Proteogenomic Profiling of Treatment-Naïve Metastatic Malignant Melanoma.

Background: Melanoma is a highly heterogeneous disease, and a deeper molecular classification is essential for improving patient stratification and treatment approaches. Here, we describe the histopathology-driven proteogenomic landscape of 142 treatment-naïve metastatic melanoma samples to uncover molecular subtypes and clinically relevant biomarkers.

Methods: We performed an integrative proteogenomic analysis to identify proteomic subtypes, assess the impact of BRAF V600 mutations, and study the molecular profiles and cellular composition of the tumor microenvironment.

A novel Janus nanomachine based on mesoporous silica nanoparticles anisotropically modified with PAMAM dendrimers for enzyme-controlled drug delivery.

A masking/toposelective modification approach was employed to prepare a new organic-inorganic Janus nanomaterial by attaching ethylenediamine core polyamidoamine G-4.5 dendrimers to a defined face of mesoporous silica nanoparticles. The anisotropic colloid was then sequentially functionalized on the mesoporous face with (3-isocyanatopropyl)triethoxysilane, 1-(4-aminophenyl)-2-phenylethane-1,2-dione and β-cyclodextrin to assemble a novel HO-sensitive gating mechanism.

Updating the American Association of Physicists in Medicine (AAPM) Diagnostic Radiology Resident Physics Curriculum: Strategies, Content, and Dissemination.

Rationale And Objectives: The Diagnostic Radiology Resident Physics Curriculum (DRRPC), initiated in 2007 by the American Association of Physicists in Medicine (AAPM) and last updated in 2018, is an essential educational resource for those teaching physics to radiology residents. Regular updates are crucial to ensure the curriculum aligns with evolving technologies and clinical practices, maintaining its relevance and effectiveness in educating the next generation of radiologists. The paper aims to describe the update strategies of the DRRPC, focusing on the current iteration, its structure, and the newest updates.

Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an ultrarare, infantile-onset leukodystrophy characterized by white matter edema for which there is no treatment. More than 70% of diagnosed cases result from biallelic loss-of-function mutations in the astrocyte-specific gene MLC1, leading to early-onset macrocephaly, cerebellar ataxia, epilepsy, and mild cognitive decline. To develop a gene therapy for MLC, we administered an adeno-associated viral vector capable of crossing the murine blood-brain barrier, delivering the human MLC1 cDNA under the control of a human astrocyte-specific promoter, to 10-month-old Mlc1 mice.

The role of leaf and root functional traits in the Espeletiinae (Asteraceae) radiation.

Premise: Key innovations within a group result in ecological divergence. Those innovations involve functional traits that may reflect the species' adaptations to environmental conditions and to interactions within the community. The subtribe Espeletiinae is considered an adaptive radiation due to their exceptional diversity.