Known pathogenic gene variants and new candidates detected in sudden unexpected infant death using whole genome sequencing.

The purpose of this study is to gain insights into potential genetic factors contributing to the infant's vulnerability to Sudden Unexpected Infant Death (SUID). Whole Genome Sequencing (WGS) was performed on 144 infants that succumbed to SUID, and 573 healthy adults. Variants were filtered by gnomAD allele frequencies and predictions of functional consequences. Variants of interest were identified in 88 genes, in 64.6% of our cohort. Seventy-three of these have been previously associated with SIDS/SUID/SUDP. Forty-three can be characterized as cardiac genes and are related to cardiomyopathies, arrhythmias, and other conditions. Variants in 22 genes were associated with neurologic functions. Variants were also found in 13 genes reported to be pathogenic for various systemic disorders and in two genes associated with immunological function. Variants in eight genes are implicated in the response to hypoxia and the regulation of reactive oxygen species (ROS) and have not been previously described in SIDS/SUID/SUDP. Seventy-two infants met the triple risk hypothesis criteria. Our study confirms and further expands the list of genetic variants associated with SUID. The abundance of genes associated with heart disease and the discovery of variants associated with the redox metabolism have important mechanistic implications for the pathophysiology of SUID.

CRM1 expression: association with high prognostic value in laryngeal cancer.

BACKGROUND: Laryngeal cancer is a very common malignant tumor of the head and neck. While laryngeal cancer does not show any obvious early symptoms, it tends to have a poor prognosis in advanced clinical stages. Chromosome region maintenance 1 (CRM1) mediates the nuclear export of some RNAs, major and tumor suppressor proteins and has been associated with the pathogenesis of many tumors. However, the clinicopathological significance of CRM1 gene expression in laryngeal cancer has not been clarified yet. Therefore, this study aims to detect the expression of CRM1 in laryngeal cancer and to investigate its relationship with clinicopathological parameters and prognosis. METHODS: CRM1 expression in matched tumor and normal tissues obtained from 43 laryngeal cancer patients were evaluated intracellular for protein and mRNA levels by immunohistochemical staining (IHC), western-blot, and quantitative real-time RT-PCR (qRT-PCR), respectively. RESULTS: IHC, western-blot, and qRT-PCR analyses showed that CRM1 expression was significantly increased in laryngeal cancer tissue compared to normal tissue. Increased expression of CRM1 has been associated with poor prognostic clinicopathological features, including advanced tumor stage, increased tumor invasion, larger tumor size, positive lymph node metastasis, distant metastasis, and invasive histological type by IHC, western-blot, and qRT-PCR. Kaplan-Meier survival analysis showed that patients with high expression of CRM1 exhibited lower overall survival compared to those with low expression (Log-rank = 7.16, p = 0.007). According to the The Cancer Genome Atlas (TCGA) datasets, elevated CRM1 expression in head and neck cancer including cases of squamous cell laryngeal origin is associated with advanced tumor stage and histological grade (p > 0.05, for all). DISCUSSION: Consequently, CRM1 plays an important role in laryngeal cancer and may serve as an indicator and prognostic factor for poor overall survival in laryngeal cancer patients.

PKNOX2 expression and regulation in the bone marrow mesenchymal stem cells of Fanconi anemia patients and healthy donors.

HOX and TALE transcription factors are important regulators of development and homeostasis in determining cellular identity. Deregulation of this process may drive cancer progression. The aim of this study was to investigate the expression of these transcription factors in the bone marrow derived mesenchymal stem cells (BM-MSCs) of Fanconi anemia (FA) patients, which is a cancer-predisposing disease. Expression levels of HOX and TALE genes in BM-MSCs were obtained from FA patients and healthy donors by RT-qPCR and highly conserved expression levels were observed between patient and donor cells, except PKNOX2, which is a member of TALE class. PKNOX2 was significantly downregulated in FA cells compared to donors (P < 0.05). PKNOX2 expression levels did not change with diepoxybutane (DEB), a DNA crosslinking agent, in either donor or FA cells except one patient's with a truncation mutation of FANCA. A difference of PKNOX2 protein level was not obtained between FA patient and donor BM-MSCs by western blot analysis. When human TGF-ß1 (rTGF-ß1) recombinant protein was provided to the cultures, PKNOX2 as well as TGF-ß1 expression increased both in FA and donor BM-MSCs in a dose dependent manner. 5 ng/mL rTGF-ß stimulation had more dominant effect on the gene expression of donor BM-MSCs compared to FA cells. Decreased PKNOX2 expression in FA BM-MSCs may provide new insights into the molecular pathophysiology of the disease and TGF-ß1 levels of the microenvironment may be the cause of PKNOX2 downregulation.

The genetic variants of thymic stromal lymphopoietin protein in children with asthma and allergic rhinitis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is expressed by airway epithelial cells and plays a key role in immunological events in asthma. Data on the genetic variants of TSLP and its association with asthma and allergic rhinitis are scarce. We aimed to investigate the effects of the genetic variants of TSLP in children with asthma and allergic rhinitis. METHODS: The genetic variants of the TSLP gene were determined by sequencing 25 asthmatic and 25 healthy children. In an association study, a population of 506 asthmatics and 157 healthy controls was screened for the following single-nucleotide polymorphisms (SNPs): rs3806933 and rs2289276 in the promoter region; rs11466741, rs11466742, and rs2289278 in intron 2; rs10073816, rs11466749, and rs11466750 in exon 4, and rs11466754 in 3'-UTR. RESULTS: In Multifactor Dimensionality Reduction analysis, presence of the rs11466749 AA genotype with atopy was significantly associated with a diagnosis of asthma (testing set accuracy: 0.720 and cross validation: 9/10). Two functional SNPs showed a gender-specific association with allergy, i.e. the rs3806933 CC genotype with asthma in boys (p = 0.032, nonsignificant after multiple testing) and the rs2289276 CC genotype with higher eosinophil numbers in asthmatic girls (p = 0.003). The presence of allergic rhinitis in asthmatic children strengthened the association of the rs11466749 GG genotype with asthma (p = 0.001), and rs2289276 was significantly associated with lower FEV1 levels in asthmatics without allergic rhinitis (p = 0.003). CONCLUSION: Variants in the gene encoding the TSLP protein may have differential effects on asthma phenotypes depending on gender, atopy, and the presence of allergic rhinitis.

Functional disability in Alzheimer disease: a validation study of the Turkish version of the disability assessment for dementia scale.

This study aimed to determine the reliability and validity of the Turkish version of Disability Assessment for Dementia (DAD) scale in the Turkish elderly population with Alzheimer disease (AD). The DAD scale was administered to the primary caregivers of 157 patients (age 77.7 ± 6.8 years) with AD. The Turkish version of the DAD scale showed high internal consistency (Cronbach α = .942), excellent test-retest, and interrater reliability (intraclass correlation coefficient [ICC] = 0.996 and ICC = 0.994, respectively). The DAD scale was significantly correlated with activities of daily living (ADL; Modified Older Americans Research Survey ADL) and instrumental activities of daily living (IADL; Lawton and Brody IADL) scales (r = .89, P < .001 and r = .90, P < .001). Disability Assessment for Dementia had a high negative correlation with the Global Deterioration Scale (GDS; r = -.880, P < .001). Post hoc comparisons with Tukey test showed significant differences in the mean DAD scores in different GDS stages. Construct validity was estimated using total score correlation analyses between the standardized Mini-Mental State Examination (MMSE) and the DAD scale. Results revealed high and significant correlation between MMSE score and DAD scale (r = .812, P < .001). The results of multivariate analysis showed that DAD score was not correlated with gender, education, and age. The DAD total score was affected mostly by GDS, MMSE, and duration of the disease. Turkish version of the DAD scale was found to be a reliable and valid instrument to assess functional disability in Turkish elderly patients with AD. This scale assists caregivers and physicians to decide for proper interventions.

A cloud-based pipeline for analysis of FHIR and long-read data.

Motivation: As genome sequencing becomes cheaper and more accurate, it is becoming increasingly viable to merge this data with electronic health information to inform clinical decisions. Results: In this work, we demonstrate a full pipeline for working with both PacBio sequencing data and clinical FHIR® data, from initial data to tertiary analysis. The electronic health records are stored in FHIR® (Fast Healthcare Interoperability Resource) format, the current leading standard for healthcare data exchange. For the genomic data, we perform variant calling on long-read PacBio HiFi data using Cromwell on Azure. Both data formats are parsed, processed and merged in a single scalable pipeline which securely performs tertiary analyses using cloud-based Jupyter notebooks. We include three example applications: exporting patient information to a database, clustering patients and performing a simple pharmacogenomic study. Availability and implementation: https://github.com/microsoft/genomicsnotebook/tree/main/fhirgenomics. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Comparison of deep learning-based recurrence-free survival with random survival forest and Cox proportional hazard models in Stage-I NSCLC patients.

BACKGROUND: The curative treatment for Stage I non-small cell lung cancer (NSCLC) is surgical resection. Even for Stage I patients, the probability of recurrence after curative treatment is around 20%. METHODS: In this retrospective study, we included 268 operated Stage I NSCLC patients between January 2008 and June 2018 to analyze the prognostic factors (pathological stage, histological type, number of sampled mediastinal lymph node stations, type of resection, SUVmax of the lesion) that may affect relapse with three different methods, Cox proportional hazard (CoxPH), random survival forest (RSF), DeepSurv, and to compare the performance of these methods with Harrell's C-index. The dataset was randomly split into two sets, training and test sets. RESULTS: In the training set, DeepSurv showed the best performance among the three models, the C-index of the training set was 0.832, followed by RSF (0.675) and CoxPH (0.672). In the test set, RSF showed the best performance among the three models, followed by DeepSurv with 0.677 and CoxPH methods with 0.625. CONCLUSION: In conclusion, machine-learning techniques can be useful in predicting recurrence for lung cancer and guide clinicians both in choosing the adjuvant treatment options and best follow-up programs.

Known pathogenic gene variants and new candidates detected in Sudden Unexpected Infant Death using Whole Genome Sequencing.

Purpose: To gain insights into potential genetic factors contributing to the infant's vulnerability to Sudden Unexpected Infant Death (SUID). Methods: Whole Genome Sequencing (WGS) was performed on 145 infants that succumbed to SUID, and 576 healthy adults. Variants were filtered by gnomAD allele frequencies and predictions of functional consequences. Results: Variants of interest were identified in 86 genes, 63.4% of our cohort. Seventy-one of these have been previously associated with SIDS/SUID/SUDP. Forty-three can be characterized as cardiac genes and are related to cardiomyopathies, arrhythmias, and other conditions. Variants in 22 genes were associated with neurologic functions. Variants were also found in 13 genes reported to be pathogenic for various systemic disorders. Variants in eight genes are implicated in the response to hypoxia and the regulation of reactive oxygen species (ROS) and have not been previously described in SIDS/SUID/SUDP. Seventy-two infants met the triple risk hypothesis criteria (Figure 1). Conclusion: Our study confirms and further expands the list of genetic variants associated with SUID. The abundance of genes associated with heart disease and the discovery of variants associated with the redox metabolism have important mechanistic implications for the pathophysiology of SUID.

High-dimensional pharmacogenetic prediction of a continuous trait using machine learning techniques with application to warfarin dose prediction in African Americans.

MOTIVATION: With complex traits and diseases having potential genetic contributions of thousands of genetic factors, and with current genotyping arrays consisting of millions of single nucleotide polymorphisms (SNPs), powerful high-dimensional statistical techniques are needed to comprehensively model the genetic variance. Machine learning techniques have many advantages including lack of parametric assumptions, and high power and flexibility. RESULTS: We have applied three machine learning approaches: Random Forest Regression (RFR), Boosted Regression Tree (BRT) and Support Vector Regression (SVR) to the prediction of warfarin maintenance dose in a cohort of African Americans. We have developed a multi-step approach that selects SNPs, builds prediction models with different subsets of selected SNPs along with known associated genetic and environmental variables and tests the discovered models in a cross-validation framework. Preliminary results indicate that our modeling approach gives much higher accuracy than previous models for warfarin dose prediction. A model size of 200 SNPs (in addition to the known genetic and environmental variables) gives the best accuracy. The R(2) between the predicted and actual square root of warfarin dose in this model was on average 66.4% for RFR, 57.8% for SVR and 56.9% for BRT. Thus RFR had the best accuracy, but all three techniques achieved better performance than the current published R(2) of 43% in a sample of mixed ethnicity, and 27% in an African American sample. In summary, machine learning approaches for high-dimensional pharmacogenetic prediction, and for prediction of clinical continuous traits of interest, hold great promise and warrant further research.

Epidemiologic trends in HBV infections at a reference centre in Turkey: an 11-year retrospective analysis.

OBJECTIVE: To identify changes in hepatitis B epidemiology after the implementation of the nationwide vaccination program in Turkey, hepatitis B virus (HBV) and related tests performed over a period of 11 years (2000-2010) at a reference centre were retrospectively overviewed and statistically analysed for trends. RESULTS: Assay results for Hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), Anti-HBs, Anti-HBe, Anti-HBc immunoglobulins and HBV DNA as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT), gama-glutamyl transpeptidase (GGT) and alkaline phosphatase (AP) levels, obtained via standardized commercial assays were included in the analysis. Overall, a stable anti-HBs incidence (43.6%) and male predominance in infected individuals were noted. Total Anti-HBc was detected in 43.3% of the Anti-HBs reactive population, demonstrating that the immunity against HBV has still been acquired through virus exposure. An intermediate HBsAg seroprevalence of 6.0% was observed with a significant decrease from 12.3% to 5.0% from 2000 to 2010. Anti-HBe positive infections were more frequent than those with HBe antigenemia (77.1% vs. 18.5%) with a notable increase from 2000 to 2003. HBV DNA was detected in 23.6-25.6% with serological markers of viral replication and was more prevalent in HBeAg positive individuals in parallel with AST, ALT and GGT levels. Evidence for horizontal transfer as the major transmission route was revealed with a reduction of childhood HBV infections, attributable to the ongoing vaccination efforts.

Antenatal corticosteroids for women at risk of preterm delivery: the "Emperor's New Clothes" tale in medical practice.

OBJECTIVE: To introduce the effect of a single course of betamethasone for pregnant women at risk of preterm delivery (PTD). MATERIALS AND METHODS: In this study, a single course of 12 mg Bethamethasone was administered twice in 24 h (between 24-34 gestational weeks) for antenatal corticosteroid prophylaxis. Four hundred ninety-three neonates fulfilled the inclusion criteria and they were categorized (259 singletons, 192 twins and 42 triplets who met the inclusion criteria) into two groups according to the utilization of antenatal corticosteroid as control (n = 202) and study (n = 291) groups. We used respiratory distress syndrome (RDS), congenital pneumonia, intraventricular hemorrhage (IVH), neonatal sepsis, and bronchopulmonary dysplasia (BPD) as primary outcomes for the evaluation of neonatal morbidity. RESULTS: Study and control groups were similar in terms of clinical characteristics. RDS, congenital pneumonia, neonatal sepsis, and BPD rates were significantly higher in the study group (betamethasone) (p = .05, p = .007, 0.003, and 0.004, respectively) between 24-34 gestational weeks (when the neonates of multiple pregnancies were excluded from the analysis, we have demonstrated that congenital pneumonia (p = .033) and neonatal sepsis (p = .030) were still significantly higher in the betamethasone group). The neonates of 24-28 gestational weeks were compared separately and we demonstrated that RDS (p = .012), congenital pneumonia (p = .022), IVH (p = .044), neonatal sepsis (p = .023), and BPD (0.001) were also more frequent in the study group. When the 28-32 gestational week data were compared, IVH (p = .020) and neonatal sepsis (p = .017) were more frequent in the single course betamethasone users. However, we could not demonstrate a significant difference between the control and study groups between 32-34 gestational weeks in terms of the primary neonatal outcomes used in this study. CONCLUSION: Single course antenatal betamethasone administration may be ineffective on the respiratory complications of preterm and very preterm infants while it may be unfavorable for extremely preterm infants. WHAT IS NEW ABOUT THE PAPER, WHAT COULD ADD TO THE CURRENT KNOWLEDGE: Pregnant women at risk for preterm labor must be under intensive antenatal care programs, and if possible, necessary precautions must be undertaken to prevent fetal hypoxia together with etiology specific treatments. This approach might contribute to better perinatal outcomes than just administering antenatal corticosteroid therapy.

Correlation of anatomical involvement patterns of insular gliomas with subnetworks of the limbic system.

OBJECTIVE: Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort. METHODS: Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21-71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters). RESULTS: The tumors involved the anterior insula (98.3%), posterior insula (67.8%), temporal operculum (47.5%), amygdala (42.4%), frontal operculum (40.7%), temporal pole (39%), parolfactory area (35.6%), hypothalamus (23.7%), hippocampus (16.9%), thalamus (6.8%), striatum (5.1%), and cingulate gyrus (3.4%). A mean 4.2 ± 2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular [11.9%], olfactocentric [15.3%], olfactoopercular [33.9%], operculoinsular [15.3%], striatoinsular [3.4%], translimbic [11.9%], and multifocal [8.5%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator. CONCLUSIONS: The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.

Exploring the Consistency of the Quality Scores with Machine Learning for Next-Generation Sequencing Experiments.

BACKGROUND: Next-generation sequencing enables massively parallel processing, allowing lower cost than the other sequencing technologies. In the subsequent analysis with the NGS data, one of the major concerns is the reliability of variant calls. Although researchers can utilize raw quality scores of variant calling, they are forced to start the further analysis without any preevaluation of the quality scores. METHOD: We presented a machine learning approach for estimating quality scores of variant calls derived from BWA+GATK. We analyzed correlations between the quality score and these annotations, specifying informative annotations which were used as features to predict variant quality scores. To test the predictive models, we simulated 24 paired-end Illumina sequencing reads with 30x coverage base. Also, twenty-four human genome sequencing reads resulting from Illumina paired-end sequencing with at least 30x coverage were secured from the Sequence Read Archive. RESULTS: Using BWA+GATK, VCFs were derived from simulated and real sequencing reads. We observed that the prediction models learned by RFR outperformed other algorithms in both simulated and real data. The quality scores of variant calls were highly predictable from informative features of GATK Annotation Modules in the simulated human genome VCF data (R2: 96.7%, 94.4%, and 89.8% for RFR, MLR, and NNR, respectively). The robustness of the proposed data-driven models was consistently maintained in the real human genome VCF data (R2: 97.8% and 96.5% for RFR and MLR, respectively).

Effect of Missing Data Imputation on Deep Learning Prediction Performance for Vesicoureteral Reflux and Recurrent Urinary Tract Infection Clinical Study.

Missing observations are always a challenging problem that we have to deal with in diseases that require follow-up. In hospital records for vesicoureteral reflux (VUR) and recurrent urinary tract infection (rUTI), the number of complete cases is very low on demographic and clinical characteristics, laboratory findings, and imaging data. On the other hand, deep learning (DL) approaches can be used for highly missing observation scenarios with its own missing ratio algorithm. In this study, the effects of multiple imputation techniques MICE and FAMD on the performance of DL in the differential diagnosis were compared. The data of a retrospective cross-sectional study including 611 pediatric patients were evaluated (425 with VUR, 186 with rUTI, 26.65% missing ratio) in this research. CNTK and R 3.6.3 have been used for evaluating different models for 34 features (physical, laboratory, and imaging findings). In the differential diagnosis of VUR and rUTI, the best performance was obtained by deep learning with MICE algorithm with its values, respectively, 64.05% accuracy, 64.59% sensitivity, and 62.62% specificity. FAMD algorithm performed with accuracy = 61.52, sensitivity = 60.20, and specificity was found out to be 61.00 with 3 principal components on missing imputation phase. DL-based approaches can evaluate datasets without doing preomit/impute missing values from datasets. Once DL method is used together with appropriate missing imputation techniques, it shows higher predictive performance.

Turkish version of the Yale Food Addiction Scale: preliminary results of factorial structure, reliability, and construct validity.

BACKGROUND: Yale Food Addiction Scale (YFAS) was established to identify individuals exhibiting signs of addiction towards certain types of food. This study aimed to develop a Turkish version of the Yale Food Addiction Scale and test its psychometric properties. METHODS: The backward translation techniques were used to develop Turkish versions of the YFAS, and its reproducibility was assessed. Turkish version of the YFAS was administered to a total of 1033 participants (439 men and 594 women), aged 19-65 years. Exploratory factor analysis and confirmatory factor analysis were used to examine the factorial structure of the tool. Construct validity was assessed by principal component factor analysis with varimax rotation. Reliabilities were estimated with Cronbach's alpha coefficient. The criterion-related validity was tested by the administration of Eating Attitude Test-26 (EAT-26) to all participants. RESULTS: The primary factor loadings for seven items were ranged between 0.45 and 0.79, and no items cross-loaded onto other factors. The fit indices showed that eight items of the YFAS were a good representation of the item responses and each item loaded significantly on the specified factor (p < 0.001 for each). YFAS subscales had a high internal consistency and test-retest reliability. The criterion-related validity of the tool showed a positive relationship with scales of the EAT-26. CONCLUSION: Current study suggested that the Turkish version of the YFAS is a reliable, valid, and useful tool for assessing the signs of food addiction in a non-clinical sample.

Use of telomerase promoter mutations to mark specific molecular subsets with reciprocal clinical behavior in IDH mutant and IDH wild-type diffuse gliomas.

OBJECTIVE Recent studies have established that hemispheric diffuse gliomas may be grouped into subsets on the basis of molecular markers; these subsets are loosely correlated with the histopathological diagnosis but are strong predictors of clinical tumor behavior. Based on an analysis of molecular and clinical parameters, the authors hypothesized that mutations of the telomerase promoter (TERTp-mut) mark separate oncogenic programs among isocitrate dehydrogenase 1 and/or 2 (IDH) mutant (IDH-mut) and IDH wild-type (IDH-wt) diffuse gliomas independent of histopathology or WHO grade. METHODS Four molecular subsets of the combined statuses of IDH and TERT-promoter mutations (double mutant, IDH only, TERT only, and double negative) were defined. Differences in age, anatomical location, molecular genetics, and survival rates in a surgical cohort of 299 patients with a total of 356 hemispheric diffuse gliomas (WHO Grade II, III, or IV) were analyzed. RESULTS TERTp-mut were present in 38.8% of IDH-mut and 70.2% of IDH-wt gliomas. The mutational status was stable in each patient at 57 recurrence events over a 2645-month cumulative follow-up period. Among patients with IDH-mut gliomas, those in the double-mutant subset had better survival and a lower incidence of malignant degeneration than those in the IDH-only subset. Of patients in the double-mutant subset, 96.3% were also positive for 1p/19q codeletions. All patients with 1p/19q codeletions had TERTp-mut. In patients with IDH-mut glioma, epidermal growth factor receptor or phosphatase and tensin homolog mutations were not observed, and copy-number variations were uncommon. Among IDH-wt gliomas, the TERT-only subset was associated with significantly higher age, higher Ki-67 labeling index, primary glioblastoma-specific oncogenic changes, and poor survival. The double-negative subset was genetically and biologically heterogeneous. Survival analyses (Kaplan-Meier, multivariate, and regression-tree analyses) confirmed that patients in the 4 molecular subsets had distinct prognoses. CONCLUSIONS Molecular subsets result in different tumor biology and clinical behaviors in hemispheric diffuse gliomas.

Push-out bond strength and dentinal tubule penetration of different root canal sealers used with coated core materials.

OBJECTIVES: The aim of this study was to compare the push-out bond strength and dentinal tubule penetration of root canal sealers used with coated core materials and conventional gutta-percha. MATERIALS AND METHODS: A total of 72 single-rooted human mandibular incisors were instrumented with NiTi rotary files with irrigation of 2.5% NaOCl. The smear layer was removed with 17% ethylenediaminetetraacetic acid (EDTA). Specimens were assigned into four groups according to the obturation system: Group 1, EndoRez (Ultradent Product Inc.); Group 2, Activ GP (Brasseler); Group 3, SmartSeal (DFRP Ltd. Villa Farm); Group 4, AH 26 (Dentsply de Trey)/gutta-percha (GP). For push-out bond strength measurement, two horizontal slices were obtained from each specimen (n = 20). To compare dentinal tubule penetration, remaining 32 roots assigned to 4 groups as above were obturated with 0.1% Rhodamine B labeled sealers. One horizontal slice was obtained from the middle third of each specimen (n = 8) and scanned under confocal laser scanning electron microscope. Tubule penetration area, depth, and percentage were measured. Kruskall-Wallis test was used for statistical analysis. RESULTS: EndoRez showed significantly lower push-out bond strength than the others (p < 0.05). No significant difference was found amongst the groups in terms of percentage of sealer penetration. SmartSeal showed the least penetration than the others (p < 0.05). CONCLUSIONS: The bond strength and sealer penetration of resin-and glass ionomer-based sealers used with coated core was not superior to resin-based sealer used with conventional GP. Dentinal tubule penetration has limited effect on bond strength. The use of conventional GP with sealer seems to be sufficient in terms of push-out bond strength.

Evaluation of the origin and branching patterns of the iliolumbar artery and its implications on pelvic and vertebral surgery.

OBJECTIVES: To evaluate the origin, distribution pattern, branches, and neighboring structures of the iliolumbar artery (ILA) concerning the anterolateral surgical approaches to the spine. METHODS: This study was performed in the Anatomy Department of Medical School, Mersin University, Mersin, Turkey between 2014 and 2015. Pelvises of 11 male formalin-fixed human cadavers were dissected by anterior and posterior approaches under surgical microscope. The origins, distribution patterns, calibers, and distances to certain structures were measured. RESULTS: The ILA was found as a single trunk on 17 sides arising either from the IIA (12 sides, 70.6%) or the PT (5 sides, 29.4%). The average caliber of those originated from the posterior trunk was significantly larger (p=0.010). The ILA started as a single trunk in 17 sides, while its lumbar and iliac branches separately originating from different arteries in 4 sides. The close relation of the posterior rami of both the lumbar and iliac branches with transverse process and spinal nerve were noted. CONCLUSION: Findings suggest that the ILA and its branches may have different and significant patterns, which may be crucial to consider during certain surgical procedures, such as far lateral disc herniation and posterior pelvic fixations.

Early Onset of Atherosclerosis of The Carotid Bifurcation in Newborn Cadavers.

INTRODUCTION: The anatomy of arterial bifurcations affects blood flow and has a significant role in the development of vascular disease. Therefore, it is important to know the structural characteristics of the Common Carotid Artery (CCA) and its branches for early onset of atherosclerosis in newborns. AIM: The present study was conducted to evaluate the characteristics of CCA in newborn cadavers. MATERIALS AND METHODS: Eight carotid arteries obtained from newborn cadavers were used. The outflow to inflow area ratios was calculated to evaluate vessel diameters. Additionally, scanning electron and light microscopic investigations were conducted with tissue samples. The brachial artery of each cadaver was used as controls. Correlation between area ratios and atherosclerotic endothelial damage was determined. RESULTS: Light microscopic investigations demonstrated that control group sections showed no positivity for Oil red O staining, while carotid bifurcation regions depicted widespread occurrence of intimal lipid accumulations. Scanning electron microscopic examination of control group sections presented regular endothelial topography, while carotid bifurcation region topography exhibited numerous blood cells and separated endothelial cells. Fibrin accumulation on endothelial surface in low area ratios was another important finding in the examination of its endothelial surface degeneration. The above-mentioned morphological findings seemed to be quite parallel to outflow to inflow area ratio data favouring low area and degeneration. CONCLUSION: The correlation between area ratios and the histological characteristic of cerebral vessels of newborn cadavers indicate that early stages of atherosclerosis began in early embryologic life.

Introduction to statistical methods for microRNA analysis.

MicroRNA profiling is an important task to investigate miRNA functions and recent technologies such as microarray, single nucleotide polymorphism (SNP), quantitative real-time PCR (qPCR), and next-generation sequencing (NGS) have played a major role for miRNA analysis. In this chapter, we give an overview on statistical approaches for gene expressions, SNP, qPCR, and NGS data including preliminary analyses (pre-processing, differential expression, classification, clustering, exploration of interactions, and the use of ontologies). Our goal is to outline the key approaches with a brief discussion of problems avenues for their solutions and to give some examples for real-world use. Readers will be able to understand the different data formats (expression levels, sequences etc.) and they will be able to choose appropriate methods for their own research and application. On the other hand, we give brief notes on most popular tools/packages for statistical genetic analysis. This chapter aims to serve as a brief introduction to different kinds of statistical methods and also provides an extensive source of references.