A two-study validation of a single-item measure of relationship satisfaction: RAS-1

Research addressing relationship satisfaction is a constantly growing area in the social sciences. The aim of the present investigation was to examine the similarities and differences between the seven-item Relationship Assessment Scale (RAS) and the single-item measure of relationship satisfaction (RAS-1), using proximal and distal constructs as correlates. Two studies using two independent samples were conducted, assessing more proximal constructs, such as love and sex mindset in Study 1 (N = 380; female = 195) and more distant ones, such as loneliness and problematic pornography use in Study 2 (N = 703; female = 360). Structural equation modeling revealed that love (beta(RAS-1) = .55; p < .01; beta(RAS) = .71; p < .01), sex mindset beliefs (beta(RAS-1) = .18; p < .01; beta(RAS) = .13; p < .01) and loneliness (beta(RAS-1) = -.35; p < .01; beta(RAS) = -.37; p < .01) had significant positive and negative associations with RAS and RAS-1, respectively; while problematic pornography use did not. These results suggest that RAS-1 may be an equally adequate instrument for measuring relationship satisfaction as the RAS with respect to proximal and distal correlates. Thus, RAS-1 is recommended to be used in large-scale studies when the number of items is limited

Significance of Off-hours in Centralized Primary Percutaneous Coronary Intervention Network

Aim To analyze the efficacy of a regionally organized primary percutaneous coronary intervention (PCI) network at the Heart Center, Semmelweis University Budapest, part of the “Budapest model,” and the factors that influence it. Methods In order to investigate the differences between regular and off-hours patient care in a 24-hour myocardial infarction primary care system, we included 1890 consecutive, unselected patients with ST-segment elevation myocardial infarction and followed them until at least one year. The follow-up was complete for all participants. Results The difference between regular hours and offhours mortality was not significant either after 30 days (8.6% vs 8.8%, respectively) or after 1 year (15.3% vs 14.7%, respectively). The rate of patients with re-infarction, frequency of re-intervention, and major adverse cardiac events, including death, re-infarction, re-intervention, and coronary artery bypass graft surgery, were similar in both patient groups. The time delay between the onset of chest pain and arrival to the clinic was 5.9 ± 5.8 hours (mean ± standard deviation) during regular hours and 5.2 ± 4.6 hours during off-hours (P = 0.235). Direct transport caused significant decrease in the 30-day and 1-year mortality independent of duty time (7.2% vs 9.9%, P = 0.027; 12.6% vs 16.7%, P = 0.028; respectively). Conclusion Centralized primary PCI network of the “Budapest model” achieved the same level of patient care during both off-hours and regular hours

Support for collective action against refugees: The role of national, European, and global identifications, and autochthony beliefs

To understand recent anti-refugee protests in Europe, we examined how different levels of inclusiveness of group identities (national, European, and global) are related to intentions to protest among native Europeans. We focused on the mediating role of autochthony (a belief that the first inhabitants of a territory are more entitled) and the moderating role of threat. Survey data from 11 European countries (N=1909) showed that national identification was positively associated with autochthony, and therefore, with the intention to protest against refugees. In contrast, global identification was related to lower protest intentions via lower autochthony. These paths were found only among Europeans who perceived refugees as a threat. European identification was not related to the endorsement of autochthony or to collective action. These findings indicate why and when majority members are willing to participate in collective action against refugees, and underscore the importance of global identification in the acceptance of refugees

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

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

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

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

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years