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We observe cARMs significantly increase target immune recognition relative to ARMs across a range of therapeutically relevant antibody concentrations. These results demonstrate that ARM therapeutic function can be dramatically enhanced by increasing the kinetic stability of ARMantibody complexes localized on cancer cells. Our findings suggest that a) high titres/concentrations of target antibody in human serum are not neccessary and b) saturative antibody recruitment to cancer cells not sufficient, to achieve maximal ARM therapeutic function.The development of a flexible, component-based synthetic route to the amino sugar fragment of the lincosamide antibiotics is described. Aprocitentan This route hinges on the application and extension of nitroaldol chemistry to forge strategic bonds within complex amino sugar targets and employs a glycal epoxide as a versatile glycosyl donor for the installation of anomeric groups. Through building-block exchange and late-stage functionalization, this route affords access to a host of rationally designed lincosamides otherwise inaccessible by semisynthesis and underpins a platform for the discovery of new lincosamide antibiotics.Carbohydrates (glycans, saccharides, and sugars) are essential molecules in all domains of life. Research on glycoscience spans from chemistry to biomedicine, including material science and biotechnology. Access to pure and well-defined complex glycans using synthetic methods depends on the success of the employed glycosylation reaction. In most cases, the mechanism of the glycosylation reaction is believed to involve the oxocarbenium ion. Understanding the structure, conformation, reactivity, and interactions of this glycosyl cation is essential to predict the outcome of the reaction. In this Account, building on our contributions on this topic, we discuss the theoretical and experimental approaches that have been employed to decipher the key features of glycosyl cations, from their structures to their interactions and reactivity.We also highlight that, from a chemical perspective, the glycosylation reaction can be described as a continuum, from unimolecular SN1 with naked oxocarbenium cations as intermediat including the counterions, the possible intra- or intermolecular participation of functional groups that may stabilize the cation and the chemical nature of the acceptor, either weak or strong nucleophile. We discuss recent investigations from different experimental perspectives, which identified the involved ionic intermediates, estimating their lifetimes and reactivities and studying their interactions with other molecules. In this context, we also emphasize the relationship between the chemical methods that can be employed to modulate the sensitivity of glycosyl cations and the way in which glycosyl modifying enzymes (glycosyl hydrolases and transferases) build and cleave glycosidic linkages in nature. This comparison provides inspiration on the use of molecules that regulate the stability and reactivity of glycosyl cations.Molecular dynamics of the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethyl sulfonyl)imide (Emim-Tf2N) with either of the four organic stable radicals, TEMPO, 4-benzoyloxy-TEMPO, BDPA, and DPPH, is studied by using Nuclear Magnetic Resonance (NMR) and Dynamic Nuclear Polarization (DNP). In complex fluids at ambient temperature, NMR signal enhancement by DNP is frequently obtained by a combination of several mechanisms, where the Overhauser effect and solid effect are the most common. Understanding the interactions of free radicals with ionic liquid molecules is of particular significance due to their complex dynamics in these systems, influencing the properties of the ion-radical interaction. A combined analysis of EPR, DNP, and NMR relaxation dispersion is carried out for cations and anions containing, respectively, the NMR active nuclei 1H or 19F. Depending on the size and the chemical properties of the radical, different interaction processes are distinguished, namely, the Overhauser effect and solid effect, driven by dominating dipolar or scalar interactions. The resulting NMR relaxation dispersion is decomposed into rotational and translational contributions, allowing the identification of the corresponding correlation times of motion and interactions. The influence of electron relaxation time and electron-nuclear spin hyperfine coupling is discussed.

Breakthrough cancer pain (BTcP) is a transient exacerbation of pain that occurs over persistent, stable, and adequately controlled cancer background pain. It is prevalent and bears severe consequences to patients’ quality-of-life. The effective management of BTcP depends on fast and reliable (re)assessment. The Breakthrough pain Assessment Tool (BAT) is one of the most concise and reliable self-report instruments adapted to clinical contexts so far, showing goodpsychometric qualities in the United Kingdom, the Netherlands, and South Korea. As to promote the effective management of BTcP in Portuguese-speaking communities this study, first aimed to culturally adapt and validate the Portuguese version of the BAT (BAT-Pt). Second, and most importantly, it sought to provide novel evidence on its criterion validity by investigating its association with measures of psychological distress, which has not been yet investigated.

The BAT was translated into European Portuguese, using the back-translation method, and The BAT-Pt may be an invaluable tool for daily clinical practice by tapping multiple aspects of BTcP experiences that are associated to patients’ physical and psychological outcomes.

The BAT-Pt is a reliable and valid measure of breakthrough pain in Portuguese cancer patients and it is strongly associated to physical and psychological outcomes. This study confirms and extends the psychometric validation of the BAT to a new cultural context, promoting its diffusion and use by researchers and clinicians in Portuguese-speaking communities. The BAT-Pt may be an invaluable tool for daily clinical practice by tapping multiple aspects of BTcP experiences that are associated to patients’ physical and psychological outcomes.