Dissecting the immune infiltrate of primary luminal B-like breast carcinomas in relation to age.

The impact of aging on the immune landscape of luminal breast cancer (Lum-BC) is poorly characterized. Understanding the age-related dynamics of immune editing in Lum-BC is anticipated to improve the therapeutic benefit of immunotherapy in older patients. To this end, here we applied the 'multiple iterative labeling by antibody neo-deposition' (MILAN) technique, a spatially resolved single-cell multiplex immunohistochemistry method.

International Variability of Barriers to Adherence to Immunosuppressive Medication in Adult Heart Transplant Recipients. A Secondary Data Analysis of the BRIGHT Study.

Non-adherence to immunosuppressive medication among transplant patients is associated with poor clinical outcomes and higher economic costs. Barriers to immunosuppressives are a proximal determinant of non-adherence. So far, international variability of barriers to adherence in transplantation has not been studied.

Caregivers' Perspective on Successful Health Care Transition Outcomes for Adolescents and Young Adults With Special Health Care Needs.

Purpose: There is limited caregiver-reported evidence determining health care transition (HCT) outcomes for their adolescents/young adults with special health care needs (AYA-SHCN). A subcommittee of the International and Interdisciplinary Healthcare Transition Research Consortium aimed to identify multidimensional outcomes of a successful HCT among AYA-SHCN based on parents/caregivers' perspectives.

Methods: After literature review and expert interviews, a three-stage Delphi process identified HCT outcomes based on parents/caregivers' perspectives.

Expanding the Scope of Aluminum Chemistry with Noninnocent Ligands.

ConspectusAluminum is the most abundant metal in the earth's crust at 8%, and it is also widely available domestically in many countries worldwide, which ensures a stable supply chain. To further the applications of aluminum (Al), such as in catalysis and electronic and energy storage materials, there has been significant interest in the synthesis and characterization of new Al coordination compounds that can support electron transfer (ET) and proton transfer (PT) chemistry. This has been achieved using redox and chemically noninnocent ligands (NILs) combined with the highly stable M(III) oxidation state of Al and in some cases the heavier group 13 ions, Ga and In.

Group 13 ion coordination to pyridyl breaks the reduction potential hydricity scaling relationship for dihydropyridinates.

The relationship Δ correlates the applied potential () needed to drive organohydride formation with the strength of the hydride donor that is formed: in the absence of kinetic effects Δ should be linear but it would be more energy efficient if could be shifted anodically using kinetic effects. Biological hydride transfers (HT) performed by cofactors including NADH and lactate racemase do occur at low potentials and functional modeling of those processes could lead to low energy HT reactions in electrosynthesis and to accurate models for cofactor chemistry. Herein we probe the influence of -alkylation or -metallation on Δ for dihydropyridinates (DHP) and on of the DHP precursors.

Electrical-biological hybrid system for carbon efficient isobutanol production.

We have developed an electrical-biological hybrid system wherein an engineered microorganism consumes electrocatalytically produced formate from CO to supplement the bioproduction of isobutanol, a valuable fuel chemical. Biological CO sequestration is notoriously slow compared to electrochemical CO reduction, while electrochemical methods struggle to generate carbon-carbon bonds which readily form in biological systems. A hybrid system provides a promising method for combining the benefits of both biology and electrochemistry.

Metallated dihydropyridinates: prospects in hydride transfer and (electro)catalysis.

Hydride transfer (HT) is a fundamental step in a wide range of reaction pathways, including those mediated by dihydropyridinates (DHPs). Coordination of ions directly to the pyridine ring or functional groups stemming therefrom, provides a powerful approach for influencing the electronic structure and in turn HT chemistry. Much of the work in this area is inspired by the chemistry of bioinorganic systems including NADH.

Group 13 ion coordination to pyridyl models NAD reduction potentials.

-alkylation and -metallation of pyridine are explored herein to understand how metal-ligand complexes can model NAD redox chemistry. Syntheses of substituted dipyrazolylpyridine (pzP) compounds (pzP)Me (1) and (pzP)GaCl (2) are reported, and compared with (pzP)AlCl(THF) and transition element pzP complexes from previous reports. Cyclic voltammetry measurements of cationic 1 and 2 show irreversible reduction events ∼900 mV anodic those for neutral pzP complexes of divalent metals.

A Bifunctional Ionic Liquid for Capture and Electrochemical Conversion of CO to CO over Silver.

Electrochemical conversion of CO requires selective catalysts and high solubility of CO in the electrolyte to reduce the energy requirement and increase the current efficiency. In this study, the CO reduction reaction (CORR) over Ag electrodes in acetonitrile-based electrolytes containing 0.1 M [EMIM][2-CNpyr] (1-ethyl-3-methylimidazolium 2-cyanopyrolide), a reactive ionic liquid (IL), is shown to selectively (>94%) convert CO to CO with a stable current density (6 mA·cm) for at least 12 h.

Pre-Equilibrium Reaction Mechanism as a Strategy to Enhance Rate and Lower Overpotential in Electrocatalysis.

Pre-equilibrium reaction kinetics enable the overall rate of a catalytic reaction to be orders of magnitude faster than the rate-determining step. Herein, we demonstrate how pre-equilibrium kinetics can be applied to breaking the linear free-energy relationship (LFER) for electrocatalysis, leading to rate enhancement 5 orders of magnitude and lowering of overpotential to approximately thermoneutral. This approach is applied to pre-equilibrium formation of a metal-hydride intermediate to achieve fast formate formation rates from CO reduction without loss of selectivity (i.

Using Substituted [FeN(CO)] as a Platform To Probe the Effect of Cation and Lewis Acid Location on Redox Potential.

The impact of cationic and Lewis acidic functional groups installed in the primary or secondary coordination sphere (PCS or SCS) of an (electro)catalyst is known to vary depending on the precise positioning of those groups. However, it is difficult to systematically probe the effect of that position. In this report, we probe the effect of the functional group position and identity on the observed reduction potentials () using substituted iron clusters, [FeN(CO)R], where R = NO, PPh-CHCH-9BBN, (PTA), (PTA), and H and = 0, -1, +1, or +3 (9-BBN is 9-borabicyclo(3.

Current practice of transitional care for adolescents and young adults in Swiss paediatric and adult rheumatology centres.

Background: About half of all children with rheumatic diseases need continuous medical care during adolescence and adulthood. A good transition into adult rheumatology is essential. Guidelines for a structured transition process have therefore been recommended by the European League Against Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PReS).

Comparison of the tumor immune microenvironment of primary hormone receptor-negative HER2-positive and triple negative breast cancer.

The vast majority of studies investigating immune checkpoint inhibition (ICI) in patients with breast cancer have focused on triple-negative breast cancer (TNBC). In this study, we compared the tumor immune microenvironment (TIME) between TNBC and hormone receptor-negative HER2-positive breast cancer based on a selection of immune markers at the protein level in an institutional retrospective series. Additionally, we performed a similar comparison using publicly available transcriptomics data.

Is degree of chronic illness management in heart transplant centers associated with better patient survival? Findings from the intercontinental BRIGHT study.

Purpose: To explore the association between the degree of Chronic illness management and survival rates at 1-, 3-, 5-years post heart transplantation.

Methods: Exploratory secondary analysis of a cross-sectional, international study (Building Research Initiative Group study). Latent profile analysis was performed to classify 36 heart transplant centers according to the degree of chronic illness management.

Metal carbonyl clusters of groups 8-10: synthesis and catalysis.

In this review article, we discuss advances in the chemistry of metal carbonyl clusters (MCCs) spanning the last three decades, with an emphasis on the more recent reports and those involving groups 8-10 elements. Synthetic methods have advanced and been refined, leading to higher-nuclearity clusters and a wider array of structures and nuclearities. Our understanding of the electronic structure in MCCs has advanced to a point where molecular chemistry tools and other advanced tools can probe their properties at a level of detail that surpasses that possible with other nanomaterials and solid-state materials.

Delocalization tunable by ligand substitution in [LAl] complexes highlights a mechanism for strong electronic coupling.

Ligand-based mixed valent (MV) complexes of Al(iii) incorporating electron donating (ED) and electron withdrawing (EW) substituents on bis(imino)pyridine ligands (IP) have been prepared. The MV states containing EW groups are both assigned as Class II/III, and those with ED functional groups are Class III and Class II/III in the (IP)(IP)Al and [(IP)(IP)Al] charge states, respectively. No abrupt changes in delocalization are observed with ED and EW groups and from this we infer that ligand and metal valence p-orbitals are well-matched in energy and the absence of LMCT and MLCT bands supports the delocalized electronic structures.

Blood Immunosenescence Signatures Reflecting Age, Frailty and Tumor Immune Infiltrate in Patients with Early Luminal Breast Cancer.

Background: Immune/senescence-related host factors play a pivotal role in numerous biological and pathological process like aging, frailty and cancer. The assessment of these host factors via robust, non-invasive, and easy-to-measure blood biomarkers could improve insights in these processes. Here, we investigated in a series of breast cancer patients in which way single circulating biomarkers or biomarker panels relate to chronological age, frailty status, and tumor-associated inflammatory microenvironment.

Cancer and Aging: Two Tightly Interconnected Biological Processes.

Age is one of the main risk factors of cancer; several biological changes linked with the aging process can explain this. As our population is progressively aging, the proportion of older patients with cancer is increasing significantly. Due to the heterogeneity of general health and functional status amongst older persons, treatment of cancer is a major challenge in this vulnerable population.

Quantification of the Electrostatic Effect on Redox Potential by Positive Charges in a Catalyst Microenvironment.

Charged functional groups in the secondary coordination sphere (SCS) of a heterogeneous nanoparticle or homogeneous electrocatalyst are of growing interest due to enhancements in reactivity that derive from specific interactions that stabilize substrate binding or charged intermediates. At the same time, accurate benchmarking of electrocatalyst systems most often depends on the development of linear free-energy scaling relationships. However, the thermodynamic axis in those kinetic-thermodynamic correlations is most often obtained by a direct electrochemical measurement of the catalyst redox potential and might be influenced by electrostatic effects of a charged SCS.

Ligand Conjugation Directs the Formation of a 1,3-Dihydropyridinate Regioisomer.

The selective formation of the 1,4-dihydropyridine isomer of NAD(P)H is mirrored by the selective formation of 1,4-dihydropyridinate ligand-metal complexes in synthetic systems. Here we demonstrate that ligand conjugation can be used to promote selective 1,3-dihydropyridinate formation. This represents an advance toward controlling and tuning the selectivity in dihydropyridinate formation chemistry.

A Stable Organo-Aluminum Analyte Enables Multielectron Storage for a Nonaqueous Redox Flow Battery.

Redox flow batteries (RFBs) operate by storing electrons on soluble molecular anolytes and catholytes, and large increases in the energy density of RFBs could be achieved if multiple electrons could be stored in each molecular analyte. Here, we report an organoaluminum analyte, [(IP)Al], in which four electrons can be stored on organic ligands, and for which charging and discharging cycles performed in a symmetric nonaqueous RFB configuration remain stable for over 100 cycles at 70% state of charge and 97% Coulombic efficiency (IP is a bis(imino)pyridine ligand). The stability of the analyte is promoted by the kinetic inertness of the anolyte to trace water in solvents and by the redox inertness of the Al(III) ion to the applied current.