Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL.

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic progenitor cells and is associated with an increased risk of thrombotic events (TEs). Established risk factors for TEs in patients with PV include advanced age, TE history, and elevated hematocrit. Although an association of TE with elevated white blood cell (WBC) counts has been suggested by retrospective studies, this relationship needs further validation.

Association Between Socioeconomic Factors, Race, and Use of a Specialty Memory Clinic.

Background And Objectives: The capacity of specialty memory clinics in the United States is very limited. If lower socioeconomic status or minoritized racial group is associated with reduced use of memory clinics, this could exacerbate health care disparities, especially if more effective treatments of Alzheimer disease become available. We aimed to understand how use of a memory clinic is associated with neighborhood-level measures of socioeconomic factors and the intersectionality of race.

Cryo-EM structure of a RAS/RAF recruitment complex.

RAF-family kinases are activated by recruitment to the plasma membrane by GTP-bound RAS, whereupon they initiate signaling through the MAP kinase cascade. Prior structural studies of KRAS with RAF have focused on the isolated RAS-binding and cysteine-rich domains of RAF (RBD and CRD, respectively), which interact directly with RAS. Here we describe cryo-EM structures of a KRAS bound to intact BRAF in an autoinhibited state with MEK1 and a 14-3-3 dimer.

Safety and Tolerability of High-Resolution Esophageal Manometry in Children and Adults.

Introduction: While high-resolution manometry (HRM) is widely accepted as a safe procedure, no study has assessed the safety profile of HRM in clinical practice. This study aimed to determine the safety and tolerability of HRM and to investigate potential determinants of intolerability.

Methods: We obtained HRM procedure reports, demographics, and clinical data (2005-2022) at a tertiary center using electronic chart review.

Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report.

Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure.

Organizational Readiness for Patient-Facing Mobile Teledermatology to Care for Established Veteran Patients in the United States.

To improve patient access to skin care, the Department of Veterans Affairs (VA) developed a patient-facing asynchronous mobile teledermatology application (app), which allows patients to follow up remotely with dermatologists. To understand how the app would be received in VA, we examined Organizational Readiness for Change (ORC), an important prelude to effective implementation, which includes the shared resolve and collective ability of organizational members to implement a change. We used a mixed-methods multiple case study approach to assess ORC at three VA facilities.

Caspase-6-cleaved tau is relevant in Alzheimer's disease and marginal in four-repeat tauopathies: Diagnostic and therapeutic implications.

Aim: Tau truncation (tr-tau) by active caspase-6 (aCasp-6) generates tau fragments that may be toxic. Yet the relationship between aCasp-6, different forms of tr-tau and hyperphosphorylated tau (p-tau) accumulation in human brains with Alzheimer's disease (AD) and other tauopathies remains unclear.

Methods: We generated two neoepitope monoclonal antibodies against tr-tau sites (D402 and D13) targeted by aCasp-6.

The Utilization and Impact of Live Interactive and Store-and-Forward Teledermatology in a Veterans Affairs Medical Center During the COVID-19 Pandemic.

Teledermatology has emerged as a promising method of continuing dermatologic care during the coronavirus 2019 (COVID-19) pandemic, including in the Department of Veterans Affairs (VA). Analysis of the utilization and impact of teledermatology within the San Francisco Veterans Affairs Health Care System (SFVAHCS) may elucidate the ways that teledermatology programs can continue to be optimized. We conducted a retrospective analysis of live interactive encounters, Veterans Affairs Video Connect (VVC), store-and-forward telehealth (SFT), and face-to-face (FTF) consultations, performed within the SFVAHCS from March 2020 to December 2020.

Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G in the CSF: Clinical Implication of Testing and Association With Disability.

Background And Objective: To investigate the clinical relevance of CSF myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) testing in a large multicenter cohort.

Methods: In this multicenter cohort study, paired serum-CSF samples from 474 patients with suspected inflammatory demyelinating disease (IDD) from 11 referral hospitals were included. After serum screening, patients were grouped into seropositive myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD, 31), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG + NMOSD, 60), other IDDs (217), multiple sclerosis (MS, 45), and non-IDDs (121).

Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

Background: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.

Methods: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19.

Implementing Teledermatology for Rural Veterans: An Evaluation Using the RE-AIM Framework.

Few systematic evaluations of implementing teledermatology programs in large health care systems exist. We conducted a longitudinal evaluation of a U.S.

Report of the National Heart, Lung, and Blood Institute Working Group on Hypertension: Barriers to Translation.

The National Heart, Lung, and Blood Institute convened a multidisciplinary working group of hypertension researchers on December 6 to 7, 2018, in Bethesda, MD, to share current scientific knowledge in hypertension and to identify barriers to translation of basic into clinical science/trials and implementation of clinical science into clinical care of patients with hypertension. The goals of the working group were (1) to provide an overview of recent discoveries that may be ready for testing in preclinical and clinical studies; (2) to identify gaps in knowledge that impede translation; (3) to highlight the most promising scientific areas in which to pursue translation; (4) to identify key challenges and barriers for moving basic science discoveries into translation, clinical studies, and trials; and (5) to identify roadblocks for effective dissemination and implementation of basic and clinical science in real-world settings. The working group addressed issues that were responsive to many of the objectives of the National Heart, Lung, and Blood Institute Strategic Vision.

Amorphous TaMnO Layer as a Diffusion Barrier for Advanced Copper Interconnects.

An amorphous TaMnO layer with 1.0 nm thickness was studied as an alternative Cu diffusion barrier for advanced interconnect. The thermal and electrical stabilities of the 1.

Safety, tolerability and pharmacokinetics and pharmacodynamics of HL2351, a novel hybrid fc-fused interleukin-1 receptor antagonist, in healthy subjects: A first-in-human study.

Aims: We performed a first-in-human study with HL2351, a novel hybrid Fc-fused interleukin (IL)-1 receptor antagonist, to evaluate its tolerability, pharmacokinetics and pharmacodynamics (PD) after a single subcutaneous (SC) administration in healthy subjects.

Methods: A randomized, double-blind, placebo- and active-controlled, dose-escalation study was conducted. Eligible subjects randomly received a single SC administration of HL2351 (1, 2, 4, 8 and 12 mg/kg) or placebo in a ratio of 8:2.

Effects of Remote Monitoring of Blood Pressure in Management of Urban Hypertensive Patients: A Systematic Review and Meta-Analysis.

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Diffusion-weighted MRI Findings Predict Pathologic Response in Neoadjuvant Treatment of Breast Cancer: The ACRIN 6698 Multicenter Trial.

Purpose To determine if the change in tumor apparent diffusion coefficient (ADC) at diffusion-weighted (DW) MRI is predictive of pathologic complete response (pCR) to neoadjuvant chemotherapy for breast cancer. Materials and Methods In this prospective multicenter study, 272 consecutive women with breast cancer were enrolled at 10 institutions (from August 2012 to January 2015) and were randomized to treatment with 12 weekly doses of paclitaxel (with or without an experimental agent), followed by 12 weeks of treatment with four cycles of anthracycline. Each woman underwent breast DW MRI before treatment, at early treatment (3 weeks), at midtreatment (12 weeks), and after treatment.

Trauma patients are safe to fly 72 hours after tube thoracostomy removal.

Background: Current recommendations for safe air travel following traumatic pneumothorax are 2 to 3 weeks after radiographic resolution. These recommendations are based on several small observational studies and expert consensus, which cite a theoretical risk of recurrence and hypoxia because of decreased oxygen tension at altitude. We sought to systematically study the timing of chest drain removal after traumatic pneumothorax and risk of recurrence in relation to air travel.

Teledermatology in the United States: An Update in a Dynamic Era.

Background: Teledermatology is rapidly advancing in the United States. The last comprehensive survey of U.S.