Association of blood-based transcriptional risk scores with biomarkers for Alzheimer disease.

Objective: To determine whether transcriptional risk scores (TRSs), a summation of polarized expression levels of functional genes, reflect the risk of Alzheimer disease (AD).

Methods: Blood transcriptome data were from Caucasian participants, which included AD, mild cognitive impairment, and cognitively normal controls (CN) in the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 661) and AddNeuroMed (n = 674) cohorts. To calculate TRSs, we selected functional genes that were expressed under the control of the AD risk loci and were identified as being responsible for AD by using Bayesian colocalization and mendelian randomization methods.

BRD4 (Bromodomain-Containing Protein 4) Interacts with GATA4 (GATA Binding Protein 4) to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes.

Background: Gene regulatory networks control tissue homeostasis and disease progression in a cell type-specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the mechanisms governing how tissue specificity of their function is achieved are poorly understood. BRD4 (bromodomain-containing protein 4), a member of the BET (bromo- and extraterminal domain) family of ubiquitously expressed acetyl-lysine reader proteins, plays a pivotal role as a coactivator of enhancer signaling across diverse tissue types in both health and disease and has been implicated as a pharmacological target in heart failure.

Two Cases With Features of Lymphocyte Variant Hypereosinophilic Syndrome With STAT3 SH2 Domain Mutations.

Lymphocyte variant hypereosinophilic syndrome (LV-HES) is a rare cause of eosinophilia that is due to eosinophilipoietic cytokine production by an immunophenotypically abnormal T-cell clone. The molecular pathogenesis of this disorder is largely unknown and only 1 case of LV-HES with a pathogenic STAT3 mutation has been described thus far. Here we report 2 cases of LV-HES with STAT3 SH2 domain mutations.

MRI-Based Assessment of the Pharyngeal Constrictor Muscle as a Predictor of Surgical Margin after Transoral Robotic Surgery in HPV-Positive Tonsillar Cancer.

Background And Purpose: Transoral robotic surgery is an emerging strategy for treating human papillomavirus-positive cancers, but the role of MR imaging in predicting the surgical outcome has not been established. We aimed to identify preoperative MR imaging characteristics that predispose the outcome of transoral robotic surgery toward an insecure (positive or close) surgical margin in human papillomavirus-positive tonsillar squamous cell carcinoma.

Materials And Methods: Between December 2012 and May 2019, sixty-nine patients underwent transoral robotic surgery at our institution.

Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue.

Background: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues.

Methods: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man).

Detecting Large Vessel Occlusion at Multiphase CT Angiography by Using a Deep Convolutional Neural Network.

Background Large vessel occlusion (LVO) stroke is one of the most time-sensitive diagnoses in medicine and requires emergent endovascular therapy to reduce morbidity and mortality. Leveraging recent advances in deep learning may facilitate rapid detection and reduce time to treatment. Purpose To develop a convolutional neural network to detect LVOs at multiphase CT angiography.

What Is the Ideal Blood Pressure Threshold for the Prevention of Atrial Fibrillation in Elderly General Population?

Intensive blood pressure (BP) lowering in patients with hypertension at increased risk of cardiovascular disease has been associated with a lowered risk of incident atrial fibrillation (AF). It is uncertain whether maintaining the optimal BP levels can prevent AF in the general elderly population. We included 115,866 participants without AF in the Korea National Health Insurance Service-Senior (≥60 years) cohort from 2002 to 2013.

Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma.

The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned.

Association between ε2 and Aβ burden in patients with Alzheimer- and vascular-type cognitive impairment.

Objective: To investigate the association between genotype and β-amyloid (Aβ) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer disease-related cognitive impairment (ADCI).

Methods: This was a cross-sectional study of 310 patients with SVCI and 999 with ADCI. To evaluate the effects of genotype or diagnostic group on Aβ positivity, we performed multivariate logistic regression analyses.

Effects of Systemic Profiles on Choroidal Thickness in Treatment-Naïve Eyes With Diabetic Retinopathy.

Purpose: The purpose of this study was to analyze the effects of systemic and ocular profiles on subfoveal choroidal thickness (SFChT) in treatment-naïve eyes with diabetic retinopathy (DR).

Methods: This study included patients with treatment-naïve DR. They underwent routine laboratory evaluations, including complete blood cell count, liver function tests, kidney function tests, and urinalysis for macroalbuminuria.

Capmatinib in Exon 14-Mutated or -Amplified Non-Small-Cell Lung Cancer.

Background: Among patients with non-small-cell lung cancer (NSCLC), exon 14 skipping mutations occur in 3 to 4% and amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation.

Methods: We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with -dysregulated advanced NSCLC.

Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8 T cell responses.

The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy. However, the adverse side effects associated with agonist antibodies have hindered their clinical development. Here, we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs.

Diagnostic Yield of Staging Brain MRI in Patients with Newly Diagnosed Non-Small Cell Lung Cancer.

Background Existing guidelines are inconsistent regarding the indications for staging brain MRI in patients with newly diagnosed, early-stage non-small cell lung cancer (NSCLC). Purpose To evaluate the diagnostic yield of staging brain MRI in the initial evaluation of lung cancer. Materials and Methods This retrospective, observational, single-institution study included patients with newly diagnosed NSCLC who underwent staging chest CT and staging brain MRI from November 2017 to October 2018.

Limbal Metabolic Support Reduces Peripheral Corneal Edema with Contact-Lens Wear.

Purpose: To assess the influence of limbal metabolic support on corneal edema during scleral-lens (SL) and soft-contact-lens (SCL) wear for healthy lens wearers.

Methods: A two-dimensional (2D) model of the cornea and sclera was designed on Comsol Multiphysics 5.4 along with SL and SCL architectures to mimic lens-wear induced hypoxia.

Effect of a Single Intravitreal Bevacizumab Injection on Proteinuria in Patients With Diabetes.

Purpose: Proteinuria is the second most common complication after hypertension after systemic administration of bevacizumab. Therefore we aimed to analyze the effect of intravitreal bevacizumab (IVB) injection on proteinuria in patients with diabetes.

Methods: Patients scheduled to receive IVB injection from May 1, 2018, to December 31, 2018, were prospectively enrolled.

Deep Learning for Pediatric Posterior Fossa Tumor Detection and Classification: A Multi-Institutional Study.

Background And Purpose: Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model for posterior fossa tumor detection and tumor pathology classification.

Initial Stroke Severity in Patients With Atrial Fibrillation According to Antithrombotic Therapy Before Ischemic Stroke.

Background And Purpose: Atrial fibrillation (AF) is the leading cause of ischemic stroke. Preventive antithrombotic use, especially for anticoagulation, reduces the incidence of ischemic stroke in patients with AF. Using data from the nationwide multicenter stroke registry, we investigated the trends of preceding antithrombotic medication use in patients with acute ischemic stroke (AIS) with AF and its association with initial stroke severity and in-hospital outcomes.

An Off-Line DPPH-GC-MS Coupling Countercurrent Chromatography Method for Screening, Identification, and Separation of Antioxidant Compounds in Essential Oil.

Essential oils are an important source of natural antioxidants and multiple methods have been established for evaluation of their overall antioxidant activity, however, the antioxidant activities of their compounds are less investigated. In the present study, the hyphenation of 2,2'-diphenyl-1-picrylhydrazyl (DPPH)-gas chromatography (GC)-mass spectrometry (MS) offline and high-speed countercurrent chromatography (HSCCC) is established for efficient screening, identification, and isolation of antioxidants from essential oils and applied to the essential oil of Y.H.

Electrical Posterior Box Isolation in Persistent Atrial Fibrillation Changed to Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Randomized Study.

Background: Persistent atrial fibrillation (AF) can change to paroxysmal AF after antiarrhythmic drug medication and cardioversion. We investigated whether electrical posterior box isolation (POBI) may improve rhythm outcome of catheter ablation in those patient groups.

Methods: We prospectively randomized 114 patients with persistent AF to paroxysmal AF (men, 75%; 59.

Factor analysis-derived cognitive profile predicting early dementia conversion in PD.

Objectives: To investigate which baseline neuropsychological profile predicts the risk of developing dementia in early-stage Parkinson disease (PD).

Methods: We retrospectively reviewed detailed medical records of 350 drug-naive patients with early-stage PD (follow-up >3 years) who underwent a detailed neuropsychological test at initial assessment. Factor analysis was conducted to determine cognitive profiles that yielded 4 cognitive function factors: factor 1, visual memory/visuospatial; factor 2, verbal memory; factor 3, frontal/executive; and factor 4, attention/working memory/language.

Distinct Mechanisms of Over-Representation of Landmarks and Rewards in the Hippocampus.

In the hippocampus, locations associated with salient features are represented by a disproportionately large number of neurons, but the cellular and molecular mechanisms underlying this over-representation remain elusive. Using longitudinal calcium imaging in mice learning to navigate in virtual reality, we find that the over-representation of reward and landmark locations are mediated by persistent and separable subsets of neurons, with distinct time courses of emergence and differing underlying molecular mechanisms. Strikingly, we find that in mice lacking Shank2, an autism spectrum disorder (ASD)-linked gene encoding an excitatory postsynaptic scaffold protein, the learning-induced over-representation of landmarks was absent whereas the over-representation of rewards was substantially increased, as was goal-directed behavior.

Long-term antithrombotic management patterns in Asian patients with acute coronary syndrome: 2-year observations from the EPICOR Asia study.

Background: Despite guideline recommendations, dual antiplatelet therapy (DAPT) is frequently used for longer than 1 year after an acute coronary syndrome (ACS) event. In Asia, information on antithrombotic management patterns (AMPs), including DAPT post discharge, is sparse. This analysis evaluated real-world AMPs up to 2 years post discharge for ACS.