Regorafenib Combined with BRAF/MEK Inhibitors for the Treatment of Refractory Melanoma Brain Metastases.

Background: There are no active treatment options for patients with progressive melanoma brain metastases (MBM) failing immune checkpoint blockade (ICB) and BRAF/MEK inhibitors (BRAF/MEKi). Regorafenib (REGO), an oral multi-kinase inhibitor (incl. RAF-dimer inhibition), can overcome adaptive resistance to BRAF/MEKi in preclinical models.

Microbial Contamination and Isolator Gloves: If It All Came Down to the Size of a Hole?

Isolators play a critical role in protecting both the product and the environment, as well as the personnel involved in pharmaceutical manufacturing, analytical procedures, and sterility testing. Gloves attached to the windows and doors of the isolator are designed to facilitate intervention, testing, and safety. However, due to their inherent characteristics and vulnerability to puncture or loss of integrity, they are recognized as a significant potential source of contamination.

In silico design of DNA sequences for in vivo nucleosome positioning.

The computational design of synthetic DNA sequences with designer in vivo properties is gaining traction in the field of synthetic genomics. We propose here a computational method which combines a kinetic Monte Carlo framework with a deep mutational screening based on deep learning predictions. We apply our method to build regular nucleosome arrays with tailored nucleosomal repeat lengths (NRL) in yeast.

FLT3L-dependent dendritic cells control tumor immunity by modulating Treg and NK cell homeostasis.

FLT3-L-dependent classical dendritic cells (cDCs) recruit anti-tumor and tumor-protecting lymphocytes. We evaluate cancer growth in mice with low, normal, or high levels of cDCs. Paradoxically, both low or high numbers of cDCs improve survival in mice with melanoma.

Determinants of mental illness and care seeking behaviours in Northern Haiti: an assessment of demographic, social, and religio-cultural factors among patients at the first mental health clinic in the region.

Populations in countries such as Haiti demonstrate a high level of need for mental health care despite a lack of services and trained professionals. In addition to the dearth of biomedical services, local belief systems and explanatory models contribute to a majority of the population relying on traditional medicine as their first option for care. Using a mixed-methods approach, we aim to characterise mental illness at the first mental health clinic in the region - Sant Sante Mantal Mòn Pele (SSMMP) - by interviewing 96 patients with a demographic questionnaire as well as Anxiety, Depression, and Functionality Scales.