Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.

The FIB-4 scores in the emergency department to predict the outcomes of COVID-19 patients in taiwan.

Objective: We aimed to determine the reliability of using the Fibrosis-4 (FIB-4) index in COVID-19 patients without underlying liver illness. Method: We employed multivariate logistic regression to identify variables that exhibited statistically significant influence on the ultimate outcome. Multilayer perceptron analysis was employed to develop a prediction model for the FIB-4 index concerning ICU admission and intubation rates. However, the scarcity of cases rendered the assessment of the mortality rate unfeasible. We plotted ROC curves to analyze the predictive strength of the FIB-4 index across various age groups. Result: In univariate logistic regression, only the FIB-4 index and respiratory rate demonstrated statistical significance on all poor outcomes. The FIB-4 index for mortality prediction had an ROC and AUC of 0.863 (95% CI: 0.781-0.9444). It demonstrates predictive power across age groups, particularly for age ≥65 (AUC: 0.812, 95% CI: 0.6571-0.9673) and age <65 (AUC: 0.878, 95% CI: 0.8012-0.9558). Its sensitivity for intubation and ICU admission prediction is suboptimal. Conclusion: FIB-4 index had promising power in prediction of mortality rate in all age groups.

Diabetic foot ulcer is associated with cardiovascular-related mortality and morbidity - a systematic review and meta-analysis of 8062 patients.

OBJECTIVES: To conduct a systematic review and meta-analysis of prevalence of cardiovascular-related morbidity and mortality in patients with diabetic foot ulcers (DFU), as well as compare risks of cardiovascular-related morbidity and mortality between diabetic patients with and without DFU. METHODS: A systematic search was conducted on Medline, Embase, and Cochrane databases for randomized controlled trials and observational studies which explored the association between DFU and cardiovascular-related morbidity & mortality, or compared differences in hazard ratios of cardiovascular diseases between diabetics with and without DFU. Frequentist, pairwise meta-analysis was performed on studies with two comparator arms, whereas single-arm studies reporting pooled incidences of cardiovascular-related mortality and morbidity were calculated based on exact binomial distributions. A random-effect meta-analysis model was used with heterogenicity of studies assessed using I2, τ2, and χ2 statistics. RESULTS: 10 studies were identified and included in the systematic review & meta-analysis of 8602 patients. DFU was consistently found to have significant association with cardiovascular-related morbidity and mortality, with pooled prevalences of all cause cardiovascular-related morbidity (37.1%), IHD (44.7%), CHF (25.1%), CAD (11.7%), and CVA (10.9%), and all cause cardiovascular-related mortality (14.6%), fatal IHD (6.2%), fatal CHF (3.67%), fatal CAD (7.92%), and fatal CVA (1.99%). Diabetic patients with DFU were found to have significantly increased risk of IHD (RR 1.25), CVA (RR 2.03), and all-cause cardiovascular-related mortality (RR 2.59) compared to those without DFU. CONCLUSIONS: The presence of DFU is associated with major adverse cardiac events. The alarming rates of cardiovascular-related morbidity and mortality in DFU patients highlight its potential role as a marker of cardiovascular complications and should prompt early clinical investigation and management.

Calibration improves the agreement in grading oral epithelial dysplasia-Findings from a National Workshop in Malaysia.

INTRODUCTION: A major pitfall of many of the established oral epithelial dysplasia (OED) grading criteria is their lack of reproducibility and accuracy to predict malignant transformation. The main objective of this study was to determine whether calibration of practicing oral pathologists on OED grading could improve the reproducibility of the WHO 2017 and the binary OED grading systems. METHODS: A nationwide online exercise was carried out to determine the influence of calibration on the reproducibility of the WHO 2017 and the binary OED grading systems. RESULTS: A significant improvement was observed in the inter-observer agreement for the WHO 2017 OED grading system (K 0.196 vs. 0.448; Kw 0.357 vs. 0.562) after the calibration exercise. The significant difference (p = 0.027) in the level of agreement between those with five or more years and less than 5 years of experience was no more observed (p = 0.426) after the calibration exercise. The percent agreement for binary grading was significantly higher (91.8%) for buccal mucosal lesions as compared to lesions on the tongue after the calibration exercise. CONCLUSION: This study validates the significance of calibration in improving the reproducibility of OED grading. The nationwide exercise resulted in a statistically significant improvement in the inter-observer agreement for the WHO 2017 OED grading system among a large number of oral pathologists. It is highly recommended that similar exercises should be organized periodically by professional bodies responsible for continuing education among oral pathologists to improve the reliability of OED grading for optimal treatment of oral potentially malignant disorders.

Independent insulin signaling modulators govern hot avoidance under different feeding states.

Thermosensation is critical for the survival of animals. However, mechanisms through which nutritional status modulates thermosensation remain unclear. Herein, we showed that hungry Drosophila exhibit a strong hot avoidance behavior (HAB) compared to food-sated flies. We identified that hot stimulus increases the activity of α'ß' mushroom body neurons (MBns), with weak activity in the sated state and strong activity in the hungry state. Furthermore, we showed that α'ß' MBn receives the same level of hot input from the mALT projection neurons via cholinergic transmission in sated and hungry states. Differences in α'ß' MBn activity between food-sated and hungry flies following heat stimuli are regulated by distinct Drosophila insulin-like peptides (Dilps). Dilp2 is secreted by insulin-producing cells (IPCs) and regulates HAB during satiety, whereas Dilp6 is secreted by the fat body and regulates HAB during the hungry state. We observed that Dilp2 induces PI3K/AKT signaling, whereas Dilp6 induces Ras/ERK signaling in α'ß' MBn to regulate HAB in different feeding conditions. Finally, we showed that the 2 α'ß'-related MB output neurons (MBONs), MBON-α'3 and MBON-ß'1, are necessary for the output of integrated hot avoidance information from α'ß' MBn. Our results demonstrate the presence of dual insulin modulation pathways in α'ß' MBn, which are important for suitable behavioral responses in Drosophila during thermoregulation under different feeding states.

A Comprehensive Review of Natural Products as Therapeutic or Chemopreventive Agents against Head and Neck Squamous Cell Carcinoma Cells Using Preclinical Models.

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that arises from the epithelium lining of the oral cavity, hypopharynx, oropharynx, and larynx. Despite the advancement of current treatments, including surgery, chemotherapy, and radiotherapy, the overall survival rate of patients afflicted with HNSCC remains poor. The reasons for these poor outcomes are due to late diagnoses and patient-acquired resistance to treatment. Natural products have been extensively explored as a safer and more acceptable alternative therapy to the current treatments, with numerous studies displaying their potential against HNSCC. This review highlights preclinical studies in the past 5 years involving natural products against HNSCC and explores the signaling pathways altered by these products. This review also addresses challenges and future directions of natural products as chemotherapeutic and chemoprevention agents against HNSCC.

Clear cell adenocarcinoma of the urinary bladder: a case report and review of literature.

The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). Clear cell adenocarcinoma (CCA) of the urinary bladder is a rare histologic subtype of adenocarcinoma in the urinary tract. The tumor primarily affects women and has histomorphological features resembling CCA of the female genital tract (or Müllerian origin). Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. Patients typically present with gross hematuria, dysuria, and discharge. In this study, we report a case of a 50-year-old male, presenting with gross hematuria, which was subsequently diagnosed with CCA at our pathology department. Furthermore, we provide a short systematic review of the literature for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.

Ambulatory uniportal versus biportal endoscopic unilateral laminotomy with bilateral decompression for lumbar spinal stenosis-cohort study using a prospective registry.

BACKGROUND: Endoscopic spine surgery has been established as a practical, minimally invasive technique for decompression in patients with lumbar spinal stenosis. However, there remains a paucity of studies prospective cohort study comparing uniportal lumbar endoscopic unilateral laminotomy with bilateral decompression and unilateral biportal endoscopic unilateral laminotomy with bilateral decompression with open spinal decompression-both viable techniques with satisfactory clinical outcomes in the treatment of lumbar spinal stenosis. OBJECTIVE/AIM: To compare the efficacy of UPE and BPE lumbar decompression surgery for patients with lumbar spinal stenosis. METHODS: A prospective registry of patients who had undergone spinal decompression for lumbar stenosis via UPE or BPE under a single fellowship trained spine surgeon was studied. Baseline characteristics, initial clinical presentation, and operative details including complications were recorded for all included patients. Clinical outcomes, such as visual analogue scale and Oswestry Disability Index, were recorded at preoperative, immediate postoperative, 2-week, 3-, 6-, and 12-month follow-up periods. RESULTS: A total of 62 patients underwent endoscopic decompression surgery for lumbar spinal stenosis (29 UPE, 33 BPE). No significant baseline differences were found between uniportal and biportal decompression, when comparing operative duration (130 vs. 140 min; p = 0.30), intraoperative blood loss (5.4 vs. 6mLs; p = 0.05), and length of hospital stay (23.6 vs. 20.3 h; p = 0.35). Two patients (7%) who underwent uniportal endoscopic decompression required conversion to open surgery due to inadequate decompression. Intraoperative complication rates were significantly higher in the UPE group (13.4% vs. 0%, p < 0.05). VAS score (leg & back) and ODI improved significantly (p < 0.001) in both endoscopic decompression groups across all follow-up time points, with no appreciable statistical differences between both groups. CONCLUSION: UPE has the same efficacy as BPE in the treatment of lumbar spinal stenosis. While UPE surgery enjoys added aesthetic benefits of only one wound, BPE had potentially lower risks of intraoperative complication, inadequate decompression, and conversion to open surgery during early period of learning curve.

Predicting Athlete Intentions for Using Sports Complexes in the Post-Pandemic Era.

In recent years, the concept of health has gradually fit into people's lives through the government's promotion. The indoor sports complex is becoming more and more popular, offering people the opportunity to engage in physical and recreational activities regardless of weather conditions. Psychological and social abundance is the key to improving happiness, and the most important thing is to treat and care for yourself. Many fitness venues have emerged to provide athletes with a wide range of choices. However, the advent of the COVID-19 pandemic, which is caused by a virus mainly transmitted through direct contact or air droplets, has had a severe impact on indoor gym users. Therefore, based on the Theory of Planned Behavior (TPB) and Health-Promoting Lifestyle (HPL), this research investigated athletes' behavioral intentions regarding sports halls and perceived risks as interfering variables. For data collection, we collected data samples from sports complexes athletes in Taiwan. A total of 263 responses were analyzed via SPSS 20.0 (IBM Corporation, New York, NY, USA) and AMOS 20.0 (IBM Corporation, New York, NY, USA) seis tests. The study's results indicate that health-promoting lifestyle cognition has a positive and significant effect on behavioral intention; athletes' attitudes, subjective norms, and perceived behavioral control significantly affects the behavioral intention of using the facilities in a sports complex. Athletes' risk perceptions have an interference effect between HPL, attitude, subjective norm, perceived behavioral control, and behavioral intentions of using the facilities in a sports complex. Sports venue managers can refer to the results of this project to develop marketing strategies and promoting.

Urban-Rural Disparity in Birth Cohort Effects on Breast Cancer Incidence.

Breast cancer is the most commonly diagnosed cancer among women worldwide. Studies have reported minimal birth cohort effects on the incidence rates of breast cancer in Western countries but have reported notable birth cohort effects in some Asian countries. The risks of breast cancer may also vary within a country. In the present study, we abstracted female invasive breast cancer data from the Taiwan Cancer Registry for the period 1997-2016. We used the age-period-cohort model to compare birth cohort effects on breast cancer incidence rates between urban and rural regions in Taiwan. We identified a notable urban-rural disparity in birth cohort effects on breast cancer incidence rates in women in Taiwan. The incidence rates in the urban regions were higher than those in the rural regions across all cohorts. However, the incidence rates rose faster in the rural regions than in the urban regions across the cohorts. The risks of breast cancer observed for women born in 1992 were approximately 22 and 11 times than those observed for women born in 1917 in rural and urban regions, respectively. The observed gap in breast cancer incidence rates between the urban and rural regions gradually disappeared across the cohorts. Accordingly, we speculate that urbanization and westernization in Taiwan may be the drivers of female breast cancer incidence rates across birth cohorts.

Dyskeratosis Congenita Links Telomere Attrition to Age-Related Systemic Energetics.

The underlying mechanisms of plasma metabolite signatures of human aging and age-related diseases are not clear but telomere attrition and dysfunction are central to both. Dyskeratosis congenita (DC) is associated with mutations in the telomerase enzyme complex (TERT, TERC, and DKC1) and progressive telomere attrition. We analyzed the effect of telomere attrition on senescence-associated metabolites in fibroblast-conditioned media and DC patient plasma. Samples were analyzed by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. We showed extracellular citrate was repressed by canonical telomerase function in vitro and associated with DC leukocyte telomere attrition in vivo, leading to the hypothesis that altered citrate metabolism detects telomere dysfunction. However, elevated citrate and senescence factors only weakly distinguished DC patients from controls, whereas elevated levels of other tricarboxylic acid cycle (TCA) metabolites, lactate, and especially pyruvate distinguished them with high significance. The DC plasma signature most resembled that of patients with loss of function pyruvate dehydrogenase complex mutations and that of older subjects but significantly not those of type 2 diabetes, lactic acidosis, or elevated mitochondrial reactive oxygen species. Additionally, our data are consistent with further metabolism of citrate and lactate in the liver and kidneys. Citrate uptake in certain organs modulates age-related disease in mice and our data have similarities with age-related disease signatures in humans. Our results have implications for the role of telomere dysfunction in human aging in addition to its early diagnosis and the monitoring of anti-senescence therapeutics, especially those designed to improve telomere function.

The most effective but largely ignored target for prostate cancer early detection and intervention.

Over the past two decades, the global efforts for the early detection and intervention of prostate cancer seem to have made significant progresses in the basic researches, but the clinic outcomes have been disappointing: (1) prostate cancer is still the most common non-cutaneous cancer in Europe in men, (2) the age-standardized prostate cancer rate has increased in nearly all Asian and African countries, (3) the proportion of advanced cancers at the diagnosis has increased to 8.2% from 3.9% in the USA, (4) the worldwide use of PSA testing and digital rectal examination have failed to reduce the prostate cancer mortality, and (5) there is still no effective preventive method to significantly reduce the development, invasion, and metastasis of prostate cancer… Together, these facts strongly suggest that the global efforts during the past appear to be not in a correlated target with markedly inconsistent basic research and clinic outcomes. The most likely cause for the inconsistence appears due to the fact that basic scientific studies are traditionally conducted on the cell lines and animal models, where it is impossible to completely reflect or replicate the in vivo status. Thus, we would like to propose the human prostate basal cell layer (PBCL) as "the most effective target for the early detection and intervention of prostate cancer". Our proposal is based on the morphologic, immunohistochemical and molecular evidence from our recent studies of normal and cancerous human prostate tissues with detailed clinic follow-up data. We believe that the human tissue-derived basic research data may provide a more realistic roadmap to guide the clinic practice and to avoid the potential misleading from in vitro and animal studies.

Travel for survive! Identifying the antecedents of vaccine tourists' travel intention: Using a stimulus-organism-response model.

The COVID-19 global pandemic and the uneven distribution of vaccines have resulted in alternative medical tourism, vaccine tourism. The purpose of this study is to identify the antecedents of vaccine tourists' travel intention. The Stimulus-organism-response model was used as a framework to understand the relationship between risk perception (stimulus), pandemic prevention attitude (organism), decision making (organism), and travel intention (response) in vaccine tourism. An online questionnaire survey method was adopted to address the purpose of the research. Purposive and snowball sampling were used to select eligible respondents who were over 18 years old and had experience in vaccine tourism. A total of 520 online questionnaires were collected, and description analysis, confirmatory factor analysis, and structural equation modeling were utilized to analyze the collected data. The findings indicated that pandemic prevention attitude is a full mediator between risk perception and travel intention. There is a significant causal relationship between risk perception and pandemic prevention attitude and between pandemic prevention attitude and travel intention. Furthermore, tourists' travel decision-making also significantly influences their travel intention. However, the relationship between tourists' risk perception and travel decision-making has no significant effect. Vaccine tourism was created based on the COVID-19 context. Therefore, in order to avoid vaccine travel becoming an infection control breach, pandemic prevention planning and the medical quality of the destination, and the prevention policies between the countries should be completely assessed and conducted.

Prediction of black carbon in marine engines and correlation analysis of model characteristics based on multiple machine learning algorithms.

Ship black carbon emissions have caused great harm to ecological environment. In order to estimate the black carbon emissions, thereby reducing the cost of black carbon experiments, here, we introduced four machine learning algorithms which are lasso regression, support vector machine, extreme gradient boosting, and artificial neural network to predict ship black carbon emissions. The prediction models were established with using the datasets acquired from similar marine engines under various steady-state conditions. The results show that SVM, XGB, and ANN have higher prediction accuracy than lasso regression, and the adjusted R2 of each model is 0.9810, 0.9850, 0.9885, and 0.6088. Although ANN shows the best prediction performance, it is inferior to SVM and XGB in terms of model stability and training cost. Then, in order to simplify the optimization process of hyperparameters and improve the prediction accuracy of the model at the same time, we use three different swarm intelligence algorithms to automatically optimize the hyperparameters of SVM and XGB. In addition, we applied mutual information to measure the correlation between the characteristics of the prediction models and black carbon concentration and found that the characteristics which related to in-cylinder combustion have a strong correlation with the black carbon concentration. The findings in this paper prove the feasibility of machine learning in ship black carbon emission prediction and could provide references for reducing ship black carbon emissions and the formulation of emission regulations.

Extracellular Prostaglandins E1 and E2 and Inflammatory Cytokines Are Regulated by the Senescence Program in Potentially Premalignant Oral Keratinocytes.

Potentially pre-malignant oral lesions (PPOLs) are composed of keratinocytes that are either mortal (MPPOL) or immortal (IPPOL) in vitro. We report here that MPPOL, but not generally IPPOL, keratinocytes upregulate various extracellular tumor-promoting cytokines (interleukins 6 and 8) and prostaglandins E1 (ePGE1) and E2 (ePGE2) relative to normal oral keratinocytes (NOKs). ePGE upregulation in MPPOL was independent of PGE receptor status and was associated with some but not all markers of cellular senescence. Nevertheless, ePGE upregulation was dependent on the senescence program, cyclo-oxygenase 2 (COX2) and p38 mitogen-activated protein kinase and was partially regulated by hydrocortisone. Following senescence in the absence of p16INK4A, ePGEs accumulated in parallel with a subset of tumor promoting cytokine and metalloproteinase (MMP) transcripts, all of which were ablated by ectopic telomerase. Surprisingly, ataxia telangiectasia mutated (ATM) function was not required for ePGE upregulation and was increased in expression in IPPOL keratinocytes in line with its recently reported role in telomerase function. Only ePGE1 was dependent on p53 function, suggesting that ePGEs 1 and 2 are regulated differently in oral keratinocytes. We show here that ePGE2 stimulates IPPOL keratinocyte proliferation in vitro. Therefore, we propose that MPPOL keratinocytes promote the progression of IPPOL to oral SCC in a pre-cancerous field by supplying PGEs, interleukins and MMPs in a paracrine manner. Our results suggest that the therapeutic targeting of COX-2 might be enhanced by strategies that target keratinocyte senescence.

How to improve the problem of hotel manpower shortage in the COVID-19 epidemic environment? Exploring the effectiveness of the hotel practice training system.

This study aimed to examine the role of effective employee training in the sustainable growth and corporate social responsibility of hotels during the postpandemic period. An initial respondent pool was selected using purposive sampling, and 280 questionnaires were finally obtained by snowball sampling from September 2019 to February 2020. The sample was analyzed using basic statistical tests, the Pearson correlation coefficient, and multivariate regression. We then interpreted the sample data through consultation with scholars and practitioners in hotel management. Finally, the data were analyzed using multivariate verification. The results indicated that China Binhai Hotel could not foster consistent employee enthusiasm and fulfill its corporate social responsibilities during the postpandemic period due to deficiencies in its human resources training, employee benefit, job rotation, and incentive systems. We suggest for hotels to promote corporate culture, improve the system of promotion, increase employee benefits, and adjust the workplace environment and equipment provided to employees. These will improve employee attitudes toward hotel management, improve work efficiency, increase retention, and solve the problem of personnel shortage during the postpandemic period.