ALBERT

Description: Background KDM6A, encoding a histone demethylase, is one of the top ten mutated epigenetic cancer genes. The effect of mutations on its structure and function are however poorly characterized. Methods Database search identified nonsense and missense mutations in the N-terminal TPR motifs and the C-terminal, catalytic JmjC domain, but also in the intrinsically disordered region connecting both these two well-structured domains. KDM6A variants with cancer-derived mutations were generated using site directed mutagenesis and fused to eGFP serving as an all-in-one affinity and fluorescence tag to study demethylase activity by an ELISA-based assay in vitro, apoptosis by FACS, complex assembly by Co-immunoprecipitation and localization by microscopy in urothelial cells and apoptosis by FACS. Results Independent of the mutation and demethylase activity, all KDM6A variants were detectable in the nucleus. Truncated KDM6A variants displayed changes in complex assemblies affecting (1) known interactions with the COMPASS complex component RBBP5 and (2) KDM6A-DNA associated assemblies with the nuclear protein Nucleophosmin. Some KDM6A variants induced a severe cellular phenotype characterized by multiple acute effects on nuclear integrity, namely, release of nuclear DNA into the cytoplasm, increased level of DNA damage indicators RAD51 and p-γH2A.X, and mitosis defects. These damaging effects were correlated with increased cell death. Conclusion These observations reveal novel effects of pathogenic variants pointing at new specific functions of KDM6A variants. The underlying mechanisms and affected pathways have to be investigated in future research to understand how tumor cells cope with and benefit from KDM6A truncations.

Description: Background One of the important components of the health system is the emergency medical services (EMS) system. The EMS system was implemented at Kerman University of Medical Sciences teaching hospitals to communicate the situation of patients being transferred to the hospital by EMS and to provide facilities tailored to the patient's condition. The objective of this study was to investigate the impact of the EMS system on the patient care process and the workflow of users. Methods The hospital information system (HIS) report was used to investigate the impact of the EMS system on the patient care process and a questionnaire was distributed among 244 participants to determine its impact on the workflow of the users. Mann–Whitney U was used to analyze HIS reports, and Chi-square was used to analyze the data collected by questionnaires. Results The EMS system reduced the patient's stay in hospital by an average of 3 h and 45 min. It also increased the number of patients' discharge from the emergency room to 2.2% and reduced the death rate by 1.3% (p 

Description: Background Cholesterol accumulation and calcium depletion induce hepatic injury via the endoplasmic reticulum (ER) stress response. ER stress regulates the calcium imbalance between the ER and mitochondria. We previously reported that phosphatase of regenerating liver-1 (PRL-1)-overexpressing placenta-derived mesenchymal stem cells (PD-MSCsPRL−1) promoted liver regeneration via mitochondrial dynamics in a cirrhotic rat model. However, the role of PRL-1 in ER stress-dependent calcium is not clear. Therefore, we demonstrated that PD-MSCsPRL−1 improved hepatic functions by regulating ER stress and calcium channels in a rat model of bile duct ligation (BDL). Methods Liver cirrhosis was induced in Sprague–Dawley (SD) rats using surgically induced BDL for 10 days. PD-MSCs and PD-MSCsPRL−1 (2 × 106 cells) were intravenously administered to animals, and their therapeutic effects were analyzed. WB-F344 cells exposed to thapsigargin (TG) were cocultured with PD-MSCs or PD-MSCsPRL−1. Results ER stress markers, e.g., eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were increased in the nontransplantation group (NTx) compared to the control group. PD-MSCsPRL−1 significantly decreased ER stress markers compared to NTx and induced dynamic changes in calcium channel markers, e.g., sarco/endoplasmic reticulum Ca2+ -ATPase 2b (SERCA2b), inositol 1,4,5-trisphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU), and voltage-dependent anion channel 1 (VDAC1) (*p 

Description: Objective To develop a collision engine (haptic force feedback simulator) compatible with a 5-degrees-of-freedom (DOF) haptic wand. This has broad applications such as telerobotic ultrasound systems. Integrating force feedback into systems is critical to optimize remote scanning. A collision engine compatible with a 5-DOF haptic wand was developed based on the Gilbert–Johnson–Keerthi algorithm. The collision engine calculated force during collision between the wand and a virtual object based on code developed using MATLAB. A proportional force was subsequently returned to a user via the haptic wand, thereby simulating the collision force for the user. Three experiments were conducted to assess the accuracy of the collision engine on curved and flat surfaces. Results The average errors in calculation of distances between the wand and virtual object were 2.1 cm, 3.4 cm, and 4.2 cm for the model of the human hand, cylinder, and cuboid, respectively. The collision engine accurately simulated forces on a flat surface, though was less accurate on curved surfaces. Future work will incorporate haptic force feedback into a telerobotic ultrasound system. The haptic force simulator presented here may also be used in the development of ultrasound simulators for training and education.

Description: Objective In previous studies using Illumina Infinium methylation arrays, we have identified DNA methylation marks associated with cancer predisposition and progression. In the present study, we have sought to find appropriate technology to both technically validate our data and expand our understanding of DNA methylation in these genomic regions. Here, we aimed to assess the repeatability of methylation measures made using QIAseq targeted methyl panel and to compare them with those obtained from the Illumina HumanMethylation450 (HM450K) assay. We included in the analysis high molecular weight DNA extracted from whole blood (WB) and DNA extracted from formalin-fixed paraffin-embedded tissues (FFPE). Results The repeatability of QIAseq-methylation measures was assessed at 40 CpGs, using the Intraclass Correlation Coefficient (ICC). The mean ICCs and 95% confidence intervals (CI) were 0.72 (0.62–0.81), 0.59 (0.47–0.71) and 0.80 (0.73–0.88) for WB, FFPE and both sample types combined, respectively. For technical replicates measured using QIAseq and HM450K, the mean ICCs (95% CI) were 0.53 (0.39–0.68), 0.43 (0.31–0.56) and 0.70 (0.59–0.80), respectively. Bland–Altman plots indicated good agreement between QIAseq and HM450K measurements. These results demonstrate that the QIAseq targeted methyl panel produces reliable and reproducible methylation measurements across the 40 CpGs that were examined.

Description: Objectives Financial protection mechanisms are in place to overcome the costs of a few diseases in India. Our objective was to estimate the costs incurred due to Oral Potentially Malignant Disorders (OPMD) and to determine predictors of such costs. Results We found that the median (Interquartile range IQR) total costs of OPMD was Indian Rupees (INR) 500 (350–750), direct medical costs was INR 0 (0–50), direct non-medical costs was INR 150 (40–200) and indirect costs was INR 350 (250–500). The travel cost to attend the health facilities [INR 100 (40–150)] and the patient’s loss of wages [INR 200 (150–400)] mainly accounted for the direct non-medical and indirect costs respectively. The median expenditure on smokeless and smoking forms of tobacco was INR 6000 (5400–7200) and INR 2400 (1800–3600) respectively. On multiple linear regression analysis, rural residence, belonging to below poverty line family, being a sole earner in the family, number of months since diagnosis and first visit at a private provider were found to be the significant predictors of total costs of OPMD. Financial protection mechanisms are needed for covering the direct non-medical and indirect costs. Early management of OPMD might mitigate the costs of OPMD.

Description: Objective Near visual impairment (VI) is a common disability in an aging population. Near vision is crucial in activity of daily living including reading, smartphone and computer use and meal preparation. This study was conducted to determine the association between near visual acuity (VA) and contrast sensitivity (CS) with activity of daily living (ADL) among visually impaired older adults. Results A total of 208 participants aged  ≥  60 were recruited from the population-based longitudinal study on neuroprotective model for healthy longevity. Habitual near VA and CS were measured using Lighthouse near VA chart and Pelli-Robson CS chart, respectively. Lawton instrumental activities of daily living (IADL) was used to assess ADL. There are 41.8% participants with near visual impairment and 28.7% among them had IADL disability. Independent t test showed significant lower mean IADL score among visually impaired participants [t(206)  =  2.03, p  =  0.04]. IADL score significantly correlated with near VA (r  =   − 0.21, p  =  0.05) but not with CS (r  =   − 0.14, p = 0.21). Near VA (B  =   − 0.44, p  =  0.03) and age (B  =   − 0.07, p  =  0.01) significantly predicted IADL. The findings show poorer VA renders higher IADL disability, which may necessitate interventions to improve ADL among visually impaired older adults.

Description: Background Undernutrition is the main cause of child death in developing countries. This paper aimed to explore the efficacy of machine learning (ML) approaches in predicting under-five undernutrition in Ethiopian administrative zones and to identify the most important predictors. Method The study employed ML techniques using retrospective cross-sectional survey data from Ethiopia, a national-representative data collected in the year (2000, 2005, 2011, and 2016). We explored six commonly used ML algorithms; Logistic regression, Least Absolute Shrinkage and Selection Operator (L-1 regularization logistic regression), L-2 regularization (Ridge), Elastic net, neural network, and random forest (RF). Sensitivity, specificity, accuracy, and area under the curve were used to evaluate the performance of those models. Results Based on different performance evaluations, the RF algorithm was selected as the best ML model. In the order of importance; urban–rural settlement, literacy rate of parents, and place of residence were the major determinants of disparities of nutritional status for under-five children among Ethiopian administrative zones. Conclusion Our results showed that the considered machine learning classification algorithms can effectively predict the under-five undernutrition status in Ethiopian administrative zones. Persistent under-five undernutrition status was found in the northern part of Ethiopia. The identification of such high-risk zones could provide useful information to decision-makers trying to reduce child undernutrition.

Description: Purpose Some predictive systems using machine learning models have been developed to predict sepsis; however, they were mostly built with a low percent of missing values, which does not correspond with the actual clinical situation. In this study, we developed a machine learning model with a high rate of missing and erroneous data to enable prediction under missing, noisy, and erroneous inputs, as in the actual clinical situation. Materials and methods The proposed artificial neural network model was implemented using the MATLAB ANN toolbox, based on stochastic gradient descent. The dataset was collected over the past decade with approval from the appropriate institutional review boards, and the sepsis status was identified and labeled using Sepsis-3 clinical criteria. The imputation method was built by last observation carried forward and mean value, aimed to simulate clinical situation. Results The mean area under the receiver operating characteristic (ROC) curve (AUC) of classifying sepsis and nonsepsis patients was 0.82 and 0.786 at 0 h and 40 h prior to onset, respectively. The highest model performance was found for one-hourly data, demonstrating that our ANN model can perform adequately with limited hourly data provided. Conclusions Our model has the moderate ability to predict sepsis up to 40 h in advance under simulated clinical situation with real-world data.

Description: Objective Although perceived neighbourhood environment is considered a predictor of leisure-time physical activity (LTPA), evidence for this is limited in South Asia. Thus, the aim was to determine the association between neighbourhood social and built environment features in carrying out LTPA among adults in Colombo District, Sri Lanka. A cross-sectional study among 1320 adults was carried out using validated questionnaires for physical activity (PA) and built environment data collection. Multiple logistic regression analysis was conducted to assess the associations between environment characteristics and LTPA after adjusting for gender, age, employment status, income level and sector of residence. Results A total of 21.7% of adults participated in some LTPA. The commonest type of LTPA was walking; carried out by 14.5%. Moderate and vigorous activity at leisure was carried out by 10.3% and 3.9% respectively. Perceived social acceptance for PA was positively associated with LTPA. Out of the built environment characteristics perceived infrastructure for walking, and recreational facilities for PA were negatively associated with LTPA. Self-efficacy emerged as an important positive correlate of LTPA. The participants were positively influenced by the self-efficacy and perceived social environment which should be addressed when promoting LTPA.