Impact of Tumor-intrinsic Molecular Features on Survival and Acquired Tyrosine Kinase Inhibitor Resistance in ALK-positive NSCLC.

Unlabelled: While tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC), clinical outcomes vary and acquired resistance remains a significant challenge. We conducted a retrospective study of patients with ALK-positive NSCLC who had clinico-genomic data independently collected from two academic institutions (n = 309). This was paired with a large-scale genomic cohort of patients with ALK-positive NSCLC who underwent liquid biopsies (n = 1,118).

Transcriptome-Wide Association Studies (TWAS): Methodologies, Applications, and Challenges.

Transcriptome-wide association study (TWAS) methodologies aim to identify genetic effects on phenotypes through the mediation of gene transcription. In TWAS, in silico models of gene expression are trained as functions of genetic variants and then applied to genome-wide association study (GWAS) data. This post-GWAS analysis identifies gene-trait associations with high interpretability, enabling follow-up functional genomics studies and the development of genetics-anchored resources.

Bounded strategic reasoning explains crisis emergence in multi-agent market games.

The efficient market hypothesis (EMH), based on rational expectations and market equilibrium, is the dominant perspective for modelling economic markets. However, the most notable critique of the EMH is the inability to model periods of out-of-equilibrium dynamics without significant external news. When such dynamics emerge endogenously, the traditional economic frameworks prove insufficient.

Evaluation of an Initial Specimen Diversion Device (ISDD) on Rates of Blood Culture Contamination in the Emergency Department.

Introduction: Blood cultures are the gold standard for identifying bloodstream infections. The Clinical and Laboratory Standards Institute recommends a blood culture contamination rate of less than 3%. Contamination can lead to misdiagnosis, increased length of stay and hospital costs, unnecessary testing, and antibiotic use.

The impact of sex on gene expression across human tissues.

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release).

The regulatory genome constrains protein sequence evolution: implications for the search for disease-associated genes.

The development of explanatory models of protein sequence evolution has broad implications for our understanding of cellular biology, population history, and disease etiology. Here we analyze the GTEx transcriptome resource to quantify the effect of the transcriptome on protein sequence evolution in a multi-tissue framework. We find substantial variation among the central nervous system tissues in the effect of expression variance on evolutionary rate, with highly variable genes in the cortex showing significantly greater purifying selection than highly variable genes in subcortical regions (Mann-Whitney U  = 1.

Life cycle assessment and economic analysis of anaerobic membrane bioreactor whole-plant configurations for resource recovery from domestic wastewater.

The use of the anaerobic membrane bioreactor (AnMBR) process for domestic wastewater treatment presents an opportunity to mitigate environmental, social, and economic impacts currently incurred from energy-intensive conventional aerobic activated sludge processes. Previous studies have performed detailed evaluations on improving AnMBR process subcomponents to maximize energy recovery and dissolved methane recovery. Few studies have broadly evaluated the role of chemical use, membrane fouling management, and dissolved methane removal technologies.

Long-term microbial community dynamics in a pilot-scale gas sparged anaerobic membrane bioreactor treating municipal wastewater under seasonal variations.

This study evaluates the microbial community development in the suspended sludge within a pilot-scale gas sparged Anaerobic membrane bioreactor (AnMBR) under ambient conditions, as well as understand the influence of microbial signatures in the influent municipal wastewater on the bioreactor using amplicon sequence analysis. The predominant bacterial phyla comprised of Bacteroidetes, Proteobacteria, Firmicutes, and Chloroflexi demonstrated resiliency with ambient temperature operation over a period of 472 days. Acetoclastic Methanosaeta were predominant during most of the AnMBR operation.

Electronic health record phenotypes associated with genetically regulated expression of CFTR and application to cystic fibrosis.

Purpose: The increasing use of electronic health records (EHRs) and biobanks offers unique opportunities to study Mendelian diseases. We described a novel approach to summarize clinical manifestations from patient EHRs into phenotypic evidence for cystic fibrosis (CF) with potential to alert unrecognized patients of the disease.

Methods: We estimated genetically predicted expression (GReX) of cystic fibrosis transmembrane conductance regulator (CFTR) and tested for association with clinical diagnoses in the Vanderbilt University biobank (N = 9142 persons of European descent with 71 cases of CF).

Holmium Laser Enucleation of the Prostate Is Safe and Feasible as a Same Day Surgery.

Objective: To assess the safety, feasibility and treatment outcomes of holmium laser enucleation of the prostate (HoLEP) as a same day surgery (SDS).

Methods: HoLEPs performed from November 2013 to December 2018 at our institution were reviewed retrospectively. Inclusion criteria for same day surgery (SDS) included living in the local metropolitan area with access to local hospital and Eastern Cooperative Oncology Group (ECOG) 0-2, regardless of prostate size and anticoagulation status.

Inferred divergent gene regulation in archaic hominins reveals potential phenotypic differences.

Sequencing DNA derived from archaic bones has enabled genetic comparison of Neanderthals and anatomically modern humans (AMHs), and revealed that they interbred. However, interpreting what genetic differences imply about their phenotypic differences remains challenging. Here, we introduce an approach for identifying divergent gene regulation between archaic hominins, such as Neanderthals, and AMH sequences, and find 766 genes that are likely to have been divergently regulated (DR) by Neanderthal haplotypes that do not remain in AMHs.

Long-Term Performance of a Pilot-Scale Gas-Sparged Anaerobic Membrane Bioreactor under Ambient Temperatures for Holistic Wastewater Treatment.

Concerns regarding ambient temperature operation, dissolved methane recovery, and nutrient removal have limited the implementation of anaerobic membrane bioreactors (AnMBRs) for domestic wastewater treatment. This study addresses these challenges using a pilot-scale gas-sparged AnMBR, with post-treatment recovery of dissolved methane and nutrients. Operating under ambient temperatures for 472 days, the AnMBR achieved an average effluent quality of 58 ± 27 mg/L COD and 25 ± 12 mg/L BOD at temperatures ranging from 12.

A comparative pilot-scale evaluation of gas-sparged and granular activated carbon-fluidized anaerobic membrane bioreactors for domestic wastewater treatment.

Two significantly different pilot-scale AnMBRs were used to treat screened domestic wastewater for over one year. Both systems similarly reduced BOD and COD by 86-90% within a 13-32 °C temperature range and at comparable COD loading rates of 1.3-1.

Slow-release permanganate versus unactivated persulfate for long-term in situ chemical oxidation of 1,4-dioxane and chlorinated solvents.

The objective of this research was to evaluate slow-release permanganate and unactivated persulfate for in situ treatment of dioxane and associated chlorinated solvents. Laboratory batch studies with unactivated persulfate in deionized water or in soil and groundwater demonstrated dioxane removal with pseudo second-order rate constants ranging from 10 to 10 M s. Flow-through column studies demonstrated over 99% dioxane removal with slow-release unactivated persulfate but not with slow-release permanganate.

Evaluating a multi-panel air cathode through electrochemical and biotic tests.

To scale up microbial fuel cells (MFCs), larger cathodes need to be developed that can use air directly, rather than dissolved oxygen, and have good electrochemical performance. A new type of cathode design was examined here that uses a "window-pane" approach with fifteen smaller cathodes welded to a single conductive metal sheet to maintain good electrical conductivity across the cathode with an increase in total area. Abiotic electrochemical tests were conducted to evaluate the impact of the cathode size (exposed areas of 7 cm, 33 cm, and 6200 cm) on performance for all cathodes having the same active catalyst material.

A pilot-scale investigation of disinfection by-product precursors and trace organic removal mechanisms in ozone-biologically activated carbon treatment for potable reuse.

Although granular activated carbon (GAC) has been broadly applied in ozone-biologically activated carbon filtration (O/BAC) systems for potable reuse of municipal wastewater, the mechanisms of various pollutant removal remain largely unknown as the regenerated GAC develops microbial populations resulting in biofiltration but loses significant adsorption capacity as it becomes spent GAC. Therefore, pilot-scale parallel performance comparisons of spent and regenerated GAC, along with a range of pre-oxidant ozone doses, were used to shed light on the mechanisms responsible for the removal of various types of treatment byproduct precursors and trace organic compounds. It was confirmed from this pilot-study that ozone alone can effectively degrade chlorinated trihalomethane (THM) and haloacetic acid (HAA) precursors, chloramine-reactive N-nitrosodimethylamine (NDMA) precursors, and 29 PPCPs.

A Prospective Study of Patient-reported Pain After Bulbar Urethroplasty.

Objective: To understand the prevalence of chronic perineal pain, activity limitations, and patient satisfaction after urethroplasty.

Methods: From 2014 to 2016, we prospectively enrolled men undergoing urethroplasty for bulbar urethral strictures. Patients, before and after surgery, completed questions from the Core Lower Urinary Tract Symptom Score assessing pain frequency in the bladder and penis or urethra, as well as nonvalidated questions assessing perineal pain.

Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis.

Background: Current practice methods are unclear as to the most safe and effective prophylactic pharmacotherapy and method of delivery to reduce postoperative endophthalmitis occurrence.

Methods: A systematic review and meta-analysis using Meta-analysis of Observational Studies in Epidemiology guidelines was performed to compare the efficacy of intracameral cefuroxime, moxifloxacin and vancomycin in preventing postphacoemulsification cataract surgery endophthalmitis. A safety analysis of intracameral antibiotics was concurrently performed.

The bioelectrosynthesis of acetate.

Risks associated with climate change are driving the search for new technologies to produce fuels and chemicals. The microbial electrosynthesis of chemical compounds, using electricity and CO as feedstock and microbes to deliver the catalysts, has the potential to be one of those technologies. Central to the production of multicarbon compounds by this process is the bioelectrosynthesis of acetate (electroacetogenesis), and significant improvements in productivity and insightful discoveries concerning the extracellular transfer of electrons to the acetogenic microorganisms have been made recently.

Continuous treatment of high strength wastewaters using air-cathode microbial fuel cells.

Treatment of low strength wastewaters using microbial fuel cells (MFCs) has been effective at hydraulic retention times (HRTs) similar to aerobic processes, but treatment of high strength wastewaters can require longer HRTs. The use of two air-cathode MFCs hydraulically connected in series was examined to continuously treat high strength swine wastewater (7-8g/L of chemical oxygen demand) at an HRT of 16.7h.

COD removal characteristics in air-cathode microbial fuel cells.

Exoelectrogenic microorganisms in microbial fuel cells (MFCs) compete with other microorganisms for substrate. In order to understand how this affects removal rates, current generation, and coulombic efficiencies (CEs), substrate removal rates were compared in MFCs fed a single, readily biodegradable compound (acetate) or domestic wastewater (WW). Removal rates based on initial test conditions fit first-order kinetics, but rate constants varied with circuit resistance.

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.

Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.

Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date.

Method: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls.

Genetic association signal near NTN4 in Tourette syndrome.

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10(-3) ) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry-matched controls. Only rs2060546 on chromosome 12q22 (p = 3.