This is not an apple! Benefits and challenges of applying computer vision to museum collections

The application of computer vision on museum collection data is at an experimental stage with predictions that it will grow in significance and use in the coming years. This research, based on the analysis of five case studies and semi-structured interviews with museum professionals, examined the opportunities and challenges of these technologies, the resources and funding required, and the ethical implications that arise during these initiatives. The case studies examined in this paper are drawn from: The Metropolitan Museum of Art (USA), Princeton University Art Museum (USA), Museum of Modern Art (USA), Harvard Art Museums (USA), Science Museum Group (UK). The research findings highlight the possibilities of computer vision to offer new ways to analyze, describe and present museum collections. However, their actual implementation on digital products is currently very limited due to the lack of resources and the inaccuracies created by algorithms. This research adds to the rapidly evolving field of computer vision within the museum sector and provides recommendations to operationalize the usage of these technologies, increase the transparency on their application, create ethics playbooks to manage potential bias and collaborate across the museum sector

A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding.

A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer.The QIMR Berghofer groups were supported by a Rio Tinto Ride to Conquer Cancer (RTCC)/Weekend to End Women's Cancers (WEWC) Grant and NHMRC project grants 1058415 to SLE and 1031333 to ABS. ABS is supported by an NHMRC Senior Research Fellowship (1061779). DFE is a Principal Research Fellow of CR-UK.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Cell Press

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Malaria is an uncommon cause of adult sepsis in south-western Uganda

Malaria is often considered a cause of adult sepsis in malaria endemic areas. However, diagnostic limitations can make distinction between malaria and other infections challenging. Therefore, the objective of this study was to determine the relative contribution of malaria to adult sepsis in south-western Uganda

Androgen receptor expression predicts breast cancer survival: the role of genetic and epigenetic events

Background: Breast cancer outcome, including response to therapy, risk of metastasis and survival, is difficult to predict using currently available methods, highlighting the urgent need for more informative biomarkers. Androgen receptor (AR) has been implicated in breast carcinogenesis however its potential to be an informative biomarker has yet to be fully explored. In this study, AR protein levels were determined in a cohort of 73 Grade III invasive breast ductal adenocarcinomas

Psychological interventions for people with psychotic experiences: protocol for a systematic review and meta-analysis.

BACKGROUND: Many people who have common mental disorders, such as depression and anxiety, also have some psychotic experiences. These experiences are associated with higher clinical complexity, poor treatment response, and negative clinical outcomes. Psychological interventions have the potential to improve outcomes for people with psychotic experiences. The aims of this systematic review are to (1) synthesise the evidence on the effectiveness and cost-effectiveness of psychological interventions to reduce psychotic experiences and their associated distress and (2) identify key components of effective interventions. METHODS: Our search strategy will combine terms for (1) psychological interventions, (2) psychotic experiences, and (3) symptoms associated with psychotic experiences. We will search the following online databases: MEDLINE, Embase, PsycINFO, all Cochrane databases, British Nursing Index (BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Health Management Information Consortium (HMIC), Education Resources Information Center (ERIC), and EconLit. Our primary outcome is the proportion of people who recovered or remitted from psychotic experiences after the intervention. Our secondary outcomes are changes in positive psychotic symptoms, negative psychotic symptoms, depression, anxiety, functioning (including social, occupational, and academic), quality of life, and cost-effectiveness. Two independent reviewers will judge each study against pre-specified inclusion and exclusion criteria and will extract study characteristics, outcome data, and intervention components. Risk of bias and methodological quality will be assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies and the Drummond Checklist. Results will be synthesised using random-effects meta-analysis and narrative synthesis. DISCUSSION: The identification of effective psychological interventions and of specific components associated with intervention effectiveness will augment existing evidence that can inform the development of a new, tailored intervention to improve outcomes related to psychotic symptoms, anxiety and depression, distress, functioning, and quality of life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033869.This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Reference Number RP-PG-0616-20003). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health

Association between breast cancer genetic susceptibility variants and terminal duct lobular unit involution of the breast

Terminal duct lobular units (TDLUs) are the predominant source of future breast cancers, and lack of TDLU involution (higher TDLU counts, higher acini count per TDLU and the product of the two) is a breast cancer risk factor. Numerous breast cancer susceptibility single nucleotide polymorphisms (SNPs) have been identified, but whether they are associated with TDLU involution is unknown. In a pooled analysis of 872 women from two studies, we investigated 62 established breast cancer SNPs and relationships with TDLU involution. Poisson regression models with robust variance were used to calculate adjusted per-allele relative risks (with the non-breast cancer risk allele as the referent) and 95% confidence intervals between TDLU measures and each SNP. All statistical tests were two-sided; P<0.05 was considered statistically significant. Overall, 36 SNPs (58.1%) were related to higher TDLU counts although this was not statistically significant (P=0.25). Six of the 62 SNPs (9.7%) were nominally associated with at least one TDLU measure: rs616488 (PEX14), rs11242675 (FOXQ1) and rs6001930 (MKL1) were associated with higher TDLU count (P=0.047, 0.045 and 0.031, respectively); rs1353747 (PDE4D) and rs6472903 (8q21.11) were associated with higher acini count per TDLU (P=0.007 and 0.027, respectively); and rs1353747 (PDE4D) and rs204247 (RANBP9) were associated with the product of TDLU and acini counts (P=0.024 and 0.017, respectively). Our findings suggest breast cancer SNPs may not strongly influence TDLU involution. Agnostic genome-wide association studies of TDLU involution may provide new insights on its biologic underpinnings and breast cancer susceptibility

Unexpected High Digestion Rate of Cooked Starch by the Ct-Maltase-Glucoamylase Small Intestine Mucosal α-Glucosidase Subunit

For starch digestion to glucose, two luminal α-amylases and four gut mucosal α-glucosidase subunits are employed. The aim of this research was to investigate, for the first time, direct digestion capability of individual mucosal α-glucosidases on cooked (gelatinized) starch. Gelatinized normal maize starch was digested with N- and C-terminal subunits of recombinant mammalian maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) of varying amounts and digestion periods. Without the aid of α-amylase, Ct-MGAM demonstrated an unexpected rapid and high digestion degree near 80%, while other subunits showed 20 to 30% digestion. These findings suggest that Ct-MGAM assists α-amylase in digesting starch molecules and potentially may compensate for developmental or pathological amylase deficiencies