The influence of 21-gene recurrence score assay on chemotherapy use in a population-based sample of breast cancer patients.

Purpose: To quantify the influence of RS assay on changing chemotherapy plans in a general practice setting using causal inference methods.

Methods: We surveyed 3880 newly diagnosed breast cancer patients in Los Angeles and Georgia in 2013-14. We used inverse propensity weighting and multiple imputations to derive complete information for each patient about treatment status with and without testing.

The Allostery Model of TCR Regulation.

The activity of the αβ TCR is controlled by conformational switches. In the resting conformation, the TCR is not phosphorylated and is inactive. Binding of multivalent peptide-MHC to the TCR stabilizes the active conformation, leading to TCR signaling.

Conserving the linear momentum in stochastic dynamics: Dissipative particle dynamics as a general strategy to achieve local thermostatization in molecular dynamics simulations.

Stochastic dynamics is a widely employed strategy to achieve local thermostatization in molecular dynamics simulation studies; however, it suffers from an inherent violation of momentum conservation. Although this short-coming has little impact on structural and short-time dynamic properties, it can be shown that dynamics in the long-time limit such as diffusion is strongly dependent on the respective thermostat setting. Application of the methodically similar dissipative particle dynamics (DPD) provides a simple, effective strategy to ensure the advantages of local, stochastic thermostatization while at the same time the linear momentum of the system remains conserved.

The Impact of Disability and Social Determinants of Health on Condition-Specific Readmissions beyond Medicare Risk Adjustments: A Cohort Study.

Background: Readmission rates after pneumonia, heart failure, and acute myocardial infarction hospitalizations are risk-adjusted for age, gender, and medical comorbidities and used to penalize hospitals.

Objective: To assess the impact of disability and social determinants of health on condition-specific readmissions beyond current risk adjustment.

Design, Setting, And Participants: Retrospective cohort study of Medicare patients using 1) linked Health and Retirement Study-Medicare claims data (HRS-CMS) and 2) Healthcare Cost and Utilization Project State Inpatient Databases (Florida, Washington) linked with ZIP Code-level measures from the Census American Community Survey (ACS-HCUP).

Pushing the limit for the grid-based treatment of Schrödinger's equation: a sparse Numerov approach for one, two and three dimensional quantum problems.

The general Numerov method employed to numerically solve ordinary differential equations of second order was adapted with a special focus on solving Schrödinger's equation. By formulating a hierarchy of novel stencil expressions for the numerical treatment of the Laplace operator in one, two and three dimensions the method could not only be simplified over the standard Numerov scheme. The improved framework enables the natural use of matrix sparsity to reduce the memory demand and the associated computing time, thus enabling the application of the method to larger problems.

Chemotherapy decisions and patient experience with the recurrence score assay for early-stage breast cancer.

Background: The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor-positive breast cancer by recurrence risk. Few studies have examined the ways in which physicians use the RS to recommend adjuvant systemic chemotherapy or patients' experiences with testing and decision making.

Methods: This study surveyed 3880 women treated for breast cancer in 2013-2014; they were identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries (response rate, 71%).

Measures to Improve Diagnostic Safety in Clinical Practice.

Timely and accurate diagnosis is foundational to good clinical practice and an essential first step to achieving optimal patient outcomes. However, a recent Institute of Medicine report concluded that most of us will experience at least one diagnostic error in our lifetime. The report argues for efforts to improve the reliability of the diagnostic process through better measurement of diagnostic performance.

Output without input: the lifelong productivity of hematopoietic stem cells.

The hematopoietic stem cell (HSC) compartment must be maintained life-long, while being replenishable only from within. HSC proliferation can compensate for cell loss by differentiation, by cell death, or by mobilization from the bone marrow niches, but the relative use of proliferation to compensate for these distinct depletion sources is unclear. Classifications of HSC states (e.

Robust classification of single-cell transcriptome data by nonnegative matrix factorization.

Motivation: Single-cell transcriptome data provide unprecedented resolution to study heterogeneity in cell populations and present a challenge for unsupervised classification. Popular methods, like principal component analysis (PCA), often suffer from the high level of noise in the data.

Results: Here we adapt Nonnegative Matrix Factorization (NMF) to study the problem of identifying subpopulations in single-cell transcriptome data.

Integrative Genome-Scale Analysis Identifies Epigenetic Mechanisms of Transcriptional Deregulation in Unfavorable Neuroblastomas.

The broad clinical spectrum of neuroblastoma ranges from spontaneous regression to rapid progression despite intensive multimodal therapy. This diversity is not fully explained by known genetic aberrations, suggesting the possibility of epigenetic involvement in pathogenesis. In pursuit of this hypothesis, we took an integrative approach to analyze the methylomes, transcriptomes, and copy number variations in 105 cases of neuroblastoma, complemented by primary tumor- and cell line-derived global histone modification analyses and epigenetic drug treatment in vitro We found that DNA methylation patterns identify divergent patient subgroups with respect to survival and clinicobiologic variables, including amplified MYCN Transcriptome integration and histone modification-based definition of enhancer elements revealed intragenic enhancer methylation as a mechanism for high-risk-associated transcriptional deregulation.

Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient.

Background: Immune-checkpoint inhibitors have been approved for the treatment of metastatic melanoma based on several phase III trials. Patients after organ transplantation and patients with impaired renal function were excluded from these studies. Recently, allograft rejections were reported in organ transplant recipients receiving PD-1 blocking antibodies.

Long-distance dispersal suppresses introgression of local alleles during range expansions.

During range expansions, even low levels of interbreeding can lead to massive introgression of local alleles into an invader's genome. Nonetheless, this pattern is not always observed in human populations. For instance, European Americans in North America are barely introgressed by Amerindian genes in spite of known contact and admixture.

The Use of Tools, Modelling Methods, Data Types, and Endpoints in Systems Medicine: A Survey on Projects of the German e:Med-Programme.

Systems medicine is the consequent continuation of research efforts on the road to an individualized medicine. Thereby, systems medicine tries to offer a holistic view on the patient by combining different data sources to highlight different perspectives on the patient's health. Our research question was to identify the main data types, modelling methods, analysis tools, and endpoints currently used and studied in systems medicine.

Enhanced susceptibility of obese mice to glycidamide-induced sperm chromatin damage without increased oxidative stress.

Diet-induced obesity is known to impair male reproduction and may aggravate the male reproductive toxicity of the food contaminant acrylamide. Exposure of male mice to acrylamide induces paternally mediated pre- and post-implantation losses because of spermatozoal toxicity and these effects are potentiated in mice fed a high-fat diet. Glycidamide - an acrylamide metabolite - is the primary mediator of reproductive effects in males.

Physician Recommendations Trump Patient Preferences in Prostate Cancer Treatment Decisions.

Objective: To assess the influence of patient preferences and urologist recommendations in treatment decisions for clinically localized prostate cancer.

Methods: We enrolled 257 men with clinically localized prostate cancer (prostate-specific antigen <20; Gleason score 6 or 7) seen by urologists (primarily residents and fellows) in 4 Veterans Affairs medical centers. We measured patients' baseline preferences prior to their urology appointments, including initial treatment preference, cancer-related anxiety, and interest in sex.

The influence of metal-ion binding on the structure and surface composition of Sonic Hedgehog: a combined classical and hybrid QM/MM MD study.

In this work, the influence of the metal ions present in vertebrate Sonic Hedgehog was assessed by a series of molecular mechanics molecular dynamics simulations with differing ionic compositions. The obtained data suggest that Ca(ii) binding has a very distinct influence on the composition of the protein surface surrounding the binding site by shaping several ionic interactions with negatively charged sidechains that otherwise would be pointing towards the solvent, repelling potential ligands. Furthermore, the Ca(ii) ions play an important role in the stability of the loop regions where they are coordinated.

Dry bulk cargo shipping - An overlooked threat to the marine environment?

Approximately 9.5billiontonnes of goods is transported over the world oceans annually with dry bulk representing the largest cargo group. This paper aims to analyse whether the transport and associated inputs of dry bulks into the sea create a risk for the marine environment.

Reviewing deaths in British and US hospitals: a study of two scales for assessing preventability.

Background: Standardised mortality ratios do not provide accurate measures of preventable mortality. This has generated interest in using case notes to assess the preventable component of mortality. But, different methods of measurement have not been compared.

Nucleic acid oxidative damage in Alzheimer's disease-explained by the hepcidin-ferroportin neuronal iron overload hypothesis?

There is strong literature support for brain metal dysregulation, oxidative stress and oxidative damage to neurons in Alzheimer's disease (AD); these processes begin early and continue throughout the disease. Here, we review current knowledge on metal dysregulation and nucleic acid oxidative damage in AD (we also include new data demonstrating increased RNA and DNA oxidative damage in hippocampus from individuals having suffered from degenerative (e.g.

Calibration of UV/Vis spectrophotometers: A review and comparison of different methods to estimate TSS and total and dissolved COD concentrations in sewers, WWTPs and rivers.

UV/Vis spectrophotometers have been used for one decade to monitor water quality in various locations: sewers, rivers, wastewater treatment plants (WWTPs), tap water networks, etc. Resulting equivalent concentrations of interest can be estimated by three ways: i) by manufacturer global calibration; ii) by local calibration based on the provided global calibration and grab sampling; iii) by advanced calibration looking for relations between UV/Vis spectra and corresponding concentrations from grab sampling. However, no study has compared the applied methods so far.

Minichromosome Maintenance Complex Is a Critical Node in the miR-183 Signaling Network of MYCN-Amplified Neuroblastoma Cells.

MYCN and HDAC2 jointly repress the transcription of tumor suppressive miR-183 in neuroblastoma. Enforced miR-183 expression induces neuroblastoma cell death and inhibits xenograft growth in mice. Here we aimed to focus more closely on the miR-183 signaling network using a label-free mass spectrometric approach.

Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.