SUMMARY To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation.

Abstract:The concept of "social role" has long been used in social science describe the intersection of behavioral, meaningful, and structural attributes that emerge regularly in particular settings and institutions. We use structural signature methods to identify key roles in a large distributed collaboration system (Wikipedia) by examining the distribution of edits across types of pages and the structure of relationships between editors. We distinguish between technical editors, substantive experts, vandal fighters, and social networkers and demonstrate key ways that their patterns of interaction and contribution differ. We conclude by considering how differential entry into and retention in particular roles may affect the operation of the large social system. IntroductionIt is difficult to gauge the social significance of Wikipedia, other than to say that, like Google, Wikipedia has forever changed how we use, find and think about information. Both pundits (like Stephen Colbert) and researchers (Stvilia et al. 2005, Giles 2005) have been pre-occupied with the question of whether the product of Wikipedia is of sufficient quality, or whether its pages constitute legitimate references (Read 2006). Others argue that the project will never achieve a sufficient level of quality relying on non-expert volunteers of unknown identity (Chesney). Instead of prognosticating about the potential of the Wikipedia project we contend that scholars should be more focused on understanding how Wikipedia has achieved the success that it has: a "pretty good" resource for a basic understanding of most any topic. How has the "pretty good" and incredibly extensive resource been achieved? And how has this been possible given the absence of the resources and controls of conventional firms and bureaucracies?Through the course of our research we have come to suspect that the success of Wikipedia has stemmed from two key sources: (1) infrastructural features that help people find their roles in the organization (2) technical innovations that allow substantial economies of scale in the performance of many of those roles. This paper concentrates on the former and is about finding roles in a double sense: to what extent can we identify the roles people play in Wikipedia by measuring general behavioral and structural features of their participation? We address this technical challenge by using a range of qualitative and quantitative methods to find signatures of social roles in Wikipedia (cite cite). The second sense asks: how do people find their roles in Wikipedia? We address this question quantitatively by comparing general patterns in editing across two different samples of Wikipedians, a cohort that first edited in January of 2005 and a sample of dedicated Wikipedians whose edits spanned a period of greater than one year. These samples allow us to compare how patterns in participation vary between cross section of new participants and those who stick around, and become the long term participants in the social system. Finding Social Role...

The numbering systems for mammalian ribosomal proteins used in several laboratories have been correlated and a proposal for a standard system is presented.

This study investigated salivary anticandidal activity and salivary composition in stimulated whole saliva of 18 advanced HIV-infected patients and compared these values to healthy controls. Stimulated whole saliva from HIV-infected patients showed decreased anticandidal activity. The flow rate was reduced by 40% as compared with controls. The saliva flow rate for HIV-infected patients who had recoverable yeast in their saliva was reduced as compared to HIV-infected patients without recoverable yeast. For HIV-infected patients, the saliva concentrations of lactoferrin, secretory IgA and Cl- were increased while the secretion rate of lysozyme, total protein and K+ were reduced. There was no difference in any parameter as a function of taking the antifungal drug fluconazole. There was no association between salivary anticandidal activity and any salivary component. This study shows reduced anticandidal activity and salivary flow rate in HIV-infected patients. These alterations may contribute to their increased incidence of oral candidal infections.

Oral cancer is a deadly and disfiguring disease that could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a noninvasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the epidermal growth factor receptor (EGFR) biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros, including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (P < 0.0001), the nuclear-to-cytoplasmic ratio (P < 0.0001), and EGFR biomarker expression (P < 0.03). Further examination using logistic regression and receiver operating characteristic curve analyses identified morphologic features as the best predictors of disease (area under the curve ≤0.93) individually, whereas a combination of all features further enhanced discrimination of oral cancer and precancerous conditions (area under the curve, 0.94) with high sensitivity and specificity. Further clinical trials are necessary to validate the regression model and evaluate other potential biomarkers, but this pilot study supports the NBC sensor technique as a promising new diagnostic tool for early detection of oral cancer, which could enhance patient care and survival.Cancer Prev Res; 3(4); 518-28. ©2010 AACR.

Background Nonalcoholic fatty liver disease (NAFLD) is a significant public health burden, with up to 30% of the US population affected. The prevalence of NAFLD among inflammatory bowel disease (IBD) patients is unknown. Understanding risk factors for NAFLD in IBD patients has implications in the treatment of these patients. The purpose of this study was to determine the prevalence of NAFLD among IBD patients and to identify risk factors associated with NAFLD development. Methods Embase and MEDLINE databases were searched using Medical Subject Headlines to find studies that assessed the prevalence of NAFLD among IBD patients. Twenty-seven English-language research abstracts/articles were identified between January 2005 and April 2018. Meta-analyses were performed using random-effects models. Prevalence of NAFLD among IBD patients was compared with prevalence of NAFLD in the general population. Results Based on data pooled from all 27 studies, the prevalence of NAFLD among IBD patients was 32% (95% CI, 24%–40%) with substantial heterogeneity (I2 = 98%). The prevalence of NAFLD among IBD patients (32%) is statistically significantly higher than the prevalence of NAFLD in the general population (25.2%; P &lt; 0.001). Factors associated with the development of NAFLD among IBD patients included age, BMI, diabetes, IBD duration, and prior history of bowel resection. Conclusions There is a higher prevalence of NAFLD among IBD patients compared with the general population. Previous treatment regimens may be a risk factor for the development of NAFLD. Future studies are needed to further clarify these risk factors and determine screening recommendations.

The etiology of salivary gland hypofunction in HIV(+) patients is unclear. This study was designed to determine the effect of early-stage HIV(+) infection (CD4(+) > 200 cells/ micro L; n = 139) on salivary gland function and the relationship of this dysfunction to the taking of xerostomic medications. Salivary flow rates and the content of electrolytes and antimicrobial proteins in stimulated parotid and submandibular/sublingual saliva were determined. Compared with healthy controls (n = 50), the HIV(+) group showed significant reductions in flow rates of unstimulated whole (35%), stimulated parotid (47%), unstimulated submandibular/sublingual (23%), and stimulated submandibular/sublingual (39%) saliva. The flow rates for the HIV(+) patients taking xerostomic medications did not differ from those of patients who did not. Concentrations of some salivary gland components were altered in the HIV(+) group. Analysis of these data suggests that salivary gland function is adversely affected early in HIV infection and that these changes do not appear to be compounded by the taking of xerostomic medications.

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