Rationale and Design of the ILIAS ANOCA Clinical Trial: a blinded-arm controlled trial for routine ad-hoc coronary function testing.

Angina with non-obstructive coronary arteries (ANOCA) is a major cause of chronic coronary syndromes, affecting nearly half of patients with anginal symptoms who undergo invasive coronary angiography. ANOCA may lead to substantial symptom burden, increased risk of adverse cardiac events, increased healthcare utilization due to ongoing symptoms, repeat hospitalizations, and invasive testing. The pathophysiology of ANOCA often involves a variety of coronary disorders, such as coronary microvascular dysfunction, epicardial or microvascular vasospasm and endothelial dysfunction.

Catheter-directed therapy with the FlowTriever system for intermediate-high and high-risk pulmonary embolism: a single-centre experience.

Background: Pulmonary embolism is an important cause of preventable mortality. Treatment strategies depend on risk stratification. High-risk patients, and some intermediate-high-risk patients, require urgent reperfusion therapy.

The impact of recipient hypernatremia on pediatric liver transplantation outcomes.

In pediatric liver transplants, dysnatremias have been found to have an impact on pretransplant and posttransplant outcomes. However, much of the current literature has focused on waitlist survival, secondary organ damage, and dysnatremia in donors rather than in recipients. To understand the effect of recipient immediate pretransplant hypernatremia on posttransplant mortality, we conducted a multivariable retrospective review analyzing data from 8011 pediatric patients undergoing liver transplantation provided by the United Network for Organ Sharing (UNOS).

Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial.

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires.

Efficacy of Deep Brain Stimulation for Treatment-Resistant Depression: Systematic Review and Meta-Analysis.

Background: Treatment-resistant depression affects about 30% of individuals with major depressive disorder. Deep brain stimulation is an investigational intervention for treatment-resistant depression with varied results. We undertook this meta-analysis to synthesize outcome data across trial designs, anatomical targets, and institutions to better establish efficacy and side-effect profiles.

High dietary K intake inhibits proximal tubule transport.

The impact of chronic dietary K loading on proximal tubule (PT) function was measured using free-flow micropuncture along with measurements of overall kidney function, including urine volume, glomerular filtration rate, and absolute and fractional Na and K excretion in the rat. Feeding animals a diet with 5% KCl [high K (HK)] for 7 days reduced glomerular filtration rate by 29%, increased urine volume by 77%, and increased absolute K excretion by 202% compared with rats on a 1% KCl [control K (CK)] diet. HK did not change absolute Na excretion but significantly increased fraction excretion of Na (1.

Explainable discovery of disease biomarkers: The case of ovarian cancer to illustrate the best practice in machine learning and Shapley analysis.

Objective: Ovarian cancer is a significant health issue with lasting impacts on the community. Despite recent advances in surgical, chemotherapeutic and radiotherapeutic interventions, they have had only marginal impacts due to an inability to identify biomarkers at an early stage. Biomarker discovery is challenging, yet essential for improving drug discovery and clinical care.

Quantitative flow ratio versus fractional flow reserve for guiding percutaneous coronary intervention: design and rationale of the randomised FAVOR III Europe Japan trial.

Quantitative flow ratio (QFR) is a computation of fractional flow reserve (FFR) based on invasive coronary angiographic images. Calculating QFR is less invasive than measuring FFR and may be associated with lower costs. Current evidence supports the call for an adequately powered randomised comparison of QFR and FFR for the evaluation of intermediate coronary stenosis.

Sex difference in kidney electrolyte transport III: Impact of low K intake on thiazide-sensitive cation excretion in male and female mice.

We compared the regulation of the NaCl cotransporter (NCC) in adaptation to a low-K (LK) diet in male and female mice. We measured hydrochlorothiazide (HCTZ)-induced changes in urine volume (UV), glomerular filtration rate (GFR), absolute (ENa, EK), and fractional (FENa, FEK) excretion in male and female mice on control-K (CK, 1% KCl) and LK (0.1% KCl) diets for 7 days.

Reproducibility of quantitative flow ratio: the QREP study.

Background: Quantitative flow ratio (QFR) is a tool for physiological lesion assessment based on invasive coronary angiography.

Aims: We aimed to assess the reproducibility of QFR computed from the same angiograms as assessed by multiple observers from different, international sites.

Methods: We included 50 patients previously enrolled in dedicated QFR studies.

Resting distal to aortic pressure ratio and fractional flow reserve discordance affects the diagnostic performance of quantitative flow ratio: Results from an individual patient data meta-analysis.

Objective: To evaluate the diagnostic performance of quantitative flow ratio (QFR) related to fractional flow reserve (FFR) and resting distal-to-aortic pressure ratio (resting Pd/Pa) concordance.

Background: QFR is a method for computation of FFR based on standard coronary angiography. It is unclear how QFR is performed in patients with discordance between FFR and resting pressure ratios (distal-to-aortic pressure ratio [Pd/Pa]).

Diagnostic performance of quantitative flow ratio in prospectively enrolled patients: An individual patient-data meta-analysis.

Objectives: We aimed to provide robust performance estimates for quantitative flow ratio (QFR) in assessment of intermediary coronary lesions.

Background: Angiography-based functional lesion assessment by QFR may appear as a cost saving and safe approach to expand the use of physiology-guided percutaneous coronary interventions. QFR was proven feasible and showed good diagnostic performance in mid-sized off-line and on-line studies with fractional flow reserve (FFR) as reference standard.

The CAMH Neuroinformatics Platform: A Hospital-Focused Brain-CODE Implementation.

Investigations of mental illness have been enriched by the advent and maturation of neuroimaging technologies and the rapid pace and increased affordability of molecular sequencing techniques, however, the increased volume, variety and velocity of research data, presents a considerable technical and analytic challenge to curate, federate and interpret. Aggregation of high-dimensional datasets across brain disorders can increase sample sizes and may help identify underlying causes of brain dysfunction, however, additional barriers exist for effective data harmonization and integration for their combined use in research. To help realize the potential of multi-modal data integration for the study of mental illness, the Centre for Addiction and Mental Health (CAMH) constructed a centralized data capture, visualization and analytics environment-the based on the Ontario Brain Institute (OBI) Brain-CODE architecture, towards the curation of a standardized, consolidated psychiatric hospital-wide research dataset, directly coupled to high performance computing resources.

Diagnostic Performance of In-Procedure Angiography-Derived Quantitative Flow Reserve Compared to Pressure-Derived Fractional Flow Reserve: The FAVOR II Europe-Japan Study.

Background: Quantitative flow ratio (QFR) is a novel modality for physiological lesion assessment based on 3-dimensional vessel reconstructions and contrast flow velocity estimates. We evaluated the value of online QFR during routine invasive coronary angiography for procedural feasibility, diagnostic performance, and agreement with pressure-wire-derived fractional flow reserve (FFR) as a gold standard in an international multicenter study.

Methods And Results: FAVOR II E-J (Functional Assessment by Various Flow Reconstructions II Europe-Japan) was a prospective, observational, investigator-initiated study.

Similar prevalence of low-abundance drug-resistant variants in treatment-naive patients with genotype 1a and 1b hepatitis C virus infections as determined by ultradeep pyrosequencing.

Background And Objectives: Hepatitis C virus (HCV) variants that confer resistance to direct-acting-antiviral agents (DAA) have been detected by standard sequencing technology in genotype (G) 1 viruses from DAA-naive patients. It has recently been shown that virological response rates are higher and breakthrough rates are lower in G1b infected patients than in G1a infected patients treated with certain classes of HCV DAAs. It is not known whether this corresponds to a difference in the composition of G1a and G1b HCV quasispecies in regards to the proportion of naturally occurring DAA-resistant variants before treatment.

Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing.

Objectives: The introduction of two new non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the past 5 years and the identification of novel NNRTI-associated mutations have made it necessary to reassess the extent of phenotypic NNRTI cross-resistance.

Methods: We analysed a dataset containing 1975, 1967, 519 and 187 genotype-phenotype correlations for nevirapine, efavirenz, etravirine and rilpivirine, respectively. We used linear regression to estimate the effects of RT mutations on susceptibility to each of these NNRTIs.

Trends in Genotypic HIV-1 Antiretroviral Resistance between 2006 and 2012 in South African Patients Receiving First- and Second-Line Antiretroviral Treatment Regimens.

Objectives: South Africa's national antiretroviral (ARV) treatment program expanded in 2010 to include the nucleoside reverse transcriptase (RT) inhibitors (NRTI) tenofovir (TDF) for adults and abacavir (ABC) for children. We investigated the associated changes in genotypic drug resistance patterns in patients with first-line ARV treatment failure since the introduction of these drugs, and protease inhibitor (PI) resistance patterns in patients who received ritonavir-boosted lopinavir (LPV/r)-containing therapy.

Methods: We analysed ARV treatment histories and HIV-1 RT and protease mutations in plasma samples submitted to the Tygerberg Academic Hospital National Health Service Laboratory.

Prototypical Recombinant Multi-Protease-Inhibitor-Resistant Infectious Molecular Clones of Human Immunodeficiency Virus Type 1.

The many genetic manifestations of HIV-1 protease inhibitor (PI) resistance present challenges to research into the mechanisms of PI resistance and the assessment of new PIs. To address these challenges, we created a panel of recombinant multi-PI-resistant infectious molecular clones designed to represent the spectrum of clinically relevant multi-PI-resistant viruses. To assess the representativeness of this panel, we examined the sequences of the panel's viruses in the context of a correlation network of PI resistance amino acid substitutions in sequences from more than 10,000 patients.

Low-level persistence of drug resistance mutations in hepatitis B virus-infected subjects with a past history of Lamivudine treatment.

We sought to determine the prevalence of hepatitis B virus (HBV) lamivudine (LAM)-resistant minority variants in subjects who once received LAM but had discontinued it prior to virus sampling. We performed direct PCR Sanger sequencing and ultradeep pyrosequencing (UDPS) of HBV reverse transcriptase (RT) of plasma viruses from 45 LAM-naive subjects and 46 LAM-experienced subjects who had discontinued LAM a median of 24 months earlier. UDPS was performed to a depth of ∼3,000 reads per nucleotide.

Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance.

Objectives: To determine whether pan-protease inhibitor (PI)-resistant virus populations are composed predominantly of viruses with resistance to all PIs or of diverse virus populations with resistance to different subsets of PIs.

Methods: We performed deep sequencing of plasma virus samples from nine patients with high-level genotypic and/or phenotypic resistance to all licensed PIs. The nine virus samples had a median of 12 PI resistance mutations by direct PCR Sanger sequencing.

Standardized representation, visualization and searchable repository of antiretroviral treatment-change episodes.

Background: To identify the determinants of successful antiretroviral (ARV) therapy, researchers study the virological responses to treatment-change episodes (TCEs) accompanied by baseline plasma HIV-1 RNA levels, CD4+ T lymphocyte counts, and genotypic resistance data. Such studies, however, often differ in their inclusion and virological response criteria making direct comparisons of study results problematic. Moreover, the absence of a standard method for representing the data comprising a TCE makes it difficult to apply uniform criteria in the analysis of published studies of TCEs.

Reconsidering Yarbus: a failure to predict observers' task from eye movement patterns.

In 1967, Yarbus presented qualitative data from one observer showing that the patterns of eye movements were dramatically affected by an observer's task, suggesting that complex mental states could be inferred from scan paths. The strong claim of this very influential finding has never been rigorously tested. Our observers viewed photographs for 10s each.

Automating HIV drug resistance genotyping with RECall, a freely accessible sequence analysis tool.

Genotypic HIV drug resistance testing is routinely used to guide clinical decisions. While genotyping methods can be standardized, a slow, labor-intensive, and subjective manual sequence interpretation step is required. We therefore performed external validation of our custom software RECall, a fully automated sequence analysis pipeline.

The HIVdb system for HIV-1 genotypic resistance interpretation.

The Stanford HIV Drug Resistance Database hosts a freely available online genotypic resistance interpretation system called HIVdb to help clinicians and laboratories interpret HIV-1 genotypic resistance tests. These tests are designed to assess susceptibility to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI and NNRTI), protease inhibitors and integrase inhibitors. The HIVdb genotypic resistance interpretation system output consists of (1) a list of penalty scores for each antiretroviral (ARV) resistance mutation in a submitted sequence, (2) estimates of decreased NRTI, NNRTI, protease and integrase inhibitor susceptibility, and (3) comments about each ARV resistance mutation in the submitted sequence.