iGenSig-Rx: an integral genomic signature based white-box tool for modeling cancer therapeutic responses using multi-omics data.

Multi-omics sequencing is poised to revolutionize clinical care in the coming decade. However, there is a lack of effective and interpretable genome-wide modeling methods for the rational selection of patients for personalized interventions. To address this, we present iGenSig-Rx, an integral genomic signature-based approach, as a transparent tool for modeling therapeutic response using clinical trial datasets.

Tumor Intrinsic Subtypes and Gene Expression Signatures in Early-Stage ERBB2/HER2-Positive Breast Cancer: A Pooled Analysis of CALGB 40601, NeoALTTO, and NSABP B-41 Trials.

Importance: Biologic features may affect pathologic complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy plus ERBB2/HER2 blockade in ERBB2/HER2-positive early breast cancer (EBC).

Objective: To define the quantitative association between pCR and EFS by intrinsic subtype and by other gene expression signatures in a pooled analysis of 3 phase 3 trials: CALGB 40601, NeoALTTO, and NSABP B-41.

Design, Setting, And Participants: In this retrospective pooled analysis, 1289 patients with EBC received chemotherapy plus either trastuzumab, lapatinib, or the combination, with a combined median follow-up of 5.

iGenSig-Rx: an integral genomic signature based white-box tool for modeling cancer therapeutic responses using multi-omics data.

Multi-omics sequencing is expected to become clinically routine within the next decade and transform clinical care. However, there is a paucity of viable and interpretable genome-wide modeling methods that can facilitate rational selection of patients for tailored intervention. Here we develop an integral genomic signature-based method called iGenSig-Rx as a white-box tool for modeling therapeutic response based on clinical trial datasets with improved cross-dataset applicability and tolerance to sequencing bias.

Implications for a mindfulness-enhanced positive affect induction: A brief commentary toward acute pain management.

Over the past decade research has increased on dynamics between mindfulness, positive affect, and pain. While there have been studies examining the direct use of positive psychology for pain management, few have examined the use of a specific mindfulness-enhanced positive affect induction (i.e.

Formalin Fixation, Delay to Fixation, and Time in Fixative Adversely Impact Copy Number Variation Analysis by aCGH.

Although molecular profiling of DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor specimens has become more common in recent years, it remains unclear how discrete FFPE processing variables may affect detection of copy number variation (CNV). To better understand such effects, array comparative genomic hybridization (aCGH) profiles of FFPE renal cell carcinoma specimens that experienced different delays to fixation (DTFs; 1, 2, 3, and 12 hours) and times in fixative (TIFs; 6, 12, 23, and 72 hours) were compared to snap-frozen tumor and blood specimens from the same patients. A greater number of regions containing CNVs relative to commercial reference DNA were detected in DNA from FFPE tumor specimens than snap-frozen tumor specimens even though they originated from the same tumor blocks.

Characterization of transcriptome diversity and in vitro behavior of primary human high-risk breast cells.

Biology and transcriptomes of non-cancerous human mammary epithelial cells at risk for breast cancer development were explored following primary isolation utilizing conditional reprogramming cell technology from mastectomy tissue ipsilateral to invasive breast cancer. Cultures demonstrated consistent categorizable behaviors. Relative viability and mammosphere formation differed between samples but were stable across three different mammary-specific media.

Treg-inducing capacity of genomic DNA of subsp. .

Allergic and autoimmune diseases comprise a group of inflammatory disorders caused by aberrant immune responses in which CD25 forkhead box P3-positive regulatory T cells (Treg) cells that normally suppress inflammatory events are often poorly functioning. This has stimulated an intensive investigative effort to find ways of increasing Tregs as a method of therapy for these conditions. Commensal microbiota known to have health benefits in humans include the lactic acid-producing, probiotic bacteria B.

NSABP B-41, a Randomized Neoadjuvant Trial: Genes and Signatures Associated with Pathologic Complete Response.

Purpose: In NSABP B-41, pathologic complete response (pCR) was associated with prolonged survival among women with HER2-positive operable breast cancer treated with neoadjuvant chemotherapy and lapatinib, trastuzumab, or the combination. We used a large human breast cancer gene expression panel to select candidate prognostic biomarkers for pCR among women treated with trastuzumab in NSABP B-41.

Patients And Methods: Eligible patients had a baseline preadjuvant treatment core biopsy sample, known pCR status, and no withdrawal of consent.

The neural bases of cognitive emotion regulation: The roles of strategy and intensity.

When confronted with unwanted negative emotions, individuals use a variety of cognitive strategies for regulating these emotions. The brain mechanisms underlying these emotion regulation strategies have not been fully characterized, and it is not yet clear whether these mechanisms vary as a function of emotion intensity. To address these issues, 30 community participants (17 females, 13 males, M = 24.

Life and its traces in Antarctica's McMurdo Dry Valley paleolakes: a survey of preservation.

The extremely cold and arid conditions of Antarctica make it uniquely positioned to investigate fundamental questions regarding the persistence of life in extreme environments. Within the McMurdo Dry Valleys and surrounding mountain ranges are multiple ancient relict lakes, paleolakes, with lacustrine deposits spanning from thousands to millions of years in age. Here we present data from light microscopy, scanning electron microscopy, electron dispersive x-ray spectroscopy, and radiocarbon dating to catalog the remarkable range of life preserved within these deposits.

I'm tired and it hurts! Sleep quality and acute pain response in a chronic pain population.

Objective/background: There are bidirectional links between sleep quality and pain, with recent research suggesting that sleep impairment more strongly predicts future pain than vice versa. Relatively few studies have examined the relationship between sleep quality and acute pain among chronic pain patients. The purpose of the current study is to investigate relationships among subjective sleep quality and behavioral and physiological responses to a cold pressor pain task (CPT) in chronic pain patients.

Somatic mutation signatures in primary liver tumors of workers exposed to ionizing radiation.

Liver cancer is associated with genetic mutations caused by environmental exposures, including occupational exposure to alpha radiation emitted by plutonium. We used whole exome sequencing (WES) to characterize somatic mutations in 3 histologically distinct primary liver tumors (angiosarcoma of the liver (ASL), cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC)) from Mayak worker subjects occupationally exposed to ionizing radiation (IR) to investigate the contribution of IR to the mutational landscape of liver cancer. DNA sequence analysis revealed these tumors harbor an excess of deletions, with a deletions:substitutions ratio similar to that previously reported in radiation-associated tumors.

Pathologic complete response and outcomes by intrinsic subtypes in NSABP B-41, a randomized neoadjuvant trial of chemotherapy with trastuzumab, lapatinib, or the combination.

Purpose: NSABP B-41, a phase three randomized trial, evaluated neoadjuvant lapatinib, trastuzumab, or the combination with chemotherapy in patients with HER2-positive operable breast cancer. Though no significant difference in pathologic complete response (pCR) was found among the three arms, pCR was associated with prolonged survival. We analyzed tumor intrinsic subtypes with Prediction Analysis of Microarray 50 in a subset of B-41 patients to determine their value in predicting HER2-targeting benefit.

Genetic Associations with Indoor Tanning Addiction among non-Hispanic White Young Adult Women.

Background: Some young people may become addicted to indoor tanning in a manner similar to other forms of addiction, but research on genetic associations with indoor tanning addiction remains limited.

Purpose: To examine if liabilities in genetic addiction reward pathways and psychiatric comorbidity influence the risk of indoor tanning addiction.

Methods: This was a cross-sectional study with a community sample of 292 non-Hispanic white young adult women aged 18-30 years who reported indoor tanning in the past year.

Composition and diameter modulation of magnetic nanowire arrays fabricated by a novel approach.

Straight magnetic nanowires composed of nickel and permalloy segments having different diameters are synthesized using a promising approach. This approach involves the controlled electrodeposition of each magnetic material into specially designed diameter-modulated porous alumina templates. Standard alumina templates are exposed to pore widening followed by a protective coating of the pore wall with ultrathin silica and further anodization.

Real-Time DNA Sequencing in the Antarctic Dry Valleys Using the Oxford Nanopore Sequencer.

The ability to sequence DNA outside of the laboratory setting has enabled novel research questions to be addressed in the field in diverse areas, ranging from environmental microbiology to viral epidemics. Here, we demonstrate the application of offline DNA sequencing of environmental samples using a hand-held nanopore sequencer in a remote field location: the McMurdo Dry Valleys, Antarctica. Sequencing was performed using a MK1B MinION sequencer from Oxford Nanopore Technologies (ONT; Oxford, United Kingdom) that was equipped with software to operate without internet connectivity.

Responsiveness of and Deficiency-Induced Mammary Preneoplasia to Selective Estrogen Modulators versus an Aromatase Inhibitor in .

An intervention study initiated at age 4 months compared the impact of tamoxifen (25 mg), raloxifene (22.5 mg), and letrozole (2.5 mg) administered by 60-day release subcutaneous pellet on mammary preneoplasia prevalence at age 6 months in conditional genetically engineered mouse models with different Breast cancer 1 () gene dosages targeted to mammary epithelial cells and germline Tumor protein P53 () haploinsufficiency (10-16/cohort).

The Russian Human Radiobiological Tissue Repository: A Unique Resource for Studies of Plutonium-Exposed Workers.

The Russian Radiobiological Human Tissue Repository (RHTR) at the Southern Urals Biophysics Institute in Ozyorsk, Russia, was established to collect and store biospecimens supporting research on health consequences of chronic, low-dose radiation exposures. The purpose of this paper is to describe the RHTR resources and the availability of high-quality biological specimens. RHTR has enrolled two groups of subjects from 1951 to the present time: exposed workers at the Mayak Production Association facilities and residents of Ozyorsk who were never occupationally exposed to ionizing radiation (controls).

Adiposity is associated with p53 gene mutations in breast cancer.

Mutations in the p53 gene are among the most frequent genetic events in human cancer and may be triggered by environmental and occupational exposures. We examined the association of clinical and pathological characteristics of breast tumors and breast cancer risk factors according to the prevalence and type of p53 mutations. Using tumor blocks from incident cases from a case-control study in western New York, we screened for p53 mutations in exons 2-11 using the Affymetrix p53 Gene Chip array and analyzed case-case comparisons using logistic regression.

A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes.

There is considerable support for the view that aerobic exercise may confer cognitive benefits to mild cognitively impaired elderly persons. However, the biological mechanisms mediating these effects are not entirely clear. As a preliminary step towards informing this gap in knowledge, we enrolled older adults confirmed to have mild cognitive impairment (MCI) in a 6-month exercise program.

[Radiobiological Human Tissue repository: progress and perspectives for solving the problems of radiation safety and health protection of personnel and population].

Radiobiological Human Tissue repository was established in order to obtain and store biological material from Mayak PA workers occupationally exposed to ionizing (α- and/or γ-) radiation in a wide dose range, from the residents exposed to long term radiation due to radiation accidents and transfer of the samples to scientists for the purpose of studying the effects of radiation for people and their offspring. The accumulated biomaterial is the informational and research potential that form the basis for the work of the scientists in different spheres of biology and medicine. The repository comprises 5 sections: tumor and non-tumor tissues obtained in the course of autopsies, biopsies, surgeries, samples of blood and its components, of DNA, induced sputum, saliva, and other from people exposed or unexposed (control) to radiation.

miRNAs in Sera of Tunisian patients discriminate between inflammatory breast cancer and non-inflammatory breast cancer.

In recent years, circulating miRNAs have attracted interest as stable, non-invasive biomarkers for various pathological conditions. Here, we investigated their potential to serve as minimally invasive, early detection markers for inflammatory breast cancer (IBC) and non-inflammatory breast cancer (non-IBC) in serum. miRNA profiling was performed on serum from 20 patients with non-IBC, 20 with IBC, and 20 normal control subjects.

Genome-wide multi-omics profiling of colorectal cancer identifies immune determinants strongly associated with relapse.

The use and benefit of adjuvant chemotherapy to treat stage II colorectal cancer (CRC) patients is not well understood since the majority of these patients are cured by surgery alone. Identification of biological markers of relapse is a critical challenge to effectively target treatments to the ~20% of patients destined to relapse. We have integrated molecular profiling results of several "omics" data types to determine the most reliable prognostic biomarkers for relapse in CRC using data from 40 stage I and II CRC patients.

Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma infection, and bladder cancer risk in Egypt.

Background: Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in

Nad(p)h: quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer.

Methods: We assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt.