Genetic variants in FOXO3 are associated with longevity. Here, we assessed whether blood DNA methylation at FOXO3 was associated with cancer risk, survival, and mortality. We used data from eight prospective case–control studies of breast (n = 409 cases), colorectal (n = 835), gastric (n = 170), kidney (n = 143), lung (n = 332), prostate (n = 869), and urothelial (n = 428) cancer and B-cell lymphoma (n = 438). Case–control pairs were matched on age, sex, country of birth, and smoking (lung cancer study). Conditional logistic regression was used to assess associations between cancer risk and methylation at 45 CpGs of FOXO3 included on the HumanMethylation450 assay. Mixed-effects Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations with cancer survival (total n = 2286 deaths). Additionally, using data from 1088 older participants, we assessed associations of FOXO3 methylation with overall and cause-specific mortality (n = 354 deaths). Methylation at a CpG in the first exon region of FOXO3 (6:108882981) was associated with gastric cancer survival (HR = 2.39, 95% CI: 1.60–3.56, p = 1.9 × 10−5). Methylation at three CpGs in TSS1500 and gene body was associated with lung cancer survival (p < 6.1 × 10−5). We found no evidence of associations of FOXO3 methylation with cancer risk and mortality. Our findings may contribute to understanding the implication of FOXO3 in longevity.

An increasing number of studies have revealed that dysregulated lipid homeostasis is associated with the pathological processes that lead to Alzheimer’s disease (AD). If changes in key lipid species could be detected in the periphery, it would advance our understanding of the disease and facilitate biomarker discovery. Global lipidomic profiling of sera/blood however has proved challenging with limited disease or tissue specificity. Small extracellular vesicles (EV) in the central nervous system, can pass the blood‐brain barrier and enter the periphery, carrying a subset of lipids that could reflect lipid homeostasis in brain. This makes EVs uniquely suited for peripheral biomarker exploration.

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease and is becoming a major public health problem. NAFLD has been recognized as a hepatic manifestation of metabolic syndrome, associated with systemic diseases such as cardiovascular disease (CVD) and chronic kidney disease (CKD). Objective: The aim of this study was to examine the role of serum LFT parameters and renal function parameters as predictors of unmanifested liver disease. Methods: In this study, the presence of possible liver disease detected by biochemical parameters and confirmed by Transient Liver Elastography (TE) in a group of patients with different stages of chronic kidney disease (CKD) was investigated. Patients with various stages of CKD were divided into five subgroups regarding aetiology: nephroangiosclerosis, diabetic nephropathy, glomerulonephritis and pyelonephritis, autoimmune kidney disease, and polycystic and another morphological kidney disease. Liver stiffness was used to quantify liver fibrosis while Controlled attenuation parameter (CAP) was used to quantify liver steatosis. Functional liver tests and biochemical parameters of kidney function were measured in all patients. Results: Statistical analysis used in this study was a decision tree as a predictive model to map observed variables resulting in the conclusion about outcomes. The application of existing laboratory parameters, in combination with other parameters in presence of the defined etiological factors of kidneys diseases, indicate development of hepatic diseases. Higher values of phosphorus and low values of ferritin in patients with autoimmune kidney disease, and polycystic and another morphological kidney disease, expresses steatosis of the hepatic parenchyma. Conclusion: In contrary, low values of phosphorus and higher values of ferritin in patients with nephroangiosclerosis, diabetic nephropathy, glomerulonephritis and pyelonephritis, are in a favour steatosis of the hepatic parenchyma. Serum values of phosphorus and ferritin are valuable predictors of the liver disease in patients with end-stage kidney diseases of different aetiology.

Apocrine carcinoma of the breast is a rare malignancy. According to 2019 WHO classification, apocrine cellular features and a characteristic steroid receptor profile (Estrogen receptor (ER)-negative and androgen receptor (AR)-positive) define apocrine carcinoma. Her-2/neu protein expression is reported in ∼30-50% of apocrine carcinomas, while NGS analysis showed frequent PIK3CA/PTEN/AKT and TP53 mutations Followed by deregulation in the mitogen-activated protein kinase pathway components (mutations of KRAS, NRAS, BRAF). A recent miRNA study indicates various miRNAs (downregulated hsa-miR-145-5p and upregulated 14 miRNAs such as hsa-miR-182-5p, hsa-miR-3135b, and hsa-miR-4417) may target the commonly altered pathways in apocrine carcinomas such as ERBB2/HER2 and mitogen-activated protein kinase signaling pathway. Although AR expression is a hallmark of apocrine carcinoma, little is known regarding the efficacy/resistance to antiandrogens. Success of bicalutamide, a non-steroidal anti-androgen, was reported in a case of Her2-negative apocrine carcinoma. Two recent studies, however, described presence of anti-androgen resistance biomarkers (a splice variant ARv7 and AR/NCOA2 co-amplification) in a subset of AR+ apocrine carcinomas, cautioning the use of anti-androgens in AR+ triple-negative breast carcinomas. Apocrine carcinomas rarely show biomarkers predictive of response to immune checkpoint inhibitors (PD-L1 expression, MSI-H status, and TMB-high). Therefore, a comprehensive cancer profiling of apocrine carcinomas is necessary to identify potential therapeutic targets for a truly individualized treatment approach.

Background: Autism spectrum disorder (ASD) is a developmental disability, which is a biologically based neurodevelopmental disorder that affects a child’s social interaction and communication skills. Core deficits are identified in two domains: social communication/interaction and restrictive, repetitive patterns of behavior. Children and youth with ASD have service needs in behavioral, educational, health, leisure, family support, and other areas. Autism is a set of heterogeneous neurodevelopmental conditions, characterized by inability to acquire social skills, repetitive behaviors and failure of speech and nonverbal communication development. Objective: To examine frequency, correlation and predictivity of communication and language skills of autistic spectrum disorders (ASD) children and their parents’ emotions. Methods: The sample consisted of 80 participants who are parents of children with ASD. The study was performed using a questionnaire made out for this research. Three groups of variables were analyzed: parental emotions variables; child’s communication variables, child’s language variables. Statistical analysis was performed by SPSS, and included basic statistical parameters and multiple regression analysis. Results: The most common ways of communicate for children with ASD are: Allowing to cuddle; Recognizes familiar faces; and Makes it known when he needs help or wants an item. The most common language forms of children ASD are: Following simple instructions; Understanding connected words/phrases; Pronouncing single words; and Looking at when called by name. Parents of children with ASD expressed the greatest agreement with the following statements: “My child is more demanding than most other children”; “It seems to me that my child is very sensitive and easily upset”; “My child can’t do much of what he’s expected to know to do”, and “I often lack energy.” Conclusion: Parents of children with ASD proved that their children have significant delays in communication and language. Developed communication and language skills of the child with ASD are valid predictors of parents’ emotions/attitudes. Speech and language therapy work focused on developing the ASD child’s communication and language skills can be expected to improve parents’ emotions/attitudes.

Background: Neurogenic stuttering is a subtype of acquired stuttering, and it is characterized by disfluencies associated with acquired brain damage. Objective: To provide an insight into pathophysiology, symptomatology, differential diagnosis, assessment, and treatment of neurogenic stuttering through a critical review of the literature. Methods: Studies published during the past and recent years were searched and analyzed on neurogenic stuttering. Results: Neurogenic stuttering is a complex disorder. The pathophysiological mechanism of neurogenic stuttering is not yet fully understood. It appears with several neurological diseases and conditions, and the use of some drugs. Differential diagnosis of neurogenic and psychogenic stuttering is a challenge for clinicians. Treatment usually requires a joint effort from speech therapists and doctors, most often neurologists Conclusion: Although research on neurogenic stuttering can be found in the literature, the complexity of this disorder still requires detailed monitoring and studying to provide the best treatment for patients.

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Abstract This paper explores the role of knowledge visualization in facilitating decision-making in cultural heritage management. The paper addresses the issue in the specific context of stećci - the tombstones from medieval Bosnia inscribed on the UNESCO world heritage list. Grounded in the distant reading paradigm, the paper introduces a series of visualizations of spatial, temporal, architectural, iconographical, epigraphical, and impact analyses of stećci data. Together, these visualizations should enable decision-makers to gain an enhanced understanding and knowledge of this important cultural heritage. In turn, this should help them make better decisions regarding their protection and promotion.

Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.

Abstract The main aim of this paper is to explore the factors determining Microfinance institutions (MFIs) self-sufficiency. The data on selected variables for this research were obtained from the public MIX Market Database and cover the year of 2017. The empirical model is constructed with application of a Principal Component Analysis (PCA) and Logistic regression analysis. Sample is consisted of 342 MFIs from all around the world, with 21 independent variables grouped into eight factors/components, and OSS (operational self-sufficiency) as dependent variable. The obtained results suggest that higher revenue and MFIs profitability combined with decrease of credit risk lead to higher probability of MFI to be self-sufficient. These results also confirm widespread belief that MFIs will not be able to achieve their social goals without achieving sustainable profitability. In addition, results also confirm importance of MFIs core mission as with increase in outreach, probability of MFIs achieving self-sustainability also increases.