Outcomes after pneumonectomy versus limited lung resection in adults with traumatic lung injury.

Pneumonectomy after traumatic lung injury (TLI) is associated with shock, increased pulmonary vascular resistance, and eventual right ventricular failure. Historically, trauma pneumonectomy (TP) mortality rates ranged between 53 and 100%. It is unclear if contemporary mortality rates have improved. Therefore, we evaluated outcomes associated with TP and limited lung resections (LLR) (i.e., lobectomy and segmentectomy) and aimed to identify predictors of mortality, hypothesizing that TP is associated with greater mortality versus LLR. We queried the Trauma Quality Improvement Program (2010-2016) and performed a multivariable logistic regression to determine the independent predictors of mortality in TLI patients undergoing TP versus LLR. TLI occurred in 287,276 patients. Of these, 889 required lung resection with 758 (85.3%) undergoing LLR and 131 (14.7%) undergoing TP. Patients undergoing TP had a higher median injury severity score (26.0 vs. 24.5, p = 0.03) but no difference in initial median systolic blood pressure (109 vs. 107 mmHg, p = 0.92) compared to LLR. Mortality was significantly higher for TP compared to LLR (64.9% vs 27.2%, p < 0.001). The strongest independent predictor for mortality was undergoing TP versus LLR (OR 4.89, CI 3.18-7.54, p < 0.001). TP continues to be associated with a higher mortality compared to LLR. Furthermore, TP is independently associated with a fivefold increased risk of mortality compared to LLR. Future investigations should focus on identifying parameters or treatment modalities that improve survivability after TP. We recommend that surgeons reserve TP as a last-resort management given the continued high morbidity and mortality associated with this procedure

Bayes Wars Redivivus - An Exchange

An electronic exchange among 10 evidence scholars that began with a discussion of the restyled Federal Rules and grew into a significant restatement of debates in evidentiary scholarship over the last 50 years, touching on relevance, probative value, inference, Bayesianism and the foundations of evidence, with an introduction by Michael Risinger

A cytoplasm-specific activity encoded by the Trithorax-like ATX1 gene

Eukaryotes produce multiple products from a single gene locus by alternative splicing, translation or promoter usage as mechanisms expanding the complexity of their proteome. Trithorax proteins, including the Arabidopsis Trithorax-like protein ATX1, are histone modifiers regulating gene activity. Here, we report that a novel member of the Trithorax family has a role unrelated to chromatin. It is encoded from an internal promoter in the ATX1 locus as an isoform containing only the SET domain (soloSET). It is located exclusively in the cytoplasm and its substrate is the elongation factor 1A (EF1A). Loss of SET, but not of the histone modifying ATX1-SET activity, affects cytoskeletal actin bundling illustrating that the two isoforms have distinct functions in Arabidopsis cells

Associations between vascular risk factor levels and cognitive decline among stroke survivors

Importance Incident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain. Objective To evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decline. Design, Setting, and Participants Individual participant data meta-analysis of 4 US cohort studies (conducted 1971-2019). Linear mixed-effects models estimated changes in cognition after incident stroke. Median (IQR) follow-up was 4.7 (2.6-7.9) years. Analysis began August 2021 and was completed March 2023. Exposures Time-dependent cumulative mean poststroke SBP, glucose, and LDL cholesterol levels. Main Outcomes and Measures The primary outcome was change in global cognition. Secondary outcomes were change in executive function and memory. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results A total of 1120 eligible dementia-free individuals with incident stroke were identified; 982 (87.7%) had available covariate data and 138 (12.3%) were excluded for missing covariate data. Of the 982, 480 (48.9%) were female individuals, and 289 (29.4%) were Black individuals. The median age at incident stroke was 74.6 (IQR, 69.1-79.8; range, 44.1-96.4) years. Cumulative mean poststroke SBP and LDL cholesterol levels were not associated with any cognitive outcome. However, after accounting for cumulative mean poststroke SBP and LDL cholesterol levels, higher cumulative mean poststroke glucose level was associated with faster decline in global cognition (−0.04 points/y faster per each 10–mg/dL increase [95% CI, −0.08 to −0.001 points/y]; P = .046) but not executive function or memory. After restricting to 798 participants with apolipoprotein E4 (APOE4) data and controlling for APOE4 and APOE4 × time, higher cumulative mean poststroke glucose level was associated with a faster decline in global cognition in models without and with adjustment for cumulative mean poststroke SBP and LDL cholesterol levels (−0.05 points/y faster per 10–mg/dL increase [95% CI, −0.09 to −0.01 points/y]; P = .01; −0.07 points/y faster per 10–mg/dL increase [95% CI, −0.11 to −0.03 points/y]; P = .002) but not executive function or memory declines. Conclusions and Relevance In this cohort study, higher poststroke glucose levels were associated with faster global cognitive decline. We found no evidence that poststroke LDL cholesterol and SBP levels were associated with cognitive decline

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