The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple-Negative Breast Cancer by Attenuating TGFβ Signaling.

The pogo transposable element-derived zinc finger protein, POGZ, is notably associated with neurodevelopmental disorders through its role in gene transcription. Many proteins involved in neurological development are often dysregulated in cancer, suggesting a potential role for POGZ in tumor biology. Here, we provided experimental evidence that POGZ influences the growth and metastatic spread of triple-negative breast cancers (TNBC).

An E3 ubiquitin ligase localization screen uncovers DTX2 as a novel ADP-ribosylation-dependent regulator of DNA double-strand break repair.

DNA double-strand breaks (DSBs) elicit an elaborate response to signal damage and trigger repair via two major pathways: nonhomologous end-joining (NHEJ), which functions throughout the interphase, and homologous recombination (HR), restricted to S/G2 phases. The DNA damage response relies, on post-translational modifications of nuclear factors to coordinate the mending of breaks. Ubiquitylation of histones and chromatin-associated factors regulates DSB repair and numerous E3 ubiquitin ligases are involved in this process.

The Deubiquitylase Otub1 Regulates the Chemotactic Response of Splenic B Cells by Modulating the Stability of the γ-Subunit Gng2.

The ubiquitin proteasome system performs the covalent attachment of lysine 48-linked polyubiquitin chains to substrate proteins, thereby targeting them for degradation, while deubiquitylating enzymes (DUBs) reverse this process. This posttranslational modification regulates key features both of innate and adaptative immunity, including antigen presentation, protein homeostasis and signal transduction. Here we show that loss of one of the most highly expressed DUBs, Otub1, results in changes in murine splenic B cell subsets, leading to a significant increase in marginal zone and transitional B cells and a concomitant decrease in follicular B cells.

The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma.

Multiple myeloma (MM) is a hematological malignancy that emerges from antibody-producing plasma B cells. Proteasome inhibitors, including the US Food and Drug Administration-approved bortezomib (BTZ) and carfilzomib (CFZ), are frequently used for the treatment of patients with MM. Nevertheless, a significant proportion of patients with MM are refractory or develop resistance to this class of inhibitors, which represents a significant challenge in the clinic.

Multi-omics data integration analysis identifies the spliceosome as a key regulator of DNA double-strand break repair.

DNA repair by homologous recombination (HR) is critical for the maintenance of genome stability. Germline and somatic mutations in HR genes have been associated with an increased risk of developing breast (BC) and ovarian cancers (OvC). However, the extent of factors and pathways that are functionally linked to HR with clinical relevance for BC and OvC remains unclear.

POGZ promotes homology-directed DNA repair in an HP1-dependent manner.

The heterochromatin protein HP1 plays a central role in the maintenance of genome stability but little is known about how HP1 is controlled. Here, we show that the zinc finger protein POGZ promotes the presence of HP1 at DNA double-strand breaks (DSBs) in human cells. POGZ depletion delays the resolution of DSBs and sensitizes cells to different DNA-damaging agents, including cisplatin and talazoparib.

Patient-centred outcomes of imaging tests: recommendations for patients, clinicians and researchers.

Background: Imaging tests are one of the most frequently used diagnostic modalities in healthcare, but the benefits of their direct impacts on clinical decision-making have been countered by concerns that they can be overused. Assessing the relative value of imaging tests has largely focused on measures of test accuracy, which overlooks more comprehensive benefits and risks of imaging tests, particularly their impact on patient-centred outcomes (PCOs). We present the findings of the Patient Reported Outcomes of Diagnostics (PROD) research study in response to a methodological gap in the area of diagnostic test comparative effectiveness research.

Provider Perspectives of Patient Experiences in Primary Care Imaging.

Background: Imaging tests are a widely used tool in primary care with many known benefits. Without an understanding of which outcomes matter the most to patients, clinicians are challenged to balance the benefits and harms of imaging tests. This study aimed to explore the perceived impacts imaging tests have on patients from the perspective of the primary care providers (PCPs) and determine PCPs' understanding of patient-centered outcomes (PCOs) from imaging tests.

Mapping global and local coevolution across 600 species to identify novel homologous recombination repair genes.

The homologous recombination repair (HRR) pathway repairs DNA double-strand breaks in an error-free manner. Mutations in HRR genes can result in increased mutation rate and genomic rearrangements, and are associated with numerous genetic disorders and cancer. Despite intensive research, the HRR pathway is not yet fully mapped.

SHLD2/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice.

DNA double-strand breaks (DSBs) can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). DNA repair pathway choice is governed by the opposing activities of 53BP1, in complex with its effectors RIF1 and REV7, and BRCA1. However, it remains unknown how the 53BP1/RIF1/REV7 complex stimulates NHEJ and restricts HR to the S/G2 phases of the cell cycle.

Consumers' Interest In Provider Ratings Grows, And Improved Report Cards And Other Steps Could Accelerate Their Use.

Encouraging patients and consumers to use data and other information in choosing health care providers is an important way to enhance patient engagement and improve the quality of care. The growing use of technology, including smart phones and near-ubiquitous Internet access, provides consumers with easy access to websites that collect and report assessments and ratings of providers, primarily physicians and hospitals. In addition to new technology, recent laws and changes in society and the delivery of care are laying the foundation for greater use by consumers of provider performance report cards.

Bringing the DERP to consumers: 'Consumer Reports Best Buy Drugs'.

Consumers Union, publisher of Consumer Reports magazine, has used the drug class reviews of the Drug Effectiveness Review Project (DERP) as one critical component of a free public information project on the comparative effectiveness, safety, and cost of prescription drugs. The project translates the DERP findings for consumers. Drawing on other sources and adding information on drug costs, the project chooses Best Buy drugs in each category it evaluates.

Consumers and quality-driven health care: a call to action.

A key strategy for driving improvements in health care quality is providing comparative quality information to consumers. This strategy will not work, and could even be counterproductive, unless (1) consumers are convinced that quality problems are real and consequential and that quality can be improved; (2) purchasers and policymakers make sure that quality reporting is standardized and universal; (3) consumers are given quality information that is relevant and easy to understand and use; (4) the dissemination of quality information is improved; and (5) purchasers reward quality improvements and providers create the information and organizational infrastructure to achieve them.

Do ads really drive pharmaceutical sales? The true effects of DTC advertising remain a mystery.

The growth in mass media drug advertising has coincided with a rapid rise in spending on prescription drugs in the United States. Our research examines the potential link between increased ad spending and the rising use and sale of these drugs. We found strong circumstantial evidence that ad spending is one of many important elements driving the sharp rise in pharmaceutical sales to consumers.