Safety of combined long-acting injectable cabotegravir and long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.

Background: Long-acting cabotegravir and long-acting rilpivirine constitute a completely intramuscular antiretroviral therapy (ART) regimen for adults with HIV. We aimed to assess the safety, antiviral activity, and pharmacokinetics of oral cabotegravir and rilpivirine followed by a combination of long-acting cabotegravir and long-acting rilpivirine in virologically suppressed adolescents with HIV.

Methods: The IMPAACT 2017/MOCHA study is a phase 1/2, multicentre, open-label, non-comparative, dose-finding trial being conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and the USA.

On the Instrumental Discrepancies in Lyman-Alpha Observations of Solar Flares.

Despite the energetic significance of Lyman-alpha (Ly ; 1216 Å) emission from solar flares, regular observations of flare related Ly have been relatively scarce until recently. Advances in instrumental capabilities and a shift in focus over previous solar cycles mean it is now routinely possible to take regular co-observations of Ly emission in solar flares. Thus, it is valuable to examine how the instruments selected for flare observations may influence the conclusions drawn from the analysis of their unique measurements.

The Solar EruptioN Integral Field Spectrograph.

The Solar eruptioN Integral Field Spectrograph (SNIFS) is a solar-gazing spectrograph scheduled to fly in the summer of 2025 on a NASA sounding rocket. Its goal is to view the solar chromosphere and transition region at a high cadence (1 s) both spatially ( ) and spectrally (33 mÅ) viewing wavelengths around Lyman alpha (1216 Å), Si iii (1206 Å), and O v (1218 Å) to observe spicules, nanoflares, and possibly a solar flare. This time cadence will provide yet-unobserved detail about fast-changing features of the Sun.

Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.

Background: Combined intramuscular long-acting cabotegravir and long-acting rilpivirine constitute the first long-acting combination antiretroviral therapy (ART) regimen approved for adults with HIV. The goal of the IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]) was to assess the safety and pharmacokinetics of these drugs in adolescents.

Methods: In this phase 1/2, multicentre, open-label, non-comparative, dose-finding study, virologically suppressed adolescents (aged 12-17 years; weight ≥35 kg; BMI ≤31·5 kg/m) with HIV-1 on daily oral ART were enrolled at 15 centres in four countries (Botswana, South Africa, Thailand, and the USA).

Sensitization of Resistant Cells with a BET Bromodomain Inhibitor in a Cell Culture Model of Deep Intrinsic Resistance in Breast Cancer.

We treated highly metabolically adaptable (SUM149-MA) triple-negative inflammatory breast cancer cells and their control parental SUM149-Luc cell line with JQ1 for long periods to determine its efficacy at inhibiting therapy-resistant cells. After 20 days of treatment with 1-2 µM of JQ1, which killed majority of cells in the parental cell line, a large number of SUM149-MA cells survived, consistent with their pan-resistant nature. Interestingly, though, the JQ1 treatment sensitized resistant cancer cells in both the SUM149-MA and SUM149-Luc cell lines to subsequent treatment with doxorubicin and paclitaxel.

On the Performance of Multi-Instrument Solar Flare Observations During Solar Cycle 24.

The current fleet of space-based solar observatories offers us a wealth of opportunities to study solar flares over a range of wavelengths. Significant advances in our understanding of flare physics often come from coordinated observations between multiple instruments. Consequently, considerable efforts have been, and continue to be, made to coordinate observations among instruments ( through the ).

Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge.

We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice.

Highly adaptable triple-negative breast cancer cells as a functional model for testing anticancer agents.

A major obstacle in developing effective therapies against solid tumors stems from an inability to adequately model the rare subpopulation of panresistant cancer cells that may often drive the disease. We describe a strategy for optimally modeling highly abnormal and highly adaptable human triple-negative breast cancer cells, and evaluating therapies for their ability to eradicate such cells. To overcome the shortcomings often associated with cell culture models, we incorporated several features in our model including a selection of highly adaptable cancer cells based on their ability to survive a metabolic challenge.