Prediction of pathologic node-negative clinical stage IA lung adenocarcinoma for optimal candidates undergoing sublobar resection

ObjectivePatients with pathologic node-negative early lung cancer may be optimal candidates for sublobar resection. We aimed to identify predictors of pathologic lymph node involvement in clinical stage IA lung adenocarcinoma.MethodsThe data from a multicenter database of 502 patients with completely resected clinical stage IA lung adenocarcinoma were retrospectively analyzed to determine the relationship between the lymph node metastasis status and tumor size on high-resolution computed tomography (HRCT) or maximum standardized uptake value (SUVmax) on [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). Revised SUVmax was used to correct interinstitutional discrepancies.ResultsIn multivariate analyses, either a solid tumor size on HRCT (P = .001) or an SUVmax on FDG-PET/CT (P = .049) was an independent predictor of lymph node metastasis. The predictive criteria of pathologic node-negative early lung cancer were a solid tumor size of less than 0.8 cm or an SUVmax of less than 1.5. Patients who met the predictive criteria of pathologic node-negative disease had less pathologic invasiveness, such as lymphatic, vascular, or pleural invasion (P < .001), and better disease-free survival (P < .0001) than those who did not, and 86 (40.4%) of the 213 patients with T1b (2-3 cm) tumors met the predictive criteria.ConclusionsEither a solid tumor size or an SUVmax was a significant independent predictor of nodal involvement in clinical stage IA lung adenocarcinoma. The pathologic node-negative status criteria of a solid tumor size of less than 0.8 cm on HRCT or an SUVmax of less than1.5 on FDG-PET/CT may be helpful for avoiding systematic lymphadenectomy for clinical stage IA lung adenocarcinoma, even in cases of T1b (2-3 cm) tumor

A single-cell multiomic analysis of kidney organoid differentiation

Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney. We infer enhancer dynamics by cis-coaccessibility analysis and validate an enhancer driving transcription o

Epigenetic reprogramming driving successful and failed repair in acute kidney injury

Acute kidney injury (AKI) causes epithelial damage followed by subsequent repair. While successful repair restores kidney function, this process is often incomplete and can lead to chronic kidney disease (CKD) in a process called failed repair. To better understand the epigenetic reprogramming driving this AKI-to-CKD transition, we generated a single-nucleus multiomic atlas for the full mouse AKI time course, consisting of ~280,000 single-nucleus transcriptomes and epigenomes. We reveal cell-specific dynamic alterations in gene regulatory landscapes reflecting, especially, activation of proinflammatory pathways. We further generated single-nucleus multiomic data from four human AKI samples including validation by genome-wide identification of nuclear factor κB binding sites. A regularized regression analysis identifies key regulators involved in both successful and failed repair cell fate, identifying the transcription factor CREB5 as a regulator of both successful and failed tubular repair that also drives proximal tubular cell proliferation after injury. Our interspecies multiomic approach provides a foundation to comprehensively understand cell states in AKI

CODE SEC.XI BASED ON FAILURE PROBABILITY

ABSTRACT Based on the faihre probability, the flaw acceptaao~ standard of ASME Code Sec. XI is examined with some concerns weather tbe faihre l~vbabflity is unif~in for flaws with various aspect ratios and failure frcquoneies are small enough. In this paper, the results of lreliminmy case studies are deseff0ed on liae failure probability of n~etor pressure vessels (RPVs) with a surface flaw specified in Scc. XI. PFM code PASCAL was used for case studies. A PTS (Pressurized Thermal Shock) Iransient prescn&apos;bcd by NRC2EPRI ITS Benchmark Study was used as an applied load. Analysis results showcd that the conditional failure probability of a RPV wilh ~m initial flaw of acceptable depth depends on the aspect mlio. h case flaw&apos; shapes ~ze close to semi-circular, the failme probability are higher than that of the eases aspect ration are less than 0.6 by one order of magnitude due to the diffczeace of fracture behavior at the surface point. A case study for determining the acceptable flaws based on failure probability was also eanied on

Mosaic loss of Y chromosome is associated with aging and epithelial injury in chronic kidney disease

BACKGROUND: Mosaic loss of Y chromosome (LOY) is the most common chromosomal alteration in aging men. Here, we use single-cell RNA and ATAC sequencing to show that LOY is present in the kidney and increases with age and chronic kidney disease. RESULTS: The likelihood of a cell having LOY varies depending on its location in the nephron. Cortical epithelial cell types have a greater proportion of LOY than medullary or glomerular cell types, which may reflect their proliferative history. Proximal tubule cells are the most abundant cell type in the cortex and are susceptible to hypoxic injury. A subset of these cells acquires a pro-inflammatory transcription and chromatin accessibility profile associated with expression of HAVCR1, VCAM1, and PROM1. These injured epithelial cells have the greatest proportion of LOY and their presence predicts future kidney function decline. Moreover, proximal tubule cells with LOY are more likely to harbor additional large chromosomal gains and express pro-survival pathways. Spatial transcriptomics localizes injured proximal tubule cells to a pro-fibrotic microenvironment where they adopt a secretory phenotype and likely communicate with infiltrating immune cells. CONCLUSIONS: We hypothesize that LOY is an indicator of increased DNA damage and potential marker of cellular senescence that can be applied to single-cell datasets in other tissues