durch die Gestaltung von Lernumwelten und -aufgaben gezielt anzuregen.
Medienkulturwissenschaftliche Perspektiven auf Augmented und Virtual Reality in formalen Bildungskontexten
Authors: Przybylka Nicola
Published: April 2022

Der Beitrag widmet sich aus einer medienkulturwissenschaftlichen Perspektive dem Einsatz von Augmented Reality (AR) und Virtual Reality (VR) in formalen Bildungskontexten. Insbesondere stehen die medientechnischen Grundlagen von AR und VR sowie deren Verschränkung mit Diskursen aus Bildungspolitik, Wirtschaft und Wissenschaft im Fokus. Zunächst wird eine Vernachlässigung der spezifischen Medialität der beiden Technologien anhand des Skalenmodells von Milgram und Kishino (‹virtuality continuum›) aus dem Jahr 1994 und der darin angelegten Verhältnisbestimmung von Virtualität und Realität sowie anhand eines Paradigmenwechsels bei der Interfacekonzeption der beiden Technologien identifiziert. Um die Relevanz der materiellen und datentechnischen Dimension zu verdeutlichen, verweist der Beitrag anschliessend anhand des Grosskonzerns Facebook bzw. Meta auf die systematische Verschränkung der Lernenden mit wirtschaftlichen Akteuren, deren popkulturell geprägten Visionen und ökonomischen Interessen. Daran anknüpfend wird auf das im Kontext von AR und vor allem VR dominante Narrativ der sogenannten ‹Empathie-Maschine› eingegangen und dessen Auswirkung auf die inhaltliche Ausgestaltung von AR- und VR-Anwendungen diskutiert. Die im Beitrag aufgeworfenen Fragen ergänzen didaktische Auseinandersetzungen mit dem Einsatz der beiden Technologien in formalen Bildungskontexten.
How Advertising Speaks to Consumers: A Case of Youth Language in Local Commercial Discourse
Authors: Mansor Nor Shahila
Published: April 2022

Like other developing countries, especially Malaysian urban youths, are continuously creating their “own language” to set themselves apart from the older generation. Referred to as Generation Z or Gen Z (post-millennials), these group of youths use slang that takes the form of code-mixing, abbreviations and ‘nonstandard variety’ of languages. First, this study aimed to reveal the patterns of youth language incorporated into local commercial discourse to attract young-adult consumers. The focus of this study is to determine how youth language is used and at the same time bring forth the different linguistic strategies employed in fashion articles. Secondly, this study investigated the perception of fellow Malaysians, especially young adults, regarding the existence of a youth language, especially code-mixing, in local fashion magazines. This was a qualitative descriptive study, but numbers and percentages were also used to support the findings. The various types of youth language patterns used were gathered based on titles of 60 commercial articles published in 3 famous local fashion magazines, namely Remaja (Youth), Keluarga (Family) and Nona (Woman). The findings showed a high usage of non-standard language and code-mixing in local advertisements. The main reason for using youth language in advertising is to attract and engage the attention of potential target consumers within the Gen Z age group. On the other hand, it was found that most respondents had positive perceptions regarding these kinds of advertisements and consider it as a good marketing skill.