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Simple Summary: The prognosis of PCa at diagnosis is assessed by classification systems that aim to group homogenous sets of patients. However, great heterogeneity exists within these risk groups, in terms of prognostic factors and treatment options. The aim of this study was to assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy at a high-volume tertiary referral center. Objectives: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained institutional database. Adverse tumor grade was defined as pathology ISUP grade group > 2. Disease progression was defined as a biochemical recurrence event and/or local recurrence and/or distant metastases. Associations were assessed by Cox's proportional hazards and logistic regression model. Results: Between January 2013 and October 2020, the study evaluated a population of 289 patients, including 178 low-risk cases (61.1%) and 111 intermediate-risk subjects (38.4%); unfavorable tumor grade was detected in 82 cases (28.4%). PCa progression, which occurred in 29 patients (10%), was independently predicted by adverse tumor grade and biopsy ISUP grade group 2, with the former showing stronger associations (hazard ratio, HR = 4.478; 95% CI: 1.840–10.895; p = 0.001) than the latter (HR = 2.336; 95% CI: 1.057–5.164; p = 0.036). Older age and biopsy ISUP grade group 2 were independent clinical predictors of adverse tumor grade, associated with larger tumors that eventually presented non-organ-confined disease. Conclusions: In a very favorable PCa patient population, adverse tumor grade was an unfavorable prognostic factor for disease progression. Active surveillance in very favorable intermediate-risk patients is still a hazard, so molecular and genetic testing of biopsy specimens is needed. [ABSTRACT FROM AUTHOR]

In the first part of this article, we discuss and generalize the complete convergence introduced by Hsu and Robbins in 1947 to the r-complete convergence introduced by Tartakovsky in 1998. We also establish its relation to the r-quick convergence first introduced by Strassen in 1967 and extensively studied by Lai. Our work is motivated by various statistical problems, mostly in sequential analysis. As we show in the second part, generalizing and studying these convergence modes is important not only in probability theory but also to solve challenging statistical problems in hypothesis testing and changepoint detection for general stochastic non-i.i.d. models. [ABSTRACT FROM AUTHOR]

Simple Summary: The number of pigmented moles is the most important risk factor for melanoma. This "real world" study conducted in 25 Australian childcare centers is the first to show it is possible to prevent a significant proportion of pigmented moles in young Caucasian children by dressing them in UPF 30-50+ clothing that covers at least half their body on a daily basis. Regularly wearing this clothing for 3.5 years was sufficient to prevent almost one-quarter of the pigmented moles that young children developed on their skin. This should, by implication, reduce their risk of developing melanoma in the future. Primary health care providers should stress the importance of garment coverage when recommending sun protection for children and should lobby for all sun-protective clothing standards to assess and report garment coverage, in addition to the transmission of ultraviolet radiation through the fabric (reported as UPF), on clothing labels and packaging for children's clothing, including school uniforms. Numerous pigmented moles are associated with sun exposure and melanomarisk. This cluster randomized controlled trial aimed to determine if sun-protective clothing could prevent a significant proportion of the moles developing in young children (ACTRN12617000621314; Australian New Zealand Clinical Trials Registry. Twenty-five childcare centers in Townsville (19.25° S), Australia, were matched on shade provision and socioeconomic status. One center from each pair was randomized to the intervention arm and the other to the control arm. Children at 13 intervention centers wore study garments and legionnaire hats at childcare and received sun-protective swimwear and hats for home use, while children at the 12 control centers did not. The 1–35-month-old children (334 intervention; 210 control) were examined for moles at baseline (1999–2002) and were re-examined annually for up to 4 years. Both groups were similar at baseline. Children at intervention centers acquired fewer new moles overall (median 12.5 versus 16, p = 0.02; 0.46 versus 0.68 moles/month, p = 0.001) and fewer new moles on clothing-protected skin (6 vs. 8; p = 0.021 adjusted for confounding and cluster sampling) than controls. Intervention children had 24.3% fewer new moles overall (26.5 versus 35) and 31.6% (13 versus 19) fewer moles on clothing-protected skin than controls after 3.5 years. Sunlight's influence on nevogenesis is mitigated when children regularly wear UPF 30-50+ clothing covering half their body, implying that increased clothing cover reduces melanoma risk. Sun-protective clothing standards should mandate reporting of the percentage of garment coverage for childrenswear. [ABSTRACT FROM AUTHOR]

In particular, the data allow us to calculate the I p i -value, which is defined as " I the probability under a specified statistical model that a statistical summary of the data would be equal to or more extreme than its observed value i " [[1]], and practically reflects the degree of data compatibility with the null hypothesis. (2) " I p-values do not measure the probability that the studied hypothesis is true, or the probability that the data were produced by random chance alone. i " They can only tell us how consistent the data are with the null hypothesis. Conventionally, if the I p i -value is lower than the 0.05 significance level, we reject the null hypothesis and accept the alternative hypothesis. At the beginning of our research training, we learned about hypothesis testing, I p i -values, and statistical inference. [Extracted from the article]

Simple Summary: Sodium butyrate (NaB) is a short-chain fatty acid produced by intestinal microbial fermentation of dietary fiber. It has been shown to be effective in inhibiting colorectal cancer (CRC), but the mechanism is not known. We verified the ability of NaB to induce ferroptosis and the effect on relevant genotypes in normal intestinal cells and colorectal tumor cells, respectively. Moreover, better inhibition of tumor cells was observed when NaB was combined with Erastin (a ferroptosis-positive drug), suggesting that NaB combined with Erastin might have a stronger anti-CRC effect. Colorectal cancer (CRC) is one of the most common malignancies, and effective treatment and prevention methods are lacking. Sodium butyrate (NaB) is a short-chain fatty acid produced by intestinal microbial fermentation of dietary fiber. It has been shown to be effective in inhibiting CRC, but the mechanism is not known. Methods: Human normal intestinal epithelial cell line FHT and colorectal tumor cell line HCT-116 were treated with NaB alone or in combination with different programmed cell death inhibitors. Cell activity was then assessed with MTT assays and PI staining; ferroptosis with Fe2+, glutathione (GSH), and lipid peroxidation assays; signaling pathway screening with PCR arrays; and CD44, SCL7A11, and GPX4 expression with Western blotting. A CD44-overexpressing HCT-116 cell line was constructed to determine the effect of the overexpression of CD44 on NaB-induced ferroptosis. The synergistic effect of co-treatment with NaB and Erastin was assessed by isobolographic analysis. Results: NaB induced apoptosis and ferroptosis in HCT-116 cells but only induced low-level apoptosis in FHC cells. Moreover, NaB significantly increased intracellular Fe2+ and promoted GSH depletion and lipid peroxidation in HCT-116 cells. Ferroptosis-related qPCR array analysis identified CD44/SLC7A11 as a potential effector molecular of NaB-induced ferroptosis. NaB significantly inhibited the expression of CD44 and SLC7A11 in mouse CRC tissues. A CD44 overexpressed HCT-116 cell line was used to verify that CD44/SLC7A11 was a key signaling pathway that NaB-induced GSH depletion, lipid peroxidation accumulation, and ferroptosis in HCT-116 cells. Examination of whether NaB can increase the effect of ferroptosis agents showed that NaB, in combination with Erastin, a ferroptosis inducer, further promoted HCT-116 cell death and increased changes of ferroptosis markers. Conclusions: Our results suggest that NaB induces ferroptosis in CRC cells through the CD44/SLC7A11 signaling pathway and has synergistic effects with Erastin. These results may provide new insights into CRC prevention and the combined use of NaB and ferroptosis-inducing agents. [ABSTRACT FROM AUTHOR]

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting. [ABSTRACT FROM AUTHOR]

Hereditary Tyrosinemia type 1 (HT1) is a metabolic liver disease caused by genetic defects of fumarylacetoacetate hydrolase (FAH), an enzyme necessary to complete the breakdown of tyrosine. The severe hepatic dysfunction caused by the lack of this enzyme is prevented by the therapeutic use of NTBC (2-[2-nitro-4-(trifluoromethyl)benzoyl] cyclohexane-1,3-dione). However despite the treatment, chronic hepatopathy and development of hepatocellular carcinoma (HCC) are still observed in some HT1 patients. Growing evidence show the important role of heat shock proteins (HSPs) in many cellular processes and their involvement in pathological diseases including cancer. Their survival-promoting effect by modulation of the apoptotic machinery is often correlated with poor prognosis and resistance to therapy in a number of cancers. Here, we sought to gain insight into the pathophysiological mechanisms associated with liver dysfunction and tumor development in a murine model of HT1. Differential gene expression patterns in livers of mice under HT1 stress, induced by drug retrieval, have shown deregulation of stress and cell death resistance genes. Among them, genes coding for HSPB and HSPA members, and for anti-apoptotic BCL-2 related mitochondrial proteins were associated with the hepatocarcinogenetic process. Our data highlight the variation of stress pathways related to HT1 hepatocarcinogenesis suggesting the role of HSPs in rendering tyrosinemia-affected liver susceptible to the development of HCC. [ABSTRACT FROM AUTHOR]

Background: Radioactive contamination and chemical pollution of the environment can affect the processes of carcinogenesis, including the formation of malignant neoplasms of the ovaries in women. We used the data of official state statistics for 2000–2020 to test the hypothesis about the effect of radioactive contamination (following the Chernobyl disaster) and chemical pollutants on the incidence of ovarian malignancies in the female population of the Bryansk region. Methods: A variety of statistical approaches were used to estimate the incidence of ovarian malignancies, including the Shapiro–Wilk test, Mann–Whitney U test, Spearman's rank correlation test and linear regression. Results: We did not establish statistically significant differences in the frequency of primary morbidity of women with malignant neoplasms of the ovaries, regardless of the environmental conditions of living. Furthermore, no significant correlations were found between the frequency of primary morbidity of ovarian malignancies, both with the level of contamination by Cesium-137 and Strontium-90, and air pollution with volatile organic compounds, carbon monoxide, sulfur dioxide and nitrogen oxides. A statistically significant increase in the long-term trend in the frequency of ovarian malignant neoplasms was revealed in the areas of chemical pollution (p = 0.02), however, in other territories, no statistically significant regularities were established. The forecast of the frequency of newly diagnosed malignant neoplasms of the ovaries on average in the Bryansk region shows an increase of 12.4% in 2020 in comparison with the real data for 2020, while the largest increase in predicted values is recorded in the territories of radioactive contamination (by 79.6%), and the least in the combined territories (by 6.9%). Conclusions: The results obtained indicate the need for further work to understand the trends in the presence/absence of independent and combined effects of pollutants and the growth of oncogynecological pathology from the perspective of assessing the distant and regional metastasis, histological and immunohistochemical profile of a specific malignant ovarian neoplasm with levels of environmental contamination. [ABSTRACT FROM AUTHOR]

This paper studies the statistical correlation in mechanical characteristics of class F fly ash based geopolymer concrete (CFGPC). Experimentally measured values of the compressive strength, elastic modulus and indirect tensile strength of CFGPC specimens made from class F fly ash (CFA) were presented and analyzed. The results were compared with those of corresponding ordinary Portland cement concrete (OPCC) using statistical hypothesis tests. Results illustrated that when possessing similar compressive and tensile strength, the elastic modulus for CFGPC is significantly lower than that of OPCC. The corresponding expressions recommended by standards for the case of OPCC is proved to be inaccurate when applied in the case of CFGPC. Statistical regression was used to identify tendencies and correlations within the mechanical characteristics of CFGPC, as well as the empirical equations for predicting tensile strength and elastic modulus of CFGPC from its compressive strength values. In conclusion, CFGPC and OPCC has significant differences in terms of the correlations between mechanical properties. The empirical equations obtained in this study could provide relatively accurate predictions on the mechanical behavior of CFGPC. [ABSTRACT FROM AUTHOR]