Relationship Between Temporomandibular Ankylosis And Maximum Mouth Opening In Children.

BACKGROUND: Pediatric dentists should have information regarding whether mouth opening is limited. In clinical practice, these professionals should collect and record oral area measurements at the pediatric patient's first medical examination. OBJECTIVES: The study's aim developed the standard mouth opening measurement in children by using ordinary least squares regression to develop a clinical prediction model in children with Temporomandibular Joint Ankylosis before preoperative surgery. METHODS: All participants completed their age, gender, and calculated height, weight, body mass index, and birth weight. Pediatric dentist performed all mouth-opening measurements. The oral-maxillofacial surgeon marked subnasal and pogonion points for the lower facial length of soft tissue. It was measured using the distance between the subnasal and pogonion with a digital vernier caliper. The widths of the three fingers (index, middle, and ring fingers) and four fingers (index, middle, ring, and little fingers) were also measured using a digital vernier caliper. RESULTS: Maximum mouth opening showed that three-finger width (R2 = 0.566, F = 185.479) and four-finger width (R2 = 0.462, F = 122.209) had a significant influence on the Maximum mouth opening (MMO) (p < 0.001). CONCLUSION: Pediatric dentists should collaborate with the treating maxillofacial surgeon to manage long-term treatment needs for individuals with Temporomandibular Joint Ankylosis.

Safety and efficacy of mesenchymal stromal cell therapy for multi-drug-resistant acute and late-acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.

Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 106/kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 106/kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3-4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3-4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (p = 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25-62%) versus 71% (95% CI, 59-86%), respectively (p = 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37-74%) versus 28% (95% CI, 13-40%), respectively (p = 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD.

Investigation of Serum Interleukin 6, High-Sensitivity C-Reactive Protein and White Blood Cell Levels during the Diagnosis and Treatment of Paediatric Appendicitis Patients Before and during the COVID-19 Pandemic.

Introduction: In this study, we prospectively investigated changes in serum interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and full white blood cell (WBC) counts during the diagnosis and treatment of paediatric patients with appendicitis. We also investigated the effects of the COVID-19 pandemic on the diagnosis and treatment processes of paediatric appendicitis patients. Materials and Methods: A non-perforated appendicitis group (n = 110), a perforated appendicitis group (n = 35) and an appendicitis + COVID-19 group (n = 8) were formed. Blood samples were taken upon admission and every day until the three studied parameters returned to normal values. To investigate the effects of the COVID-19 pandemic on paediatric appendicitis patients, the perforated appendicitis rates and the times from the onset of the first symptoms to the operation before and during the pandemic were compared. Results: WBC, IL-6, and hsCRP dropped below the upper limits on the second postoperative day in the non-perforated appendicitis group, four to six days postoperatively in the perforated appendicitis group, and three to six days postoperatively in the appendicitis + COVID-19 group. These parameters were not within normal range in patients who developed complications during follow-up. The time from the onset of abdominal pain to the surgery was significantly longer during than before the pandemic in both the non-perforated appendicitis group and the perforated appendicitis group. Conclusions: Our results show that WBC, IL-6, and hsCRP are useful laboratory parameters that can complete clinical examinations in the diagnosis of appendicitis in paediatric patients and the identification of complications that may develop postoperatively.

Comprehensive analysis of circulating viral DNA in maternal plasma at population-scale using low-pass whole-genome sequencing.

As the most readily adopted molecular screening test, low-pass WGS of maternal plasma cell-free DNA for aneuploidy detection generates a vast amount of genomic data. This large-scale method also allows for high-throughput virome screening. NIPT sequencing data, yielding 6.57 terabases of data from 187.8 billion reads, from 12,951 pregnant Turkish women was used to investigate the prevalence and abundance of viral DNA in plasma. Among the 22 virus sequences identified in 12% of participants were human papillomavirus, herpesvirus, betaherpesvirus and anellovirus. We observed a unique pattern of circulating viral DNA with a high prevalence of papillomaviruses. The prevalence of herpesviruses/anellovirus was similar among Turkish, European and Dutch populations. Hepatitis B prevalence was remarkably low in Dutch, European and Turkish populations, but higher in China. WGS data revealed that herpesvirus/anelloviruses are naturally found in European populations. This represents the first comprehensive research on the plasma virome of pregnant Turkish women.

The Beneficial Clinical Effects of Teriflunomide in Experimental Autoimmune Myasthenia Gravis and the Investigation of the Possible Immunological Mechanisms.

Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disease characterized by skeletal muscle weakness exacerbated with exercise. There is a need for novel drugs effective in refractory MG. We aimed to test the potential of teriflunomide, an immunomodulatory drug currently used in rheumatoid arthritis and multiple sclerosis treatment, in a murine experimental autoimmune myasthenia gravis (EAMG) model. EAMG was induced by immunizations with recombinant acetylcholine receptor (AChR). Teriflunomide treatment (10 mg/kg/day, intraperitoneal) was initiated to one group of mice (n = 21) following the third immunization and continued for 5 weeks. The disease control group (n = 19) did not receive medication. Naïve mice (n = 10) received only mock immunization. In addition to the clinical scorings, the numbers of B cells and T cells, and cytokine profiles of T cells were examined by flow cytometry. Anti-AChR-specific antibodies in the peripheral blood serum were quantified by ELISA. Teriflunomide significantly reduced clinical disease scores and the absolute numbers of CD4+ T cells and some of their cytokine-producing subgroups (IFN-γ, IL 2, IL22, IL-17A, GM-CSF) in the spleen and the lymph nodes. The thymic CD4+ T cells were also significantly reduced. Teriflunomide mostly spared CD8+ T cells' numbers and cytokine production, while reducing CD138+CD19+lambda+ plasma B cells' absolute numbers and CD138 mean fluorescent intensities, probably decreasing the number of IgG secreting more mature plasma cells. It also led to some selective changes in the measurements of anti-AChR-specific antibodies in the serum. Our results showed that teriflunomide may be beneficial in the treatment of MG in humans.

Ultra-structural and histopathological features of liver biopsy taken during laparotomy to confirm the diagnosis of biliary atresia.

Background: Neonatal cholestasis is caused by a group of diseases that cause jaundice, which can be encountered in the neonatal period. Biliary atresia (BA) and idiopathic neonatal hepatitis (INH) are among neonatal cholestasis diseases. Aims: The aim of this study was to perform histopathological and ultra-structural examinations of liver biopsy tissue samples from BA and INH patients with liver biopsies taken during laparotomy to confirm the diagnosis of biliary atresia. Settings and Design: A total of patients undergoing Kasai surgery before the age of 60 days were included in an "early" group (n = 7), whereas patients undergoing surgery after the age of 60 days were included in a "late" group (n = 11). The control group (n = 11) included INH patients. Materials and Methods: For histopathological examinations, liver tissue samples obtained intra-operatively were subjected to routine histopathological procedures after being stained with caspase-3 and cytokeratin-7 antibodies. Ultra-structural evaluations were also performed. Statistical analysis used: For comparisons between the groups, a one-way analysis of variance (ANOVA) test and the Mann-Whitney U test were used for continuous variables. Results: Histopathological findings reflected the specific liver pathologic findings seen in biliary atresia. Although there was no significant difference between the BA groups, these parameters were not detected in the control group. The histopathological evaluations revealed no significant differences in the findings of liver parenchyma damage between the early, late, and control groups. Electron microscopic examinations showed that the patients in the late group had more severe signs of intra-cellular damage to the liver. Conclusions: Although the histopathological examination revealed no significant differences in liver damage between the three groups, in ultra-structural evaluation, intra-cellular damage was found to be less in groups with better prognosis. Electron microscopy evaluations of intra-cellular damage may be more useful in this respect.

Evaluation of the relationship between anxiety and nutritional habits in Turkish patients with multiple sclerosis during the Covid-19 outbreak / Avaliação da relação entre ansiedade e hábitos nutricionais em pacientes turcos com esclerose múltipla durante o surto da Covid-19

ABSTRACT Objective The Coronavirus disease 2019 is a global public health problem that has led to psychological disorders (depression, anxiety, etc.), especially in fragile individuals such as those affected by multiple sclerosis. This study investigated the relationship between anxiety and nutritional habits during the Coronavirus disease 2019 outbreak in multiple sclerosis patients. Methods This cross-sectional study was an online survey of multiple sclerosis patients living in Turkey. The total sample consisted of 294 multiple sclerosis patients. A questionnaire containing general demographic data, the Beck Anxiety Inventory, and nutritional attitudes and habits was applied to multiple sclerosis patients. Results Moderate or severe anxiety scores were found in 42.2% of multiple sclerosis patients. Weight gain was reported in 40.5% of them during the outbreak. A statistically significant difference was found in the distribution of individuals' Beck Anxiety Inventory scores for consumption of nuts/seeds, rice/pasta, cake/cookies, and water. A 1-unit increase in Beck Anxiety Inventory scores led to a 1.04 times increased consumption of bread and rice/pasta and a 1.05 times increased consumption of cake/cookies either before or after controlling for potential confounders. A 1-unit increase in Beck Anxiety Inventory scores led to a 1.06 times decreased consumption of water and a 1.04 times decreased consumption of meat and poultry, fruit (fresh), and rice/pasta, either before or after controlling for potential confounders. Conclusion During the Coronavirus disease 2019 outbreak, anxiety led to changes in multiple sclerosis patients' nutritional habits and food preferences. The continuous surveillance of psychological consequences and nutritional counseling during outbreaks should become routine as part of preparedness efforts worldwide.

RESUMO Objetivo A doença do Coronavírus - 2019, causada pelo Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), é um problema de saúde pública global e tem levado os indivíduos desenvolverem distúrbios psicológicos (depressão, ansiedade, etc.), especialmente indivíduos frágeis, como aqueles afetados por esclerose múltipla. O objetivo deste trabalho foi investigar a relação entre ansiedade e hábitos nutricionais em pacientes com esclerose múltipla durante o surto de coronavírus. Métodos Este estudo transversal é resultado de uma pesquisa online com pacientes com esclerose múltipla que vivem na Turquia (n=294). Um formulário de questionário contendo dados demográficos gerais, o Inventário de Ansiedade de Beck e atitudes e hábitos nutricionais foi aplicado a pacientes com esclerose múltipla. Resultados Escores de ansiedade moderados ou graves foram encontrados em 42,2% dos pacientes com esclerose múltipla. O ganho de peso foi relatado em 40,5% durante o surto. Foi encontrada diferença estatisticamente significativa na distribuição dos escores do Inventário de Ansiedade de Beck dos indivíduos para o consumo de nozes/sementes, arroz/massa, bolo/biscoitos e água. Um aumento de uma unidade nas pontuações do Inventário de Ansiedade de Beck levou a um aumento de 1,04 vezes no consumo de pão e arroz/massa e 1,05 vezes no consumo de bolo/biscoitos antes ou depois de controlar possíveis fatores de confusão. Um aumento de uma unidade nas pontuações do Inventário de Ansiedade de Beck levou a uma redução de 1,06 vezes no consumo de água e 1,04 vezes no consumo de carnes e aves, frutas (frescas) e arroz/massa antes ou depois de controlar possíveis fatores de confusão. Conclusão Durante o surto de coronavírus, a ansiedade levou a mudanças nos hábitos nutricionais e nas preferências alimentares dos pacientes com esclerose múltipla. A vigilância contínua das consequências psicológicas e o aconselhamento nutricional para surtos devem se tornar rotina como parte dos esforços de preparação em todo o mundo.

Hypoxia-inducible factors in arteriovenous fistula maturation: A prospective cohort study.

BACKGROUND: Neointimal hyperplasia is the main cause of arteriovenous fistula (AVF) failure. Hypoxia-inducible factors (HIFs) factors are associated with neointimal hyperplasia. Thus, we investigated the association between HIF-2 alpha (HIF-2α) and AVF maturation in end-stage kidney disease (ESKD) patients. METHODS: This prospective cohort study was conducted in 21 voluntary healthy subjects and 50 patients with ESKD who were eligible for AVF creation. Inclusion criteria were being ESKD patients without a history of AVF surgery and dialysis. Eight patients excluded from the study due to having unavailable veins six patients were excluded due to acute thrombosis after surgery. One patient lost to follow-up. A total of 35 patients were included in final analysis. The blood samples were collected a day before the AVF surgery for biochemical parameters and HIF-2α measurement. HIF-2α levels were measured by the ELISA method. RESULTS: Compared with healthy subjects, ESKD patients had a significantly higher level of HIF-2α. [1.3 (1.0-1.9) vs 2.2 (1.6-3.0)] (P = .002). Patients were divided into two groups after the evaluation of AVF maturation, as the mature group (n = 19) and the failure group (n = 16). Serum HIF-2α level was 1.7 (1.1-1.8) in the mature group; however, it was 3.1 (2.8-3.3 in failure group (P < .001). Multiple logistic regression analyses showed that HIF-2α independently predicted AVF maturation. The ROC curve analysis showed that HIF-2α > 2.65 predicted AVF maturation failure with the 87% sensitivity and 94% specificity [AUC:0.947, 95% CI (0.815-0.994), P < .001]. CONCLUSIONS: HIF-2-α levels were higher in ESKD patients than healthy subjects. HIF-2-α could be a marker of AVF maturation failure.

Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1ß Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension.

BACKGROUND AND OBJECTIVES: Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via IL-1ß activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, HIF-1α gene expression from whole blood and urine samples and IL-1ßgene expression from whole blood were measured. METHODS: One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for HIF-1α and IL-1ß geneexpression by using quantitative real-time PCR. RESULTS: There were significant differences in whole blood HIF-1α, IL-1ß geneexpression, and serumsuccinate levels between the ADPKD patients and the control subjects. Whole blood HIF-1αgene expression, IL-1ß geneexpression, and serumsuccinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (p < 0.05). Serum succinate levels and blood IL-1ß geneexpression were increased in ADPKD patients with high levels of HIF-1α geneexpression (p = 0.018 and p = 0.029, respectively). CONCLUSIONS: Increased age,low eGFR, and HIF-1α and IL-1ß geneexpressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD.

Evaluation of factors affecting the duration of disease-modifying anti-rheumatic drugs application in patients with enthesitis-related arthritis.

OBJECTIVE: Treatments for enthesitis-related arthritis (ERA) consist of a mono- or combination therapy with non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (DMARDs), and biological agents, and they are primarily based on adult studies and studies on other forms of juvenile idiopathic arthritis, depending on whether there is axial or peripheral involvement. We use DMARDs frequently in our daily practice, even in patients with axial involvement. The main reason for this is that the health insurance system in Turkey does not allow the use of Tumor Negrosis Factor (TNF) blockers as the first line of treatment. The aim of this study is to evaluate the factors affecting the duration of DMARDs application in patients with ERA. METHODS: Fifty-two patients with ERA were accepted in this retrospective cohort study. These patients did not have an inflammatory bowel disease, reactive arthritis or undifferentiated arthritis, psoriasis, and familial Mediterranean fever. Demographic characteristics, medical history, the initial and follow-up physical examination, initial Juvenile Spondyloarthritis Disease Activity Index (JSpADA), initial laboratory tests, radiographic tests, Juvenile Arthritis Damage Index-articulary (JADI-A) and extra-articulary (JADI-E) on the last admission, and data on medical treatments were recorded from the registered data. The univariate Cox proportional hazards regression analyses was used to determine factors affecting the non-response time of ERA patients to DMARDs before the biological treatment was started. RESULTS: Twenty-seven patients (52%) achieved remission with DMARDs, while 25 (48%) patients did not. The age at diagnosis (HR=1.12; p=0.247); gender (HR=2.53; p=0.210); family history of ankylosing spondylitis (HR=1.17; p=0.730); inflammatory back pain (HR=0.57; p=0.175); the shoulder (HR=0.75 p=0.706), hip (HR=0.45; p=0.129), and small-joint involvement (HR=1.53; p=0.439); sacroiliitis with physical examination (HR=0.90; p=0.814) and magnetic resonance imaging (MRI) (HR=2.84; p=0.110); enthesitis (HR=0.83; p=0.670); presence of uveitis (HR=2.04; p=0.342); presence of HLA-B27 (HR=1.39; p=0.524); initial high acute phase reactants levels(HR=1.89; p=0.183); initial JSpADA score (HR=0.98; p=0.944); and last JADI-A (HR=1.41; p=0.060) score did not affect the duration of DMARDs treatment before switching to biological treatments. CONCLUSION: In our study, the absence of factors affecting the duration of DMARDs application in patients with ERA showed that DMARDs may still be applied as the first line of treatment.

MLSeq: Machine learning interface for RNA-sequencing data.

BACKGROUND AND OBJECTIVE: In the last decade, RNA-sequencing technology has become method-of-choice and prefered to microarray technology for gene expression based classification and differential expression analysis since it produces less noisy data. Although there are many algorithms proposed for microarray data, the number of available algorithms and programs are limited for classification of RNA-sequencing data. For this reason, we developed MLSeq, to bring not only frequently used classification algorithms but also novel approaches together and make them available to be used for classification of RNA sequencing data. This package is developed using R language environment and distributed through BIOCONDUCTOR network. METHODS: Classification of RNA-sequencing data is not straightforward since raw data should be preprocessed before downstream analysis. With MLSeq package, researchers can easily preprocess (normalization, filtering, transformation etc.) and classify raw RNA-sequencing data using two strategies: (i) to perform algorithms which are directly proposed for RNA-sequencing data structure or (ii) to transform RNA-sequencing data in order to bring it distributionally closer to microarray data structure, and perform algorithms which are developed for microarray data. Moreover, we proposed novel algorithms such as voom (an acronym for variance modelling at observational level) based nearest shrunken centroids (voomNSC), diagonal linear discriminant analysis (voomDLDA), etc. through MLSeq. MATERIALS: Three real RNA-sequencing datasets (i.e cervical cancer, lung cancer and aging datasets) were used to evalute model performances. Poisson linear discriminant analysis (PLDA) and negative binomial linear discriminant analysis (NBLDA) were selected as algorithms based on dicrete distributions, and voomNSC, nearest shrunken centroids (NSC) and support vector machines (SVM) were selected as algorithms based on continuous distributions for model comparisons. Each algorithm is compared using classification accuracies and sparsities on an independent test set. RESULTS: The algorithms which are based on discrete distributions performed better in cervical cancer and aging data with accuracies above 0.92. In lung cancer data, the most of algorithms performed similar with accuracies of 0.88 except that SVM achieved 0.94 of accuracy. Our voomNSC algorithm was the most sparse algorithm, and able to select 2.2% and 6.6% of all features for cervical cancer and lung cancer datasets respectively. However, in aging data, sparse classifiers were not able to select an optimal subset of all features. CONCLUSION: MLSeq is comprehensive and easy-to-use interface for classification of gene expression data. It allows researchers perform both preprocessing and classification tasks through single platform. With this property, MLSeq can be considered as a pipeline for the classification of RNA-sequencing data.

Biological variation of peripheral blood T-lymphocytes.

BACKGROUND: Flow cytometric analysis of the lymphocyte subsets has become one of the most commonly used techniques in the routine clinical laboratory. It is frequently used in monitoring lymphocyte recovery after hematopoietic stem cell transplantation (HSCT), as well as diagnosis and treatment of acquired immunodeficiency syndrome (AIDS). Reliable biological variation (BV) data is needed for safe clinical application of these tests. In this study, similar preanalytical and analytical protocols to the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) checklist were followed and a stringent statistical approach was applied to define BV of T-lymphocytes. METHODS: During the 10 weeks study period, weekly blood samples were obtained from 30 healthy individuals (20 females, 10 males) and analyzed with Facs Canto (BD Biosciences, San Jose, CA, USA) analyzer using 4-colour BD Multitest CD3/CD8/CD45/CD4 reagents. Data were assessed in terms of normality, tendencies, outliers and variance homogeneity prior to applying coefficient of variance (CV)- analysis of variance (ANOVA) test. Sex-stratified within-individual (CVI) and between-individual (CVG) BV estimates of CD3+, CD3 + CD4+, CD3 + CD8+, and CD3 + CD4 + CD8+ T lymphocytes were calculated. RESULTS: No difference was found between males and females. Except for the CD3 + CD4 + CD8+ subset, stable BV was found for CD3+, CD3 + CD4+, and CD3 + CD8+ subsets. CONCLUSSION: Instead of using the conventional reference ranges of CD3+, CD3 + CD4+ and CD3 + CD8+ counts for monitoring HIV positive or post-HSCT patients, RCV should be used. Because individualityis characteristic of lymphocytes subsets RCVs should be used instead of RIs for patient monitoring.

voomDDA: discovery of diagnostic biomarkers and classification of RNA-seq data.

RNA-Seq is a recent and efficient technique that uses the capabilities of next-generation sequencing technology for characterizing and quantifying transcriptomes. One important task using gene-expression data is to identify a small subset of genes that can be used to build diagnostic classifiers particularly for cancer diseases. Microarray based classifiers are not directly applicable to RNA-Seq data due to its discrete nature. Overdispersion is another problem that requires careful modeling of mean and variance relationship of the RNA-Seq data. In this study, we present voomDDA classifiers: variance modeling at the observational level (voom) extensions of the nearest shrunken centroids (NSC) and the diagonal discriminant classifiers. VoomNSC is one of these classifiers and brings voom and NSC approaches together for the purpose of gene-expression based classification. For this purpose, we propose weighted statistics and put these weighted statistics into the NSC algorithm. The VoomNSC is a sparse classifier that models the mean-variance relationship using the voom method and incorporates voom's precision weights into the NSC classifier via weighted statistics. A comprehensive simulation study was designed and four real datasets are used for performance assessment. The overall results indicate that voomNSC performs as the sparsest classifier. It also provides the most accurate results together with power-transformed Poisson linear discriminant analysis, rlog transformed support vector machines and random forests algorithms. In addition to prediction purposes, the voomNSC classifier can be used to identify the potential diagnostic biomarkers for a condition of interest. Through this work, statistical learning methods proposed for microarrays can be reused for RNA-Seq data. An interactive web application is freely available at http://www.biosoft.hacettepe.edu.tr/voomDDA/.

geneSurv: An interactive web-based tool for survival analysis in genomics research.

Survival analysis methods are often used in cancer studies. It has been shown that the combination of clinical data with genomics increases the predictive performance of survival analysis methods. But, this leads to a high-dimensional data problem. Fortunately, new methods have been developed in the last decade to overcome this problem. However, there is a strong need for easily accessible, user-friendly and interactive tool to perform survival analysis in the presence of genomics data. We developed an open-source and freely available web-based tool for survival analysis methods that can deal with high-dimensional data. This tool includes classical methods, such as Kaplan-Meier, Cox proportional hazards regression, and advanced methods, such as penalized Cox regression and Random Survival Forests. It also offers an optimal cutoff determination method based on maximizing several test statistics. The tool has a simple and interactive interface, and it can handle high dimensional data through feature selection and ensemble methods. To dichotomize gene expressions, geneSurv can identify optimal cutoff points. Users can upload their microarray, RNA-Seq, chip-Seq, proteomics, metabolomics or clinical data as a nxp dimensional data matrix, where n refers to samples and p refers to genes. This tool is available free at www.biosoft.hacettepe.edu.tr/geneSurv. All source code is available at https://github.com/selcukorkmaz/geneSurv under the GPL-3 license.

Which method is gold standard for determination of thyroid volume? / ¿Cual es el método gold standard para determinar el volumen de la glándula tiroides?

Change of the thyroid gland volume is often the symptom of most common pathological conditions some thyroid diseases. The exact calculation for the thyroid volume is very important for the assessment and management of thyroid disorders. The volume of thyroid gland, using computed tomography (CT), ultrasound (USG) and magnetic resonance imaging (MRI) has been accessed in few studies published; however a gold standard method has not yet been determined. The purpose of this study was to estimate the volume of normal thyroid gland to define an optimal correction factor therefore was to compare different techniques using the CT. We used computed tomography images obtained from 8 cadavers (2 females, 6 males) to calculate the thyroid volumes. In the present study, the actual thyroid volumes were measured using the water-displacement method as a gold standard, point-counting as a stereology, and ellipsoid methods. Mean squared errors and correction factors were calculated and modeled for each model to find an optimal correction factor and from 0.450 to 0.600 in steps of 0.001 separately for thyroid volume estimation. The average volume of the thyroid glands were 14.58 ± 9.84, 15.28 ± 9.38, and 14.97 ± 8.35 cm3 by fluid displacement, stereology and ellipsoid formula, respectively. No significant difference was found among the methods (P >0.05). The results of this study suggested that the volume of thyroid gland can be measured on CT scans stereologically for diagnosis, as will as provide reliable measure of thyroid volume, management and follow-up of thyroid diseases and for preoperative planning.

El cambio de volumen de la glándula tiroides es a menudo el síntoma de las condiciones patológicas más comunes de algunas enfermedades de dicha glándula. El cálculo exacto del volumen tiroideo es muy importante para la evaluación y el tratamiento de los trastornos tiroideos. El volumen de la glándula tiroides, utilizando la tomografía computarizada (TC), el ultrasonido (USG) y la resonancia magnética (RM) ha sido presentados en varias publicaciones. Sin embargo, aún no se ha determinado un gold standard. El propósito de este estudio fue estimar el volumen de la glándula tiroides normal para definir un factor de corrección óptimo, por lo que se compararon diferentes técnicas utilizando TC. Para calcular los volúmenes tiroideos se utilizaron imágenes de tomografía computarizada obtenidas de 8 cadáveres (dos mujeres y seis hombres). En el presente estudio, los volúmenes reales de la glándula tiroides se midieron utilizando como gold standard los métodos esterológicos de desplazamiento de agua y conteo de puntos y el método volumétrico elipsoide. Se calcularon y modelaron los errores cuadráticos medios y los factores de corrección para cada modelo con el objetivo de encontrar un factor de corrección óptimo y de 0,450 a 0,600 en pasos de 0,001 por separado para la estimación del volumen tiroideo. El volumen medio de las glándulas tiroides fue de 14,58 ± 9,84, 15,28 ± 9,38 y 14,97 ± 8,35 cm3 calculados por desplazamiento de fluido, estereología y fórmula elipsoide, respectivamente. No se encontró diferencia significativa entre los métodos (P>0,05). Los resultados de este estudio sugieren que el volumen de la glándula tiroides puede ser medido estereológicamente por TC, estableciéndose como una medida fiable del volumen tiroideo, para el diagnóstico, manejo y seguimiento de las enfermedades tiroideas y la planificación preoperatoria.

Utility of the Aspergillus galactomannan antigen testing for neutropenic paediatric patients.

Invasive aspergillosis (IA) is an increasingly important cause of morbidity and mortality particularly in paediatric patients. Early diagnosis and the initiation of efficacious antifungal treatments could affect the prognosis of these patients. The aim of this study was to determine the clinical contribution of Galactomannan (GM) screening in paediatric patients. We reviewed the records of all in-patients, and followed up, in the various units at the Medical Faculty Children's Hospital of Erciyes University (Kayseri, Turkey), those who had at least one GM assay result from August 2009 to April 2012. Paediatric patients were classified as proven, probable or possible, according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG). Twenty-five patients, with proven IA (n=3), probable IA (n=9) and possible IA (n=13) were included in the study. The GM antigen assay results were analysed in 158 blood samples from 47 patients. At the cut-off value of 0.5 ng/ml, the sensitivity was 68% [95% confidence interval (CI); 47-85]; specificity, 77% (95% CI; 55-92). To obtain more accurate results with GM testing, the diagnosis of IA should be confirmed by clinical investigation and the factors causing false positivity of the test should also be considered.

TcRαß-depleted haploidentical transplantation results in adult acute leukemia patients.

INTRODUCTION: The use of αß+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αß T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia. 84.4% of patients were in the high-risk group, and 55.9% were not in remission. The preparative regimen included thiotepa, melphalan, fludarabine, and anti-thymocyte globulin-Fresenius. Grafts were peripheral blood stem cells engineered by TcR-alpha/beta depletion. RESULTS: Neutrophil and platelet engraftment was achieved on days +12 (range, 10.5-15) and +11 (range, 10-12). All but three patients were engrafted with full donor chimerism. Grade III-IV acute GVHD occurred in two (5.9%) patients and chronic GVHD in two (6.1%). Disease-free survival and overall survival were 42 and 54% at 1 year, respectively. AML as disease type (HR: 4.87, 95% CI: 1.50-15.87) and mother as donor (HR: 1.05, 95% CI: 1.00-1.11) were found to be independent risk factors on patient survival. Mortality and NRM in the first 100 days were 5 of 34 (14.7%) and 4 of 34 (11.7%). Relapse was the main cause of death (56.3%). T-cell reconstitution appears to be faster than that reported in published data with CD3/CD19-depleted grafts. CONCLUSION: αß T-cell-depleted haploidentical transplantation may be a good alternative for high-risk patients if there are no human leukocyte antigen matched donors.

Palatine tonsil volume estimation using different methods after tonsillectomy.

This study was carried out to measure the volume of the palatine tonsil in otorhinolaryngology outpatients with complaints of adenotonsillar hypertrophy and chronic tonsillitis who had undergone tonsillectomy. To date, no study has investigated palatine tonsil volume using different methods and compared with subjective tonsil size in the literature. For this purpose, we used three different methods to measure palatine tonsil volume. The correlation of each parameter with tonsil size was assessed. After tonsillectomy, palatine tonsil volume was measured by Archimedes, Cavalieri and Ellipsoid methods. Mean right-left palatine tonsil volumes were calculated as 2.63 ± 1.34 cm3 and 2.72 ± 1.51 cm3 by the Archimedes method, 3.51 ± 1.48 cm3 and 3.37 ± 1.36 cm3 by the Cavalieri method, and 2.22 ± 1.22 cm3 and 2.29 ± 1.42 cm3 by the Ellipsoid method, respectively. Excellent agreement was found among the three methods of measuring volumetric techniques according to Bland-Altman plots. In addition, tonsil grade was correlated significantly with tonsil volume.

Increased Bone Marrow Iron Scores Are Strongly Correlated With Elevated Serum Ferritin Levels and Poorer Survival in Patients With Iron Overload That Underwent Allogeneic Hematopoietic Stem Cell Transplantation: A Single Center Experience.

BACKGROUND: Iron overload is one of the most significant problems as a leading cause of death in patients with leukemia and those who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). METHODS: In the current study, we retrospectively evaluated the bone marrow iron scores (BMIS) in patients who underwent alloHSCT (n = 125). The first available bone marrow biopsy specimens prior to the alloHSCT procedure or date of hospitalization (control group) were assessed in a blinded fashion using a standardized scoring system. RESULTS: A total of 125 patients were enrolled in the study. Seventy-six (60.8%) of the patients were male, and 49 (39.2%) were female. The median level of pre-transplant serum ferritin was 1023.00 ng/mL (range, 393.80-1627.50 ng/mL). The majority of the patients were diagnosed with acute leukemia (83; 66.4%) and lymphomas (20; 16.0%). The median time for neutrophil engraftment was 14.00 days (range, 13.00-16.00 days) and 11.00 days (range, 10.00-14.00 days) for platelet engraftment. The peri-transplant mortality was similar to international mortality rates (3; 2.4%). The overall survival and disease-free survival were strongly correlated with the degree of BMIS, and both were significantly poorer in patients with high bone marrow iron content (P < .001 and P = .012, respectively). CONCLUSION: The validation of BMIS for risk stratification in patients who undergo alloHSCT may predict posttransplant outcomes.

The role of platelet count, mean platelet volume, and the mean platelet volume/platelet count ratio in predicting postoperative vomiting in children after deep sedation.

OBJECTIVES: To determine the role of hemogram parameters such as platelet count (PLT), mean platelet volume (MPV), and the MPV/PLT ratio in predicting the risk of postoperative vomiting (POV) in children after tooth extraction under deep sedation. METHODS: A total of 100 American Society of Anesthesiology Classification I and II pediatric patients who underwent tooth extraction procedures under a standard anesthetic method were included in the study between 2012 and 2014. The study took place at the Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Erciyes University, Erciyes, Turkey Fifty patients without POV (group 1) and 50 patients with POV (group 2) were retrospectively selected randomly from the records of 885 consecutive patients. Age, gender, duration of the operation, and preoperative hemogram findings were recorded. RESULTS: There was a statistically significant difference between the 2 groups in terms of MPV (p less than 0.001), PLT (p=0.006), and MPV/PLT (p less than 0.001) ratio. Mean platelet volume and MPV/PLT ratio were higher in group 2, whereas PLT was higher in group 1. CONCLUSION: The PLT count, MPV, and MPV/PLT ratio may be used to predict POV in children.