Intestinal S100/Calgranulin Expression in Cats with Chronic Inflammatory Enteropathy and Intestinal Lymphoma.

Diagnosing chronic inflammatory enteropathies (CIE) in cats and differentiation from intestinal lymphoma (IL) using currently available diagnostics is challenging. Intestinally expressed S100/calgranulins, measured in fecal samples, appear to be useful non-invasive biomarkers for canine CIE but have not been evaluated in cats. We hypothesized S100/calgranulins to play a role in the pathogenesis of feline chronic enteropathies (FCE) and to correlate with clinical and/or histologic disease severity. This retrospective case-control study included patient data and gastrointestinal (GI) tissues from 16 cats with CIE, 8 cats with IL, and 16 controls with no clinical signs of GI disease. GI tissue biopsies were immunohistochemically stained using polyclonal α-S100A8/A9 and α-S100A12 antibodies. S100A8/A9+ and S100A12+ cells were detected in all GI segments, with few significant differences between CIE, IL, and controls and no difference between diseased groups. Segmental inflammatory lesions were moderately to strongly correlated with increased S100/calgranulin-positive cell counts. Clinical disease severity correlated with S100A12+ cell counts in cats with IL (ρ = 0.69, p = 0.042) and more severe diarrhea with colonic lamina propria S100A12+ cells with CIE (ρ = 0.78, p = 0.021) and duodenal S100A8/A9+ cells with IL (ρ = 0.71, p = 0.032). These findings suggest a role of the S100/calgranulins in the pathogenesis of the spectrum of FCE, including CIE and IL

DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial.

Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2- patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2- patients (VC: 72 and concurrent controls: 44). We also evaluated the 70-gene ultra-high risk signature (MP1/2), one of the biomarkers used to define subtype in the trial. We used logistic modeling to assess biomarker performance. Successful biomarkers were combined using a simple voting scheme to refine the 'predicted sensitive' group and Bayesian modeling used to estimate the pathologic complete response rates. BRCA1/2 germline mutation status associated with VC response, but its low prevalence precluded further evaluation. PARPi-7, BRCA1ness, and MP1/2 specifically associated with response in the VC arm but not the control arm. Neither CIN70 nor PARP1 protein specifically predicted VC response. When we combined the PARPi-7 and MP1/2 classifications, the 42% of triple negative patients who were PARPi7-high and MP2 had an estimated pCR rate of 75% in the VC arm. Only 11% of HR+/HER2- patients were PARPi7-high and MP2; but these patients were also more responsive to VC with estimated pathologic complete response rates of 41%. PARPi-7, BRCA1ness and MP1/2 signatures may help refine predictions of VC response, thereby improving patient care

Development of a Data Management Framework in Support of Southeastern Tidal Creek Research

2008 S.C. Water Resources Conference - Addressing Water Challenges Facing the State and Regio

The selection and definition of indicators in public health monitoring for the 65+ age group in Germany

Selecting relevant indicators is an important step in the development of public health monitoring for older people. Indicators can be used to combine information comprehensively from various data sources and enable recurring, comparable findings to be made about the health of older people. Indicators were systematically compiled from existing international monitoring systems. An indicator set on health in old age was developed using a multistage, structured consensus-based process together with an interdisciplinary panel of experts. The resulting 18 indicators were assigned to three health areas: (1) environmental factors, (2) activities and participation, and (3) personal factors. Data sources that can be used for the indicators are the health surveys within the framework of the Robert Koch Institute’s (RKI) health monitoring system, as well as surveys from other research institutes and official statistics. In the future, the indicator set is to be developed further and integrated into an overall approach that is geared towards health reporting and the monitoring of chronic diseases in all phases of life

Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150514/1/cpt1211.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150514/2/cpt1211_am.pd

Serial expression analysis of breast tumors during neoadjuvant chemotherapy reveals changes in cell cycle and immune pathways associated with recurrence and response

Abstract Introduction The molecular biology involving neoadjuvant chemotherapy (NAC) response is poorly understood. To elucidate the impact of NAC on the breast cancer transcriptome and its association with clinical outcome, we analyzed gene expression data derived from serial tumor samples of patients with breast cancer who received NAC in the I-SPY 1 TRIAL. Methods Expression data were collected before treatment (T1), 24–96 hours after initiation of chemotherapy (T2) and at surgery (TS). Expression levels between T1 and T2 (T1 vs. T2; n = 36) and between T1 and TS (T1 vs. TS; n = 39) were compared. Subtype was assigned using the PAM50 gene signature. Differences in early gene expression changes (T2 − T1) between responders and nonresponders, as defined by residual cancer burden, were evaluated. Cox proportional hazards modeling was used to identify genes in residual tumors associated with recurrence-free survival (RFS). Pathway analysis was performed with Ingenuity software. Results When we compared expression profiles at T1 vs. T2 and at T1 vs. TS, we detected significantly altered expression of 150 and 59 transcripts, respectively. We observed notable downregulation of proliferation and immune-related genes at T2. Lower concordance in subtype assignment was observed between T1 and TS (62 %) than between T1 and T2 (75 %). Analysis of early gene expression changes (T2 − T1) revealed that decreased expression of cell cycle inhibitors was associated with poor response. Increased interferon signaling (TS − T1) and high expression of cell proliferation genes in residual tumors (TS) were associated with reduced RFS. Conclusions Serial gene expression analysis revealed candidate immune and proliferation pathways associated with response and recurrence. Larger studies incorporating the approach described here are warranted to identify predictive and prognostic biomarkers in the NAC setting for specific targeted therapies. Clinical trial registration ClinicalTrials.gov identifier: NCT00033397 . Registered 9 Apr 2002

Memory in Microbes: Quantifying History-Dependent Behavior in a Bacterium

Memory is usually associated with higher organisms rather than bacteria. However, evidence is mounting that many regulatory networks within bacteria are capable of complex dynamics and multi-stable behaviors that have been linked to memory in other systems. Moreover, it is recognized that bacteria that have experienced different environmental histories may respond differently to current conditions. These “memory” effects may be more than incidental to the regulatory mechanisms controlling acclimation or to the status of the metabolic stores. Rather, they may be regulated by the cell and confer fitness to the organism in the evolutionary game it participates in. Here, we propose that history-dependent behavior is a potentially important manifestation of memory, worth classifying and quantifying. To this end, we develop an information-theory based conceptual framework for measuring both the persistence of memory in microbes and the amount of information about the past encoded in history-dependent dynamics. This method produces a phenomenological measure of cellular memory without regard to the specific cellular mechanisms encoding it. We then apply this framework to a strain of Bacillus subtilis engineered to report on commitment to sporulation and degradative enzyme (AprE) synthesis and estimate the capacity of these systems and growth dynamics to ‘remember’ 10 distinct cell histories prior to application of a common stressor. The analysis suggests that B. subtilis remembers, both in short and long term, aspects of its cell history, and that this memory is distributed differently among the observables. While this study does not examine the mechanistic bases for memory, it presents a framework for quantifying memory in cellular behaviors and is thus a starting point for studying new questions about cellular regulation and evolutionary strategy

Rapid automatized naming as an index of genetic liability to autism

This study investigated rapid automatized naming (RAN) ability in high functioning individuals with autism and parents of individuals with autism. Findings revealed parallel patterns of performance in parents and individuals with autism, where both groups had longer naming times than controls. Significant parent-child correlations were also detected, along with associations with language and personality features of the broad autism phenotype (retrospective reports of early language delay, socially reticent personality). Together, findings point towards RAN as a potential marker of genetic liability to autism

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin