With the addition of several European sponsoring agencies, including the European Research Council, UKPMC was renamed Europe PMC as of November 1, 2012. Europe PMC is an outgrowth and expansion of UKPMC, which was first launched in January 2007 with sponsorship from the Wellcome Trust and several other funders of biomedical research in the UK. Europe PMC receives all of its final published articles directly from the U.S. PMC archive. It also accepts and processes author manuscripts of journal articles funded by the Europe PMC sponsoring agencies and makes them available to U.S. PMC and PMC Canada. For more information, see PMC International.

You can now search for Open Access articles that have certain types of licenses, by using special filters in both PMC and PubMed. These filters are based on license information that is provided to PMC by publishers and other content providers, as encoded by machine-readable identifiers in the source XML of each article. For more information, see our updated Open Access Subset page.

Collaboration with publishers and funders to ensure the openness and preservation of the scientific record is one of PMC’s core principles. Open Access Week offers an opportunity to celebrate some of the recent outcomes of these collaborations:

• In July 2018, the PMC corpus of publicly accessible articles hit 5 million articles.
• In May 2018, the PMC Open Access Subset surpassed the 2 million article mark.
• The Author Manuscript Collection now includes more than 500,000 papers for text mining.
• The PMC and Research Funder Policy page underwent an update in September 2018 to increase transparency around funder support in PMC for publishers, authors, and the public.
• Funder policy support in PMC has been extended to the US Department of Homeland Security, in addition to several new US private research funders via the Health Research Alliance.

In FY2018 more than 200 new journals committed to archiving their complete contents in PMC, to be made publicly accessible in 12 months or less.

On March 18, 2019, PMC will no longer provide bulk packages of Open Access (OA) Subset text and XML at the top level directory of the FTP Service. These files were superseded in August 2016 by the Commercial Use and Non-Commercial Use bulk packages located in the oa_bulk subdirectory. One set comprises articles that may be used for commercial purposes (the Commercial Use Collection); the other contains articles that can be used only for non-commercial purposes. Anyone planning to use OA subset content for non-commercial purposes will need to download both “non_comm_use.*.tar.gz” and “comm_use.*.tar.gz” to access the complete collection. See the Open Access Subset page for additional details. Questions should be directed to pubmedcentral@ncbi.nlm.nih.gov.

Peer review documents, including review reports and editor decision letters, are increasingly being published along with the articles they review. This practice is intended to make the publishing process more transparent. To support these efforts, PMC’s Tagging Guidelines have been updated to include the tagging of peer review documents. NLM encourages PMC-participating publishers, journals, and data providers to review this guidance. Please contact us at pubmedcentral@ncbi.nlm.nih.gov if you have any questions.

Title: An Expert's Guide to a Safe Run in Cold Weather
Category: Health News
Created: 3/14/2020 12:00:00 AM
Last Editorial Review: 3/16/2020 12:00:00 AM

Title: How Many Steps Per Day to Lengthen Your Life?
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 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: Family Ties Help Young Adults With Type 1 Diabetes Flourish
Category: Health News
Created: 4/8/2020 12:00:00 AM
Last Editorial Review: 4/8/2020 12:00:00 AM

Title: Obesity Is Biggest Type 2 Diabetes Risk Factor
Category: Health News
Created: 4/16/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: Heart Attacks, Strokes Are Declining Among People With Diabetes
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 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: Certain Gene Might Help Shield At-Risk People From Alzheimer's
Category: Health News
Created: 4/13/2020 12:00:00 AM
Last Editorial Review: 4/14/2020 12:00:00 AM

Title: Herpes Virus Yields Up Genetic Secrets
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Aspergillus Infection (Aspergillosis)
Category: Diseases and Conditions
Created: 3/13/2020 12:00:00 AM
Last Editorial Review: 3/13/2020 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: Allow Dead Men to Be Sperm Donors, Medical Ethicists Say
Category: Health News
Created: 1/22/2020 12:00:00 AM
Last Editorial Review: 1/22/2020 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: Taking Steroids for Rheumatoid Arthritis, IBD? Your Odds for Hypertension May Rise
Category: Health News
Created: 3/23/2020 12:00:00 AM
Last Editorial Review: 3/24/2020 12:00:00 AM

Title: Experimental Drug Shows Promise for Schizophrenia
Category: Health News
Created: 4/16/2020 12:00:00 AM
Last Editorial Review: 4/17/2020 12:00:00 AM

Title: U.S. Deaths From High Blood Pressure Soar, Especially in the South: Study
Category: Health News
Created: 3/23/2020 12:00:00 AM
Last Editorial Review: 3/24/2020 12:00:00 AM

Title: Blood Pressure Spikes at Night May Spell Trouble for Brain
Category: Health News
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/20/2020 12:00:00 AM

Title: AHA News: Being an African American 'Superwoman' Might Come With a Price
Category: Health News
Created: 2/11/2020 12:00:00 AM
Last Editorial Review: 2/12/2020 12:00:00 AM

Title: Birth Control Options (Types and Side Effects)
Category: Diseases and Conditions
Created: 9/13/1999 12:00:00 AM
Last Editorial Review: 4/10/2020 12:00:00 AM

Title: Remdesivir (RDV): Experimental Antiviral for Coronavirus (COVID-19)
Category: Medications
Created: 3/26/2020 12:00:00 AM
Last Editorial Review: 5/5/2020 12:00:00 AM

Title: Haldol (haloperidol) vs. Abilify (aripiprazole)
Category: Medications
Created: 7/30/2019 12:00:00 AM
Last Editorial Review: 4/10/2020 12:00:00 AM

Title: Can Men Dine Their Way to Higher Sperm Counts?
Category: Health News
Created: 2/21/2020 12:00:00 AM
Last Editorial Review: 2/24/2020 12:00:00 AM

Title: How Common Are STDs? Most People Have No Clue
Category: Health News
Created: 2/25/2020 12:00:00 AM
Last Editorial Review: 2/25/2020 12:00:00 AM

Title: First Treatment for Peanut Allergy Approved by FDA
Category: Health News
Created: 2/3/2020 12:00:00 AM
Last Editorial Review: 2/3/2020 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: Perimenopause
Category: Diseases and Conditions
Created: 7/5/2005 12:00:00 AM
Last Editorial Review: 9/17/2019 12:00:00 AM

Title: HIV Could Speed Menopause Onset
Category: Health News
Created: 11/6/2019 12:00:00 AM
Last Editorial Review: 11/7/2019 12:00:00 AM

Title: Menopause May Someday Disappear as Women Postpone Pregnancy: Study
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: AHA News: Dropping Blood Pressure May Predict Frailty, Falls in Older People
Category: Health News
Created: 3/30/2020 12:00:00 AM
Last Editorial Review: 3/31/2020 12:00:00 AM

Title: How Pets Can Be True Lifesavers for Seniors
Category: Health News
Created: 4/3/2020 12:00:00 AM
Last Editorial Review: 4/3/2020 12:00:00 AM

Title: Long Periods in Space Alter Astronauts' Brains
Category: Health News
Created: 4/14/2020 12:00:00 AM
Last Editorial Review: 4/15/2020 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: Flu Season That's Sickened 26 Million May Be at Its Peak
Category: Health News
Created: 2/21/2020 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: 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: Replace That Old Carpet to Shield Your Kids From Toxins
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Too Much Super Bowl Can Mean Too Little Sleep
Category: Health News
Created: 1/31/2020 12:00:00 AM
Last Editorial Review: 1/31/2020 12:00:00 AM

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.

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.

KRAS mutation is a negative predictive biomarker of anti-EGFR agents in patients with metastatic colorectal cancer (mCRC), and remains an elusive target. Pelareorep, a double-stranded RNA virus selectively replicates in KRAS-mutated cells, and is synergistic with irinotecan. A dose escalation trial of FOLFIRI/bevacizumab [irinotecan (150–180 mg/m²) and pelareorep (1 x 10¹⁰ TCID₅₀–3 x 10¹⁰ TCID₅₀)] was implemented in adult patients with oxaliplatin refractory/intolerant, KRAS-mutant mCRC. Pelareorep was administered intravenously over 1 hour on days 1–5 every 4 weeks. Additional studies included pharmacokinetics, tumor morphology, and immune responses. Among FOLFIRI-naïve patients, the highest dose of FOLFIRI/bevacizumab (180 mg/m² irinotecan) and pelareorep (3 x 10¹⁰ TCID₅₀) was well tolerated, without a dose-limiting toxicity. At the recommended phase II dose, 3 of 6 patients (50%) had a partial response; the median progression-free and overall survival (PFS, OS) were 65.6 weeks and 25.1 months, respectively. Toxicities included myelosuppression, fatigue, and diarrhea. Transmission electron microscopy revealed viral factories (viral collections forming vesicular structures), at various stages of development. Immunogold staining against viral capsid -1 protein demonstrated viral "homing" in the tumor cells. The nucleus displayed sufficient euchromatin regions suggestive of active transcription. Flow cytometry revealed rapid dendritic cell maturation (48 hours) with subsequent activation of cytotoxic T cells (7 days). The combination of pelareorep with FOLFIRI/bevacizumab is safe. The PFS and OS data are encouraging and deserve further exploration. Pelareorep leads to a clear recurrent immune stimulatory response with cytotoxic T-cell activation, and homes and replicates in the tumor.

The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development. Initial analysis of clinical survival trends for breast cancer and BCBM determined improvement of breast cancer survival rates; however, this has failed to positively affect the prognostic milestones of triple-negative breast cancer (TNBC) brain metastases (BM). ALDH1A3 and a representative epithelial–mesenchymal transition (EMT) gene signature (mesenchymal markers, CD44 or Vimentin) were compared in tumors derived from BM, lung metastases (LM), or bone metastases (BoM) of patients as well as mice after injection of TNBC cells. Selective elevation of the EMT signature and ALDH1A3 were observed in BM, unlike LM and BoM, especially in the tumor edge. Furthermore, ALDH1A3 was determined to play a role in BCBM establishment via regulation of circulating tumor cell adhesion and migration phases in the BCBM cascade. Validation through genetic and pharmacologic inhibition of ALDH1A3 via lentiviral shRNA knockdown and a novel small-molecule inhibitor demonstrated selective inhibition of BCBM formation with prolonged survival of tumor-bearing mice. Given the survival benefits via targeting ALDH1A3, it may prove an effective therapeutic strategy for BCBM prevention and/or treatment.