Selonsertib in Patients with Diabetic Kidney Disease: A Phase 2b Randomized Active Run-In Clinical Trial.

Key Points: In a randomized, placebo-controlled, phase 2b study, we compared the effects of selonsertib with placebo on eGFR decline in people with type 2 diabetes and CKD. Patients taking selonsertib had slower eGFR decline but were more likely to reach a composite kidney outcome and report AKI. A larger trial with longer-term follow-up would more precisely assess the relative benefits and risks of selonsertib in this setting.

Machine learning to detect the SINEs of cancer.

We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer.

Quantification and statistical modeling of droplet-based single-nucleus RNA-sequencing data.

In complex tissues containing cells that are difficult to dissociate, single-nucleus RNA-sequencing (snRNA-seq) has become the preferred experimental technology over single-cell RNA-sequencing (scRNA-seq) to measure gene expression. To accurately model these data in downstream analyses, previous work has shown that droplet-based scRNA-seq data are not zero-inflated, but whether droplet-based snRNA-seq data follow the same probability distributions has not been systematically evaluated. Using pseudonegative control data from nuclei in mouse cortex sequenced with the 10x Genomics Chromium system and mouse kidney sequenced with the DropSeq system, we found that droplet-based snRNA-seq data follow a negative binomial distribution, suggesting that parametric statistical models applied to scRNA-seq are transferable to snRNA-seq.

Evaluating the impact of multicancer early detection testing on health and economic outcomes: Toward a decision modeling strategy.

Emerging data provide initial support for the concept that a single, minimally invasive liquid biopsy test, performed in conjunction with confirmatory radiologic or other diagnostic testing, when indicated, could be deployed on a broad scale to screen individuals for multiple types of cancer. Ideally, such a test could do this in a way that yields a clinically important percentage of true-positive indications of cancer while minimizing false-positive signals. Modern decision modeling approaches can and should be deployed to investigate the health and economic consequences of such multicancer early detection (MCED) testing within defined at-risk populations.

Non-steroidal anti-inflammatory drugs, intravenous fluids, pancreatic stents, or their combinations for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and network meta-analysis.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous RCTs to systematically compare the direct and indirect evidence and rank NSAIDs, intravenous fluids, pancreatic stents, or combinations of these to determine the most efficacious method of prophylaxis for post-ERCP pancreatitis.

Methods: We searched PubMed, Embase, and the Cochrane Central Register from inception to Nov 15, 2020, for full-text RCTs that evaluated the efficacy of NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for post-ERCP pancreatitis prevention in adult (aged ≥18 years) patients undergoing ERCP.

Supervised mutational signatures for obesity and other tissue-specific etiological factors in cancer.

Determining the etiologic basis of the mutations that are responsible for cancer is one of the fundamental challenges in modern cancer research. Different mutational processes induce different types of DNA mutations, providing 'mutational signatures' that have led to key insights into cancer etiology. The most widely used signatures for assessing genomic data are based on unsupervised patterns that are then retrospectively correlated with certain features of cancer.

Intracranial hemorrhage after prehospital administration of intramuscular epinephrine.

Background: The administration of epinephrine by the intramuscular route can be life-saving in cases of anaphylaxis or severe allergic reactions. However, the use of this drug can lead to a rapid rise in blood pressure, which theoretically could lead to deleterious effects in patients of any age, with elderly patients at greatest risk.

Objectives: To present a rare case of intracranial hemorrhage potentially resulting from the administration of intramuscular epinephrine in an elderly patient with an allergic reaction.

Simulation of water quality and plankton dynamics in the Danshuei River estuary, Taiwan.

An ecosystem model was developed to simulate the water quality and plankton dynamics in the Danshuei River estuary, Taiwan. The model simulates the hydrodynamics with a laterally integrated 2-dimensional intratidal numerical model, which supplies the physical transport processes for simulation of water quality and plankton state variables. The application of the model to the Danshuei River estuary indicates that the point source loadings are mainly responsible for the degraded water quality and very high nutrient concentrations in the estuary.

Water quality modeling to determine minimum instream flow for fish survival in tidal rivers.

The Hsintien Stream is one of the major branches of the Danshuei River system, which runs through the metropolitan capital city of Taipei, Taiwan and receives a large amount of wastewater. The dissolved oxygen concentration is generally low in the tidal portion of the Hsintien Stream. Hypoxia/anoxia occurs often, particularly during the low-flow period when the Feitsui Reservoir, Chingtan Dam and Chihtan Dam impound the freshwater for municipal water supply.

Recognition of undiagnosed HIV infection: an evaluation of missed opportunities in a predominantly urban minority population.

The goals of this study were to quantify delays in diagnosing HIV infection in patients presenting for medical care prior to the identification of their HIV infection, and to determine characteristics of visits preceding the identification of HIV infection. This was a retrospective cohort study of consecutive newly diagnosed HIV infected patients in a large urban setting. Patients were predominantly minorities and identified from all inpatient and outpatient HIV tests performed between December 29, 1998 and December 27, 1999.

Modelling of hydrodynamics and cohesive sediment transport in Tanshui River estuarine system, Taiwan.

A laterally averaged two-dimensional numerical model is used to simulate hydrodynamics and cohesive sediment transport in the Tanshui River estuarine system. The model handles tributaries as well as the main stem of the estuarine system. Observed time series of salinity data and tidally averaged salinity distributions have been compared with model results to calibrate the turbulent diffusion coefficients.