Viral Bad News Sent by EVAIL.

This article reviews the current knowledge on how viruses may utilize Extracellular Vesicle Assisted Inflammatory Load (EVAIL) to exert pathologic activities. Viruses are classically considered to exert their pathologic actions through acute or chronic infection followed by the host response. This host response causes the release of cytokines leading to vascular endothelial cell dysfunction and cardiovascular complications.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial.

Purpose: The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).

Methods: Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks).

Silver linings: a qualitative study of desirable changes to cancer care during the COVID-19 pandemic.

Introduction: Public health emergencies and crises such as the current COVID-19 pandemic can accelerate innovation and place renewed focus on the value of health interventions. Capturing important lessons learnt, both positive and negative, is vital. We aimed to document the perceived positive changes (silver linings) in cancer care that emerged during the COVID-19 pandemic and identify challenges that may limit their long-term adoption.

Gender Harassment Persists in Medical Training.

Medical students start their career with enthusiasm for a profession that emphasizes caring for others so as to promote health, treat injury, and prevent disease. The profession of medicine selects those who have demonstrated compassion, knowledge, and leadership. As students enter the profession, many possess a certain naiveté with the expectation for equity.

Correction: [On Becoming a Global Citizen: Transformative Learning Through Global Health Experiences].

[This corrects the article DOI: 10.1016/j.aogh.

Symptoms and symptom clusters associated with SARS-CoV-2 infection in community-based populations: Results from a statewide epidemiological study.

Background: Prior studies examining symptoms of COVID-19 are primarily descriptive and measured among hospitalized individuals. Understanding symptoms of SARS-CoV-2 infection in pre-clinical, community-based populations may improve clinical screening, particularly during flu season. We sought to identify key symptoms and symptom combinations in a community-based population using robust methods.

Managing work flow in high enrolling trials: The development and implementation of a sampling strategy in the PREPARE trial.

Introduction: Pragmatic trials in comparative effectiveness research assess the effects of different treatment, therapeutic, or healthcare options in clinical practice. They are characterized by broad eligibility criteria and large sample sizes, which can lead to an unmanageable number of participants, increasing the risk of bias and affecting the integrity of the trial. We describe the development of a sampling strategy tool and its use in the PREPARE trial to circumvent the challenge of unmanageable work flow.

Three-Dimensional Bioprinting of Anatomically Realistic Tissue Constructs for Disease Modeling and Drug Testing.

Three-dimensional (3D) bioprinting is an emerging tissue engineering technology, already with several remarkable accomplishments and with more promises to fulfill. Besides the enduring goal of making tissues for implantation, it could also become an essential tool in the worldwide trend to replace animal experimentation with improved models for disease mechanism studies, or with new high-throughput pharmacological and toxicology assays. All these require the speed, reproducibility, and standardization that bioprinting could easily provide.

Identification of novel alternative splicing biomarkers for breast cancer with LC/MS/MS and RNA-Seq.

Background: Alternative splicing isoforms have been reported as a new and robust class of diagnostic biomarkers. Over 95% of human genes are estimated to be alternatively spliced as a powerful means of producing functionally diverse proteins from a single gene. The emergence of next-generation sequencing technologies, especially RNA-seq, provides novel insights into large-scale detection and analysis of alternative splicing at the transcriptional level.

Folate Receptor Beta Designates Immunosuppressive Tumor-Associated Myeloid Cells That Can Be Reprogrammed with Folate-Targeted Drugs.

Although immunotherapies of tumors have demonstrated promise for altering the progression of malignancies, immunotherapies have been limited by an immunosuppressive tumor microenvironment (TME) that prevents infiltrating immune cells from performing their anticancer functions. Prominent among immunosuppressive cells are myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) that inhibit T cells via release of immunosuppressive cytokines and engagement of checkpoint receptors. Here, we explore the properties of MDSCs and TAMs from freshly isolated mouse and human tumors and find that an immunosuppressive subset of these cells can be distinguished from the nonimmunosuppressive population by its upregulation of folate receptor beta (FRβ) within the TME and its restriction to the TME.

The cascade of benzodiazepine prescribing for hospitalized geriatric patients.

Background: Hospitalists increasingly provide care for geriatric patients and little is known about the extent to which hospitalists adhere to evidence-based medication guidelines. This study aimed to characterize hospitalist adherence to BEERS guidelines for prescribing and monitoring benzodiazepines for older adults.

Methods: We conducted a retrospective chart review of admitted patients aged 70-85 years who had been prescribed benzodiazepine.

CGPE: an integrated online server for Cancer Gene and Pathway Exploration.

Summary: Cancer Gene and Pathway Explorer (CGPE) is developed to guide biological and clinical researchers, especially those with limited informatics and programming skills, performing preliminary cancer-related biomedical research using transcriptional data and publications. CGPE enables three user-friendly online analytical and visualization modules without requiring any local deployment. The GenePub HotIndex applies natural language processing, statistics and association discovery to provide analytical results on gene-specific PubMed publications, including gene-specific research trends, cancer types correlations, top-related genes and the WordCloud of publication profiles.

Symptoms and symptom clusters associated with SARS-CoV-2 infection in community-based populations: Results from a statewide epidemiological study.

Background: Prior studies examining symptoms of COVID-19 are primarily descriptive and measured among hospitalized individuals. Understanding symptoms of SARS-CoV-2 infection in pre-clinical, community-based populations may improve clinical screening, particularly during flu season. We sought to identify key symptoms and symptom combinations in a community-based population using robust methods.

Incorporating Nonsurgical Options and Aesthetic Services into Your Facial Plastic Surgery Practice.

The facial plastic surgeon faces increasing competition in the aesthetic world for both surgical and nonsurgical services. Incorporating nonsurgical options in practice, such as "liquid facelifts," aesthetic services, and products, increases both patient satisfaction and office revenue stream. A successful nonsurgical practice can be built with minimal expense by focusing on the most critical and popular options to offer patients.

Mesenchymal stem cell secretions improve donor heart function following ex vivo cold storage.

Objectives: Heart transplantation is the gold standard of treatments for end-stage heart failure, but its use is limited by extreme shortage of donor organs. The time "window" between procurement and transplantation sets the stage for myocardial ischemia/reperfusion injury, which constrains the maximal storage time and lowers use of donor organs. Given mesenchymal stem cell (MSC)-derived paracrine protection, we aimed to evaluate the efficacy of MSC-conditioned medium (CM) and extracellular vesicles (EVs) when added to ex vivo preservation solution on ameliorating ischemia/reperfusion-induced myocardial damage in donor hearts.

Use of Transcarotid Artery Revascularization to Treat Symptomatic Carotid Artery Stenosis Associated with Free-Floating Thrombus.

Background: Free-floating thrombus in the internal carotid artery (ICA) has traditionally been treated via an open surgical approach through a longitudinal incision and exposure similar to that for carotid endarterectomy (CEA). In this case report, we present a novel use of transcarotid artery revascularization (TCAR) for the treatment of recurrent carotid stenosis associated with free-floating ICA thrombus.

Case Description: We describe a 67-year-old female who presented with a diagnosis of right hemispheric stroke in evolution and prior history of right CEA and a mechanical mitral valve.

Clinical characteristics, outcomes and prognosticators in adult patients hospitalized with COVID-19.

Background: COVID-19 is a novel disease caused by SARS-CoV-2.

Methods: We conducted a retrospective evaluation of patients admitted with COVID-19 to one site in March 2020. Patients were stratified into 3 groups: survivors who did not receive mechanical ventilation (MV), survivors who received MV, and those who received MV and died during hospitalization.

The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin-6 Associates with Decreased Survival in Clear Cell Renal Cell Carcinoma.

Clear cell renal carcinoma (ccRCC) is frequently associated with cachexia which is itself associated with decreased survival and quality of life. We examined relationships among body phenotype, tumor gene expression, and survival. Demographic, clinical, computed tomography (CT) scans and tumor RNASeq for 217 ccRCC patients were acquired from the Cancer Imaging Archive and The Cancer Genome Atlas (TCGA).

Combined administration of a small-molecule inhibitor of TRAF6 and Docetaxel reduces breast cancer skeletal metastasis and osteolysis.

Tumour necrosis factor receptor-associated factor 6 (TRAF6) has been implicated in breast cancer and osteoclastic bone destruction. Here, we report that 6877002, a verified small-molecule inhibitor of TRAF6, reduced metastasis, osteolysis and osteoclastogenesis in models of osteotropic human and mouse breast cancer. First, we observed that TRAF6 is highly expressed in osteotropic breast cancer cells and its level of expression was higher in patients with bone metastasis.

Redefining Palliative Care-A New Consensus-Based Definition.

Context: The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief.

Objective: The main objective of this article is to present the research behind the new definition.

Methods: The three-phased consensus process involved health care workers from countries in all income levels.

JZL184, A Monoacylglycerol Lipase Inhibitor, Induces Bone Loss in a Multiple Myeloma Model of Immunocompetent Mice.

Multiple myeloma (MM) patients develop osteolysis characterised by excessive osteoclastic bone destruction and lack of osteoblast bone formation. Pharmacological manipulation of monoacylglycerol lipase (MAGL), an enzyme responsible for the degradation of the endocannabinoid 2-arachidonoyl glycerol (2-AG), reduced skeletal tumour burden and osteolysis associated with osteosarcoma and advanced breast and prostate cancers. MM and hematopoietic, immune and bone marrow cells express high levels of type 2 cannabinoid receptor and osteoblasts secrete 2-AG.

Development and Retrospective Review of a Pediatric Ethics Consultation Service at a Large Academic Center.

The primary objective was to review pediatric ethics consultations (PECs) at a large academic health center over a nine year period, assessing demographics, ethical issues, and consultant intervention. The secondary objective was to describe the evolution of PECs at our institution. This was a retrospective review of Consultation Summary Sheets compiled for PECs at our Academic Health Center between January 2008 and April 2017.

Increasing Nephrologist Awareness of Symptom Burden in Older Hospitalized End-Stage Renal Disease Patients.

Background: End-stage renal disease (ESRD) patients have significant symptom burden. Reduced provider awareness of symptoms contributes to underutilization of symptom management resources.

Method: We hypothesized that improved nephrologist awareness of symptoms leads to symptom improvement.

Dengue virus capsid anchor modulates the efficiency of polyprotein processing and assembly of viral particles.

The assembly and secretion of flaviviruses are part of an elegantly regulated process. During maturation, the viral polyprotein undergoes several co- and post-translational cleavages mediated by both viral and host proteases. Among these, sequential cleavage at the N and C termini of the hydrophobic capsid anchor (Ca) is crucial in deciding the fate of viral infection.