Tightly integrated genomic and epigenomic data mining using tensor decomposition.

Motivation: Complex diseases such as cancers often involve multiple types of genomic and/or epigenomic abnormalities. Rapid accumulation of multiple types of omics data demands methods for integrating the multidimensional data in order to elucidate complex relationships among different types of genomic and epigenomic abnormalities.

Results: In the present study, we propose a tightly integrated approach based on tensor decomposition.

A cross-sectional study of asymptomatic Plasmodium falciparum infection burden and risk factors in general population children in 12 villages in northern Uganda.

Background: Plasmodium falciparum malaria is an important cause of morbidity in northern Uganda. This study was undertaken to assess village-, household-, and individual-level risk factors of asymptomatic falciparum malaria in children in 12 villages in northern Uganda.

Methods: Between 10/2011 and 02/2014, 1006 apparently healthy children under 16 years old were enrolled in 12 villages using a stratified, multi-stage, cluster survey design and assessed for P.

State Prevalence and Ranks of Adolescent Substance Use: Implications for Cancer Prevention.

Introduction: This study statistically ranked states' performance on adolescent substance use related to cancer risk (past-month cigarette smoking, binge alcohol drinking, and marijuana use).

Methods: Data came from 69,200 adolescent participants (50 states and the District of Columbia) in the National Survey on Drug Use and Health (NSDUH) and 450,050 adolescent participants (47 states) in the Youth Risk Behavior Surveillance System (YRBSS). Adolescents were aged 14 to 17 years.

Estimating onset time from longitudinal and cross-sectional data with an application to estimating gestational age from longitudinal maternal anthropometry during pregnancy and neonatal anthropometry at birth.

Determining the date of conception is important for estimating gestational age and monitoring whether the fetus and mother are on track in their development and pregnancy. Various methods based on ultrasound have been proposed for dating a pregnancy in high resource countries. However, such techniques may not be available in under-resourced countries.

Correlation of gene expression and associated mutation profiles of APOBEC3A, APOBEC3B, REV1, UNG, and FHIT with chemosensitivity of cancer cell lines to drug treatment.

Background: The APOBEC gene family of cytidine deaminases plays important roles in DNA repair and mRNA editing. In many cancers, APOBEC3B increases the mutation load, generating clusters of closely spaced, single-strand-specific DNA substitutions with a characteristic hypermutation signature. Some studies also suggested a possible involvement of APOBEC3A, REV1, UNG, and FHIT in molecular processes affecting APOBEC mutagenesis.

The Immune Landscape of Cancer.

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers.

Lens Dose Reduction by Patient Posture Modification During Neck CT.

Objective: Radiation exposure of the lens during neck CT may increase a patient's risk of developing cataracts. Radiologists at the National Institutes of Health worked with technicians to modify the neck CT scanning procedure to include a reduction in the scanning range, a reduction in the tube potential (kilovoltage), and a change in neck positioning using a head tilt. We objectively quantified the organ dose changes after this procedure modification using a computer simulation.

Male urinary biomarkers of antimicrobial exposure and bi-directional associations with semen quality parameters.

Antimicrobials including parabens, triclosan, and triclocarban have endocrine disrupting properties. Among 501 male partners of couples planning to become pregnant, preconception urinary biomarkers of parabens, triclosan and triclocarban exposure were quantified in spot urine samples. Men also provided two fresh semen samples collected approximately one month to undergo 24-h semen quality analysis.

A U.S. Multicenter Study of Recorded Occupational Radiation Badge Doses in Nuclear Medicine.

Purpose To summarize occupational badge doses recorded for a sample of U.S. nuclear medicine technologists.

Five criteria for using a surrogate endpoint to predict treatment effect based on data from multiple previous trials.

A surrogate endpoint in a randomized clinical trial is an endpoint that occurs after randomization and before the true, clinically meaningful, endpoint that yields conclusions about the effect of treatment on true endpoint. A surrogate endpoint can accelerate the evaluation of new treatments but at the risk of misleading conclusions. Therefore, criteria are needed for deciding whether to use a surrogate endpoint in a new trial.

A computational study of the inhibition mechanisms of P-glycoprotein mediated paclitaxel efflux by kinase inhibitors.

Background: Drug resistance mediated by P-glycoprotein (P-gp) renders many cancer therapies ineffective. One P-gp substrate is the widely used chemotherapy drug paclitaxel. Co-administration of paclitaxel and another drug that inhibits P-gp may enhance the therapeutic effectiveness of paclitaxel by preventing its efflux from tumor cells.

Ultrasound tomography imaging with waveform sound speed: Parenchymal changes in women undergoing tamoxifen therapy.

Ultrasound tomography (UST) is an emerging modality that can offer quantitative measurements of breast density. Recent breakthroughs in UST image reconstruction involve the use of a waveform reconstruction as opposed to a ray-based reconstruction. The sound speed (SS) images that are created using the waveform reconstruction have a much higher image quality.

Cataract Risk in a Cohort of U.S. Radiologic Technologists Performing Nuclear Medicine Procedures.

Purpose To estimate the risk of cataract in a cohort of nuclear medicine (NM) radiologic technologists on the basis of their work histories and radiation protection practices. Materials and Methods In the years 2003-2005 and 2012-2013, 42 545 radiologic technologists from a U.S.

Lung Cancer Risk Associated With New Solid Nodules in the National Lung Screening Trial.

Objective: As low-dose CT (LDCT) lung cancer screening moves into routine clinical practice, evaluation of nodules identified as new becomes critical. We examine the frequency and clinical outcomes of new lung nodules reported at the two postbaseline annual screening examinations (hereafter referred to as postbaseline time 1 [T1] and time 2 [T2]), compared with those detected at baseline in the National Lung Screening Trial.

Materials And Methods: Radiologists classified nodules detected at T1 and T2 as new or preexisting on the basis of comparison with findings from prior LDCT screening examinations.

Livestock and poultry density and childhood cancer incidence in nine states in the USA.

Background: Parental occupational and childhood exposures to farm animals have been positively associated with childhood brain tumors, whereas associations with childhood leukemia are equivocal. The developing immune system may be influenced by allergen, virus, or other exposures from animal sources, which may contribute to childhood cancer incidence.

Methods: Incident cancers (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], central nervous system [CNS], peripheral nervous system [PNS]) for children aged 0-4 diagnosed between 2003 and 2008 were obtained from nine National Cancer Institute Surveillance, Epidemiology and End Results (SEER) registries and were linked to U.

p53 signaling pathway polymorphisms, cancer risk and tumor phenotype in TP53 R337H mutation carriers.

Li-Fraumeni and Li-Fraumeni-like syndrome (LFS/LFL) are clinically heterogeneous cancer predisposition syndromes characterized by diagnosis of early-onset and often multiple cancers with variable tumor patterns and incomplete penetrance. To date, the genetic modifiers described in LFS/LFL have been shown to map to either TP53 or its main negative regulator, MDM2. Additionally, all studies were focused on families with different TP53 germline mutations.

Leukocyte telomere length and renal cell carcinoma survival in two studies.

Background: Leukocyte telomere length (LTL) is a potential biomarker of cancer prognosis; however, evidence for renal cell carcinoma (RCC) is inconsistent.

Methods: We investigated LTL and RCC-specific survival among 684 cases from the US kidney cancer study (USKC) and 241 cases from the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO). Leukocyte telomere length was measured by quantitative polymerase chain reaction, and hazard ratios (HRs) and 95% confidence intervals (CIs) computed using multivariable Cox models.

DATS, the data tag suite to enable discoverability of datasets.

Today's science increasingly requires effective ways to find and access existing datasets that are distributed across a range of repositories. For researchers in the life sciences, discoverability of datasets may soon become as essential as identifying the latest publications via PubMed. Through an international collaborative effort funded by the National Institutes of Health (NIH)'s Big Data to Knowledge (BD2K) initiative, we have designed and implemented the DAta Tag Suite (DATS) model to support the DataMed data discovery index.

Clinical decisions surrounding genomic and proteomic testing among United States veterans treated for lung cancer within the Veterans Health Administration.

Background: Current clinical guidelines recommend epidermal growth factor receptor (EGFR) mutational testing in patients with metastatic non-small cell lung cancer (NSCLC) to predict the benefit of the tyrosine kinase inhibitor erlotinib as first-line treatment. Proteomic (VeriStrat) testing is recommended for patients with EGFR negative or unknown status when erlotinib is being considered. Departure from this clinical algorithm can increase costs and may result in worse outcomes.

Using Bayesian modeling in frequentist adaptive enrichment designs.

Our increased understanding of the mechanistic heterogeneity of diseases has pushed the development of targeted therapeutics. We do not expect all patients with a given disease to benefit from a targeted drug; only those in the target population. That is, those with sufficient dysregulation in the biomolecular pathway targeted by treatment.

Occupational Radiation Exposure and Deaths From Malignant Intracranial Neoplasms of the Brain and CNS in U.S. Radiologic Technologists, 1983-2012.

Objective: Childhood exposure to acute, high-dose radiation has consistently been associated with risk of benign and malignant intracranial tumors of the brain and CNS, but data on risks of adulthood exposure to protracted, low-to-moderate doses of radiation are limited. In a large cohort of radiologic technologists, we quantified the association between protracted, low-to-moderate doses of radiation and malignant intracranial tumor mortality.

Materials And Methods: The study population included 83,655 female and 26,642 male U.

Cervical cancer prevention in El Salvador (CAPE)-An HPV testing-based demonstration project: Changing the secondary prevention paradigm in a lower middle-income country.

•CareHPV tests were used to compare screen-and-treat and colposcopy management.•Screen-and-treat strategy with HPV testing was found to be very cost-effective.•CAPE has screened > 25,000 women in the Paracentral region.

Body Size-Specific Organ and Effective Doses of Chest CT Screening Examinations of the National Lung Screening Trial.

Objective: We calculated body size-specific organ and effective doses for 23,734 participants in the National Lung Screening Trial (NLST) using a CT dose calculator.

Materials And Methods: We collected participant-specific technical parameters of 23,734 participants who underwent CT in the clinical trial. For each participant, we calculated two sets of organ doses using two methods.

Mortality in U.S. Physicians Likely to Perform Fluoroscopy-guided Interventional Procedures Compared with Psychiatrists, 1979 to 2008.

Purpose To compare total and cause-specific mortality rates between physicians likely to have performed fluoroscopy-guided interventional (FGI) procedures (referred to as FGI MDs) and psychiatrists to determine if any differences are consistent with known radiation risks. Materials and Methods Mortality risks were compared in nationwide cohorts of 45 634 FGI MDs and 64 401 psychiatrists. Cause of death was ascertained from the National Death Index.

MEN1 and microRNAs: The link between sporadic pituitary, parathyroid and adrenocortical tumors?

Sporadic tumors of the pituitary, parathyroids and adrenal cortex are unique, as their benign forms are very common, but malignant forms are exceptionally rare. Hereditary forms of these tumors occur in multiple endocrine neoplasia syndrome type 1 (MEN1). We hypothesize that the pathogenic link among the sporadic tumors of these organs of different germ layers might be represented by common molecular pathways involving the MEN1 gene and microRNAs (miR).