Integration of FUNDC1-associated mitochondrial protein import and mitochondrial quality control contributes to TDP-43 degradation.

Though TDP-43 protein can be translocated into mitochondria and causes mitochondrial damage in TDP-43 proteinopathy, little is known about how TDP-43 is imported into mitochondria. In addition, whether mitochondrial damage is caused by mitochondrial mislocalization of TDP-43 or a side effect of mitochondria-mediated TDP-43 degradation remains to be investigated. Here, our bioinformatical analyses reveal that mitophagy receptor gene FUNDC1 is co-expressed with TDP-43, and both TDP-43 and FUNDC1 expression is correlated with genes associated with mitochondrial protein import pathway in brain samples of patients diagnosed with TDP-43 proteinopathy.

Low-fat dietary pattern reduces urinary incontinence in postmenopausal women: post hoc analysis of the Women's Health Initiative Diet Modification Trial.

Background: Urinary incontinence affects >40% of women in the United States, with an annual societal cost of >$12 billion and demonstrated associations with depressive symptoms, social isolation, and loss of work productivity. Weight has been established as an exposure that increases urinary incontinence risk and certain dietary components have been associated with urinary incontinence symptoms. We hypothesized that diet plays a key role in the association between weight and urinary incontinence in US women.

Palliative Care and End-of-Life Outcomes Following High-risk Surgery.

Importance: Palliative care has the potential to improve care for patients and families undergoing high-risk surgery.

Objective: To characterize the use of perioperative palliative care and its association with family-reported end-of-life experiences of patients who died within 90 days of a high-risk surgical operation.

Design, Setting, And Participants: This secondary analysis of administrative data from a retrospective cross-sectional patient cohort was conducted in the Department of Veterans Affairs (VA) Healthcare System.

Validation of a novel automated signal analysis tool for ablation of Wolff-Parkinson-White Syndrome.

Background: In previous pilot work we demonstrated that a novel automated signal analysis tool could accurately identify successful ablation sites during Wolff-Parkinson-White (WPW) ablation at a single center.

Objective: We sought to validate and refine this signal analysis tool in a larger multi-center cohort of children with WPW.

Methods: A retrospective review was performed of signal data from children with WPW who underwent ablation at two pediatric arrhythmia centers from 2008-2015.

Multiple listing in lung transplant candidates: A cohort study.

Lung transplant candidates can be waitlisted at more than one transplant center, a practice known as multiple listing. The factors associated with multiple listing and whether multiple listing modifies waitlist mortality or likelihood of lung transplant is unknown. US lung transplant waitlist candidates were identified as either single or multiple listed using data from the Scientific Registry of Transplant Recipients.

Definitions of peri-procedural myocardial infarction and the association with one-year mortality: Insights from CHAMPION trials.

Background: Controversies exist over the appropriate definition for peri-procedural myocardial infarction (PPMI) and its association with mortality. This study aims to evaluate one-year survival following percutaneous coronary intervention (PCI) and the association of different definitions of PPMI with survival among patients with stable angina (SA) or acute coronary syndrome (ACS) in the contemporary era.

Methods: We used data from the CHAMPION PLATFORM and CHAMPION PCI trials of patients undergoing PCI and conducted univariable and multivariable Cox proportional hazard regression models to evaluate mortality risk during the first year after PCI.

Melanoma risk prediction using a multilocus genetic risk score in the Women's Health Initiative cohort.

Background: Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk.

Objective: We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women.

ACIST-FFR Study (Assessment of Catheter-Based Interrogation and Standard Techniques for Fractional Flow Reserve Measurement).

Background: Measurement of fractional flow reserve (FFR) to guide coronary revascularization lags despite robust supportive data, partly because of the handling characteristics of traditional coronary pressure wires. An optical pressure-monitoring microcatheter, which can be advanced over a traditional coronary guidewire, facilitates FFR assessment but may underestimate pressure wire-derived FFR.

Methods And Results: In this prospective, multicenter trial, 169 patients underwent FFR assessment with a pressure wire alone and with a pressure microcatheter over the pressure wire.

Deep Learning to Classify Radiology Free-Text Reports.

Purpose To evaluate the performance of a deep learning convolutional neural network (CNN) model compared with a traditional natural language processing (NLP) model in extracting pulmonary embolism (PE) findings from thoracic computed tomography (CT) reports from two institutions. Materials and Methods Contrast material-enhanced CT examinations of the chest performed between January 1, 1998, and January 1, 2016, were selected. Annotations by two human radiologists were made for three categories: the presence, chronicity, and location of PE.

Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in Nonmyeloablative Allogeneic Stem Cell Transplantation.

The Hematopoietic Cell Transplantation (HCT)-Specific Comorbidity Index (HCT-CI) has been extensively studied in myeloablative and reduced-intensity conditioning regimens, with less data available regarding the validity of HCT-CI in nonmyeloablative (NMA) allogeneic transplantation. We conducted a retrospective analysis to evaluate the association between HCT-CI and nonrelapse mortality (NRM) and all-cause mortality (ACM) in patients receiving the total lymphoid irradiation and antithymocyte globulin (TLI/ATG) NMA transplantation preparative regimen. We abstracted demographic and clinical data from consecutive patients, who received allogeneic HCT with the TLI/ATG regimen between January 2008 and September 2014, from the Stanford blood and marrow transplantation database.

Cangrelor reduces the risk of ischemic complications in patients with single-vessel and multi-vessel disease undergoing percutaneous coronary intervention: Insights from the CHAMPION PHOENIX trial.

Objective: To examine the safety and efficacy of cangrelor in patients with single-vessel disease (SVD) and multi-vessel disease (MVD).

Background: Cangrelor, an intravenous, rapidly acting P2Y inhibitor, is superior to clopidogrel in reducing ischemic events among patients receiving percutaneous coronary intervention (PCI).

Methods: We studied a modified intention to treat population of patients with SVD and MVD from the CHAMPION PHOENIX trial.

Outpatient vs Inpatient Anterior Cervical Discectomy and Fusion: A Population-Level Analysis of Outcomes and Cost.

Background: Outpatient anterior cervical discectomy and fusion (ACDF) is a promising candidate for US healthcare cost reduction as several studies have demonstrated that overall complications are relatively low and early discharge can preserve high patient satisfaction, low morbidity, and minimal readmission.

Objective: To compare clinical outcomes and associated costs between inpatient and ambulatory setting ACDF.

Methods: Demographics, comorbidities, emergency department (ED) visits, readmissions, reoperation rates, and 90-d charges were retrospectively analyzed for patients undergoing elective ACDF in California, Florida, and New York from 2009 to 2011 in State Inpatient and Ambulatory Databases.

Development and validation of a major adverse transplant event (MATE) score to predict late graft loss in pediatric heart transplantation.

Background: There is inadequate power to perform a valid clinical trial in pediatric heart transplantation (HT) using a conventional end-point, because the disease is rare and hard end-points, such as death or graft loss, are infrequent. We sought to develop and validate a surrogate end-point involving the cumulative burden of post-transplant complications to predict death/graft loss to power a randomized clinical trial of maintenance immunosuppression in pediatric HT.

Methods: Pediatric Heart Transplant Study (PHTS) data were used to identify all children who underwent an isolated orthotopic HT between 2005 and 2014 who survived to 6 months post-HT.

Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.

Background: Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood.

Methods: We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case-control study of African-American females and males (1078 lung cancer cases and 822 controls).

Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical Approach.

Genetic risk scores are an increasingly popular tool for summarizing the cumulative risk of a set of Single Nucleotide Polymorphisms (SNPs) with disease. Typically only the set of the SNPs that have reached genome-wide significance compose these scores. However recent work suggests that including additional SNPs may aid risk assessment.

Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis.

Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion.

Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion; however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.

Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans.