This paper proposes a non-extensive entropy econometric technique to predict energy efficiency at province (NUT-2) level based on imperfect knowledge of the national overall efficiency in the sectors of industry, transport, households and services. The model is applied to the polish case. As acknowledged in recent literature, non-extensive entropy model should remain a valuable device for econometric modelling even in the case of low frequency series since outputs provided by the Gibbs-Shannon entropy approach correspond to the Tsallis entropy limiting case of the Gaussian law when the Tsallis q-parameter converges to unity. Therefore, we set up a q-Tsallis-Kullback-Leibler entropy criterion function with a priori consistency moment and model data constraints, including province energy intensity (known with uncertainty), regional climate differentiation and regular conditions. The model outputs continue to conform to empirical expectations. In spite of the close to unity q-Tsallis parameter, this Tsallis related approach reflects higher stability for parameter computation in comparison with the Shannon-Gibbs entropy econometrics technique. The proposed technique can be applied in different EU countries and elsewhere for example in the context of experimental official statistics.

Generally playing group management performance and financial management performance of sports clubs are assessed separately. We adopt a non-parametric methodology to assess overall performance first conceptualising overall management as a production process comprising of two serially-linked subprocesses; playing group management and financial management. Thereafter, we decompose overall performance to obtain estimates of performance at the subprocess level. Through this procedure it is possible to determine whether it is a sports club’s on-field performance or off-field performance or both may contribute towards its inefficiency, if any, in overall management. Further, a model is developed to determine targets for inefficient clubs to become overall efficient. The method is applied to 18 clubs in Australian rules football league. In 2021 season, the results reveal that on-field performance, on average, is better than off-field performance and variability in off-field performance is higher than that of on-field performance. Observed overall management inefficiency is mainly due to inefficiency in financial management. Results are robust to weighting scheme adopted in overall efficiency configuration.

Modified FOLFIRINOX is effective for advanced pancreatic cancer but frequently causes severe neutropenia. The present study was designed to investigate the influence of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients receiving modified FOLFIRINOX. Fifty-one advanced pancreatic cancer patients who received modified FOLFIRINOX during January 2014 and May 2018 were subjects of the present study. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was determined as the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were measured as secondary endpoints. Severe neutropenia (grade≥3) occurred in 39 patients (76.4%), in which high level of total bilirubin (>0.6mg/dL) was a significant risk as assessed by a multivariate logistic regression analysis. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (15.2 months versus 7.2 months, P=0.032). Moreover, there was a significant correlation between OS and the grade of neutropenia (R=0.306, P=0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRNOX therapy.

Background The metabolic syndrome increases the risk of developing various systemic cancers. The prevalence of the metabolic syndrome in newly diagnosed glioblastoma patients is unknown. Further, there have been contradictory reports about how the metabolic syndrome affects clinical outcomes. Therefore, the purpose of this study is to test the hypothesis that the metabolic syndrome is associ-ated with increased prevalence of glioblastoma and worsened survival outcomes. Methods This retrospective cohort study examines seventy-three patients with isocitrate dehydrogenase (IDH)-wild type glioblastoma as it provides for a relatively homogeneous population to examine. Patient characteristics, vital signs, lab results, tumor molecular markers, and overall survival were analyzed. Patients with the metabolic syndrome and individual risk factors were identified and survival outcomes were examined. Results Our results demonstrate that there is a higher prevalence of the metabolic syndrome in our cohort of patients with glioblastoma than the general population (41% vs 33%). We also demonstrate that after correction for confounding variables, the metabolic syndrome is not significantly asso-ciated with overall survival (p = 0.1). When analyzing individual metabolic risk factors, we demonstrate that there is a significant association between the accumulation of metabolic risk factors and decreased survival (p = 0.03), and hyperglycemia emerges as a significant independent risk factor for decreased survival (p = 0.05). Conclusion These results suggest that metabolic risk factors can affect survival in patients with glioblastoma, which can have significant implications for clinical practice. These findings need to be further ex-plored through further clinical and mechanistic studies.

Galectins play a role in lung cancer oncogenic pathways including apoptosis, t-cell immune responses, and tumor metastasis. Biomarkers that diagnose, prognose, and assist with treatment remain important, and galectins represent biomarkers that have the potential to impact lung cancer management through these pathways. Using enzyme-linked immunosorbent assay (ELISA) we examined galectin-1, -3, and -9 levels from lung cancer patient serum. Through comprehensive chart review: patient demographics, staging information, tumor biology, treatment data, and outcomes including overall survival (OS) and metastasis were retrospectively collected. Galectin levels were then compared to these numerous factors. Galectin-1, -3, and -9 levels did not correlate with cancer stage, however galectin-3 levels were lower in small cell lung cancer (SCLC) and squamous cell lung cancer than in adenocarcinoma. There was no correlation between galectin levels and previous treatment or future metastasis. Patients that had an abnormal galectin-1 level had decreased OS. Furthermore, patients with curative surgically resectable NSCLC with abnormal galectin-1 levels had decreased OS, but there was no difference in those with SCLC or that were non-resectable treated palliatively. These findings provide insight into galectin levels in various lung cancer histology and highlight the potential for galectin-1 to assist in prognosis of surgically resectable NSCLC.

The prognostic value of inflammatory indices such as absolute monocyte count (AMC) has been a subject of interest in recent prostate cancer (PCa) literature, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized disease. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data was available for all cases based on the National Cancer Registry with a median observation time of 120 months (IQR 80.9-144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox proportional hazards regression model was used for analysis. The median age was 68.8 years (IQR 63.3-73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0-19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, ISUP Grade Group, clinical T stage and maximum PSA concentration. The study demonstrated that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.

Yijing possesses inherent principles and logic, and it has achieved consensus as an auxiliary decision-making function. Research on Yijing has been validated in the field of superpsychology, primarily focusing on individuals. However, the universal value of Yijing extends beyond individual divination or telepsychological induction, and there are untapped scientific potential values associated with it. Consequently, many scholars studying Yijing, including those in Chinese medicine, attempt to decipher its internal scientific mechanism through quantitative methods. In summary, scientific quantitative analysis of Yijing can be categorized into several approaches. These include quantification based on Yijing itself (binary and hexagram order), as well as quantification based on mathematical statistics, probability, and calculus. Another approach involves quantification based on expert knowledge, as well as the quantification of timewave curves and Yi-globle. Significant progress has been made in all of these quantitative research areas within the scientific paradigm. Nevertheless, future quantification of Yijing may explore rule-based evolutionary analysis, incorporating artificial intelligence technology, and conduct quantitative analysis based on the evolutionary process and results. There is even potential to deepen this research with tools such as ChatGPT. Additionally, the focus of Yijing divination may shift from individual events to group events, accompanied by space-time modeling and analysis through the construction of a new coordinate system.

Abstract: Autophagy has a dual role in gliomagenesis in a microRNA-modulated environment. We investigated the potential relevance of autophagy in glioma development and survival by exploring the association of autophagy-associated genes and microRNAs in low- and high-grade gliomas. Real-time PCR (qPCR) was used to determine the expression of genes and microRNAs in 50 fresh glioma tissues while Formalin-fixed paraf-fin-embedded tissues of the same patients were used for immunohistochemistry. The Mann-Whitney U-test test, Spearman correlation test, and Kaplan-Meier survival analysis were performed to evaluate the expression, association, and overall survival in patients respectively. The expression of LC3, AKT, and miR-21 was increased in high-grade glioma compared to low-grade glioma while ULK2 expression was decreased in high-grade glioma. A strong positive correlation was observed for ULK2 with UVRAG, PTEN, miR-7, and miR-100, while the moderate correlation with mTOR, Beclin1, miR-30, miR-204, miR-374, miR-21 and miR-126 in low-grade glioma, while a moderate positive correlation between ULK2 and PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, AKT and miR-374, and between AKT and ULK1, VPS34, UVRAG, and miR-7 in high-grade gliomas. The low ULK2 and LC3 expression group was significantly associated with better overall survival in gliomas while miR-21 overexpression showed a poor prognosis in glioma patients. Therefore, miR-21, ULK2, and LC3 may serve as prognostic biomarkers for survival outcomes in glioblastoma.

This study aimed to evaluate the diagnostic and prognostic roles of GATA3 immunohistochemistry in urothelial carcinoma (UC) through a meta-analysis. We investigated GATA3 immunohistochemical expression rates and performed a subgroup analysis based on tumor site, study location, and histological subtypes. The overall survival rates of patients with GATA3-positive and negative UC were compared. The estimated GATA3 expression rate was 0.748 (95% confidence interval [CI]: 0.704–0.787). GATA3 expression rates in the urinary bladder and urinary tract were 0.775 (95% CI: 0.727–0.818) and 0.614 (95% CI: 0.426–0.774), respectively. The GATA expression rates of noninvasive and invasive UCs were 0.965 (95% CI: 0.938–0.980) and 0.644 (95% CI: 0.581–0.702), respectively. In invasive UCs, there was a significant difference in GATA3 expression between non-muscular invasion and muscular invasion subgroups (0.937, 95% CI: 0.883–0.967 vs. 0.753, 95% CI: 0.645–0.836). GATA3 expression was the highest in the microcytic subtype among the histologic subtypes (0.952, 95% CI: 0.724–0.993). There was a significant correlation between GATA3 expression and better prognosis (hazard ratio: 0.402, 95% CI: 0.311–0.521). Taken together, GATA3 expression significantly correlated with low-stage and better prognosis in UC. GATA3 expression is highly variable across histological subtypes and it is careful interpreting GATA3 expression.

Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with a poor median overall survival (OS), ranging from 8 to 13 months. There exists considerable heterogeneity in the survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival utilizing a large patient sample in the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinic-pathological, treatment data, and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: 2,273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on the OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help improve prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

Colorectal cancer is the third most diagnosed cancer in males and in females, representing 8% of estimated new cases and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9 – 12% are eligible for local treatments with radical intent, including surgical resection, SBRT and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.

Objective: To compare the overall survival (OS) and surgical outcomes between open and minimally invasive surgery (MIS) in a large cohort of women with Type II endometrial cancer. Methods: Using the National Cancer Database, we identified a cohort of women who underwent hysterectomy for type II endometrial cancer (serous, clear cell, carcinosarcoma) between January 2010 and December 2014. Primary outcome was the comparison of OS between MIS and the open approach. Secondary outcomes included the length of hospital stay, readmission rate, 30- and 90-day mortality. Multivariable logistic regression and inverse propensity weighting analyses were performed. Results: A total of 12,905 patients with Type II, Stage I-III endometrial cancer who underwent hysterectomy were identified. Among these patients, 7,123 (55.2%) underwent MIS. The utilization of MIS increased from 39% to 64% over the four-year period. In propensity-score-weighted analysis, MIS was associated with superior OS (101.7 vs. 86.7 months, p=0.0003 by the log-rank test), with a hazard ratio of 0.9 (CI 0.857-0.954, p=0.0002). MIS was also associated with improved perioperative outcomes, including a shorter length of stay (1 vs. 4 days, p<0.001), lower 30-day readmission rate (2.5% vs. 5%), and lower 30- and 90-day postoperative mortality (0.5% vs. 1.3% and 1.5% vs. 3.6%, respectively; p<0.001). The time interval between surgery and initiation of chemotherapy was shorter in the MIS group (38 vs. 41 days, p<0.001).The increase in MIS adoption correlated with a decrease in 90-day postoperative mortality (2.8% to 2.2%, r=-0.89; p=0.003) and 12-month overall mortality (51% to 38%, r=-0.95, p=0.006). Conclusions: In an epidemiologic study, MIS is associated with improved overall survival and superior perioperative outcomes compared to open surgery in women with Type II endometrial cancer.

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein involved in mitochondrial morphology and homeostasis. LETM1 is highly expressed in many human solid cancers and correlates with poor prognosis possibly due to mitochondrial dysfunction. However, the functional role of LETM1 in the progression of hematological malignancies remains to be elucidated. In this study, we found that higher LETM1 expression was associated with a short overall survival in Diffuse Large B-Cell Lymphoma (DLBCL) and in Acute Myeloid Leukemias (AML) patients. The transcriptomic analysis showed that LETM1 expression is positively correlated with oncogenic pathways (e.g., glucose transport, stem cell maintenance, mTOR and Wnt signaling pathways, mitotic G2/M phase transition, and cell proliferation) and negatively correlated with autophagy-related processes and apoptosis. In contrast, low expression of LETM1 associated with upregulation of BECLIN-1-dependent mitophagy, which in turn improves the prognosis in both DLBCL and AML patients. Our data suggest that LETM1 is a valuable prognostic marker and a possible therapeutic target for improving the clinical outcome in hematological malignancies.

Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.

In this study, an experimental study was conducted on the performance characteristics of large-diameter submersible pumps with 400A and 1350A for drainage according to various flow rate changes. As a result, the total head of the submersible pump with a diameter of 400A decreased by approximately 36.28% from 5.43m to 3.46m, and the pump efficiency also decreased by 7.81% from 83.48% to 76.93%. As the discharge flow rate increased, the input power and the overall efficiency also tended to decrease. It was confirmed that the increase in the discharge flow rate decreased the total head and the input power, and thus the pump efficiency and the overall efficiency decreased. The total head of the submersible pump for the 1350A diameter decreased by about 34.4% from 4.36m to 2.86m, and the pump efficiency decreased by about 3.39% from 76.29% to 73.7%. As with the submersible pump with a diameter of 400A, the input power and overall efficiency tended to decrease as the discharge flow increased. As the diameter increased, the input power of the submersible pump was consumed more, and the total head, pump efficiency, and overall efficiency were lower.

The aims of this research were to know the physicochemical parameters, texture properties and sensory profile of vegetarian sausages through the flash profile, overall liking and purchase intention. Additionally, protein, fat and carbohydrate contents, pH, water activity, color, instrumental texture and descriptive profile were quantified with the overall liking and purchase intention of four sausages: ovo-vegetarian (SO), classic vegan (SC), fine herb vegan (SH) and vegan quinoa (SQ). Regarding the physicochemical properties, significant differences (p &lt; 0.05) were obtained. Using the flash profile, consumers described SO with attributes of elasticity, tamale smell, strange smell, characteristic flavor, pastiness, softness, pastel color. SC described as soft, pale color, characteristic odor, characteristic flavor, porous and flexible; SH and SQ characterized by the presence of ingredients, stew flavor, spices, pale and soft color. The SO sample presented greater overall liking and purchase intention compared to the other samples, and had a better texture and higher protein content. Through the HMFA analysis, a positive correlation was obtained between the texture and descriptive sensory of the flash profile, and on the other hand, a correlation between the physicochemical characteristics pH, aw, color, overall liking and purchase intention.

This paper studied the combined influences of the hot streak and swirl on the cooling performances of the NASA C3X guide vane coated with or without TBCs. The results show that: (1) Even under uniform velocity inlet conditions, the hot streak core can be stretched as it impinges the leading edge which causes higher heat load on the suction side of the forward portion. (2) The swirl significantly affects circumferential and radial migration of the hot streak core in the NGV passage. On the passage inlet plane, positive swirl leads to a hotter tip region on the suction side. In comparison, negative swirl leads to a hotter hub region on the pressure side. (3) Under the influence of swirl, migration of coolant improve the coverage of film cooling close to the midspan, while in the regions close to the hub and tip end-wall, the overall cooling performance decrease simultaneously. (4) In the regions with enough internal cooling, the cooling effectiveness increment is always larger than that in other regions. Besides, the overall cooling effectiveness increment decreases on the region covered by film cooling for the coated vane, especially in the region with negative local heat flux.

Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders, including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumor-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Proton pump inhibitors decreased dacomitinib exposure. This anal-ysis summarizes the effect of H2RA on dacomitinib exposure. A within-patient comparison of steady-state trough concentrations (Ctrough,ss) of dacomitinib and its active metabolite and active moiety with and without concomitant use of H2RA was conducted using a linear mixed effects model with pooled data from 11 clinical studies in patients with NSCLC. An oral absorption PBPK model was constructed and verified using clinical PK data after a single dose of dacomitinib in healthy volunteers to estimate the effect of gastric pH altered by an H2RA on dacomitinib PK. The adjusted geometric mean of dacomitinib Ctrough,ss of dacomitinib parent, metabolite and active moiety following co-administration with H2RA was approximately 86%, 104% and 100% relative to that following dacomitinib 45 mg administration without H2RA (P>0.05). The PBPK modeling showed negligible change in dacomitinib Cmax and AUC over 0-24 hours after H2RA administra-tion, when compared with those administered dacomitinib alone. Co-administration of an H2RA with dacomitinib is not expected to have any clinically relevant effect on dacomitinib exposure.

Background. This study aimed to establish a prognostic nomogram for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with early-onset endometrial cancer (EOEC). Methods. Patients diagnosed with EOEC during 2004-2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were performed to ascertain the independent factors impacting the prognosis of EOEC patients, while a prognostic nomogram was established. Its performance was verified by the receiver operating characteristic (ROC) curves, and calibration plots. The prediction accuracy and clinical net benefit between the model, TNM stage and SEER stage were further compared by the concordance index (C-index) and decision curve analysis (DCA). Results. A total of 4415 eligible patients with EOEC were identified and enrolled in this study. Independent prognostic factors for OS and CSS were confirmed by multivariate Cox regression, which were further incorporated to constructed a nomogram. ROC curves and calibration curves indicated an optimal accuracy of the nomogram. Meanwhile, the C-index and DCA showed the predictive capability and the clinical applicability of the nomogram was superior over the TNM stage and SEER stage. Conclusions. Nomogram based on risk factors was developed as an individualized tool to predict OS and CSS for EOEC patients. The novel tool will assist in patient counseling and selection of appropriate therapeutic regimens.

Flood inundation causes socioeconomic losses for coastal tourism under climate extremes, progressively attracting global attention. Mapping, evaluating, and predicting the flood inundation risk (FIR) is significant for coastal tourism. The study develops a spatial tourism–aimed framework integrating a weighted k-Nearest Neighbors (WkNN), Geographic Information Systems, and flood-related spatially environmental criteria such as precipitation, elevation, soil, and drainage systems. These model inputs were standardized and weighted using distance, and integrated into WkNN to infer regional probability and distribution of FIR. Zhejiang province, China, was selected as a case study. The resulting map was pictured to denote the likelihood of the criteria at various risk categories, which was validated by historical Maximum Inundation Extent (MIE) extracted from World Environment Situation Room. The result indicates 80.59% of WkNN results reasonably confirm the MIE. Precipitation and elevation make a negative contribution to high-medium risk, and drainage systems positively alleviate the regional stress of FIR. The results can help stakeholders make suitable strategies to protect coastal tourism, and also weigh WkNN is superior to kNN in FIR assessment. The framework provides a productive way to yield a reliable assessment of FIR and can also be extended to other risk-related environmental studies under climate change.

Megalin (LRP2) is a rapidly recycling multiligand endocytic receptor, primarily expressed in polarized epithelial cells. Despite megalin could promote tumor growth and invasiveness through several mechanisms, it has been understudied in the field of molecular oncology so far. The present study aimed to evaluate the impact of megalin expression in oral squamous cell carcinoma (OSCC) on disease progression. Megalin expression was evaluated immunohistochemically in 63 OSCC specimens. Data obtained were retrospectively compared with patients’ clinicopathological features and survival. The proportion of megalin-expressing cells in primary OSCC tissue was significantly associated with metastatic spreading to lymph nodes, vascular invasion and lower overall survival rate. Results obtained by the study suggest that megalin can be considered as a novel molecule involved in OSCC pathogenesis, but also useful as a potential biomarker for cancer progression.

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.

Personalized medicine is an aspect of the P4 medicine (predictive, preventive, personalized and participatory) based precisely on the customization of all medical characters of each subject. In personalized medicine, the development of medical treatments and drugs is tailored to the individual characteristics and needs of each subject, according to the study of diseases at different scales from genotype to phenotype scale. To make concrete the goal of personalized medicine, it is necessary to employ high-throughput methodologies such as Next Generation Sequencing (NGS), Genome-Wide Association Studies (GWAS), Mass Spectrometry or Microarrays, that are able to investigate a single disease from a broader perspective. For example, by using genotyping microarrays (e.g. collections of Single Nucleotide Polymorphism - SNP) it is possible to uncover the reasons (i.e. mutation in genes) because a treatment works properly in some patients (for example absence of mutated genes), but it does not work (presence of mutated genes) in others. A side effect of high-throughput methodologies is the massive amount of data produced for each single experiment, that poses several challenges (e.g. high execution time and required memory) to bioinformatic software. Thus a main requirement of modern bioinformatic software is the use of good software engineering methods and efficient programming techniques, able to face those challenges, that include the use of parallel programming and efficient and compact data structures. Thus, to exploit all the potential of this massive amount of data in the short possible time (before that data becomes obsolete), the necessity to develop parallel software tools for efficient data collection and analysis arise. Moreover, due to the heterogeneity of the data produced by the different kinds of experimental platforms, it is necessary to automatize in a comprehensive software pipeline, the various steps that compose a bioinformatic analysis, such as: the preprocessing of raw data to remove noise or corrupted data; the annotation of data with external knowledge (e.g. Gene Ontology), and the integration of molecular data with clinical data. It should be noted that such steps are necessary to make statistical or data mining analysis more effective. This paper presents the design and the experimentation of a comprehensive software pipeline, named microPipe, for the preprocessing, annotation and analysis of microarray-based SNP genotyping data. A case study in pharmacogenomics is presented. The main advantages of using microPipe are: the reduction of errors that may happen when trying to make data compatible among different tools; the possibility to analyze in parallel huge datasets; the easy annotation and integration of data.

The paper presents the results of the theoretical and practical research on developing the infrastructure for assessment of overall risk (explosion / occupational / terrorist attack) associated with unwanted events such as major accidents that can occur at explosive storehouses for civilian use. The scientific research outlined in this article was carried out within the Nucleu Project PN 16 43 02 15 - “Research on increasing safety levels at technical facilities for storage of explosives for civil use”.

A Clinical Prognostic Index (CPI) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included. Overall survival was 11.9 months and 9.4 months in the HCC group and metastatic groups, respectively. In the combined dataset, Child-Pugh Score (CPS) (p=0.002), serum albumin (p=0.039) and presence of extrahepatic disease (p=0.012) were significant predictors of early death on multivariable analysis and were included in the CPI (total score 0 to 5). Median survival was 23.8, 9.1, 4.5 and 2.6 months for patients with 0, 1-2, 3 and 4-5 points, respectively. In the HCC dataset, CPS (p&lt;0.001) and gross tumor volume (p=0.013) were predictive of early death. In the metastatic dataset, serum albumin (p&lt;0.001) and primary disease site (p=0.003) were predictive of early death. The AUC for the combined, HCC, and metastatic datasets are 0.78, 0.84, 0.80 respectively. Poor liver function (defined by CPS and serum albumin) and extrahepatic disease were most predictive of early death, providing clinically important expected survival information for patients and caregivers.

This paper addresses the pressing concern of corporate tax evasion recognized by several nations, employing insights from public choice theory and tax compliance theory. The research aims to evaluate the ramifications of corporate tax evasion on public revenue, public expenditures, tax rates, and the prevailing budget deficit. Methodologically, the study utilizes questionnaire data and employs structural equation modeling for analysis. The findings indicate that tax evasion is significantly influenced by multiple factors, encompassing tax income, public expenditures, tax rates, and the budget deficit. The article offers a comprehensive exploration of both theoretical frameworks and practical implications, contributing valuable insights to the ongoing discourse on corporate tax evasion and its multifaceted impact on fiscal dynamics.

Background: Colorectal cancer (CRC) is prevalent globally, constituting 11.9% of cases in Mexico. Lymph node metastases are established prognostic indicators, with extracapsular lymph node extension (ENE) playing a crucial role in modifying prognosis. While ENE is associated with adverse factors, certain aspects, like lymph node conglomerates, are underexplored. Matted nodes, clusters of lymph nodes infiltrated by cancer cells, are recognized as an independent prognostic factor in other cancers. This study investigates the prognostic implications of lymph node conglomerates, particularly matted nodes, in colon cancer. Methods: A retrospective analy-sis of 502 colon cancer cases (2005–2018) identified 255 with lymph node metastasis. Cases were categorized into two groups: 1) lymph node metastasis alone (n=208), and 2) lymph node metas-tasis with matted nodes (n=47). A comparative survival analysis was performed. Results: Of the 255 patients, 38% had lymph node metastasis. Patients with matted nodes (18.4%) showed an association with higher pN stage and lymphovascular invasion. The 5-year survival rate for pa-tients with matted nodes was 47.7%, compared to 60% without; however, this association demonstrated only a statistical tendency. Multivariate analysis identified clinical stage and ad-juvant chemotherapy use as independent factors contributing to survival. Conclusion: This study underscores matted nodes as potential prognostic indicators in colon cancer, emphasizing their association with higher pN stage and reduced survival. Further research is essential for validat-ing these findings and integrating matted nodes into the broader context of colorectal cancer management.

Immunotherapy, particularly Immune Checkpoint Blockade (ICB), has demonstrated significant efficacy in treating melanoma in recent years. However, accurately predicting treatment success and avoiding ineffective therapies remains an unresolved challenge. Therefore, this study aims to develop statistical models utilizing neural networks to forecast the effectiveness of immune checkpoint therapies for melanoma patients. Our models primarily rely on Artificial Neural Networks (ANN) to anticipate both Overall Survival (OS) and Progression-Free Survival (PFS) among melanoma patients undergoing anti-CTLA4 and anti-PD1/anti-PDL1 therapy. We incorporate gene expression data, measured in Transcripts per Million (TPM), derived from bulk tumor RNA-sequencing datasets. Additionally, clinical variables such as gender, age, and treatment type are factored into our analysis. The ANN underwent optimization to attain the highest feasible precision in anticipating the predetermined survival outcome. Issues stemming from high-dimensional data, such as overfitting, were tackled through regularization and feature selection methods. Consequently, the ANN-based model incorporating feature selection exhibited the capacity to forecast survival (PFS) in response to ICB therapy with a maximal precision of 86%. Conversely, the ANN lacking feature selection but incorporating regularization achieved accuracies of up to 72% for PFS and 71% for OS, correspondingly. In order to confront the challenge posed by limited patient samples and to assess replicability, the model underwent training and validation based on the amalgamation of all five datasets. However, this amalgamation failed to enhance predictive performance, necessitating further investigations.

Whole-brain radiation therapy and stereotactic radiosurgery are two treatment modalities commonly utilized to treat brain metastases (BMs). The aim of this study is to retrospectively analyze the main radio-oncologic and clinical-demographic aspects of a cohort of BM patients treated with Volumetric Modulated Arc Therapy for radiosurgery (VMAT-RS). This is a cross-sectional observational design study with retrospective review of medical records of patients with brain metastases treated with VMAT- RS between 2012 and 2018. Clinical and demographic data, with special attention to sex, age, primary tumor, brain tumor-related epilepsy (BTRE), number and brain location of BMs, Karnofsky Performance Status (KPS), the updated DS-GPA prognostic index and the survival estimated according to the Kaplan-Meier model from the date of radiosurgery were analyzed. One hundred and twenty-one patients with 229 BMs were treated with VMAT-RS. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. Sixty-eight percent of the patients had lung cancer and 35% of the BMs were in the frontal lobe. Proportion of local control was 88.5%. BTRE prevalence was 30.6%. The median survival time (MST) was 7.7 months. In the multivariate analysis of the Cox Regression model KPS70 (HRKPS&lt;70=2.59; p=0.001) and higher DS-GPA (HRDS-GPAII =0.55, p=0.022; HRDS-GPAIII-IV =0.38, p=0.006) were associated with improved survival. In the univariate analysis, primary tumor, age and the presence of metastases in the posterior fossa (PFBMs) were also significative. In conclusion, the VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The median survival is significantly longer in those with higher KPS and DS-GPA. Other variables such as the type of primary tumor, age and PFBMs could also influence survival, although further studies are needed.

This study aimed to compare the prognosis and characteristics of patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab (AB) combination therapy and hepatic artery infusion chemotherapy (HAIC). We retrospectively assessed 179 and 72 patients treated with HAIC and AB combination therapy, respectively, between January 2018 and January 2023. The progression-free survival of patients treated with HAIC was significantly superior than that of patients treated with AB (P&lt;0.05), but there was no significant difference in overall survival and objective response rate (ORR) between the two groups (P=0.1056 and P=0.137, respectively). After propensity score matching (PSM), our data revealed that there was no significant difference in PFS between patients who received AB combination therapy and HAIC therapy (P=0.8888). However, patients who received AB combination therapy had significantly better overall survival than those who received HAIC therapy (P=0.0133). In addition, after PSM, significant differences in ORR and disease control rate were not observed. In conclusion, our propensity score study reveals that patients treated with AB therapy have a significantly longer OS than those treated with HAIC.

Background: Patients with locally advanced/metastatic urothelial cancer have been conventionally treated with platinum-based chemotherapy. Recently, numerous new treatments have been proposed to improve overall survival (OS) and reduce adverse effects, but no head-to-head direct comparison is available. Methods: We considered: a) monotherapy with immune checkpoint inhibitors (ICI); b) combinations of an ICI with chemotherapy; c) combinations of an ICI with other drugs. An indirect comparison was performed to identify the regimens most effective in prolonging OS compared to each other and to chemotherapy. Results: A total of 6 articles were included. In our final analysis, nivolumab plus chemotherapy showed better OS compared to chemotherapy (HR= 0.70, 95%CI: .59-0.82); while durvalumab plus tremelimumab showed no OS benefit (HR=0.95, 95%CI 0.82-1.11). More interestingly, enfortumab vedotin plus pembrolizumab significantly prolonged OS compared to both chemotherapy alone (HR=0.53, 95%CI 0.45-0.63) and nivolumab plus chemotherapy (HR= 0.76, 95%CI 0.60-0.97). Discussion and conclusion: Among new treatments for locally advanced and metastatic urothelial cancer, enfortumab vedotin + pembrolizumab showed the best efficacy in terms of OS. Our results support the use of this combination as first-line treatment in this setting.

Employees’ organizational commitment is considered to be a critical issue in higher educational setting for the success of its visions and goals, as well as to keep its employees motivation granted for achieving better work performance. This subject has therefore, been studied so as to draw attention to enhance effectiveness of higher educational institution in Ethiopia, particularly in reference to Haramaya University. The major objective of study was to find out the level of academic staffs’ commitment. The study assessed whether significant difference exist in academic staffs’ commitment level in terms of their gender and level of education. Researchers used cross-sectional research design and both primary and secondary data sources were used for the study; 242 participants were selected using stratified sampling technique. Questionnaire, focus group discussion and document review were used to collect data. The quantitative data were analyzed using descriptive and inferential statistics; and the qualitative data were also analyzed using narration methods of analysis. Study result showed there was moderate level of in overall commitment and in specific commitment dimensions among academic staffs. The study further indicated that there is no significance difference in commitment of academic staffs with reference to gender; however, a significant difference in commitment was existed in reference to level of education.

Combined hepatocellular cholangiocarcinoma (cHCC-ICC) is a rare malignancy that involves a combination of features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC). cHCC-ICC is generally considered to exhibit a more aggressive clinical course compared to ICC; however, its risk factors and outcomes remain largely undefined. A single-center retrospective study of 82 patients diagnosed with ICC or cHCC-ICC from June 2011 and January 2023, all of whom underwent surgical resection. Our analysis included 70 patients with resected ICC and 12 with resected cHCC-ICC. The overall survival (OS) for the entire cohort was 21.6 months, with a recurrence-free survival (RFS) of 11.8 months. The cHCC-ICC group had significantly higher levels of AST and ALT (AST median 206 vs. 46; ALT median 165.5 vs. 48; p=0.012 and p=0.013, respectively), whereas the ICC group had higher alkaline phosphatase (median 66 vs. 104; p=0.03). CA 19-9 values (p=0.02) were higher in the ICC group, while AFP values were higher in the cHCC-ICC group (p=0.0004). The cHCC-ICC group had a significantly higher rate of recurrence (83% vs. 47%, p=0.028) with a significantly decreased RFS (4.7 months vs. 12.4 months; log-rank p=0.007). cHCC-ICC is a rare entity that needs to be further studied to improve patient outcomes. Our study showed that RFS is lower in the cHCC-ICC group as compared to ICC patients alone. Further studies are warranted and possibly suggest the need for more aggressive initial treatment strategies in patients diagnosed with cHCC-ICC.

Background: Malnutrition was associated with worse survival outcomes, impaired quality of life, and deteriorated performance status across various cancer types. We aimed to identify risk factors for malnutrition in patients with epithelial ovarian(EOC) and impact on survival. Methods: In our prospective study, we included the patients with primary and recurrent EOC, tubal or peritoneal cancer conducted. We assessed serum laboratory parameters, body mass index, nutritional risk index, nutritional risk screening score(NRS-2002), and bio-electrical impedance analysis. Results: We recruited a total of 152. Patients >65 years-old, with ascites of >500 ml, or with platinum-resistant EOC showed statistically significant increased risk of malnutrition when evaluated by NRS-2002(p-values = 0.014, 0.001, and 0.007, respectively). An NRS-2002<3 was an independent predictive factor for complete tumor resectability (p=0.009). The patients with NRS-2002≥3 had a median overall survival(OS) of seven months (95% CI=0-24 months), as compared to the patients with NRS-2002<3 where median OS was 46 months(p=0,001). Phase angle(PhAα)≤ 4.5 was the strongest predictor of OS. Conclusion: Malnutrition is an independent predictor of incomplete cytoreduction in study population. It is an independent prognostic factor for poor OS. Preoperative nutritional assessment is an effective tool in identification of high-risk groups within EOC characterized by poor clinical outcome.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

Background CDK4/6 inhibitors are the standard of care for HR+/HER2-negative metastatic breast cancer in combination with endocrine therapy. However, the real-world efficacy and safety of standard versus reduced doses in elderly patients remain unclear. This study aims to compare the clinical outcomes of standard versus reduced doses of CDK4/6 inhibitors in elderly patients with metastatic breast cancer. Methods This multicenter retrospective cohort study included 158 patients aged ≥70 years diagnosed with HR+/HER2-negative metastatic breast cancer who received either standard or reduced doses of CDK4/6 inhibitors (Ademaciclib, Ribociclib, Palbociclib) as first-line therapy. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. PFS and OS were estimated using the Kaplan-Meier method, and comparisons between groups were performed using the log-rank test. Results Of the total population, 108 patients (68.4%) received the standard dose, and 50 patients (31.6%) received a reduced dose. The standard dose group had significantly longer median PFS compared to the reduced dose group (21.3 vs. 15.2 months, p = 0.014), while median OS did not differ significantly (37.2 vs. 37.2 months, p = 0.103). Subgroup analyses revealed no significant differences in PFS or OS between standard and reduced doses for Ademaciclib and Ribociclib, while Palbociclib at standard dose showed superior PFS (21.9 vs. 12.7 months, p = 0.029) and OS (50.5 vs. 28.6 months, p = 0.026). The incidence of Grade 2-4 AEs was higher in the standard dose group (74.2% vs. 56.8%, p = 0.044). Conclusions Dose reduction of CDK4/6 inhibitors, particularly Ademaciclib and Ribociclib, is a viable option in elderly patients, maintaining comparable OS outcomes to standard dosing while reducing the risk of adverse events. Palbociclib at standard dose may offer superior outcomes. These findings support personalized dosing strategies to optimize efficacy and tolerability in frail or elderly patients.

(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lym-phoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analysed patient records (1984–2016) from 27 clinical sites in Eurpe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS), and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. Median (range) times from start of first-line therapy to first R/R MF and from first to second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radio-therapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). Median (95% confidence interval [CI]) OS from the diagnosis of first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); es-timated median PFS (95% CI) from the time of first R/R MF was 1.3 (1.0–2.1) years. (4) Conclu-sion: High rates of R/R disease were observed after second- and third-line treatments in this re-al-world cohort, with longer median OS in patients receiving non-chemotherapy versus chemo-therapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.

Keywords: head-and-neck cancer; chemoradiation; cisplatin; carboplatin; loco-regional control; metastases-free survival; overall survival; toxicity.

Abstract: The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state,” has the potential to cause a deleterious effect on clock gene expression and disrupted regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, appetite and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases. The consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantage of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

Background: Video assisted thoracoscopic surgery (VATS) has become the recommended approach for treatment of resectable lung cancer. However, no large randomized clinical trial has been conducted formally comparing surgical resections completed by VATS to those done by open thoracotomy (OT) in low volume centers. The current study sought to assess differences in recurrence-free survival (RFS), overall survival (OS), positive margins and postoperative length of stay (LOS) between VATS and OT lobectomies in our center. Method: A single institution retrospective chart review from May 2005 through May 2015 was conducted. All patients diagnosed with stage I through III lung cancer who underwent surgical resection were selected. Patient and tumor characteristics recorded included age at diagnosis, sex, tobacco use, tumor location (side and lobe), stage, size and receipt of chemotherapy or radiotherapy. Chis-square and Wilcoxon-Mann-Whitney tests were used to compare demographics, tumor characteristics and LOS. Multiple logistic and Cox regression analyses were used to compute relative risk (RR) for positive margins and mortality hazard ratios along with 95 percent confidence intervals (95%CI), respectively. Results: Of the 235 patients, 101 subjects had VATS while OT was performed in 134 patients. Age at diagnosis, sex, tobacco use, tumor location, and size were comparable for VATS and OT. No significant difference was observed in the relative risk of positive margins for VATS versus OT, RR = 0.56 (95%CI = 0.26, 1.05). However, VATS had shorter median LOS compared to OT (4 vs. 6 days, respectively), p = 0.002. A comparison of VATS versus OT showed no significant difference in the risk of recurrence, HR = 1.21 (95%CI = 0.74, 2.00), or death, HR = 1.34 (95%CI = 0.88, 2.06), in the intent-to-treat population. Similarly, no significant differences in recurrence or mortality risk were observed between VATS versus OT for analyses conducted separately for each cancer stage group or those limited to patients with negative margins. Conclusion: Our study indicates that compared to OT, VATS leads to shorter LOS while achieving comparable margins status, recurrence-free and overall survival regardless of tumor stage at diagnosis.

In the evolving landscape of vibration analysis, the integration of machine learning technologies for semi-automated analytical processes presents challenges in establishing clear cause-and-effect relationships in decision-making formulas. This research addresses this gap by exploring analytical diagnosis through residual signals, enabling the identification of anomalies and underperformance in machinery. Vibration signature analysis, focusing on distinctive vibration patterns, proves instrumental in detecting bearing defects and optimizing maintenance for enhanced operational efficiency and safety. Mathematical modeling, particularly worst-case analysis, provides a structured framework for decision-making under uncertainty. The research employs descriptive methods to analyze bearing wear data, transforming it into quantitative data for multiple regression equations. The derived equations reveal the dominance of harmonics in determining bearing wear stages, with PeakVue and overall vibration further indicating damage progression. The findings emphasize the significance of harmonic detection and high-frequency vibration analysis in predicting bearing health, offering a comprehensive approach to enhance machinery reliability. The study concludes with practical recommendations for bearing damage diagnosis based on the developed mathematical models, providing valuable insights for predictive maintenance strategies.

The aim of the study is to evaluate the predictive factors of response to induction chemotherapy in patients with resectable NSCLC, treated at the unit of Thoracic Surgery of Siena University Hospital with radical surgery. From January 1, 2013 to December 31, 2020, 78 patients were recruited. We analyzed the outcomes in terms of 5-years OS based on the Estimated Regression Rate, N2 downstaging and age; two patients’ subgroups were created by age (Group A: age &lt;66 years-old; Group B: age &gt;66 years-old). No 5-year OS difference was observed based on age, while it was observed in patients with N2 downstaging (p=0.031). Bewtween patients with N2 downstaging, only patients in Group A had a significantly increased 5-year OS (p=0.019), while this was not observed in Group B (p=0-321); the same result was observed with the Estimated Regression Rate &gt; 50% (Group A p=0.005; Group B p=0.391). The percentage of disease regression and the N2 down-staging after induction chemotherapy have great value on the survival, although this advantage seems to be observed mostly in younger patients. A multidisciplinary oncologic discussion of clinical cases could provide support in the careful selection of the ideal patients to undergo neoadjuvant treatment before radical surgery.

We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen progression–free survival (PSA-PFS) from ARSI initiation were assessed using Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA-PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥3.67 ng/ml at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

In this work we looked for a stable and accurate procedure to perform feature selection in datasets with a much higher number of predictors than individuals, as in Genome-Wide Association Studies. Due to the instability in feature selection when many potential predictors are measured, a variable selection procedure is proposed that combines several replications of shrinkage regression models. A weighted formulation is used to define the final predictors. The procedure is applied to investigate Single Nucleotide Polymorphisms (SNPs) predictors associated to Alzheimer’s disease in the Alzheimer’s disease Neuroimaging Initiative (ADNI) dataset. Two data scenarios are investigated: one considering only the set of SNPs and another with the covariates age, sex, educational level and APOE4 genotype. The SNP rs2075650 and the APOE4 genotype are given as risk factors for AD, which is in line with the literature, and other four new SNPs are pointed, opening new hypotheses for in vivo analyses. These experiments demonstrate the potential of the new method for stable feature selection.

Background: Glioblastoma is the most common primary brain neoplasm in adults, with still a poor prognosis despite a constant effort to improve patients’ survival. Some neuroradiological volumetric parameters seem to play a predictive role on Overall Survival (OS) and Progression Free Survival (PFS). The aim of this study is to analyze the impact that the volumetric areas of contrast-enhancing tumor and perineoplastic edema have on survival of patients treated for glioblastoma; Methods: A series of 87 patients who underwent surgery was retrospectively analyzed; OS and PFS were considered as the end points of the study. For each patient a multidisciplinary revision was conducted in collaboration with the Neuroradiology and Neuro-Oncology board. A manual and semi-automatic measurement were adopted to perform the radiological evaluation: contrast Enhancement Preoperative (CE-PTV) and Postoperative Tumor Volume (CE-RTV), Edema/Infiltration Preoperative (T2/FLAIR-PV) and Postoperative Volume (T2/FLAIR-RV); necrosis volume inside the tumor (NV); total tumor volume, including necrosis (TV); Results: The median OS value was 9 months and the median PFS value was 4 m; the mean values were respectively 12,3 m and 6,9 m. Multivariate analysis showed that the OS related factors were: adjuvant chemo-radiotherapy (p &lt; 0,0001), CE-PTV &lt; 15 cm³ (p=0,03), surgical resection &gt; 95% (p=0,004) and the presence of a “pseudo-capsulated” radiological morphology (p=0,04); Conclusions: maximal safe resection is one of the most relevant predictive factors for patients’ survival. The semi-automatic pre-operative MRI evaluation could play a key role in prognostically categorizing these tumors.

Background: Gestational trophoblastic neoplasia (GTN) is a rare tumor with an excellent prognosis. This study aimed to refine the FIGO risk score by incorporating immune nutritional factors. Methods: A retrospective analysis was conducted on women diagnosed with GTN between 2005 and 2019 who received chemotherapy (CT). Statistical tests (Wilcoxon, univariate, multivariate analyses) were used to assess associations with response to CT, and Cox regression models were applied to identify factors influencing overall survival (OS). immune nutritional FIGO (in-FIGO) risk score was calculated using significant variables and compared to the original FIGO score using ROC curves. Results: A total of 160 GTN patients were included. There was a positive association between CR and prognostic nutritional index (PNI) (p <0.0001) and neutrophils lymphocyte ratio (NLR) (p <0.001). In multivariate analysis, only PNI had a significant association (p= 0.001). A significant association was found between higher PNI (HR 0.95-IC 0.91-0.99, p= 0.019) and OS. ROC curves of the in-FIGO risk and FIGO risk scores were compared. For CR to chemotherapy, the in-FIGO score had higher sensitivity (71.6 vs. 61.5%), specificity (74.3 vs. 62.9%), and AUC (0.719 vs. 0.633) than the original FIGO score. For OS, the in-FIGO score demonstrated higher sensitivity (92% vs. 72.4%) but lower specificity (45.0% vs. 61.8%) and AUC (0.691 vs. 0.710) compared to the original FIGO score. Conclusions: PNI is a significant predictor of both CR and OS in women with GTN receiving CT. The in-FIGO score demonstrated improved sensitivity and specificity in predicting complete response to CT compared to the original FIGO score.

The lack of defect image data is one of the main factors affecting the accuracy of supervised deep learning-based defect detection models. In response to the insufficient training data of defect images with complex backgrounds such as rust and surface oil leakage in substation equipment, leading to poor performance of the detection model, this paper proposed a novel adversarial deep learning model for substation defect generation: ADD-GAN. In comparison to existing generative adversarial networks, this model generates defect images based on effectively segmented local areas of substation equipment images, avoiding image distortion caused by global style changes. Additionally, the model utilizes a joint discriminator for overall image and defect image to address the issue of low attention to local defect areas, thereby improving the loss of image features. This enhances the overall quality of generated images as well as locally generated defect images, ultimately improving image realism. Experimental results demonstrate that the YOLOV7 object detection model trained on the dataset generated using the ADD-GAN method achieves an mAP of 81.5% on the test dataset, representing an improvement of 9.6% over the original dataset, 5.7% over traditional augmentation methods, and 7% over typical adversarial deep learning methods. This confirms that the ADD-GAN method can generate a high-fidelity dataset of substation equipment defects.

Background: Metastatic oral squamous cell carcinoma (OSCC) is associated with poor patient prognosis. Metastasis is a complex process involving various proteins, tumor cell alterations including changes caused by the epithelial-to-mesenchymal transition (EMT) process, and interactions with the tumor microenvironment (TME). In this study, we investigate a combined protein marker system consisting of connexin 43 (Cx43), EMMPRIN (CD147), E-cadherin and vimentin during the invasive metastatic process of OSCC and the possibility of using this system for prognosis prediction. Methods: The protein expression profiles of Cx43, EMMPRIN, E-cadherin and vimentin were investigated by immunohistochemistry in tissue samples from 24 OSCC patients. The metastatic process was mapped through different regions of interest (ROI) of adjacent healthy oral mucosa (OM), center of primary OSCC, invasive front (IF), and local cervical lymph node metastases (LNM). Disease-free survival (DFS) and overall survival (OS) were the primary clinical endpoints. Results: Significant changes in the expression profiles of the different marker proteins were detected between the different ROIs (all p values &lt; 0.05). Multivariable Cox regression analysis revealed a significant effect of increased EMMPRIN expression towards IF on DFS (p = 0.019) and OS (p = 0.023). The combined predictive analysis showed a significant predictive value of the marker system for DFS (p = 0.0017) and OS (p = 0.00044). Conclusions: The combined marker system was able to significantly predict patient prognosis. An increase in EMMPRIN expression towards IF showed the strongest effect and could be an interesting new antimetastatic therapy approach.

Glioblastomas (GBMs) are the most malignant and intractable of all cancers, with an unfavourable clinical prognosis for affected patients. The objective was analysis the sensitivity of GBM cells to the antimicrobial peptides (AMPs) cathelicidin (LL-37) and protegrin-1 (PG-1), both alone and in combination with chemotherapy, to predict overall survival (OS) in the patients. The study was conducted on 27 GBM patients treated in the neurosurgical departments of the Almazov Medical Research Centre (Saint-Petersburg, Russia) from 2021 to 2024. The cytotoxic effects of chemo-therapy, AMPs and their combinations on brain tumor cells were assessed by MTT assay using 50%-inhibitory concentration (IC50). In GBM cells from the patients, LL-37 and PG-1 exhibited strong anticancer effects, surpassing those of chemotherapy drugs. These LL-37 and PG-1 anti-cancer effects were associated with a statistically significant increase in life expectancy and OS in GBM patients. These findings were confirmed by the experiments on rats with C6 glioma, where intranasal administration of LL-37 (300 μM) and PG-1 (600 μM) increased the life expectancy of the animals to 69 and 55 days, respectively, compared to 24 days in the control group (HR=4.139, p=0.0005; HR=2.542, p=0.0759). Additionally, the combination of LL-37 and PG-1 with chemo-therapy drugs showed that a high IC50 of LL-37 with cisplatin (cutoff >800 μM) in GBM cells was associated with increased life expectancy (19 vs 5 months, HR=4.708, p=0.0101) and OS in GBM patients. These combinations could be used in future GBM treatments.

Purpose: We aimed to develop a nomogram able to predict treatment failure, skeletal events and overall survival (OS) in patients with castration-resistant prostate cancer with bone metastases (CRPC-BM) treated with Radium-223 dichloride (223Ra). Patients and Methods: Patients from Castilla-La Mancha Spanish region was prospectively included in ChoPET-Rad multicenter study, from January 2015 to December 2022. Patients underwent baseline, interim, and end-of-treatment bone scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH PET/CT) scans, obtaining multiple imaging radiomics as well as clinical and biochemical variables during follow-up and studying their association with the previously defined end-points. Survival analysis was performed using Kaplan-Meier method and Cox regression. Multivariate logistic and Cox regression models were calculated, and these models were depicted by means of nomograms. Results: Median progression-free survival (PFS) and OS for our population were 4 and 14 months (mo), respectively. The variables that showed the most robust independent significant association with therapeutic failure were baseline alkaline phosphatase (AP) levels (p=0.022) and the characteristics of BM on CT portion of PET/CT (p=0.017). In the case of OS, the significant variables were therapeutic failure (p=0.038), the number of lines received after 223Ra (p

Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such data for first-line ICI therapy and especially for chemotherapy-ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n=70) or as monotherapy (n=15). Maximum and mean standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis and bone marrow-/ spleen to liver ratio (BLR/SLR) were calculated. Kaplan-Meier analyses and Cox-regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p<0.001). Median PFS/OS were significantly longer in patients with MTV≤70mL versus >70mL (PFS: 10 months (M; 95% confidence interval 4-16) vs. 4M (3-5), p=0.001; OS: not reached vs. 10M (5-15), p=0.004). Disease control rate was 81% vs. 53% for MTV≤/>70mL (p=0.007). BLR ≤1.06 versus >1.06 was associated with better outcomes (PFS: 8M (4-13) vs. 4M (3-6), p=0.034; OS: 19M (12-/) vs. 6M (4-12), p=0.005). In patients with MTV>70mL, concomitant BLR≤1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI treated NSCLC, with BLR allowing additional risk stratification.

Background: This study retrospective evaluates patients with stage IV melanoma treated with Nivolumab and Ipilimumab combination therapy from two regional oncology centers from Romania between the years of 2019 up to the end of 2022. Methods: The data were analyzed in SAS for Windows, V9.4. The survival curves were estimated using the Kaplan-Meier method, and survival distributions were compared with log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. Results: Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150-NA) and a median PFS of 211 days (95% CI: 113-430). 45.3% of the patients experienced adverse events during the Nivolumab + Ipilimumab treatment with some of them having multiple organ systems involved. Discussion: The OS values were lower than that reported in approval clinical trials, but the results show a marked improvement when comparing to results obtained by chemotherapy regimens previously used in these scenarios. Conclusion: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.

Trans-arterial radioembolization (TARE) is a form of radiation therapy performed for hepatocellular carcinoma (HCC) via selective intra-arterial injection of Yttrium-90 loaded microspheres. This was a multicenter retrospective study of consecutive patients with HCC who underwent TARE between July 2009 and May 2019. Using pre-treatment computed tomography imaging, the total cross-sectional area (cm2) of the abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing the muscle area to patient height. In total, 347 patients (median age, 65 years; 284 male) were included in the study. A total of 108 (31.1%) patients had portal vein tumor thrombus (PVTT) and 126 (36.3%) were classified as sarcopenic. The median overall survival (OS) was 28.1 months (95% CI, 24.8-35.7) and median progression-free survival was 8.0 months (95% CI, 6.4-9.4). Multivariate Cox regression analysis revealed that sarcopenia (hazard ratio [HR], 1.36; 95% CI, 1.00-1.85, p = 0.05), PVTT (HR, 1.82; 95% CI, 1.33-2.49, p &lt; 0.01), alpha-fetoprotein (AFP) (≥200 ng/mL) (HR 1.41; 95% CI, 1.04-1.92, p = 0.03), and albumin-bilirubin grade (2-3) (HR 1.74; 95% CI, 1.24-2.43, p &lt; 0.01) were independently associated with poor OS. TARE provided favorable long-term outcomes for patients with advanced HCC. Pre-treatment sarcopenia independently associated with survival, suggesting its utility as a surrogate biomarker for identifying TARE candidates.

(1)Background: Among new anti-angiogenetic agents being developed and everchanging guidelines indications, the question of benefits/safety ratio remains unclear. (2)Methods: we have conducted a systematic review and meta-analysis of 25 randomized controlled trials (15487 patients), evaluating overall survival – OS, progression free survival– PFS and toxicity (grade ≥3 adverse effects, type and number of all adverse effects. (3)Results: analysis showed improvement of pooled-PFS (HR 0.72, 95%CI 0.66–0.78, I2 = 77%, P<0.00001) regardless of treatment settings (first-line - HR 0.83, 95%CI 0.77-0.90, P<0.00001, recurrent cancer – HR 0.61, 95%CI 0.54-0.68, P<0.00001 or maintenance – HR 0.82, 95%CI 0.67-1.00, P=0.04) and type of anti-angiogenetic drug used (VEGF inhibitors, VEGF-R inhibitors or angiopoietin inhibitors). Improved OS was also observed (HR 0.95, 95%CI 0.91–0.99, P=0.02). OS benefits were only observed in recurrent platinum-sensitive or platinum-resistant cancers. Grade≥3 adverse effects were increased across all trials. Anti-angiogenetic therapy increased the risk of hypertension, infection, thromboembolic/ hemorrhagic events, gastro-intestinal perforations but not the risk of wound related issues, anemia or posterior leukoencephalopathy syndrome. (4)Conclusions: Although angiogenesis inhibitors improve PFS, there is little to no OS benefits. Given the high risk of severe adverse reactions a careful selection of patients is required for obtaining the best results possible.

In this paper, based on the symmetrical reliability theory, a research method for the safety factor of overall overturning stability of continuous beam bridge under carbon fiber reinforced polymers (CFRP) during cantilever and horizontal rotation construction is proposed. Under the premise that the given target reliability index is known, the method solves the overall overturning stability safety factor of continuous beam bridge under carbon fiber reinforced polymers during cantilever and horizontal rotation construction by using the symmetrical reliability analysis theory and considering the randomness of structural parameters. This method is used to calculate the safety factor and the design reinforcement aera of CRFP of overturning stability and the design reinforcement aera of CRFP of a continuous beam bridge, and the parameters are analyzed. The calculation results show that the randomness of parameters will have a great impact on the overall safety factor and the CRFP aera of overturning stability of cantilever and horizontal rotation construction of continuous beam bridge, and ignoring the influence of randomness of parameters will lead to overestimation of the overall safety factor and underestimation of the CRFP aera of overturning stability of cantilever and horizontal rotation construction of continuous beam bridge.