Bayesian Statistics Improves Biological Interpretability of Metabolomics Data from Human Cohorts.

Univariate analyses of metabolomics data currently follow a frequentist approach, using -values to reject a null hypothesis. We here propose the use of Bayesian statistics to quantify evidence supporting different hypotheses and discriminate between the null hypothesis versus the lack of statistical power. We used metabolomics data from three independent human cohorts that studied the plasma signatures of subjects with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

C-Terminal p53 Palindromic Tetrapeptide Restores Full Apoptotic Function to Mutant p53 Cancer Cells In Vitro and In Vivo.

We previously demonstrated that a synthetic monomer peptide derived from the C-terminus of p53 (aa 361−382) induced preferential apoptosis in mutant p53 malignant cells, but not normal cells. The major problem with the peptide was its short half-life (half-life < 10 min.) due to a random coil topology found in 3D proton NMR spectroscopy studies.

DNA repair phenotype and cancer risk: a systematic review and meta-analysis of 55 case-control studies.

DNA repair phenotype can be measured in blood and may be a potential biomarker of cancer risk. We conducted a systematic review and meta-analysis of epidemiological studies of DNA repair phenotype and cancer through March 2021. We used random-effects models to calculate pooled odds ratios (ORs) of cancer risk for those with the lowest DNA repair capacity compared with those with the highest capacity.

Incidence of hepatocellular carcinoma in a community-based Taiwanese population without chronic HBV/HCV infection.

Background & Aims: In addition to HBV/HCV causing hepatocellular carcinoma (HCC), other risk factors including obesity and alcohol drinking also increase risk. We describe the cumulative risk of HCC and mortality from liver-related disease by selected modifiable risk factors among a non-hepatitis virus-infected population.

Methods: For a community-based cohort, residents aged 30-65 years living in 7 townships in Taiwan were recruited, and have been followed up since 1991.

Environmental exposure and clinical correlates of hepatocellular carcinoma in New York City: a case only study.

In the U.S., Hepatocellular carcinoma (HCC) incidence rates have increased.

Reproductive and environmental exposures and the breast cancer risk in Taiwanese women.

Breast cancer (BC) incidence is increasing around the globe, including in Taiwan, though the cause of the increasing incidence is less clear. We followed up 11,296 Taiwanese females who did not have BC at baseline, and ascertained new invasive BC (N = 351) through data linkage to the National Cancer Registry from 1991 to 2018 to examine whether reproductive, lifestyle and environmental risk factors including polycyclic aromatic hydrocarbons (PAH) were associated with BC risk. We conducted a nested case-control study using baseline blood available from a total of 305 women with BC and 598 women without BC matched on time in cohort.

Odor identification impairment and cholinesterase inhibitor treatment in Alzheimer's disease.

Introduction: This study evaluated acute change in odor identification following atropine nasal spray challenge, and 8-week change in odor identification ability, as a predictor of long-term improvement in patients with mild to moderate Alzheimer's disease (AD) who received open-label cholinesterase inhibitor treatment.

Methods: In patients with clinical AD, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Patients were then treated with donepezil for 52 weeks.

Evaluating Nonresponse Weighting Adjustment for the Population-Based HIV Impact Assessment Surveys on Incorporating Survey Outcomes.

Background: The nonresponse weighting adjustment of the Population-based HIV Impact Assessment (PHIA) surveys uses the weighting class method in combination with a tree analysis to identify predictors significant to response propensity. Variable selection for this type of nonresponse adjustment identifies auxiliary variables correlated with response propensity alone and produces 1 set of weights applicable for all analyses of the survey data. An alternative approach identifies auxiliary variables correlated to both the response probability and selected key outcome variables.

Influence of pubertal development on urinary oxidative stress biomarkers in adolescent girls in the New York LEGACY cohort.

Puberty is a time of intense growth and differentiation of breast tissue and a window of susceptibility (WOS) for breast cancer. Although oxidative stress markers have been associated with breast cancer risk, it is unclear whether oxidative stress levels are different during the pubertal WOS, and if so, whether these differences are related to breast cancer susceptibility. We measured urinary biomarkers of whole body oxidative stress (urinary F2-Isoprostanes and 8-oxodeoxyguanosine (8-oxodG)) in 158 girls (ages 6-13 years), 71 with and 87 without a breast cancer family history (BCFH) from a cohort of adolescent girls from the New York site of the LEGACY cohort (Lessons in Epidemiology and Genetics in Adults Cancer from Youth).

The Diversity and Distribution of Viruses Associated with Mosquitoes from the Kimberley Region of Western Australia.

Metagenomics revealed an impressive breadth of previously unrecognized viruses. Here, we report the virome of the Skuse mosquito, an important vector of pathogenic arboviruses in Australia. Mosquitoes were collected from three sites in the Kimberley region of Western Australia.

High levels of global genome methylation in patients with retinoblastoma.

Retinoblastoma is a tumor of the embryonic neural retina in young children. The DNA methyltransferase 1 () gene has been demonstrated to be transcriptionally activated in cells lacking retinoblastoma 1 (). Thus, there is a direct interaction between and .

Discordant attitudes and beliefs about cancer clinical trial participation between physicians, research staff, and cancer patients.

Background/aims: Essential to bringing innovative cancer treatments to patients is voluntary participation in clinical trials but approximately 8% of American cancer patients are enrolled onto a trial. We used a domain-oriented framework to assess barriers to cancer clinical trial enrollment.

Methods: Physicians (MD, DO, fellows, residents) and research staff (physician assistants, nurse practitioners, staff and research nurses, clinical assistants, and program coordinators) involved in clinical research at a comprehensive cancer center completed an online survey in 2017; adult cancer patients not currently enrolled in a trial were interviewed in 2018.

DEvis: an R package for aggregation and visualization of differential expression data.

Background: Existing tools for the aggregation and visualization of differential expression data have discrete functionality and require that end-users rely on multiple software packages with complex dependencies or manually manipulate data for analysis and interpretation. Furthermore, at present, data aggregation and visualization are laborious, time consuming, and subject to human error. This is a serious limitation on the current state of differential transcriptomic analysis, which makes it necessary to expend extensive time and resources to reach the point where biological meaning can be interpreted.

DDT exposure during pregnancy and DNA methylation alterations in female offspring in the Child Health and Development Study.

Studies measuring dichlorodiphenyltrichloroethane (DDT) exposure during key windows of susceptibility including the intrauterine period suggest that DDT exposure is associated with breast cancer risk. We hypothesized that prenatal DDT exposure is associated with DNA methylation. Using prospective data from 316 daughters in the Child Health and Development Study, we examined the association between prenatal exposure to DDTs and DNA methylation in blood collected in midlife (mean age: 49 years).

Cancer screening in the homeless population.

Annually, 100 million people experience homelessness worldwide. Most adults that are struggling with homelessness are living to age 50 years or older and need age-appropriate screening for cancer. Cancer-related death in homeless adults is twice as high as the average in the adult population in the USA.

Soot and the city: Evaluating the impacts of Clean Heat policies on indoor/outdoor air quality in New York City apartments.

New York City has had a long history of implementing local policies to reduce air pollution. Enacted as a part of PlaNYC, the Clean Heat policies aim to lower wintertime ambient air pollution by phasing out dirty No. 6 heating fuel oil and transitioning to comparatively cleaner No.

Breast cancer family history and allele-specific DNA methylation in the legacy girls study.

Family history, a well-established risk factor for breast cancer, can have both genetic and environmental contributions. Shared environment in families as well as epigenetic changes that also may be influenced by shared genetics and environment may also explain familial clustering of cancers. Epigenetic regulation, such as DNA methylation, can change the activity of a DNA segment without a change in the sequence; environmental exposures experienced across the life course can induce such changes.

Change in Odor Identification Impairment is Associated with Improvement with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment.

Background: Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease pathology.

Objective: To determine if decline in odor identification ability with anticholinergic challenge can predict improvement with donepezil, a cholinesterase inhibitor (ChEI), in patients with mild cognitive impairment (MCI).

Methods: At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge.

Plasma DNA methylation marker and hepatocellular carcinoma risk prediction model for the general population.

Metastases in the later stages of hepatocellular carcinoma (HCC) cause the majority of deaths associated with the disease, making early detection crucial to patient survival. Risk models assessing HCC risk in the general population can be used for risk stratification for further HCC surveillance, however, none have been validated externally. Methylation of circulating DNA shows potential for non-invasive diagnosis of HCC.

Towards precision prevention: Technologies for identifying healthy individuals with high risk of disease.

The rise of advanced technologies for characterizing human populations at the molecular level, from sequence to function, is shifting disease prevention paradigms toward personalized strategies. Because minimization of adverse outcomes is a key driver for treatment decisions for diseased populations, developing personalized therapy strategies represent an important dimension of both precision medicine and personalized prevention. In this commentary, we highlight recently developed enabling technologies in the field of DNA damage, DNA repair, and mutagenesis.

Prenatal tobacco exposure, birthweight, and offspring psychopathology.

Although prenatal tobacco exposure (PTE) is associated with several adverse offspring mental health outcomes, mechanisms remain unclear. We test whether associations between PTE and offspring psychopathology are explained by birthweight, one of the earliest-occurring outcomes of PTE. The analysis focuses on 238 offspring from a family study of depression with (1) collected prenatal histories and (2) at least one clinical interview in adulthood to assess psychiatric problems.

DNA Methylation in Breast Tumor from High-risk Women in the Breast Cancer Family Registry.

To examine DNA methylation profiles in breast tumors of women with a strong breast cancer family history, we measured methylation by bisulfite sequencing in 40 genes in 40 breast tumor tissues from women in the Breast Cancer Family Registry. We selected candidate genes from analysis of the Cancer Genome Atlas project (TCGA) breast data. Compared to TCGA breast cancer, BCFR cases are younger and more likely to be ER-negative.