South Africa's central bank has temporarily prohibited the use of debt issued by the Land Bank as collateral after the state agricultural lender was downgraded deeper into junk status and missed $2.7 billion in loan repayments.

David Rhodes, the former president of CBS News who started his career at Fox News, is returning to Rupert Murdoch's News Corp to help the company's News UK operations in the video business, a source familiar with the matter said.

A non-profit organization brings dogs to the Buffalo/Niagra airport to help relieve the stress of holiday traveling. Diane Hodges reports.

Across Africa, centuries-old cultural traditions are being foregone in the wake of the COVID-19 pandemic, which has seen governments impose restrictions on gatherings and other practices around death and burial. Francesca Lynagh reports.

The UK’s exit from the EU has had a mixed effect on scientists’ assessment of their international mobility and future job market prospects, according to the 2020 STEM Survey

Many people are turning to virtual therapy and mental health apps to cope with the stress of the coronavirus pandemic, but they may not be as helpful as talking face to face

Wall Street's indexes climbed Thursday, with the Nasdaq erasing losses for 2020, following a clutch of upbeat earnings reports led by PayPal. Fred Katayama reports.

Title: Common Treatment May Not Help Seniors With Underactive Thyroid
Category: Health News
Created: 5/4/2020 12:00:00 AM
Last Editorial Review: 5/5/2020 12:00:00 AM

Title: Veramyst Treats Seasonal and Year-Round Allergies
Category: Health News
Created: 5/1/2007 2:00:00 AM
Last Editorial Review: 5/1/2007 12:00:00 AM

Title: Health Tip: Foods to Avoid If You Have Ulcerative Colitis
Category: Health News
Created: 4/28/2010 8:10:00 AM
Last Editorial Review: 4/28/2010 12:00:00 AM

Title: Even Moderate Drinking Puts Many Older Adults at Risk
Category: Health News
Created: 4/28/2010 6:10:00 PM
Last Editorial Review: 4/29/2010 12:00:00 AM

Title: Low Health Literacy May Have Deadly Consequences
Category: Health News
Created: 4/27/2011 11:00:00 AM
Last Editorial Review: 4/27/2011 12:00:00 AM

Title: Two-Drug Therapy Helped Kids With Type 2 Diabetes
Category: Health News
Created: 4/29/2012 6:05:00 PM
Last Editorial Review: 4/30/2012 12:00:00 AM

Title: TV Ads May Play Role in Underage Drinking, Obesity
Category: Health News
Created: 4/29/2012 10:05:00 AM
Last Editorial Review: 4/30/2012 12:00:00 AM

Title: Study: Gene Therapy for HIV Safe, But Effectiveness Still Unclear
Category: Health News
Created: 5/2/2012 4:05:00 PM
Last Editorial Review: 5/3/2012 12:00:00 AM

Title: A Heart Disease Veteran at Just Age 12
Category: Health News
Created: 5/4/2012 10:05:00 AM
Last Editorial Review: 5/4/2012 12:00:00 AM

Title: General Anesthesia Not Linked to Raised Risk for Dementia
Category: Health News
Created: 5/1/2013 12:35:00 PM
Last Editorial Review: 5/2/2013 12:00:00 AM

Title: Stem Cells Used to Regenerate Heart Muscle in Monkeys
Category: Health News
Created: 4/30/2014 2:36:00 PM
Last Editorial Review: 5/1/2014 12:00:00 AM

Title: News Coverage of Teen Suicides May Have Ripple Effect
Category: Health News
Created: 5/2/2014 7:35:00 AM
Last Editorial Review: 5/2/2014 12:00:00 AM

Title: Breast Reconstruction Often Involves Multiple Operations
Category: Health News
Created: 4/30/2015 12:00:00 AM
Last Editorial Review: 5/1/2015 12:00:00 AM

Title: Mindfulness Therapy May Help Ease Recurrent Depression
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: The 7 Deadliest Emergency General Surgeries
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Trump Administration Rolls Back Obama-Era School Lunch Rules
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/2/2017 12:00:00 AM

Title: Arthritis Drug Shows Promise for Ulcerative Colitis
Category: Health News
Created: 5/3/2017 12:00:00 AM
Last Editorial Review: 5/4/2017 12:00:00 AM

Title: Reading to Babies Translates Into More Literate Preschoolers
Category: Health News
Created: 5/4/2017 12:00:00 AM
Last Editorial Review: 5/5/2017 12:00:00 AM

Title: Gene Therapy May Help Fight Tough-to-Treat Blood Cancer
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Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Title: Trump Says Federal Guidelines on Social Distancing Set to Expire
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM

Title: Eating Fish in Moderation During Pregnancy Benefits Fetus: Study
Category: Health News
Created: 3/20/2020 12:00:00 AM
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Title: With Macular Degeneration, 1 Missed Visit to Eye Doc Can Mean Vision Loss
Category: Health News
Created: 2/7/2020 12:00:00 AM
Last Editorial Review: 2/10/2020 12:00:00 AM

Adjust oxygen and fluid therapy thresholds for pregnant patients with severe disease, experts advise; early use of a high-flow nasal cannula and prone positioning may help avoid mechanical ventilation.

Striking differences in how men and women are affected by COVID-19 might be explained by deleterious effects of androgens in males, say Italian researchers.

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

These are the coronavirus stories you need to know about today.

Since March 2016, the NIH Manuscript Submission (NIHMS) system has added support for researchers from the following federal agencies to deposit in PMC any manuscripts that fall under the agency’s public access policy:

• Assistant Secretary for Preparedness and Response (ASPR/HHS; intramural only at this time)
• Environmental Protection Agency (EPA; intramural only at this time)
• National Aeronautics and Space Administration (NASA; intramural/civil servants and grantees)

Manuscript deposit support for all Administration for Community Living (ACL/HHS) researchers will be available in NIHMS by October 2017 and for Department of Homeland Security researchers in early 2018.

Additionally, the Bill & Melinda Gates Foundation Open Access Policy now requires their grantees to make their published research results available in PMC immediately upon publication under a Creative Commons Attribution (CC-BY) license. Manuscript deposit support is not provided in NIHMS for Gates-funded researchers; rather the final published version of any Gates-funded article is to be deposited directly to PMC by the publisher or a funder-supported data provider without author involvement. More information on this open access policy is available on the Gates Foundation website.

PMC will continue to update the list of participating funding agencies at Public Access and PMC as support is implemented.

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: How Does Cognitive Behavioral Therapy Treat Depression?
Category: Procedures and Tests
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 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
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Title: Lasix Side Effects, Warnings, and Drug Interactions
Category: Medications
Created: 3/4/2020 12:00:00 AM
Last Editorial Review: 3/4/2020 12:00:00 AM

Title: How Dangerous Is General Anesthesia?
Category: Procedures and Tests
Created: 3/5/2020 12:00:00 AM
Last Editorial Review: 4/7/2020 12:00:00 AM

Title: New Study Shakes Up Thinking on Hormone Replacement Therapy
Category: Health News
Created: 12/13/2019 12:00:00 AM
Last Editorial Review: 12/13/2019 12:00:00 AM

Title: AHA News: Estrogen Therapy in Early Menopause May Help Keep Arteries Clear
Category: Health News
Created: 3/3/2020 12:00:00 AM
Last Editorial Review: 3/4/2020 12:00:00 AM

Title: Therapy by Phone Helps Parkinson's Patients Manage Depression
Category: Health News
Created: 4/10/2020 12:00:00 AM
Last Editorial Review: 4/13/2020 12:00:00 AM

Title: Is Electroconvulsive (ECT) Therapy Safe?
Category: Procedures and Tests
Created: 3/6/2020 12:00:00 AM
Last Editorial Review: 3/6/2020 12:00:00 AM

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.

Expression of the DNA/RNA helicase schlafen family member 11 (SLFN11) has been identified as a sensitizer of tumor cells to DNA-damaging agents including platinum chemotherapy. We assessed the impact of SLFN11 expression on response to platinum chemotherapy and outcomes in patients with metastatic castration-resistant prostate cancer (CRPC). Tumor expression of SLFN11 was assessed in 41 patients with CRPC treated with platinum chemotherapy by RNA sequencing (RNA-seq) of metastatic biopsy tissue (n = 27) and/or immunofluorescence in circulating tumor cells (CTC; n = 20). Cox regression and Kaplan–Meier methods were used to evaluate the association of SLFN11 expression with radiographic progression-free survival (rPFS) and overall survival (OS). Multivariate analysis included tumor histology (i.e., adenocarcinoma or neuroendocrine) and the presence or absence of DNA repair aberrations. Patient-derived organoids with SLFN11 expression and after knockout by CRISPR-Cas9 were treated with platinum and assessed for changes in dose response. Patients were treated with platinum combination (N = 38) or platinum monotherapy (N = 3). Median lines of prior therapy for CRPC was two. Median OS was 8.7 months. Overexpression of SLFN11 in metastatic tumors by RNA-seq was associated with longer rPFS compared with those without overexpression (6.9 vs. 2.8 months, HR = 3.72; 95% confidence interval (CI), 1.56–8.87; P < 0.001); similar results were observed for patients with SLFN11-positive versus SLFN11-negative CTCs (rPFS 6.0 vs. 2.2 months, HR = 4.02; 95% CI, 0.77–20.86; P = 0.002). A prostate-specific antigen (PSA) decline of ≥50% was observed in all patients with SLFN11 overexpression. No association was observed between SLFN11 expression and OS. On multivariable analysis, SLFN11 was an independent factor associated with rPFS on platinum therapy. Platinum response of organoids expressing SLFN11 was reduced after SLFN11 knockout. Our data suggest that SLFN11 expression might identify patients with CRPC with a better response to platinum chemotherapy independent of histology or other genomic alterations. Additional studies, also in the context of PARP inhibitors, are warranted.

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.

2-fluorofucose (2FF) inhibits protein and cellular fucosylation. Afucosylation of IgG antibodies enhances antibody-dependent cell-mediated cytotoxicity by modulating antibody affinity for FcRIIIa, which can impact secondary T-cell activation. Immune responses toward most common solid tumors are dominated by a humoral immune response rather than the presence of tumor-infiltrating cytotoxic T cells. IgG antibodies directed against numerous tumor-associated proteins are found in the sera of both patients with breast cancer and transgenic mice bearing mammary cancer. We questioned whether 2FF would have antitumor activity in two genetically distinct transgenic models; TgMMTV-neu (luminal B) and C3(1)-Tag (basal) mammary cancer. 2FF treatment significantly improved overall survival. The TgMMTV-neu doubled survival time compared with controls [P < 0.0001; HR, 7.04; 95% confidence interval (CI), 3.31–15.0], and survival was significantly improved in C3(1)-Tag (P = 0.0013; HR, 3.36; 95% CI, 1.58–7.14). 2FF treated mice, not controls, developed delayed-type hypersensitivity and T-cell responses specific for syngeneic tumor lysates (P < 0.0001). Serum IgG from 2FF-treated mice enhanced tumor lysis more efficiently than control sera (P = 0.004). Administration of 2FF for prophylaxis, at two different doses, significantly delayed tumor onset in both TgMMTV-neu; 20 mmol/L (P = 0.0004; HR, 3.55; 95% CI, 1.60–7.88) and 50 mmol/L (P = 0.0002; HR: 3.89; 95% CI, 1.71–8.86) and C3(1)-Tag; 20 mmol/L (P = 0.0020; HR, 2.51; 95% CI, 1.22–5.18), and 50 mmol/L (P = 0.0012; HR, 3.36; 95% CI, 1.57–7.18). Mammary cancer was prevented in 33% of TgMMTV-neu and 26% of C3(1)-Tag. 2FF has potent antitumor effects in mammary cancer models. The agent shows preclinical efficacy for both cancer treatment and prevention.

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.