Multi-ancestry GWAS of Fuchs corneal dystrophy highlights roles of laminins, collagen, and endothelial cell regulation.

Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular pathophysiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program (MVP) and meta-analyzed with the previous largest FECD GWAS, finding twelve significant loci (eight novel). We further confirmed the TCF4 locus in admixed African and Hispanic/Latino ancestries, and found an enrichment of European-ancestry haplotypes at TCF4 in FECD cases.

Foveation dynamics in congenital nystagmus IV: vergence.

Purpose: To evaluate foveation dynamics and characteristics of vergence eye movements during fixation of static targets at different distances and while tracking a target moving in depth in a subject with congenital nystagmus (CN).

Method: Eye movements of a well-studied subject with CN were recorded using the magnetic search coil technique and analyzed using the OMtools software, including the eXpanded Nystagmus Acuity Function (NAFX).

Results: Both the phase planes and NAFX values during fixation of targets at various near distances were equivalent to those during fixation of a far target.

Predictors of recurrent TB in sputum smear and culture positive adults: a prospective cohort study.

Objective: To explore simple inexpensive non-culture based predictors of recurrent pulmonary tuberculosis (PTB).

Setting And Study Population: HIV-infected and uninfected adults with the first episode of smear positive, culture-confirmed pulmonary tuberculosis in a high tuberculosis burden country.

Design: A nested prospective cohort study of participants with pulmonary tuberculosis (PTB) presenting to a hospital out-patient clinic.

MiR-644a Disrupts Oncogenic Transformation and Warburg Effect by Direct Modulation of Multiple Genes of Tumor-Promoting Pathways.

Castration-resistant prostate cancer (CRPC) is defined by tumor microenvironment heterogeneity affecting intrinsic cellular mechanisms including dysregulated androgen signaling, aerobic glycolysis (Warburg effect), and aberrant activation of transcription factors including androgen receptor (AR) and c-Myc. Using , and animal models, we find a direct correlation between miR-644a downregulation and dysregulation of essential cellular processes. MiR-644a downregulated expression of diverse tumor microenvironment drivers including c-Myc, AR coregulators, and antiapoptosis factors Bcl-xl and Bcl2.

Ocular Motor System Control Models and the Cerebellum: Hypothetical Mechanisms.

To review our studies and "top-down" models of saccadic intrusions and infantile nystagmus syndrome with the aim of hypothesizing areas of cerebellar connections controlling parts of the ocular motor subsystems involved in both types of function and dysfunction. The methods of eye-movement recording and modeling are described in detail in the cited references. Saccadic intrusions, such as square-wave jerks and square-wave oscillations, can be simulated by a single malfunction, whereas staircase saccadic intrusions required two independent malfunctions.

Medication-related osteonecrosis of the jaw: An institution's experience.

This study aimed to evaluate and report the outcomes associated with the management of patients who were treated surgically for medication-related osteonecrosis of the jaw (MRONJ).: Demographic and medical profiles of patients with a diagnosis of MRONJ were created. The type of surgical treatment, complications, and treatment outcomes were identified.

Clinical and ocular motor complications of extraocular muscle extirpation for infantile nystagmus syndrome.

Purpose: To describe the effects of extraocular muscle extirpation performed after previous eye muscle surgery in a 20-year-old woman with infantile nystagmus syndrome (INS) for whom we have 19 years of follow-up data.

Methods: Clinical examinations were performed. Eye movement data analysis was carried out using the eXpanded Nystagmus Acuity Function (NAFX) and longest foveation domain (LFD).

No Difference in Conventional Polyethylene Wear Between Yttria-stabilized Zirconia and Cobalt-chromium-molybdenum Femoral Heads at 10 Years.

Background: Concerns have arisen regarding deterioration of wear properties of yttria-stabilized zirconia (YSZ) femoral head on conventional polyethylene (PE) bearings due to YSZ phase transformation.

Questions/purposes: The purpose of this study was to determine if there is a difference in long-term PE wear properties between YSZ and cobalt-chromium-molybdenum (Co-Cr-Mo) femoral heads.

Methods: Ten-year radiographic wear assessment was performed on a cohort of patients enrolled in a prospective randomized clinical trial comparing total hip arthroplasty with YSZ or Co-Cr-Mo femoral heads on conventional, non-cross-linked PE.

Risk Factors for Abnormal Cervical Cytology in Women Undergoing Kidney Transplant Evaluation.

Objectives: Cervical cytology screening has been successful in reducing deaths from cervical cancer. We sought to determine risk factors for abnormal Pap test results in women undergoing kidney transplant evaluation.

Materilas And Methods: We retrospectively examined women undergoing kidney transplant evaluations from 2008 to 2011.

Optimal FDG PET/CT volumetric parameters for risk stratification in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial.

Purpose: In recent years, multiple studies have demonstrated the value of volumetric FDG-PET/CT parameters as independent prognostic factors in patients with non-small cell lung cancer (NSCLC). We aimed to determine the optimal cut-off points of pretreatment volumetric FDG-PET/CT parameters in predicting overall survival (OS) in patients with locally advanced NSCLC and to recommend imaging biomarkers appropriate for routine clinical applications.

Methods: Patients with inoperable stage IIB/III NSCLC enrolled in ACRIN 6668/RTOG 0235 were included.

Using analytic morphomics to describe body composition associated with post-kidney transplantation diabetes mellitus.

Background: Better risk assessment tools are needed to predict post-transplantation diabetes mellitus (PTDM). Using analytic morphomic measurements from computed tomography (CT) scans, we aimed to identify specific measures of body composition associated with PTDM.

Methods: We retrospectively reviewed 99 non-diabetic kidney transplant recipients who received pre-transplant CT scans at a single institution between 1/2005 and 5/2014.

Cognitive Function and Kidney Disease: Baseline Data From the Systolic Blood Pressure Intervention Trial (SPRINT).

Background: Chronic kidney disease is common and is associated with cardiovascular disease, cerebrovascular disease, and cognitive function, although the nature of this relationship remains uncertain.

Study Design: Cross-sectional cohort using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT).

Setting & Participants: Participants in SPRINT, a randomized clinical trial of blood pressure targets in older community-dwelling adults with cardiovascular disease, chronic kidney disease, or high cardiovascular disease risk and without diabetes or known stroke, who underwent detailed neurocognitive testing in the cognition substudy, SPRINT-Memory and Cognition in Decreased Hypertension (SPRINT-MIND).

The LargPAD Trial: Phase IIA evaluation of l-arginine infusion in patients with peripheral arterial disease.

Objective: Endothelial function is improved by l-arginine (l-arg) supplementation in preclinical and clinical studies of mildly diseased vasculature; however, endothelial function and responsiveness to l-arg in severely diseased arteries is not known. Our objective was to evaluate the acute effects of catheter-directed l-arg delivery in patients with chronic lower extremity ischemia secondary to peripheral arterial disease.

Methods: The study enrolled 22 patients (45% male) with peripheral arterial disease (mean age, 62 years) requiring lower extremity angiography.

Chemosensitive Relapse in Small Cell Lung Cancer Proceeds through an EZH2-SLFN11 Axis.

Small cell lung cancer is initially highly responsive to cisplatin and etoposide but in almost every case becomes rapidly chemoresistant, leading to death within 1 year. We modeled acquired chemoresistance in vivo using a series of patient-derived xenografts to generate paired chemosensitive and chemoresistant cancers. Multiple chemoresistant models demonstrated suppression of SLFN11, a factor implicated in DNA-damage repair deficiency.

Motor-Coordinative and Cognitive Dysfunction Caused by Mutant TDP-43 Could Be Reversed by Inhibiting Its Mitochondrial Localization.

Dominant missense mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS), and the cytoplasmic accumulation of TDP-43 represents a pathological hallmark in ALS and frontotemporal lobar degeneration (FTD). Behavioral investigation of the transgenic mouse model expressing the disease-causing human TDP-43 M337V mutant (TDP-43 mice) is encumbered by premature death in homozygous transgenic mice and a reported lack of phenotype assessed by tail elevation and footprint in hemizygous transgenic mice. Here, using a battery of motor-coordinative and cognitive tests, we report robust motor-coordinative and cognitive deficits in hemizygous TDP-43 mice by 8 months of age.

Synchronized navigation of current and prior studies using image registration improves radiologist's efficiency.

Purpose: The purpose of this study was to investigate how the use of multi-modal rigid image registration integrated within a standard picture archiving and communication system affects the efficiency of a radiologist while performing routine interpretations of cases including prior examinations.

Methods: Six radiologists were recruited to read a set of cases (either 16 neuroradiology or 14 musculoskeletal cases) during two crossover reading sessions. Each radiologist read each case twice, one time with synchronized navigation, which enables spatial synchronization across examinations from different study dates, and one time without.

Radiosensitization of non-small-cell lung cancer cells and xenografts by the interactive effects of pemetrexed and methoxyamine.

Background And Purpose: The anti-folate pemetrexed is a radiosensitizer. In pre-clinical models, pemetrexed is more effective along with the base-excision-repair inhibitor methoxyamine. We tested whether methoxyamine enhances pemetrexed-mediated radiosensitization of lung adenocarcinoma cells and xenografts.

Effects of Extreme Prematurity on Numerical Skills and Executive Function in Kindergarten Children: An Application of Partially Ordered Classification Modeling.

Although mathematics disabilities (MD) are common in extremely preterm/extremely low birth weight (EPT/ELBW) children, little is known about the nature of these problems. In this study partially ordered set (POSET) models were applied to classify 140 EPT/ELBW kindergarten children (gestational age <28 weeks and/or birth weight <1000 g) and 110 normal birth weight (NBW) controls into profiles of numerical and cognitive skills. Models based on five numerical skills and five executive function and processing speed skills provided a good fit to performance data.

Osteosarcoma of the Mandible Arising in Fibrous Dysplasia-A Case Report.

Fibrous dysplasia (FD) is a benign fibro-osseous lesion that typically behaves as a painless, slowly expanding tumor. On rare occasion, FD will undergo malignant transformation. When sarcomatous change occurs, osteosarcoma is the typical variant, followed by chondrosarcoma and fibrosarcoma.

Improved Screening Mammogram Workflow by Maximizing PACS Streamlining Capabilities in an Academic Breast Center.

The aim of this study was to perform an operational improvement project targeted at the breast imaging reading workflow of mammography examinations at an academic medical center with its associated breast centers and satellite sites. Through careful analysis of the current workflow, two major issues were identified: stockpiling of paperwork and multiple worklists. Both issues were considered to cause significant delays to the start of interpreting screening mammograms.

Reader variability and validation of the Timika X-ray score during treatment of pulmonary tuberculosis.

Setting: Chest radiographs (CXRs) are widely used for diagnosing pulmonary TB and assessing response to therapy. The Timika X-ray score has been proposed as a tool for measuring disease severity and predicting treatment outcome.

Objective: To evaluate inter- and intra-reader agreement of Timika scores and assess the ability of the score to predict microbiologic outcome at 2 months.

Human leukocyte antigen class 1 genotype distribution and analysis in persons with active tuberculosis and household contacts from Central Uganda.

Background: To determine the distribution of Human leukocyte antigen (HLA) class I genotypes in a Ugandan population of persons with tuberculosis (TB) and establish the relationship between class I HLA types and Mycobacterium tuberculosis (MTB) disease.

Methods: Blood samples were drawn from HIV negative individuals with active TB and HIV negative household controls. DNA was extracted from blood samples and HLA typed by the polymerase chain reaction-sequence specific primer method.

Abdominal Organ Transplant Center Tobacco Use Policies Vary by Organ Program Type.

Background: Smoking is a modifiable risk factor for cardiovascular disease, malignancy, and surgical complications. Transplant center practices toward smokers vary widely and evoke the classic tension between the ethical principles of justice and utility. We sought to assess current smoking policy variation in U.

Evaluation and comparison of 3D intervertebral disc localization and segmentation methods for 3D T2 MR data: A grand challenge.

The evaluation of changes in Intervertebral Discs (IVDs) with 3D Magnetic Resonance (MR) Imaging (MRI) can be of interest for many clinical applications. This paper presents the evaluation of both IVD localization and IVD segmentation methods submitted to the Automatic 3D MRI IVD Localization and Segmentation challenge, held at the 2015 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI2015) with an on-site competition. With the construction of a manually annotated reference data set composed of 25 3D T2-weighted MR images acquired from two different studies and the establishment of a standard validation framework, quantitative evaluation was performed to compare the results of methods submitted to the challenge.