Artificial intelligence assisted patient blood and urine droplet pattern analysis for non-invasive and accurate diagnosis of bladder cancer.

Bladder cancer is one of the most common cancer types in the urinary system. Yet, current bladder cancer diagnosis and follow-up techniques are time-consuming, expensive, and invasive. In the clinical practice, the gold standard for diagnosis remains invasive biopsy followed by histopathological analysis. In recent years, costly diagnostic tests involving the use of bladder cancer biomarkers have been developed, however these tests have high false-positive and false-negative rates limiting their reliability. Hence, there is an urgent need for the development of cost-effective, and non-invasive novel diagnosis methods. To address this gap, here we propose a quick, cheap, and reliable diagnostic method. Our approach relies on an artificial intelligence (AI) model to analyze droplet patterns of blood and urine samples obtained from patients and comparing them to cancer-free control subjects. The AI-assisted model in this study uses a deep neural network, a ResNet network, pre-trained on ImageNet datasets. Recognition and classification of complex patterns formed by dried urine or blood droplets under different conditions resulted in cancer diagnosis with a high specificity and sensitivity. Our approach can be systematically applied across droplets, enabling comparisons to reveal shared spatial behaviors and underlying morphological patterns. Our results support the fact that AI-based models have a great potential for non-invasive and accurate diagnosis of malignancies, including bladder cancer.

Effect of non-thermal plasma treatment and resin cements on the bond strength of zirconia ceramics with different yttria concentrations.

OBJECTIVES: To investigate the effect of different surface treatments and resin cements on the shear bond strength of zirconia ceramics with different yttria concentrations. METHODS: Zirconia blocks characterized by different yttria concentrations [Vita YZ HT (HT), Vita YZ ST (ST) and Vita YZ XT (XT)] were used to prepare disc-shaped specimens (n=252). Specimens prepared to investigate shear bond strength (SBS), water contact angle and surface roughness (Ra) were divided into four subgroups; control (C), sandblasting (S), sandblasting + nonthermal plasma treatment (SNTP) and nonthermal plasma treatment (NTP). For SBS testing, specimens were further divided into two groups (n=108) according to the luting cement used [Panavia F2.0 (P) and Rely X U200 (R)]. The water contact angles were determined by sessile drop technique and Ra was analyzed with optical profilometer. SBS tests were performed in a universal testing machine at a crosshead speed of 0.5 mm/min. The data sets were statistically analyzed with two and three-way ANOVAs followed by post-hoc comparisons (α=0.05). RESULTS: The water contact angle and Ra data were significantly affected by surface treatments. The mean Ra values of ST and XT were significantly lower than HT for the surface treatment groups of C and NTP. The SBS values were significantly different among the groups subjected to different surface treatments. The mean SBS values of surface treatment groups (S, SNTP and NTP) when cemented with R were significantly higher than the groups of C (p<0.05). CONCLUSIONS: For the tested zirconia ceramics with different yttria concentrations, non-thermal plasma activation helps to improve SBS and is a promising tool in practical use.

Pressure Injury Prevalence and Risk Factors: A National Multicenter Analytical Study.

PURPOSE: The purpose of this study was to determine the point prevalence (PP) of general pressure injuries (PIs), hospital-acquired PIs, PI-related risk factors, and PI preventive interventions performed by nurses. DESIGN: Descriptive, multicenter, prospective, analytical study. SUBJECTS AND SETTING: The sample comprised 5088 patients cared for in 13 hospitals in 12 geographic regions of Turkey. Data were collected between November 5, 2018, and July 17, 2019. METHODS: The study was carried out in 2 stages. First, nurses who collected data were trained in the diagnosis of PI, risk assessment, staging, and prevalence studies, and informed about the purpose and methods of the study, including data collection. Second, nurses and researchers who had received training related to data collection for this study conducted a PP study for PIs in their inpatient clinics using the ASSIST II method. The PI Prevalence Study Tool and the Braden Scale for Predicting Pressure Sore Risk were also used during data collection. RESULTS: The PP of general PIs was 9.5%; the prevalence of PIs with hospitalization in intensive care units was 43.2%; medical device-related pressure injuries prevalence was 10.7%. We found that 65.1% of the PIs were acquired after hospital admission. CONCLUSIONS: Similarities exist between PI prevalence in Turkey and reported PI prevalence rates worldwide. However, the prevalence of nosocomial PIs related to intensive care units and the prevalence of all nosocomial injuries were higher than rates previously reported. Based on results, there is a need to develop strategies to reduce the prevalence of nosocomial PIs.

Association of ACTN3 R577X Polymorphism with Elite Basketball Player Status and Training Responses.

The α-actinin-3 (ACTN3) gene rs1815739 (C/T, R577X) polymorphism is a variant frequently associated with athletic performance among different populations. However, there is limited research on the impact of this variant on athlete status and physical performance in basketball players. Therefore, the aim of this study was twofold: (1) to determine the association of ACTN3 rs1815739 polymorphism with changes in physical performance in response to six weeks of training in elite basketball players using 30 m sprint and Yo-Yo Intermittent Recovery Test Level 2 (IR 2) tests, and (2) to compare ACTN3 genotype and allelic frequencies between elite basketball players and controls. The study included a total of 363 individuals, comprising 101 elite basketball players and 262 sedentary individuals. Genomic DNA was isolated from oral epithelial cells or leukocytes, and genotyping was performed by real-time PCR using KASP genotyping method or by microarray analysis. We found that the frequency of the ACTN3 rs1815739 XX genotype was significantly lower in basketball players compared to controls (10.9 vs. 21.4%, p = 0.023), suggesting that RR/RX genotypes were more favorable for playing basketball. Statistically significant (p = 0.045) changes were observed in Yo-Yo IRT 2 performance measurement tests in basketball players with the RR genotype only. In conclusion, our findings suggest that the carriage of the ACTN3 rs1815739 R allele may confer an advantage in basketball.

Acute effect of moderate and high-intensity interval exercises on asprosin and BDNF levels in inactive normal weight and obese individuals.

This study aimed to examine the acute effects of moderate-intensity aerobic and high-intensity interval exercise protocols on Asprosin and Brain-Derived Neurotrophic Factor (BDNF) levels in inactive normal weight and obese individuals. A total of 20 male individuals aged 18-65 years, ten normal weight (NW) (Body Mass Index (BMI): 18.5-24.99 kg/m2) and 10 obese (Ob) (BMI: 24.99-35.00 kg/m2) participated in this study, voluntarily. Moderate aerobic exercise (AE) (main circuit 30 min, between 40 and 59% of Heart Rate Reserve: HRR) and High-Intensity Interval exercise (HIIE) running protocols (main circuit 20 min, between 75 and 90% of the HRR for 1 min*10 times, and 1-min active rest at 30% of the HRR) was applied to the volunteer participants in the morning hours (08.00-10.00 a.m.), following the night fasting (at least 8-10 h) for at least 3 days between each other. Blood samples were collected from the participants before and immediately after each exercise protocol, and serum asprosin and BDNF hormone levels were determined by Enzyme-Linked Immunosorbent Assay" method. Basal serum asprosin was found to be significantly higher in the Ob group compared to the NW group (p < .001), while the basal serum BDNF hormone was found to be lower (p < 0.05). It was observed that the serum asprosin level of both groups decreased significantly after both AE and HIIE protocols (p < 0.05). In addition, there was a significantly higher decrease in serum asprosin level in the Ob group compared to the NW group after HIIE protocol. For the Ob group, serum BDNF level increased considerably after HIIE protocol compared to AE protocol (p < 0.05). Serum asprosin was found to be higher in the Ob group, while the serum BDNF was found to be lower. In addition, the acute exercises of different intensity significantly affected hormones that regulate appetite metabolism. In particular, it was observed that the HIIE protocol had a greater effect on the regulation of appetite (hunger-satiety) in the Ob group. This result can be taken into account when planning training programs for these individuals.

Four Human Mpox Cases from Turkey.

Human mpox (formerly monkeypox) disease has recently been reported in a number of European countries among individuals with no history of international travel or animal contact, causing global epidemic concerns. We describe the demographic, clinical characteristics, and laboratory data of four male patients with mpox disease, three of whom were human immunodeficiency virus (HIV)-positive, and one who was HIV-negative but had type 1 diabetes mellitus and a recent history of urological surgery. The HIV-negative patient attracted interest because he had no history of suspected sexual contact; however, he used shared bathrooms and towels at work, which could explain the potential transmission route. The remaining three male patients engaged in sexual activity with men recently. All four patients had prodromal symptoms such as short-term fever, myalgia, or fatigue, followed by a vesicular-pustular rash that began in the genital area, and two also had lesions on other parts of their bodies. Mpox is not generally considered in the differential diagnosis intitally because it is rare in Turkey; however, the diagnosis should be considered in patients with pustular umbilicated lesions and a history of risky sexual behavior.

Prospective Cohort Study of Incidence and Risk Factors for Catheter-associated Urinary Tract Infections in 212 Intensive Care Units of Nine Middle Eastern Countries.

Objectives: To identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in nine Middle Eastern countries. Methods: We conducted a prospective cohort study between 1 January 2014 and 2 December 2022 in 212 intensive care units (ICUs) of 67 hospitals in 38 cities in nine Middle Eastern countries (Bahrain, Egypt, Jordan, Kuwait, Lebanon, Morocco, Saudi Arabia, Turkey, and the UAE). To estimate CAUTI incidence, we used the number of UC days as denominator and the number of CAUTIs as numerator. To estimate CAUTI RFs, we analyzed the following 10 variables using multiple logistic regression: patient sex, age, length of stay (LOS) before CAUTI acquisition, UC-days before CAUTI acquisition, UC-device utilization (DU) ratio, hospitalization type, ICU type, facility-ownership, country income level classified by World Bank, and time period. Results: Among 50 637 patients hospitalized for 434 523 patient days, there were 580 cases of acquired CAUTIs. The pooled CAUTI rate per 1000 UC days was 1.84. The following variables were independently associated with CAUTI: age, rising risk 1.0% yearly (adjusted odds ratio [aOR] = 1.01, 95% CI: 1.01-1.02; p < 0.0001); female sex (aOR = 1.31, 95% CI: 1.09-1.56; p < 0.0001); LOS before CAUTI acquisition, rising risk 6.0% daily (aOR = 1.06, 95% CI: 1.05-1.06; p < 0.0001); and UC/DU ratio (aOR = 1.11, 95% CI: 1.06-1.14; p < 0.0001). Patients from lower-middle-income countries (aOR = 4.11, 95% CI: 2.49-6.76; p < 0.0001) had a similar CAUTI risk to the upper-middle countries (aOR = 3.75, 95% CI: 1.83-7.68; p < 0.0001). The type of ICU with the highest risk for CAUTI was neurologic ICU (aOR = 27.35, 95% CI: 23.03-33.12; p < 0.0001), followed by medical ICU (aOR = 6.18, 95% CI: 2.07-18.53; p < 0.0001) when compared to cardiothoracic ICU. The periods 2014-2016 (aOR = 7.36, 95% CI: 5.48-23.96; p < 0.001) and 2017-2019 (aOR = 1.15, 95% CI: 3.46-15.61; p < 0.001) had a similar risk to each other, but a higher risk compared to 2020-2022. Conclusions: The following CAUTI RFs are unlikely to change: age, sex, ICU type, and country income level. Based on these findings, it is suggested to focus on reducing LOS, UC/DU ratio, and implementing evidence-based CAUTI prevention recommendations.

The Privacy Consciousness of Undergraduate Students: Comparison Between Turkey and Japan.

AIM: This study was designed to compare the privacy consciousness of undergraduate students in Turkey and Japan. METHOD: A comparative cross-sectional study was carried out. First-year undergraduate students at a university in Turkey (n = 235) and a university in Japan (n = 242) voluntarily participated in the study. Data were collected via a web-based structured questionnaire, using the Descriptive Characteristics Form and the Privacy Consciousness Scale, between November and December 2020. Written approval was obtained from the universities and the ethics board. Written informed consent was obtained from all participants. RESULTS: The privacy consciousness of the Turkish students was significantly higher than that of the Japanese students (p < .05). CONCLUSION: Privacy consciousness can be affected by individual, social, and cultural value differences, beliefs, and perceptions. It is suggested that similar studies be conducted with a greater number of samples and between different countries.

Transcriptional Factor Repertoire of Breast Cancer in 3D Cell Culture Models.

Intratumor heterogeneity of breast cancer is driven by extrinsic factors from the tumor microenvironment (TME) as well as tumor cell-intrinsic parameters including genetic, epigenetic, and transcriptomic traits. The extracellular matrix (ECM), a major structural component of the TME, impacts every stage of tumorigenesis by providing necessary biochemical and biomechanical cues that are major regulators of cell shape/architecture, stiffness, cell proliferation, survival, invasion, and migration. Moreover, ECM and tissue architecture have a profound impact on chromatin structure, thereby altering gene expression. Considering the significant contribution of ECM to cellular behavior, a large body of work underlined that traditional two-dimensional (2D) cultures depriving cell-cell and cell-ECM interactions as well as spatial cellular distribution and organization of solid tumors fail to recapitulate in vivo properties of tumor cells residing in the complex TME. Thus, three-dimensional (3D) culture models are increasingly employed in cancer research, as these culture systems better mimic the physiological microenvironment and shape the cellular responses according to the microenvironmental cues that will regulate critical cell functions such as cell shape/architecture, survival, proliferation, differentiation, and drug response as well as gene expression. Therefore, 3D cell culture models that better resemble the patient transcriptome are critical in defining physiologically relevant transcriptional changes. This review will present the transcriptional factor (TF) repertoire of breast cancer in 3D culture models in the context of mammary tissue architecture, epithelial-to-mesenchymal transition and metastasis, cell death mechanisms, cancer therapy resistance and differential drug response, and stemness and will discuss the impact of culture dimensionality on breast cancer research.

Medicolegal evaluation in terms of physical abuse of children aged 0-3 years presenting at the emergency department with brain hemorrhage.

BACKGROUND: Physical abuse of children covers all types of non-accidental and preventable physical violence and injury perpetrated by the caregiver. METHODS: The study included children in the 0-3 years age group who presented at the Emergency Department (ED) with the finding of intracranial hemorrhage during the 5-year period of 2017-2021. These children were evaluated retrospectively, and findings that should be considered were revealed. RESULTS: In the 32 cases included in the study, the most common cranial finding was subdural hematoma, and the most common extracranial finding was ecchymoses. Presentation at the ED was seen to be 2 days after the trauma in 9.37% of the cases. CONCLUSION: Any physician who encounters findings related to physical abuse of a child must make a forensic and social services report. Physicians who do not make the necessary reports or act to the contrary have both a legal and moral responsibility in the subsequent process.

Impact of tailored training about pressure injuries on nurses' knowledge levels and pressure injury point prevalence: The case of Turkey.

AIM: This study was conducted to determine the impact of tailored training provided to nurses for preventing pressure injuries (PIs) on nurses' knowledge levels and the PI point prevalence (PP). MATERIALS AND METHODS: This interventional study was carried out in a university hospital with a bed capacity of 1114 in an urban center in Turkey. Ethics committee approval (28.06.2018/31) and institutional permission were obtained for the study, in addition to the nurses' written, informed consent. The study was completed in three stages. In the first stage an initial PP study was conducted in the clinics with the participation of the nurses and the members of the research team (n = 422 patients). In the second stage the knowledge levels of 194 nurses were measured before training was given on following-up and preventing PIs. The nurses then participated in the tailored training and their knowledge levels were re-measured afterwards. All the nurses were given individual advice related to the prevention of PIs for 30 days after they had completed the training. In the third stage a second PP study was conducted four months after the first PP study (n = 454 patients). The data were collected using the Pressure Injury Prevalence Form, the Braden Pressure Ulcer Risk Assessment Tool and the Knowledge Level Measurement Form. Descriptive values, the paired samples t-test, Pearson's chi-squared test and Fisher's Exact test were used to evaluate the data. RESULTS: The nurses' pretest mean knowledge score was 55.36% ± 14.40 and their posttest mean score was 69.92% ± 9.73. The difference between these scores was statistically significant (p < 0.05). The study found no significant difference between the first PP ratio and the second PP ratio (p > 0.05), and the nurses were better able to evaluate skin and PIs after the training. CONCLUSION: The study determined that the tailored training given to the nurses increased their knowledge; however, it had no impact on the PP after four months. It is recommended that any training programs using this model be continued and that PP studies of institutions be conducted annually.

International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2013-2018, Adult and Pediatric Units, Device-associated Module.

BACKGROUND: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific. METHODS: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied. RESULTS: We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated urinary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeruginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases. CONCLUSIONS: DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them.

MITF-MIR211 axis is a novel autophagy amplifier system during cellular stress.

Macroautophagy (autophagy) is an evolutionarily conserved recycling and stress response mechanism. Active at basal levels in eukaryotes, autophagy is upregulated under stress providing cells with building blocks such as amino acids. A lysosome-integrated sensor system composed of RRAG GTPases and MTOR complex 1 (MTORC1) regulates lysosome biogenesis and autophagy in response to amino acid availability. Stress-mediated inhibition of MTORC1 results in the dephosphorylation and nuclear translocation of the TFE/MITF family of transcriptional factors, and triggers an autophagy- and lysosomal-related gene transcription program. The role of family members TFEB and TFE3 have been studied in detail, but the importance of MITF proteins in autophagy regulation is not clear so far. Here we introduce for the first time a specific role for MITF in autophagy control that involves upregulation of MIR211. We show that, under stress conditions including starvation and MTOR inhibition, a MITF-MIR211 axis constitutes a novel feed-forward loop that controls autophagic activity in cells. Direct targeting of the MTORC2 component RICTOR by MIR211 led to the inhibition of the MTORC1 pathway, further stimulating MITF translocation to the nucleus and completing an autophagy amplification loop. In line with a ubiquitous function, MITF and MIR211 were co-expressed in all tested cell lines and human tissues, and the effects on autophagy were observed in a cell-type independent manner. Thus, our study provides direct evidence that MITF has rate-limiting and specific functions in autophagy regulation. Collectively, the MITF-MIR211 axis constitutes a novel and universal autophagy amplification system that sustains autophagic activity under stress conditions. Abbreviations: ACTB: actin beta; AKT: AKT serine/threonine kinase; AKT1S1/PRAS40: AKT1 substrate 1; AMPK: AMP-activated protein kinase; ATG: autophagy-related; BECN1: beclin 1; DEPTOR: DEP domain containing MTOR interacting protein; GABARAP: GABA type A receptor-associated protein; HIF1A: hypoxia inducible factor 1 subunit alpha; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPKAP1/SIN1: mitogen-activated protein kinase associated protein 1; MITF: melanogenesis associated transcription factor; MLST8: MTOR associated protein, LST8 homolog; MRE: miRNA response element; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR complex 2; PRR5/Protor 1: proline rich 5; PRR5L/Protor 2: proline rich 5 like; RACK1: receptor for activated C kinase 1; RPTOR: regulatory associated protein of MTOR complex 1; RICTOR: RPTOR independent companion of MTOR complex 2; RPS6KB/p70S6K: ribosomal protein S6 kinase; RT-qPCR: quantitative reverse transcription-polymerase chain reaction; SQSTM1: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TFE3: transcription factor binding to IGHM enhancer 3; TFEB: transcription factor EB; TSC1/2: TSC complex subunit 1/2; ULK1: unc-51 like autophagy activating kinase 1; UVRAG: UV radiation resistance associated; VIM: vimentin; VPS11: VPS11, CORVET/HOPS core subunit; VPS18: VPS18, CORVET/HOPS core subunit; WIPI1: WD repeat domain, phosphoinositide interacting 1.

Cloning of Autophagy-Related MicroRNAs.

Autophagy is a cellular survival pathway that is necessary for the degradation of cellular constituents such as long-lived proteins and damaged organelles. Conditions resulting in cellular stress such as starvation or hypoxia might activate autophagy. Being at the crossroads of various cellular response pathways, dysregulation of autophagy might result in pathological states including cancer and neurodegenerative diseases. Autophagy has also been shown to participate in stemness. MicroRNAs were introduced as novel regulators of autophagy, and accumulating results underlined the fact that they constituted an important layer of biological control mechanism on the autophagic activity.MicroRNAs are protein noncoding small RNAs that control cellular levels of transcripts and proteins through posttrancriptional mechanisms. Novel miRNAs in human and mouse genomes are yet to be identified. Considering the emerging role of autophagy in health and disease, identification of novel autophagy-regulating miRNAs and determination of relations between miRNA expression and physiological and pathological conditions might contribute to a better understanding of mechanisms governing health and disease. High-throughput techniques were developed for miRNA profiling, yet for a thorough characterization and miRNA target determination, miRNA cloning remains as an important step. Here, we describe a modified miRNA cloning method for the characterization of novel autophagy-regulating miRNAs.

The effect of unilateral forced nostril breathing on sleep in healthy right-handed men: a preliminary report.

PURPOSE: Although we spend about one-third of our lives in sleep and recognize its necessity for good health, sleep has only been partially elucidated in the last century. The nasal cycle of congestion and decongestion during sleep has various effects on human physiology. The aim of the present study was to investigate the effect of unilateral forced nostril breathing on sleep. METHODS: Twenty-one healthy male volunteers aged 18-24 years were included in the study. Only individuals with right-hand dominance were included. Subjects were observed during sleep for three nights under different conditions: no obstruction (normal sleep) on the first night, right nasal obstruction on the second night, and left nasal obstruction on the third night. RESULTS: The main findings of our study are that sleep efficiency, NREM stage III, and total sleep duration were greater during left nasal obstruction (right nostril dominant respiration), while apnea-hypopnea index (AHI), frequency of periodic limb movements, and oxygen desaturation were higher during right nasal obstruction (left nostril dominant respiration). CONCLUSION: The nasal cycle has a significant impact on sleep which is reflected in sleep recordings. Our result supports that nasal obstructions, due to deviations, concha hypertrophy, or congestion/decongestion, might affect the physiology of respiration and sleep. Nasal obstruction should be taken into consideration when evaluating patients in sleep laboratories and further studies are required to elucidate the situation in the patients with nasal obstruction.

A window-based time series feature extraction method.

This study proposes a robust similarity score-based time series feature extraction method that is termed as Window-based Time series Feature ExtraCtion (WTC). Specifically, WTC generates domain-interpretable results and involves significantly low computational complexity thereby rendering itself useful for densely sampled and populated time series datasets. In this study, WTC is applied to a proprietary action potential (AP) time series dataset on human cardiomyocytes and three precordial leads from a publicly available electrocardiogram (ECG) dataset. This is followed by comparing WTC in terms of predictive accuracy and computational complexity with shapelet transform and fast shapelet transform (which constitutes an accelerated variant of the shapelet transform). The results indicate that WTC achieves a slightly higher classification performance with significantly lower execution time when compared to its shapelet-based alternatives. With respect to its interpretable features, WTC has a potential to enable medical experts to explore definitive common trends in novel datasets.

Autophagy-Regulating microRNAs and Cancer.

Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway that is responsible for the degradation of long-lived proteins, protein aggregates, as well as damaged organelles in order to maintain cellular homeostasis. Consequently, abnormalities of autophagy are associated with a number of diseases, including Alzheimers's disease, Parkinson's disease, and cancer. According to the current view, autophagy seems to serve as a tumor suppressor in the early phases of cancer formation, yet in later phases, autophagy may support and/or facilitate tumor growth, spread, and contribute to treatment resistance. Therefore, autophagy is considered as a stage-dependent dual player in cancer. microRNAs (miRNAs) are endogenous non-coding small RNAs that negatively regulate gene expression at a post-transcriptional level. miRNAs control several fundamental biological processes, and autophagy is no exception. Furthermore, accumulating data in the literature indicate that dysregulation of miRNA expression contribute to the mechanisms of cancer formation, invasion, metastasis, and affect responses to chemotherapy or radiotherapy. Therefore, considering the importance of autophagy for cancer biology, study of autophagy-regulating miRNA in cancer will allow a better understanding of malignancies and lead to the development of novel disease markers and therapeutic strategies. The potential to provide study of some of these cancer-related miRNAs were also implicated in autophagy regulation. In this review, we will focus on autophagy, miRNA, and cancer connection, and discuss its implications for cancer biology and cancer treatment.

Demographics, treatment and outcomes of atrial fibrillation in a developing country: the population-based TuRkish Atrial Fibrillation (TRAF) cohort.

AIMS: Although atrial fibrillation (AF) is increasingly common in developed countries, there is limited information regarding its demographics, co-morbidities, treatments and outcomes in the developing countries. We present the profile of the TuRkish Atrial Fibrillation (TRAF) cohort which provides real-life data about prevalence, incidence, co-morbidities, treatment, healthcare utilization and outcomes associated with AF. METHODS AND RESULTS: The TRAF cohort was extracted from MEDULA, a health insurance database linking hospitals, general practitioners, pharmacies and outpatient clinics for almost 100% of the inhabitants of the country. The cohort includes 507 136 individuals with AF between 2008 and 2012 aged >18 years who survived the first 30 days following diagnosis. Of 507 136 subjects, there were 423 109 (83.4%) with non-valvular AF and 84 027 (16.6%) with valvular AF. The prevalence was 0.80% in non-valvular AF and 0.28% in valvular AF; in 2012 the incidence of non-valvular AF (0.17%) was higher than valvular AF (0.04%). All-cause mortality was 19.19% (97 368) and 11.47% (58 161) at 1-year after diagnosis of AF. There were 35 707 (7.04%) ischaemic stroke/TIA/thromboembolism at baseline and 34 871 (6.87%) during follow-up; 11 472 (2.26%) major haemorrhages at baseline and 10 183 (2.01%) during follow-up, and 44 116 (8.69%) hospitalizations during the follow-up. CONCLUSION: The TRAF cohort is the first population-based, whole-country cohort of AF epidemiology, quality of care and outcomes. It provides a unique opportunity to study the patterns, causes and impact of treatments on the incidence and outcomes of AF in a developing country.

Predictors of sinus rhythm after electrical cardioversion of atrial fibrillation: results from a data mining project on the Flec-SL trial data set.

AIMS: Data mining is the computational process to obtain information from a data set and transform it for further use. Herein, through data mining with supportive statistical analyses, we identified and consolidated variables of the Flecainide Short-Long (Flec-SL-AFNET 3) trial dataset that are associated with the primary outcome of the trial, recurrence of persistent atrial fibrillation (AF) or death. METHODS AND RESULTS: The 'Ranking Instances by Maximizing the Area under the ROC Curve' (RIMARC) algorithm was applied to build a classifier that can predict the primary outcome by using variables in the Flec-SL dataset. The primary outcome was time to persistent AF or death. The RIMARC algorithm calculated the predictive weights of each variable in the Flec-SL dataset for the primary outcome. Among the initial 21 parameters, 6 variables were identified by the RIMARC algorithm. In univariate Cox regression analysis of these variables, increased heart rate during AF and successful pharmacological conversion (PC) to sinus rhythm (SR) were found to be significant predictors. Multivariate Cox regression analysis revealed successful PC as the single relevant predictor of SR maintenance. The primary outcome risk was 3.14 times (95% CI:1.7-5.81) lower in those who had successful PC to SR than those who needed electrical cardioversion. CONCLUSIONS: Pharmacological conversion of persistent AF with flecainide without the need for electrical cardioversion is a powerful and independent predictor of maintenance of SR. A strategy of flecainide pretreatment for 48 h prior to planned electrical cardioversion may be a useful planning of a strategy of long-term rhythm control.

Data mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial: 'exposing the invisible'.

AIMS: The aims of this study include (i) pursuing data-mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial dataset containing atrial fibrillation (AF) burden scores of patients with many clinical parameters and (ii) revealing possible correlations between the estimated risk factors of AF and other clinical findings or measurements provided in the dataset. METHODS: Ranking Instances by Maximizing the Area under a Receiver Operating Characteristics (ROC) Curve (RIMARC) is used to determine the predictive weights (Pw) of baseline variables on the primary endpoint. Chi-square automatic interaction detector algorithm is performed for comparing the results of RIMARC. The primary endpoint of the ANTIPAF-AFNET 2 trial was the percentage of days with documented episodes of paroxysmal AF or with suspected persistent AF. RESULTS: By means of the RIMARC analysis algorithm, baseline SF-12 mental component score (Pw= 0.3597), age (Pw= 0.2865), blood urea nitrogen (BUN) (Pw= 0.2719), systolic blood pressure (Pw= 0.2240), and creatinine level (Pw= 0.1570) of the patients were found to be predictors of AF burden. Atrial fibrillation burden increases as baseline SF-12 mental component score gets lower; systolic blood pressure, BUN and creatinine levels become higher; and the patient gets older. The AF burden increased significantly at age >76. CONCLUSIONS: With the ANTIPAF-AFNET 2 dataset, the present data-mining analyses suggest that a baseline SF-12 mental component score, age, systolic blood pressure, BUN, and creatinine level of the patients are predictors of AF burden. Additional studies are necessary to understand the distinct kidney-specific pathophysiological pathways that contribute to AF burden.