Evaluating the risk of malignancy in adnexal masses: validation of O-RADS and comparison with ADNEX model, SA, and RMI

Objectives: To evaluate the diagnostic value of Ovarian-adnexal Reporting and Data System (O-RADS), and to compare it with Assessment of Different NEoplasias in the adnexa (ADNEX) model, Subjective Assessment (SA), and Risk of Malignancy Index (RMI) in differentiating benign and malignant adnexal masses (AMs). Material and methods: Ultrasound characteristics of 445 patients included in the study were retrospectively analyzed and evaluated using diagnostic models. The diagnostic performances of ultrasound diagnostic models were measured by assessing, receiver-operating characteristic curves, sensitivities, positive predictive values, positive likelihood ratios, specificities, negative predictive values, and negative likelihood ratios. Kappa values were used to evaluate inter-reviewer agreement (IRA). Results: Of the 445 AMs, 265 were benign and 180 were malignant. The area under the curve (AUC) of O-RADS (0.941), ADNEX model (0.925), and SA (0.931) were higher than RMI (0.815) (all p < 0.05). The sensitivity of O-RADS (93.3%), ADNEX model (94.4%), and SA (96.1%) were higher than RMI (70.6%) (p > 0.05), and there was no statistical significance among them (p > 0.05). The specificity of O-RADS, ADNEX model, SA, and RMI was 90.2%, 90.6%, 90.2%, and 92.5%, respectively, with no statistical significance (p > 0.05). All four ultrasound diagnostic methods showed better IRA. Conclusions: O-RADS, ADNEX model and SA have better diagnostic value in differentiating benign and malignant AMs than RMI

Structure of the Mouse TRPC4 Ion Channel

Members of the transient receptor potential (TRP) ion channels conduct cations into cells. They mediate functions ranging from neuronally mediated hot and cold sensation to intracellular organellar and primary ciliary signaling. Here we report a cryo-electron microscopy (cryo-EM) structure of TRPC4 in its unliganded (apo) state to an overall resolution of 3.3 Å. The structure reveals a unique architecture with a long pore loop stabilized by a disulfide bond. Beyond the shared tetrameric six-transmembrane fold, the TRPC4 structure deviates from other TRP channels with a unique cytosolic domain. This unique cytosolic N-terminal domain forms extensive aromatic contacts with the TRP and the C-terminal domains. The comparison of our structure with other known TRP structures provides molecular insights into TRPC4 ion selectivity and extends our knowledge of the diversity and evolution of the TRP channels

SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies

We have developed a set of web-based SNP selection tools (freely available at http://www.niehs.nih.gov/snpinfo) where investigators can specify genes or linkage regions and select SNPs based on GWAS results, linkage disequilibrium (LD), and predicted functional characteristics of both coding and non-coding SNPs. The algorithm uses GWAS SNP P-value data and finds all SNPs in high LD with GWAS SNPs, so that selection is from a much larger set of SNPs than the GWAS itself. The program can also identify and choose tag SNPs for SNPs not in high LD with any GWAS SNP. We incorporate functional predictions of protein structure, gene regulation, splicing and miRNA binding, and consider whether the alternative alleles of a SNP are likely to have differential effects on function. Users can assign weights for different functional categories of SNPs to further tailor SNP selection. The program accounts for LD structure of different populations so that a GWAS study from one ethnic group can be used to choose SNPs for one or more other ethnic groups. Finally, we provide an example using prostate cancer and demonstrate that this algorithm can select a small panel of SNPs that include many of the recently validated prostate cancer SNPs

A mini review on antiwetting studies in membrane distillation for textile wastewater treatment

The textile industry is an important contributor to the growth of the global economy. However, a huge quantity of wastewater is generated as a by-product during textile manufacturing, which hinders the ongoing development of textile industry in terms of environmental sustainability. Membrane distillation (MD), which is driven by thermal-induced vapor pressure difference, is being considered as an emerging economically viable technology to treat the textile wastewater for water reuse. So far, massive efforts have been put into new membrane material developments and modifications of the membrane surface. However, membrane wetting, direct feed solution transport through membrane pores leading to the failure of separation, remains as one of the main challenges for the success and potential commercialization of this separation process as textile wastewater contains membrane wetting inducing surfactants. Herein, this review presents current progress on the MD process for textile wastewater treatment with particular focuses on the fundamentals of membrane wetting, types of membranes applied as well as the fabrication or modification of membranes for anti-wetting properties. This article aims at providing insights in membrane design to enhance the MD separation performance towards commercial application of textile wastewater treatment

Function Annotation of an SBP-box Gene in Arabidopsis Based on Analysis of Co-expression Networks and Promoters

The SQUAMOSA PROMOTER BINDING PROTEIN–LIKE (SPL) gene family is an SBP-box transcription family in Arabidopsis. While several physiological responses to SPL genes have been reported, their biological role remains elusive. Here, we use a combined analysis of expression correlation, the interactome, and promoter content to infer the biological role of the SPL genes in Arabidopsis thaliana. Analysis of the SPL-correlated gene network reveals multiple functions for SPL genes. Network analysis shows that SPL genes function by controlling other transcription factor families and have relatives with membrane protein transport activity. The interactome analysis of the correlation genes suggests that SPL genes also take part in metabolism of glucose, inorganic salts, and ATP production. Furthermore, the promoters of the correlated genes contain a core binding cis-element (GTAC). All of these analyses suggest that SPL genes have varied functions in Arabidopsis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Genetic Ancestry, Self-Reported Race and Ethnicity in African Americans and European Americans in the PCaP Cohort

Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP