Circulating cytokine associations with clinical outcomes in melanoma patients treated with combination nivolumab plus ipilimumab.

Nivolumab plus ipilimumab (aCTLA-4/aPD-1) combination therapy has significantly improved clinical outcomes in patients with metastatic melanoma, with 50%-60% of patients responding to treatment, but predictors of response are poorly characterized. We hypothesized that circulating cytokines and peripheral white blood cells may predict response to therapy and evaluated 15 cytokines and complete blood counts (CBC with differentials) from 89 patients with advanced melanoma treated with combination therapy from three points in time: pre-treatment, one month and approximately three months after starting therapy. Clinical endpoints evaluated included durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS).

Targeting RAF1 gene fusions with MEK inhibition in metastatic melanoma.

The biological and clinical relevance of gene fusions in melanoma is unknown. Reports and preclinical data have suggested that tumor cells with specific rearrangements such as RAF1 gene fusions could be therapeutically targeted. To investigate the relevance of targeted therapy in patients with melanoma harboring RAF1 gene fusions, we reviewed records of 1268 melanoma patients with targeted sequencing data at the Dana-Farber Cancer Institute.

Craters on the melanoma surface facilitate tumor-immune interactions and demonstrate pathologic response to checkpoint blockade in humans.

Immunotherapy leads to cancer eradication despite the tumor's immunosuppressive environment. Here, we used extended long-term in-vivo imaging and high-resolution spatial transcriptomics of endogenous melanoma in zebrafish, and multiplex imaging of human melanoma, to identify domains that facilitate immune response during immunotherapy. We identified crater-shaped pockets at the margins of zebrafish and human melanoma, rich with beta-2 microglobulin (B2M) and antigen recognition molecules.

Recurrent peritonsillar abscess in adults: Incidence and risk factors in a prospective longitudinal cohort.

Objective: The incidence of recurrent peritonsillar abscess (7.4-22%) was estimated in retrospective studies. The aim of this prospective study was to estimate the cumulative incidence of recurrent peritonsillar abscess and related risk factors.

Fine Tuning the Hydrophobicity of a New Three-Dimensional Cu MOF through Single Crystal Coordinating Ligand Exchange Transformations.

The synthesis, characterization, and single-crystal-to-single-crystal (SCSC) exchange reactions of a new 3D Cu MOF based on 5-aminoisophthalic acid (HAIP), [Cu(μ-ΟΗ)(ΑΙΡ)(HΑΙΡ)]·6DMF·HO - ·6DMF·HO, are reported. It exhibits a 3D structure based on two [Cu(μ-OH)] butterfly-like secondary building units, differing in their peripheral ligation, bridged through HAIP/AIP ligands. This compound displays the capability to exchange the coordinating ligand(s) and/or guest solvent molecules through SCSC reactions.

Ziv-aflibercept plus pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment.

Background: Vascular endothelial growth factor is associated with reduced immune response and impaired anti-tumor activity. Combining antiangiogenic agents with immune checkpoint inhibition can overcome this immune suppression and enhance treatment efficacy.

Methods: This study investigated the combination of ziv-aflibercept anti-angiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment.

Using Dancesport as an Educational Resource for Improving Institutionalized Children's Learning Strategies.

Introduction: Specialized studies mention that extracurricular activities (including dance) contribute to the stimulation of multiple intelligences, on whose development the educational process and academic success depend. The aims of the study were to investigate the benefits of dancesport for the development of institutionalized children's learning strategies, and to examine gender-dependent differences in learning strategies, as well as to formulate possible recommendations regarding the practice of dance at the age of preadolescence, from the perspective of school success vectors.

Methods: Through the School Motivation and Learning Strategies Inventory (SMALSI), we could observe the changes produced in children from the initial phase to the final assessment at the end of a dancesport program.

Brief Communication on Pathologic Assessment of Persistent Stable Metastatic Lesions in Patients Treated With Anti-CTLA-4 or Anti-CTLA-4 + Anti-PD-1 Therapy.

Despite the wide use of immune checkpoint inhibition for the treatment of melanoma, the mechanisms leading to long-term stable disease are incompletely understood. Patients with metastatic melanoma who had received ipilimumab alone or ipilimumab plus nivolumab 2+years prior and attained at least 6 months of stable disease were identified. Positron emission tomography/computed tomography (PET/CT) was performed.

Clonal dynamics of alloreactive T cells in kidney allograft rejection after anti-PD-1 therapy.

Kidney transplant recipients are at particular risk for developing tumors, many of which are now routinely treated with immune checkpoint inhibitors (ICIs); however, ICI therapy can precipitate transplant rejection. Here, we use TCR sequencing to identify and track alloreactive T cells in a patient with melanoma who experienced kidney transplant rejection following PD-1 inhibition. The treatment was associated with a sharp increase in circulating alloreactive CD8 T cell clones, which display a unique transcriptomic signature and were also detected in the rejected kidney but not at tumor sites.

Composite Materials Based on a Zr MOF and Aluminosilicates for the Simultaneous Removal of Cationic and Anionic Dyes from Aqueous Media.

Environmental pollution has been a reality for many decades, with its contamination intensifying daily due to rapid urbanization and the ever-increasing world population. Dyes, and especially synthetic ones, constitute a category of pollutants that not only affect the quality of water but also exhibit high toxicity toward living organisms. This study was thoroughly planned to explore the removal of two toxic dyes, namely the methylene blue (MB) and methyl orange (MO) compounds from contaminated aqueous media.

Germline variants associated with toxicity to immune checkpoint blockade.

Immune checkpoint inhibitors (ICIs) have yielded remarkable responses but often lead to immune-related adverse events (irAEs). Although germline causes for irAEs have been hypothesized, no individual variant associated with developing irAEs has been identified. We carried out a genome-wide association study of 1,751 patients on ICIs across 12 cancer types.

Highly efficient sorption and luminescence sensing of oxoanionic species by 8-connected alkyl-amino functionalized Zr MOFs.

In the present study we provide the sorption properties of four 8-connected Zr MOFs with the general formula H[ZrO(RNH-BDC)]·solvent (RNH-BDC = 2-alkyl-amine-terephthalate; R = ethyl-, ; R = propyl-, ; R = isobutyl-, ; R = -butyl, ) towards toxic Cr(VI) and radionuclide-related ReO oxoanions. These MOFs represent superior sorbents for the removal of oxoanionic species, in terms of kinetics, sorption isotherms, selectivity and regeneration/reusability. The excellent sorption capability of the MOFs is due to a combination of surface and intra-framework sorption phenomena.

Characterizing metastatic uveal melanoma patients who develop symptomatic brain metastases.

Metastatic uveal melanoma (mUM) is an advanced ocular malignancy characterized by a hepatotropic pattern of spread. As the incidence of brain metastases (BM) in mUM patients has been thought to be low, routine CNS surveillance has not been recommended. Notably, no formal assessment of BM incidence in mUM has to date been published to support this clinical practice.

Mixed-Metal and Mixed-Ligand Lanthanide Metal-Organic Frameworks Based on 2,6-Naphthalenedicarboxylate: Thermally Activated Sensitization and White-Light Emission.

Trivalent lanthanide ions (Ln) hold an exceptional position in the field of optoelectronic materials due to their atomic-like emission spectra and long luminescence lifetimes. Metal-organic frameworks (MOFs) and coordination polymers are particularly suited as luminescent materials due to their structural diversity and ease of functionalization both at bridging ligands and/or metal centers. In this contribution, we present a series of mixed-metal Ln/Eu (Ln = La, Gd) and mixed-ligand (2,6-naphthalenedicarboxylate (ndc) and 4-aminonaphthalene-2,6-dicarboxylate (andc)) MOFs belonging to three different structural types, with emissions spanning most of the visible region, thereby constituting favorable materials for color tuning and white-light emission.

Zr-terephthalate MOFs with 6-connected structures, highly efficient As(III/V) sorption and superhydrophobic properties.

The use of terephthalate ligands with CHNH-chains ( ≥ 6) led to the isolation of the first examples of Zr-terephthalate MOFs with 6-connected frameworks. The material with hexyl-amino functional groups has been proved to be an exceptional sorbent for the removal of As(III/V) toxic species from aqueous media, whereas MOFs with heptyl to dodecyl-amino moieties are superhydrophobic with promising oil-water separation properties.

Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit.

Purpose: In metastatic triple-negative breast cancer (mTNBC), consistent biomarkers of immune checkpoint inhibitor (ICI) therapy benefit remain elusive. We evaluated the immune, genomic, and transcriptomic landscape of mTNBC in patients treated with ICIs.

Methods: We identified 29 patients with mTNBC treated with pembrolizumab or atezolizumab, either alone (n = 9) or in combination with chemotherapy (n = 14) or targeted therapy (n = 6), who had tumor tissue and/or blood available before ICI therapy for whole-exome sequencing.