Title: Drink Up! Coffee Won't Harm Your Heart, Study Finds
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Title: Experts Cast Doubt on Notion That New Strain of Coronavirus Is More Infectious
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Two new graphics from Diabetes UK's COVID-19 task force address inpatient use of subcutaneous insulin for managing hyperglycemia and ketoacidosis when intravenous equipment is unavailable.

The FDA today approved a new use for the diabetes drug, dapagliflozin (Farxiga), to reduce the risk of a hospital stay or death in people who have a type of heart failure.

COVID-19 has led the ESC to transition its annual congress to a virtual format; ESC 2020 Congress 'Challenging Times, Infinite Possibilities' will run online from August 29 to September 1.

Calls to relax social distancing policies emphasize the need for increased testing, but a closer look at current SARS-CoV-2 tests leaves Anish Koka, MD, doubtful that more tests will be the solution.

Infectious viruses commonly are found in semen, with Zika being one recent notable example. The Chinese researchers noted that 27 different viruses have been detected in human semen.

Based on a review of more than 1,000 patients who've already sought care for respiratory illnesses since the coronavirus was declared a pandemic in March, researchers at Harvard Medical School are offering up a new list of symptoms to watch out for.

Researchers report evidence of SARS-CoV-2, which causes COVID-19, in the semen of patients; the data raise the possibility of sexual transmission, but experts say there is no evidence of infectivity.

Dr Aaron Holley warns against following 'false prophets' as we confront treatment decisions for patients with COVID-19.

A child psychologist advises parents to address the threat of internet challenges with continual, preemptive conversations with kids -- and with special phone settings.

Americans are reporting high levels of emotional distress from the coronavirus pandemic – levels that some experts warn may lead to national mental health crisis.

PMC released a new and improved journal list on March 31, 2009, after a comprehensive redesign for greater clarity and organization.

The new design not only combines the full-list and tabbed-list views of the previous version but also includes some new or updated features to provide users with a greater overview of the total PMC archive. Looking at this new list, you will find:

1. An Expanded View of PMC journals that includes NIH Portfolio
2. Special Collections
3. A New “Participation Level” Journal Category
4. Hide/Show Display Option for Predecessor Titles
5. Article and Journal Search Feature

For more information, see the complete article in the May-June issue of the NLM Technical Bulletin: https://www.nlm.nih.gov/pubs/techbull/mj09/mj09_pmc_redesign.html

For any journal issue that has at least one open access or early access article, PMC is now displaying the table of contents (TOC) in advance of the whole issue becoming available. Not to worry, though—only those articles specified for early release are immediately viewable in PMC. As consistent with the terms of access in the journal agreement, the other articles will only become available on their specified release date, as shown in the TOC below.

The journal's accessiblity, as indicated on the PMC Journal list also has not changed; for example, Plant Physiology's embargo period is still 12 months. What has changed is that the issues with “preview” TOCs now additionally appear on the journal's archive page. Publishers and others can rest assured, however, that no access terms for any journal have been changed with the unveiling of this new format.

The PMC user's guide, PMC Help has been updated to include new and improved information on navigating the site as well as descriptions and instructions on using the new search functions, such as Limits and Advanced Search Builder. Further updates will also be forthcoming.

PMC has created a new email list for announcements of new or updated tools and utilities to help you keep better track of improvements to the archive. To find out more information about the list, or to subscribe, please visit PMC-Utils-Announce.

PMC has recently released an updated version of its PubReader view. The new version (1.2) includes a "search this page" feature that allows you to find specific terms within the article. The latest source code is also available from the GitHub repository.

Title: Indoor Athletes Often Lacking in Vitamin D
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 12:00:00 AM

Title: Doctors Describe First Drone Delivery of Diabetes Meds to Patient
Category: Health News
Created: 3/30/2020 12:00:00 AM
Last Editorial Review: 3/31/2020 12:00:00 AM

Title: Patch Pump Device Could Offer Cheaper Insulin Delivery
Category: Health News
Created: 4/1/2020 12:00:00 AM
Last Editorial Review: 4/2/2020 12:00:00 AM

Title: Study Ties Brain Inflammation to Several Types of Dementia
Category: Health News
Created: 3/18/2020 12:00:00 AM
Last Editorial Review: 3/18/2020 12:00:00 AM

Title: Raking Your Leaves to the Edge of Your Yard an Invitation to Ticks
Category: Health News
Created: 3/22/2020 12:00:00 AM
Last Editorial Review: 3/23/2020 12:00:00 AM

Title: Balanitis (Inflammation of the Head of the Penis)
Category: Diseases and Conditions
Created: 6/24/2013 12:00:00 AM
Last Editorial Review: 11/22/2019 12:00:00 AM

Title: Peyronie's Disease (Curvature of the Penis)
Category: Diseases and Conditions
Created: 11/14/2002 12:00:00 AM
Last Editorial Review: 12/5/2019 12:00:00 AM

Title: Drinking Takes Toll on Bones of People With HIV: Study
Category: Health News
Created: 3/6/2020 12:00:00 AM
Last Editorial Review: 3/9/2020 12:00:00 AM

Title: After 2nd Patient Cured of HIV, Hope Revives for an End to AIDS
Category: Health News
Created: 3/10/2020 12:00:00 AM
Last Editorial Review: 3/11/2020 12:00:00 AM

Title: Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide)
Category: Medications
Created: 4/16/2020 12:00:00 AM
Last Editorial Review: 4/16/2020 12:00:00 AM

Title: Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide)
Category: Medications
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: Money Not a Good Measure of Your Self-Worth
Category: Health News
Created: 4/14/2020 12:00:00 AM
Last Editorial Review: 4/15/2020 12:00:00 AM

Title: Religion Helps Protect Against 'Deaths of Despair': Study
Category: Health News
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM

Title: AHA News: Could Sunshine Lower Blood Pressure? Study Offers Enlightenment
Category: Health News
Created: 2/28/2020 12:00:00 AM
Last Editorial Review: 3/2/2020 12:00:00 AM

Title: Birth Control Pills (List of Oral Contraceptives and Side Effects)
Category: Medications
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 1/30/2020 12:00:00 AM

Title: One Dose of HPV Vaccine May Protect Against Cervical Cancer
Category: Health News
Created: 2/10/2020 12:00:00 AM
Last Editorial Review: 2/10/2020 12:00:00 AM

Title: First Drug Approved for Treatment of Peanut Allergy in Children
Category: Health News
Created: 2/3/2020 12:00:00 AM
Last Editorial Review: 2/4/2020 12:00:00 AM

Title: An Allergist Offers His Expert Advice for a Sneeze-Free Spring
Category: Health News
Created: 3/7/2020 12:00:00 AM
Last Editorial Review: 3/9/2020 12:00:00 AM

Title: FDA Warns of Defective EpiPen Dangers
Category: Health News
Created: 3/25/2020 12:00:00 AM
Last Editorial Review: 3/26/2020 12:00:00 AM

Title: Seniors, Getting Off the Sofa Brings Big Health Benefits
Category: Health News
Created: 3/5/2020 12:00:00 AM
Last Editorial Review: 3/6/2020 12:00:00 AM

Title: Aftermath of Seizures Troubling for Those With Epilepsy
Category: Health News
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/20/2020 12:00:00 AM

Title: Pets May Help Parents of Kids With Autism Fight Stress
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Title: Could the Weather Swings of Climate Change Make Flu Seasons Worse?
Category: Health News
Created: 2/20/2020 12:00:00 AM
Last Editorial Review: 2/21/2020 12:00:00 AM

Title: Drug Offers Hope Against Tough-to-Treat Chronic Cough
Category: Health News
Created: 2/26/2020 12:00:00 AM
Last Editorial Review: 2/26/2020 12:00:00 AM

Title: The Doctor Gap: In Areas of Greatest Need, Primary Care Is a Team Effort
Category: Health News
Created: 3/19/2020 12:00:00 AM
Last Editorial Review: 3/20/2020 12:00:00 AM

Title: High Heat, Humidity Could Affect More Than 1.2 Billion People by End of Century
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 12:00:00 AM

Title: Obamacare May Have Boosted Use of Mammograms
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM

Title: Erratic Sleep Habits May Boost Risk of Heart Problems: Study
Category: Health News
Created: 3/4/2020 12:00:00 AM
Last Editorial Review: 3/5/2020 12:00:00 AM

This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5–25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days. For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed. The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.

There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC₅₀ and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma.

Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic KIT mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST. We found that an anti-KIT DNA aptamer bound cells in a KIT-dependent manner and was highly specific for GIST cell labeling in vitro. Functionally, the KIT aptamer bound extracellular KIT in a manner similar to KIT mAb staining, and was trafficked intracellularly in vitro. The KIT aptamer bound dissociated primary human GIST cells in a mutation agnostic manner such that tumors with KIT and PDGFRA mutations were labeled. In addition, the KIT aptamer specifically labeled intact human GIST tissue ex vivo, as well as peritoneal xenografts in mice with high sensitivity. These results represent the first use of an aptamer-based method for targeted detection of GIST in vitro and in vivo.

Overexpression of transcription factor 3 in alveolar soft part sarcoma(ASPS) results in upregulation of cell proliferation pathways. No standard treatment algorithm exists for ASPS; multikinase inhibitors[tyrosine kinase inhibitor (TKI)] and immune checkpoint inhibitors (ICI) have shown clinical benefit. To date, no studies have reported on management strategies or sequencing of therapy. We evaluated ASPS treatment patterns and responses in an experimental therapeutics clinic. Genomic and morphoproteomic analysis was performed to further elucidate novel targets. We retrospectively reviewed patients with ASPS treated on clinical trials. Demographic and clinical next-generation sequencing (NGS) profiles were collected. AACR GENIE database was queried to further evaluate aberrations in ASPS. Morphoproteomic analysis was carried out to better define the biology of ASPS with integration of genomic and proteomic findings. Eleven patients with ASPS were identified; 7 received NGS testing and mutations in CDKN2A (n = 1) and hepatocyte growth factor (n = 1) were present. Ten patients were treated with TKIs with stable disease as best response and 4 patients with ICI (three partial responses). Within GENIE, 20 patients were identified harboring 3 called pathogenic mutations. Tumor mutation burden was low in all samples. Morphoproteomic analysis confirmed the expression of phosphorylated c-Met. In addition, fatty acid synthase and phosphorylated-STAT3 were detected in tumor cell cytoplasm and nuclei. Patients with ASPS have a quiescent genome and derive clinical benefit from VEGF-targeting TKIs. Morphoproteomic analysis has provided both additional correlative pathways and angiogenic mechanisms that are targetable for patients with ASPS. Our study suggests that sequential therapy with TKIs and immune checkpoint inhibitors is a reasonable management strategy.