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BACKGROUND: Juvenile Dermatomyositis (JDM) is the most common chronic idiopathic inflammatory myopathy in children. The diagnosis is clinical. Baseline laboratory and complementary studies trace the phenotype of these patients. The objective of this study was to describe epidemiological, clinical and laboratory characteristics at diagnosis of JDM patients included in the Spanish JDM registry, as well as to identify prognostic factors on these patients. METHODS: We retrospectively reviewed clinical features, laboratory tests, and complementary studies at diagnosis of JDM patients included on the Spanish JDM registry. These data were analyzed to assess whether there was a relationship with the development of complications and time to disease inactivity. RESULTS: One hundred and sixteen patients from 17 Spanish paediatric rheumatology centres were included, 76 girls (65%). Median age at diagnosis was 7.3 years (Interquartile range (IQR) 4.5-10.2). All patients had pathognomonic skin lesions at the beginning of the disease. Muscle weakness was present in 86.2%. Median Childhood Muscle Assessment Scale was 34 (IQR 22-47). Twelve patients (34%) had dysphagia and 3,5% dysphonia. Anti-p155 was the most frequently detected myositis specific antibody, followed by anti-MDA5. Twenty-nine patients developed calcinosis and 4 presented with macrophage activation syndrome. 70% reached inactivity in a median time of 8.9 months (IQR 4.5-34.8). 41% relapsed after a median time of 14.4 months (IQR 8.6-22.8) of inactivity. Shorter time to treatment was associated with better prognosis (Hazard ratio (HR) = 0.95 per month of evolution, p = 0.02). Heliotrope rash at diagnosis correlates with higher risk of development complications. CONCLUSIONS: We describe heliotrope rash as a risk factor for developing complications in our cohort of JDM patients, an easy-to-evaluate clinical sign that could help us to identify the group of patients we should monitor closely for this complication.

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Triazole hosts allow cooperative binding of anions via hydrogen bonds, which makes them versatile systems for application in anion binding catalysis to be performed in organic solvents. The anion binding behavior of a tetratriazole host is systematically studied by employing a variety of salts, including chloride, acetate, and benzoate, as well as different cations. Classical nuclear magnetic resonance (1H NMR) titrations demonstrate a large influence of cation structures on the anion binding constant, which is attributed to poor dissociation of most salts in organic solvents and corrupts the results of classical titration techniques. We propose an approach employing electrophoretic NMR (eNMR), yielding drift velocities of each species in an electric field and thus allowing a distinction between charged and uncharged species. After the determination of the dissociation constants KD for the salts, electrophoretic mobilities are measured for all species in the host-salt system and are analyzed in a model which treats anion binding as a consecutive reaction to salt dissociation, yielding a corrected anion binding constant KA. Interestingly, dependence of KA on salt concentration occurs, which is attributed to cation aggregation with the anion-host complex. Finally, by the extrapolation to zero salt concentration, the true anion-host binding constant is obtained. Thus, the approach by eNMR allows a fully quantitative analysis of two factors that might impair classical anion binding studies, namely, an incomplete salt dissociation as well as the occurrence of larger aggregate species.

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An enantioselective anion-binding organocatalytic approach with versatile N,N-dialkylhydrazones (DAHs) as polarity-reversed (umpolung) nucleophiles is presented. For the application of this concept, a highly ordered hydrogen-bond (HB) network between a carefully selected CF3 -substituted triazole-based multidentate HB-donor catalyst, the ionic substrate and the hydrazone in a supramolecular chiral ion-pair complex was envisioned. The formation of such a network was further supported by both experimental and computational studies, which showed the crucial role of the anion as a template unit. The asymmetric Reissert-type reaction of quinolines as a model test reaction chemoselectively delivered highly enantiomerically enriched hydrazones (up 95:5 e.r.) that could be further derivatized to value-added compounds with up to three stereocenters.

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H-bond donor catalysts able to modulate the reactivity of ionic substrates for asymmetric reactions have gained great attention in the past years, leading to the development of cooperative multidentate H-bonding supramolecular structures. However, there is still a lack of understanding of the forces driving the ion recognition and catalytic performance of these systems. Herein, insight into the cooperativity nature, anion binding strength, and folding mechanism of a model chiral triazole catalyst is presented. Our combined experimental and computational study revealed that multi-interaction catalysts exhibiting weak binding energies (≈3-4 kcal mol-1 ) can effectively recognize ionic substrates and induce chirality, while strong dependencies on the temperature and solvent were quantified. These results are key for the future design of catalysts with optimal anion binding strength and catalytic activity in target reactions.

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A general and highly enantioselective synthesis of oxygen heterocycles from readily available in situ generated pyrylium derivatives has been realized by embracing a multi-coordination approach with helical anion-binding tetrakistriazole catalysts. The high activity of the tetrakistriazole (TetraTri) catalysts, with distinct confined anion-binding pockets, allows for remarkably low catalyst loadings (down to 0.05 mol %), while providing a simple access to chiral chromanones and dihydropyrones in high enantioselectivities (up to 98:2 e.r.). Moreover, experimental and theoretical studies provide new insights into the hydrogen-donor ability and key binding interactions of the TetraTri catalysts and its host:guest complexes, suggesting the formation of a 1:3 species.

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Pd(II)-catalyzed C-H functionalization of nondirected arenes has been realized using an inexpensive and easily accessible type of bidentate S,O-ligand. The catalytic system shows high efficiency in the C-H olefination reaction of electron-rich and electron-poor arenes. This methodology is operationally simple, scalable, and can be used in late-stage functionalization of complex molecules. The broad applicability of this catalyst has been showcased in other transformations such as Pd(II)-catalyzed C-H acetoxylation and allylation reactions.

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The synthesis and the evaluation as organocatalysts of new chiral guanidines derived from benzimidazoles in the enantioselective α-amination of 1,3-dicarbonyl compounds using di-t-butylazodicarboxylate as aminating agent is herein disclosed. The catalysts are readily synthesized through the reaction of 2-chlorobezimidazole and a chiral amine in moderate-to-good yields. Among all of them, those derived from (R)-1-phenylethan-1-amine (1) and (S)-1-(2-naphthyl)ethan-1-amine (3) turned out to be the most efficient for such asymmetric transformation, rendering good-to-high yields and moderate-to-good enantioselectivities for the amination products.

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