Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer.

Prostate cancer has substantial heterogeneity in clinical outcomes and therapeutic responses, posing challenges in predicting disease progression and tailoring treatment strategies. Recent studies have highlighted the potential prognostic value of evaluating the tumor microenvironment, including the presence of a histologically overt stromal response (HOST-response) characterized by peri-glandular stromal changes and architectural distortions. This retrospective study examined patient records from The Cancer Genome Atlas database to identify genomic alterations associated with the HOST-response in prostate cancer. Among 348 patients who underwent radical prostatectomy, 160 (45.98%) were identified as having a HOST-response. A gene expression analysis revealed 1263 genes with significantly higher expression in patients with a HOST-response. A protein-protein interaction network analysis identified seven hub genes (KIF2C, CENPA, CDC20, UBE2C, ESPL1, KIF23, and PLK1) highly interconnected in the network. A functional enrichment analysis revealed alterations in the cell division, cytoskeletal organization, cytokinesis, and interleukin-16 signaling pathways in patients with a HOST-response, suggesting dysregulated proliferation and inflammation. The distinct molecular signature associated with the HOST-response provides insights into the tumor-stroma interactions driving adverse outcomes and potential targets for tailored therapeutic interventions in this subset of patients with prostate cancer.

Reliability and Validity of the Turkish Version of the Screening Index for Voice Disorder (SIVD-TR).

OBJECTIVES: We investigated the reliability and validity of the Turkish version of the Screening Index for Voice Disorder (SIVD-TR). METHODS: The original SIVD1 translated into Turkish, followed by a translation back into English by a linguist. The text was finalized by an evaluation committee. This translated version was then administered to a cohort of 223 teachers in Ankara, Turkey, encompassing both those with and without voice disorders (WVD and WOVD). After a duration of 7-14days, a random selection of 53 teachers underwent the questionnaire once more. Statistical analyses were conducted to evaluate the reliability and validity of the index. Cronbach's alpha and test-retest methods were used to scale the reliability. A cutoff point was determined to decide the risk of a voice disorder, by using a Receiver Operating Characteristic curve. The validation process is concluded by computing sensitivity and specificity values, comparing mean scores between WVD and WOVD subjects, and finally examining correlations between SIVD-TR and the Turkish version of the Voice Handicap Index (VHI-10). RESULTS: The internal consistency reliability exhibited high significance, with Cronbach's alpha measuring at 0.872. The test-retest correlation coefficient for the total scores was 0.80. The SIVD-TR consists of 12 symptoms, each accounting for 1 point on the scale. The identified cutoff for identifying the risk of a voice disorder is 4 (four) symptoms, with a sensitivity of 55.2%. A correlation of 69% was observed between SIVD-TR and VHI-TR. A significant association was noted between the risk of having a voice disorder and the actual presence of a voice disorder. Subjects with a voice disorder exhibited higher mean SIVD scores, providing further evidence of the questionnaire's discriminative validity. CONCLUSION: The Turkish adaptation of SIVD demonstrated both reliability and validity, establishing itself as a robust tool for identifying voice disorders.

Prostate Cancer Awareness in the Middle East: A Cross-Sectional International Study.

PURPOSE: Prostate cancer has emerged as a significant public health challenge in the Middle East, characterized by rising incidence rates and a concerning mortality-to-incidence ratio. Yet, despite these alarming trends, data regarding prostate cancer awareness in the region remain limited. To address this critical knowledge gap, this study investigates prostate cancer awareness within the Middle East. MATERIALS AND METHODS: A cross-sectional survey was performed among 5,913 men age 40 years and older across 14 Middle Eastern countries between January 1, 2022, and July 31, 2023. Excluding those with a history of prostate cancer, a validated questionnaire assessed prostate cancer awareness. Data were analyzed using frequencies and percentages for categorical variables, medians and ranges for continuous variables, and Pearson chi-square analysis for relationships between education levels and awareness of prostate cancer. RESULTS: The survey achieved a 74.9% response rate, with 4,431 male participants. Regarding prostate cancer awareness, 83.8% of participants had heard of the disease. However, only 31.0% correctly identified it as the most common malignancy in men, and 21.8% believed it affects both sex. Awareness of screening was limited, with just 19.1% recognizing the prostate-specific antigen test's role. Additionally, participants had a pessimistic view, with a mean perception that 75% of patients with prostate cancer die from the disease, rather than from other causes. Higher education levels were associated with significantly increased awareness of prostate cancer (P < .001). CONCLUSION: This study reveals that while general awareness of the disease exists, crucial knowledge deficits regarding risk factors, screening, and prognosis are evident. Addressing these knowledge gaps through culturally tailored education may improve early detection rates, treatment outcomes, and ultimately reduce the burden of prostate cancer in the Middle East.

Histologically Overt Stromal Response and the Risk of Progression after Radical Prostatectomy for Prostate Cancer.

PURPOSE: Given the variable clinical course of prostate cancer and the limitations of current prognostic factors, this study was conducted to investigate the impact of a histologically overt stromal response (HOST-response) to prostate cancer on clinical outcomes after radical prostatectomy. METHODS: This retrospective analysis utilized The Cancer Genome Atlas (TCGA) to evaluate data from individuals with a confirmed diagnosis of prostate cancer who underwent radical prostatectomy and had available pathology slides. These slides were assessed for the presence of a HOST-response, similar to desmoplasia. The primary endpoint was progression-free survival (PFS). A multivariable competing risk regression analysis was used to assess whether a significant association existed between HOST-response and PFS, adjusting for known prostate cancer prognostic factors. RESULTS: Among the 348 patients analyzed, 166 (47.70%) demonstrated a HOST-response. After a median follow-up of 37.87 months (IQR: 21.20, 65.50), the presence of a HOST-response was significantly associated with a shorter PFS (SDHR, 2.10; 95% CI, 1.26 to 3.50; p = 0.004), after adjusting for covariates. CONCLUSIONS: HOST-response in prostate cancer patients treated with radical prostatectomy is significantly associated with reduced PFS, suggesting a potential benefit from adjuvant therapy and highlighting the need for further investigation in a prospective randomized clinical trial.

Prognostic Significance of the Cribriform Pattern in Prostate Cancer: Clinical Outcomes and Genomic Alterations.

PURPOSE: Given the diverse clinical progression of prostate cancer (PC) and the evolving significance of histopathological factors in its management, this study aimed to explore the impact of cribriform pattern 4 (CP4) on clinical outcomes in PC patients and examine its molecular characteristics. METHODS: This retrospective study analyzed data from The Cancer Genome Atlas (TCGA) database and included PC patients who underwent radical prostatectomy (RP) and had pathology slides available for the assessment of CP4. A multivariable competing risk regression analysis was used to assess the association between CP4 and progression-free survival (PFS) while adjusting for established PC prognostic factors. The frequency of genomic alterations was compared between patients with and without CP4 using the Fisher's exact test. RESULTS: Among the 394 patients analyzed, 129 (32.74%) had CP4. After a median follow-up of 40.50 months (IQR: 23.90, 65.60), the presence of CP4 was significantly associated with lower PFS (AHR, 1.84; 95% CI, 1.08 to 3.114; p = 0.023) after adjusting for covariates. Seven hub genes-KRT13, KRT5, KRT15, COL17A1, KRT14, KRT16, and TP63-had significantly lower mRNA expression levels in patients with CP4 compared to those without. CONCLUSIONS: PC patients with CP4 have distinct genomic alterations and are at a high risk of disease progression following RP. Therefore, these patients may benefit from additional post-RP treatments and should be the subject of a prospective randomized clinical trial.

Empirical likelihood estimation for linear regression models with AR(p) error terms with numerical examples.

Linear regression models are useful statistical tools to analyze data sets in different fields. There are several methods to estimate the parameters of a linear regression model. These methods usually perform under normally distributed and uncorrelated errors. If error terms are correlated the Conditional Maximum Likelihood (CML) estimation method under normality assumption is often used to estimate the parameters of interest. The CML estimation method is required a distributional assumption on error terms. However, in practice, such distributional assumptions on error terms may not be plausible. In this paper, we propose to estimate the parameters of a linear regression model with autoregressive error term using Empirical Likelihood (EL) method, which is a distribution free estimation method. A small simulation study is provided to evaluate the performance of the proposed estimation method over the CML method. The results of the simulation study show that the proposed estimators based on EL method are remarkably better than the estimators obtained from CML method in terms of mean squared errors (MSE) and bias in almost all the simulation configurations. These findings are also confirmed by the results of the numerical and real data examples.

Validating the Turkish version of the Weinstein noise sensitivity scale: effects of age, sex, and education level

Background/aim: Subjective noise sensitivity (SNS) is not only one of the most important predictors of perceived noise annoyance for the subjects exposed to the noise, but also strongly related with some psychological conditions and poor health perception of the subjects. Weinstein's Noise Sensitivity Scale (WNSS) is widely used for measuring of SNS. Materials and methods: In this study we adapted WNSS to Turkish (Tr-WNSS) and evaluated its psychometric properties and effect of age, sex and education level on SNS. Results: The study included 105 males and 105 female subjects between 18 and 55 years of age. Conclusion: Our data demonstrated that Tr-WNSS was a reliable, valid, and invariant scale for the Turkish population, and not affected by sex, age and education level.