It's official—PMC has just become home to two million articles! The record-breaking article, which came from the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, became publicly available in the PMC archive on June 23. This new PMC milestone has occurred almost three years to the day since PMC reached its last one: the one-million article mark in June 2007. See also: PubMed Central Hits One Million Article Mark.

Four new members have been appointed to serve on the PMC National Advisory Committee: Philip Bourne, of the University of California, San Diego; Sophia Colamarino, an independent consultant in San Francisco; Paul Courant, of the University of Michigan; and Patricia Thibodeau, of Duke University. Each member will serve a 4-year term. The next meeting of the committee is scheduled for Friday, June 17, 2011. For more information on the committee, see PMC National Advisory Committee.

PMC marked its 10th anniversary in 2010 with a celebratory event at its annual Advisory Committee meeting, held at the National Library of Medicine last June. This milestone event was recently featured in the February 17th edition of NLM In Focus, in an article NLM Milestones: The Hits Just Keep on Coming. For more information on the ten years of PMC, see the article in the May-June issue of the NLM Technical Bulletin.

The PMC Advisory Committee will hold its annual meeting at the National Library of Medicine on Friday, June 17, 2011 from 9:30 am to 3 pm. Four new committee members will be joining the group, see New Members Appointed to PMC Advisory Committee. Presentations will include discussions relating to the NIH Public Access policy and a viewing of the PMC 10th Anniversary video. For more information, see PMC National Advisory Committee.

The second annual Journal Article Tag Suite Conference (JATS-Con) will be held on September 26 and 27, 2011, at the Natcher Conference Center on the NIH Campus in Bethesda, Maryland. The 2011 conference will feature a host of presenters who will discuss topics ranging from Best Practices to PMC Tagging Guidelines. For more information on the conference and the program, see JATS-Con.

The following new members have been appointed to serve on the PMC National Advisory Committee: Martha Bedard, Dean of Libraries at the University of New Mexico; and Lorraine Haricombe, Dean of Libraries at the University of Kansas and a member of SPARC's board. The next meeting of the committee is scheduled for June 19, 2012. For more information, see PMC National Advisory Committee.

As of February 1, 2013, the following new members have been appointed to serve on the PMC National Advisory Committee: Ms. Sharon Terry of the Genetic Alliance; Dr. C. Victor Jongneel of the University of Illinois at Urbana-Champaign; Dr. Bevin Engelward of the Massachusetts Institute of Technology; Dr. Randall Morse of the Wadsworth Center; and Dr. Adelita Cantu of the University of Texas. For more information, see PMC National Advisory Committee.

As of February 21, 2014, PMC became home to three million articles! As listed on our home page, the content has been provided in part by 1441 full participation journals, 277 NIH Portfolio journals and 2470 selective deposit journals. For related information on PMC milestones, see these announcements from 2007 and 2010, respectively.

This year's PMC Advisory Committee meeting will be held on Tuesday, June 10. The meeting will take place in the NLM Board room starting at 9:30 am. Stay tuned for further details.

The PMC Overview and FAQ have been updated to provide more information on the Scientific Quality Review Process for journals that apply to participate in PMC.

In 2014, PMC implemented a scientific and editorial quality review procedure whereby expert consultants from outside the National Library of Medicine (NLM) conduct an independent review of journals seeking to participate in PMC. This was in response to a significant increase in new publishers and journals applying to participate in PMC, many of which are unknown to NLM in terms of quality and publishing practices. The independent review, which was approved by the PMC National Advisory Committee (see minutes from June 10, 2014), follows an assessment by NLM that the journal meets NLM’s criteria for its collection, as outlined in the Collection Development Manual.

PMC also recently updated the minimum requirement on the number of substantive, peer-reviewed articles needed before a journal can apply to PMC. The new 25-article minimum ensures that the reviewers have a sufficient amount of content on which to base their recommendation for inclusion in PMC. The new minimum article requirement takes effect on January 1, 2016. Publishers are encouraged to use the 25-article minimum as a guideline in the interim when submitting applications.

NIH-supported scientists have made over 300,000 author manuscripts available in PMC. Now NIH is making these papers accessible to the public in a format that will allow robust text analyses.

You can download the PMC collection of NIH-supported author manuscripts as a package in either XML or plain-text format at ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/manuscript/. The collection encompasses all NIH manuscripts posted to PMC that were published in July 2008 or later. While the public can access the manuscripts’ full text and accompanying figures, tables, and multimedia via the PMC website, the newly available XML and plain-text files include full text only. In addition to text mining, the files may be used consistent with the principles of fair use under copyright law.

Please note that these author manuscript files are not part of the PMC Open Access Subset.

The NIH Office of Extramural Research developed this resource to increase the impact of NIH funding. Through this collection, scientists will be able to analyze these manuscripts, further apply NIH research findings, and generate new discoveries.

For more information, please visit the PMC author manuscript collection webpage.

PMC has reorganized its FTP Service site for users interested in accessing the Text Mining Collections, which include the original Open Access (OA) Subset. New top-level FTP directories help users quickly locate the content available for bulk download that best suits their research needs. These directories include:

• oa_package - article packages for individual OA articles
• oa_pdf – individual PDFs for OA articles
• oa_bulk – bulk packages of text from OA articles
• manuscript – author manuscripts collected under a funding agency’s public access policy
• historical_ocr – select OCR texts from the PMC Back Issue Digitization project

To make it easier for users to identify and comply with the different licenses that apply to OA articles, new file lists have been created and the file lists for individual OA articles now include a “license-type” field for each article. Similarly, the bulk packages of OA article text have been divided into two sets. 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. See the Open Access Subset page for details.

To allow regular users to transition to the new arrangement, the previous arrangement of files and directories will be maintained in parallel for at least four weeks (i.e., until the end of August 2016).

A large-scale update of the file names used for articles available via the PMC FTP service for bulk download was undertaken in early January 2017. The new file naming convention is PMCID-based (e.g., PMC4855680.tar.gz) rather than being built from article citation data (i.e., journal abbreviation_pub date_volume_issue_page). This update was made following user reports that the previous naming convention was resulting in missing contents in cases where citation data was duplicated across multiple articles. The new convention will ensure that file names are unique and that the corpus available via the FTP service is complete.

Title: Heading to Work on a Bike? You Might Live Longer
Category: Health News
Created: 2/25/2020 12:00:00 AM
Last Editorial Review: 2/26/2020 12:00:00 AM

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: 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: Baqsimi (glucagon)
Category: Medications
Created: 4/22/2020 12:00:00 AM
Last Editorial Review: 4/22/2020 12:00:00 AM

Title: Heart Drug Combos Might Also Lower Your Dementia Risk: Study
Category: Health News
Created: 3/13/2020 12:00:00 AM
Last Editorial Review: 3/16/2020 12:00:00 AM

Title: Dirty Air Might Raise Your Odds for Dementia
Category: Health News
Created: 3/31/2020 12:00:00 AM
Last Editorial Review: 4/1/2020 12:00:00 AM

Title: Which Foods Might Reduce Your Odds for Dementia?
Category: Health News
Created: 4/14/2020 12:00:00 AM
Last Editorial Review: 4/14/2020 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: New Polio Vaccine Promising in Early Test
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Modern Livestock Farming Can Pose Public Health Risk
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 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: Vitamin D Might Aid Seniors' Recovery From Hip Fracture: Study
Category: Health News
Created: 4/2/2020 12:00:00 AM
Last Editorial Review: 4/3/2020 12:00:00 AM

Title: Lupus (Systemic Lupus Erythematosus or SLE)
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 4/9/2020 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: Middle Age More Stressful Now Than in 1990s: Study
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM

Title: Blood Pressure Dips Upon Standing Might Not Be as Dangerous as Thought
Category: Health News
Created: 1/28/2020 12:00:00 AM
Last Editorial Review: 1/29/2020 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 Pill vs. Shot (Depo-Provera): Similarities and Differences
Category: Diseases and Conditions
Created: 6/15/2017 12:00:00 AM
Last Editorial Review: 4/13/2020 12:00:00 AM

Title: Cuddling Brings Two Minds Together, MRI Study Reveals
Category: Health News
Created: 5/4/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM

Title: Many With Dog Allergies Might Only Be Allergic to Male Dogs
Category: Health News
Created: 1/7/2020 12:00:00 AM
Last Editorial Review: 1/8/2020 12:00:00 AM

Title: Helping Seniors Manage Meds After Hospital Reduces Readmission: Study
Category: Health News
Created: 3/3/2020 12:00:00 AM
Last Editorial Review: 3/4/2020 12:00:00 AM

Title: Mindfulness a Powerful Tool for Aging
Category: Health News
Created: 4/2/2020 12:00:00 AM
Last Editorial Review: 4/3/2020 12:00:00 AM

Title: Some NFL Players May Be Misdiagnosed With Brain Disease: Study
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 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: Many Car Crash Deaths Involve Alcohol Levels Below Legal Limit: Study
Category: Health News
Created: 3/16/2020 12:00:00 AM
Last Editorial Review: 3/17/2020 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: AHA News: Stroke Survivors Might Need Better Screening for Depression
Category: Health News
Created: 2/12/2020 12:00:00 AM
Last Editorial Review: 2/13/2020 12:00:00 AM

Title: Is the 'Gratitude Movement' Overrated? Study Finds It Has Limits
Category: Health News
Created: 3/16/2020 12:00:00 AM
Last Editorial Review: 3/17/2020 12:00:00 AM

Title: Magnetic Brain 'Zap' Shows Promise Against Severe Depression
Category: Health News
Created: 4/7/2020 12:00:00 AM
Last Editorial Review: 4/8/2020 12:00:00 AM

Title: Kyprolis (carfilzomib)
Category: Medications
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM

Title: Fewer Kids in Cancer Trials, Which Might Not Be a Bad Thing
Category: Health News
Created: 5/5/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM

Long noncoding RNAs (lncRNA) have been found to play critical roles in tumorigenesis and the development of various cancers, including hepatocellular carcinoma (HCC). Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) has been identified as an oncogene and prognostic biomarker in HCC. Here, we demonstrated that MALAT1 expression was obviously high in sorafenib-resistant HCC cells. Furthermore, knockdown of MALAT1 increased sorafenib sensitivity in nonresponsive HCC cells, whereas forced expression of MALAT1 conferred sorafenib resistance to responsive HCC cells in vitro. In addition, loss/gain-of-function assays revealed that MALAT1 promoted cell proliferation, migration, and epithelial–mesenchymal transition in HCC cells. Mechanistically, MALAT1 regulated Aurora-A expression by sponging miR-140-5p, thus promoting sorafenib resistance in HCC cells. Moreover, MALAT1 inhibition enhanced the antitumor efficacy of sorafenib in vivo. Clinically, we found that MALAT1 expression was negatively correlated with miR-140-5p expression but positively correlated with Aurora-A expression in patients with HCC and that upregulated MALAT1 was closely correlated with poor survival outcomes in patients with HCC. These findings indicated that MALAT1 may be a novel target for prognosis prediction and therapeutic strategies in patients with HCC treated with sorafenib.

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.