Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey‐Holden Prostate Cancer Academy Meeting

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138883/1/pros23424.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138883/2/pros23424_am.pd

Tumor cell heterogeneity and resistance; report from the 2018 Coffey‐Holden Prostate Cancer Academy Meeting

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147081/1/pros23729.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147081/2/pros23729_am.pd

Towards an effective potential for the monomer, dimer, hexamer, solid and liquid forms of hydrogen fluoride

We present an attempt to build up a new two-body effective potential for hydrogen fluoride, fitted to theoretical and experimental data relevant not only to the gas and liquid phases, but also to the crystal. The model is simple enough to be used in Molecular Dynamics and Monte Carlo simulations. The potential consists of: a) an intra-molecular contribution, allowing for variations of the molecular length, plus b) an inter-molecular part, with three charged sites on each monomer and a Buckingham "exp-6" interaction between fluorines. The model is able to reproduce a significant number of observables on the monomer, dimer, hexamer, solid and liquid forms of HF. The shortcomings of the model are pointed out and possible improvements are finally discussed.Comment: LaTeX, 24 pages, 2 figures. For related papers see also http://www.chim.unifi.it:8080/~valle

Limits to scale invariance in alluvial rivers

Assumptions about fluvial processes and process–form relations are made in general models and in many site‐specific applications. Many standard assumptions about reach‐scale flow resistance, bed‐material entrainment thresholds and transport rates, and downstream hydraulic geometry involve one or other of two types of scale invariance: a parameter (e.g. critical Shields number) has the same value in all rivers, or doubling one variable causes a fixed proportional change in another variable in all circumstances (e.g. power‐law hydraulic geometry). However, rivers vary greatly in size, gradient, and bed material, and many geomorphologists regard particular types of river as distinctive. This review examines the tension between universal scaling assumptions and perceived distinctions between different types of river. It identifies limits to scale invariance and departures from simple scaling, and illustrates them using large data sets spanning a wide range of conditions. Scaling considerations and data analysis support the commonly made distinction between coarse‐bed and fine‐bed reaches, whose different transport regimes can be traced to the different settling‐velocity scalings for coarse and fine grains. They also help identify two end‐member sub‐types: steep shallow coarse‐bed ‘torrents’ with distinctive flow‐resistance scaling and increased entrainment threshold, and very large, low‐gradient ‘mega rivers’ with predominantly suspended load, subdued secondary circulation, and extensive backwater conditions

Sexual dysfunction among married couples living in Kumasi metropolis, Ghana

<p>Abstract</p> <p>Background</p> <p>Sexuality and its manifestation constitute some of the most complex of human behaviour and its disorders are encountered in community. Sexual dysfunction is more prevalent in women than in men. While studies examining sexual dysfunction among males and females in Ghana exist, there are no studies relating sexual problems in males and females as dyadic units. This study therefore investigated the prevalence and type of sexual disorders among married couples.</p> <p>Method</p> <p>The study participants consisted of married couples between the ages of 19 and 66 living in the province of Kumasi, Ghana. Socio-demographic information and Golombok-Rust Inventory of Sexual Satisfaction (GRISS) questionnaires were administered to 200 couples who consented to take part in the study. All 28 questions of the GRISS are answered on a five-point (Likert type) scale from "always", through "usually', "sometimes", and "hardly ever", to "never". Responses are summed up to give a total raw score ranging from 28-140. The total score and subscale scores are transformed using a standard nine point scale, with high scores indicating greater problems. Scores of five or more are considered to indicate SD. The study was conducted between July and September 2010.</p> <p>Results</p> <p>Out of a total of 200 married couples, 179 completed their questionnaires resulting in a response rate of 89.5%. The mean age of the participating couples as well as the mean duration of marriage was 34.8 ± 8.6 years and 7.8 ± 7.6 years respectively. The husbands (37.1 ± 8.6) were significantly older (p < 0.0001) than their corresponding wives (32.5 ± 7.9). After adjusting for age, 13-18 years of marriage life poses about 10 times significant risk of developing SD compared to 1-6 years of married life among the wives (OR: 10.8; CI: 1.1 - 49.1; p = 0.04). The total scores (6.0) as well as the percentage above the cut-off (59.2) obtained by the husbands compared to the total score (6.2) and the percentage above cut-off (61.5) obtained by the wives, indicates the likely presence of sexual dysfunction. The prevalence of impotence and premature ejaculation were 60.9% and 65.4% respectively from this study and the prevalence of vaginismus and anorgasmia were 69.3% and 74.9% respectively. The highest prevalence of SD subscales among the men was dissatisfaction with sexual act followed by infrequency, whereas the highest among the women was infrequency followed by anorgasmia. Dissatisfaction with sexual intercourse among men correlated positively with anorgasmia and wife's non-sensuality and infrequency of sex.</p> <p>Conclusion</p> <p>The prevalence of sexual dysfunction in married couples is comparable to prevalence rates in the general male and female population and is further worsened by duration of marriage. This could impact significantly on a couple's self-esteem and overall quality of life.</p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

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

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment