Developing Children's Oral Health Assessment Toolkits Using Machine Learning Algorithm.

ObjectivesEvaluating children's oral health status and treatment needs is challenging. We aim to build oral health assessment toolkits to predict Children's Oral Health Status Index (COHSI) score and referral for treatment needs (RFTN) of oral health. Parent and Child toolkits consist of short-form survey items (12 for children and 8 for parents) with and without children's demographic information (7 questions) to predict the child's oral health status and need for treatment.MethodsData were collected from 12 dental practices in Los Angeles County from 2015 to 2016. We predicted COHSI score and RFTN using random Bootstrap samples with manually introduced Gaussian noise together with machine learning algorithms, such as Extreme Gradient Boosting and Naive Bayesian algorithms (using R). The toolkits predicted the probability of treatment needs and the COHSI score with percentile (ranking). The performance of the toolkits was evaluated internally and externally by residual mean square error (RMSE), correlation, sensitivity and specificity.ResultsThe toolkits were developed based on survey responses from 545 families with children aged 2 to 17 y. The sensitivity and specificity for predicting RFTN were 93% and 49% respectively with the external data. The correlation(s) between predicted and clinically determined COHSI was 0.88 (and 0.91 for its percentile). The RMSEs of the COHSI toolkit were 4.2 for COHSI (and 1.3 for its percentile).ConclusionsSurvey responses from children and their parents/guardians are predictive for clinical outcomes. The toolkits can be used by oral health programs at baseline among school populations. The toolkits can also be used to quantify differences between pre- and post-dental care program implementation. The toolkits' predicted oral health scores can be used to stratify samples in oral health research.Knowledge transfer statementThis study creates the oral health toolkits that combine self- and proxy- reported short forms with children's demographic characteristics to predict children's oral health and treatment needs using Machine Learning algorithms. The toolkits can be used by oral health programs at baseline among school populations to quantify differences between pre and post dental care program implementation. The toolkits can also be used to stratify samples according to the treatment needs and oral health status

Rapid Identification of Pathogenic Variants in Two Cases of Charcot-Marie-Tooth Disease by Gene-Panel Sequencing

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Patient dosimetry for 90Y selective internal radiation treatment based on 90Y PET imaging

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Increasing access to erectile dysfunction treatment via pharmacies to improve healthcare provider visits and quality of life: Results from a prospective real-world observational study in the United Kingdom

OBJECTIVES: The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) formally reclassified sildenafil citrate 50 mg tablets as a pharmacy medicine (sildenafil-P) in 2017 for adult men with erectile dysfunction (ED). A 1-year prospective real-world observational study was conducted to track men's health behaviour, particularly their healthcare resource utilisation (HCRU) and quality of life (QoL) before and after the availability of sildenafil-P. METHODS: Adult men with ED aged ≥18 years provided data at baseline (prior to launch of sildenafil-P) and every 3 months after the launch. Demographics, health characteristics, treatments at baseline and HCRU, including number of pharmacist and physician/nurse practitioner visits over time are reported. QoL-related outcomes were assessed via the Self-Esteem and Relationship Questionnaire (SEAR), 2-Item Patient Health Questionnaire and ratings of sexual satisfaction. Generalised linear models were used to assess the association of sildenafil-P use with total physician/nurse practitioner and pharmacist visits and QoL-related outcomes at 12 months. RESULTS: Overall, 1162 men completed the survey at all 5 time points. The mean ± SD age was 59.02 ± 12.06 years; 55.42% reported having a moderate-to-severe ED. Hypertension (37.52%) and hypercholesterolaemia (31.50%) were the most common risk factors for ED. At baseline, 62.99% were not using any ED treatment. After adjusting for baseline visits/other covariates, mean physician/nurse practitioner (3.68 vs 2.87; P = .003) and pharmacist visits for any reason (2.10 vs 1.34; P < .001) at 12 months were significantly higher among sildenafil-P users than those who never used sildenafil-P. Sildenafil-P users also had significantly higher SEAR total and domain (sexual relationship and self-esteem) scores at 12 months. CONCLUSION: Following the reclassification to a pharmacy medicine in the UK, sildenafil-P was associated with a higher number of physician/nurse practitioner and pharmacist visits for any reason. Sildenafil-P use was also associated with better QoL, although group differences were small in magnitude

A simple and robust method for connecting small-molecule drugs using gene-expression signatures

Interaction of a drug or chemical with a biological system can result in a gene-expression profile or signature characteristic of the event. Using a suitably robust algorithm these signatures can potentially be used to connect molecules with similar pharmacological or toxicological properties. The Connectivity Map was a novel concept and innovative tool first introduced by Lamb et al to connect small molecules, genes, and diseases using genomic signatures [Lamb et al (2006), Science 313, 1929-1935]. However, the Connectivity Map had some limitations, particularly there was no effective safeguard against false connections if the observed connections were considered on an individual-by-individual basis. Further when several connections to the same small-molecule compound were viewed as a set, the implicit null hypothesis tested was not the most relevant one for the discovery of real connections. Here we propose a simple and robust method for constructing the reference gene-expression profiles and a new connection scoring scheme, which importantly allows the valuation of statistical significance of all the connections observed. We tested the new method with the two example gene-signatures (HDAC inhibitors and Estrogens) used by Lamb et al and also a new gene signature of immunosuppressive drugs. Our testing with this new method shows that it achieves a higher level of specificity and sensitivity than the original method. For example, our method successfully identified raloxifene and tamoxifen as having significant anti-estrogen effects, while Lamb et al's Connectivity Map failed to identify these. With these properties our new method has potential use in drug development for the recognition of pharmacological and toxicological properties in new drug candidates.Comment: 8 pages, 2 figures, and 2 tables; supplementary data supplied as a ZIP fil

Finite Fault Analysis and Near Field Dynamic Strains and Rotations due to the 11/05/2011 (Mw5.2) Lorca Earthquake, South-Eastern Spain

The 11/5/2011 Lorca, Spain earthquake (Mw5.2) and related seismicity produced extensive damage in the town of Lorca and vicinity. During these earthquakes, evidence of rotations and permanent deformations in structures were observed. To analyze these aspects and study the source properties from the near field, the displacement time histories were obtained including the static component at Lorca station. Displacement time histories were computed by an appropriate double time integration procedure of accelerograms. Using these data, the foreshock and mainshock slip distributions were calculated by means of a complete waveform kinematic inversion. To study the dynamic deformations, the 3D tensor of displacement gradients at Lorca station was first estimated by a single station method. Using the finite fault inversion results and by means of a first order finite difference approach, the dynamic deformations tensor at surface was calculated at the recording site. In order to estimate the distribution of the peak dynamic deformations, the calculation was extended to the close neighboring area of the town. The possible influence of the near-field deformations on the surface structures was analyzed.Comment: 29 pages, 8 figure

In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

GENIE: a software package for gene-gene interaction analysis in genetic association studies using multiple GPU or CPU cores

<p>Abstract</p> <p>Background</p> <p>Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs) have multiple cores, whereas Graphics Processing Units (GPUs) also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits.</p> <p>Findings</p> <p>Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1) the interaction of SNPs within it in parallel, and 2) the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run.</p> <p>Conclusions</p> <p>GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from <url>http://www.cceb.upenn.edu/~mli/software/GENIE/</url>.</p

Association of decreased mitochondrial DNA content with ovarian cancer progression

Mitochondrial DNA (mtDNA) content in ovarian carcinomas was assessed by quantitative PCR. Results show that mtDNA content in tumour cell was significantly higher than that in normal ovary. Change in mtDNA content was not related with patients' age or tumour stages. However, the average mtDNA copy number in pathological low-grade tumours was over two-fold higher than that in high-grade carcinomas (P=0.012). Moreover, type I carcinomas also had a significantly higher mtDNA copy number than in type II carcinomas (P=0.019). Change in mtDNA content might be an important genetic event in the progression of ovarian carcinomas