bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facile Synthesis and Isolation of Secondary Amines via a Sequential Titanium(IV)‐Catalyzed Hydroamination and Palladium‐Catalyzed Hydrogenation
Authors: Lui Erica K. J. , Schafer Laurel L. 
Published: February 2016

AbstractAn atom economical and catalytic route for the synthesis of aryl‐ and alkyl‐substituted secondary amines has been developed. Using a bis(amidate)bis(amido)titanium(IV) precatalyst, the hydroamination of terminal alkynes with a range of amines results in the selective formation of the anti‐Markovnikov product. The crude enamine/imine mixtures are effectively hydrogenated using palladium on carbon (Pd/C) and H2 to afford the corresponding secondary amine in excellent yields. Simple work‐up procedures allow for the isolation of pure compounds while avoiding purification via column chromatography.magnified image
Organophotocatalytic Synthesis of Phosphoramidates
Authors: Meazza Marta , Kowalczuk Agnieszka , Shirley Luke , Yang Jung Woon , Guo Hao , Rios Ramon 
Published: February 2016

AbstractWe describe the use of visible light in conjunction with an organic dye for the synthesis of phosphoramidates. Cross dehydrogenative coupling reactions between phosphites and amines are reported using organic dyes and light as catalysts for the first time. It is not only a novel application of organic dyes but also fulfils the requirement of sustainability and green chemistry avoiding the use of chromatographic purification techniques. The product was simply isolated from the reaction mixture via an acid‐base work‐up procedure, rendering the pure product in good yields.magnified image
The Lateral Cross‐Linking of Polyurethane Using Grafted Epichlorohydrin and the Impact on the Tensile and Thermal Properties
Authors: Chung Yong‐Chan , Lee Byung Hee , Choi Jae Won , Chun Byoung Chul 
Published: February 2016

ABSTRACTEpichlorohydrin (ECH) was used as a cross‐linking agent for a series of polyurethanes (PU series). The spectroscopic, thermal, tensile, shape memory, low‐temperature flexibility, and water vapor permeability properties of these PUs were compared with those of a control polyurethane series (CPU series) without ECH cross‐linking. In the thermal test, the soft segment crystallization of the PU series disappeared as the ECH cross‐linking increased. The glass transition temperature (Tg) of the PU and CPU series slightly increased with the increase in ECH content. The tensile strength of the PU series sharply increased at a critical ECH content, whereas that of the CPU series did not. The breaking strain of the PU and CPU series remained the same with the increase in ECH content. The shape recovery of the PU series remained above 90% at 45°C but increased moderately with the increase in ECH content at 0°C. Finally, the PU series with ECH cross‐linking demonstrated better low‐temperature flexibility and lower water vapor permeability than the unmodified PU.
Rhodium‐Catalyzed Enantioselective Arylation of N‐Substituted α,β‐Unsaturated γ‐Lactams: Preparation of Chiral 4‐Aryl‐2‐Pyrrolidones
Authors: Fang Jo‐Hsuan , Chang Chiung‐An , Gopula Balraj , Kuo Ting‐Shen , Wu Ping‐Yu , Henschke Julian P. , Wu Hsyueh‐Liang 
Published: February 2016

AbstractThe preparation of chiral 4‐aryl‐2‐pyrrolidones by conjugate addition catalyzed by a rhodium(I) complex, comprising the chiral bicyclo[2.2.1] diene ligand 1 e, is reported. The reaction of various arylboronic acids and α,β‐unsaturated γ‐lactams 2 bearing various N‐substituents proceeds in a highly stereoselective fashion (93–99.5 % ee) even in the presence of only 0.5 mol % of the Rh catalyst affording the corresponding addition products in 31–99 % yield.
Ocular Fluid Analysis in Children Reveals Interleukin‐29/Interferon‐λ1 as a Biomarker for Juvenile Idiopathic Arthritis–Associated Uveitis
Authors: Haasnoot Anne‐Mieke J. W. , Kuiper Jonas J. W. , Hiddingh Sanne , Schellekens Peter A. W. J. F. , de Jager Wilco , Imhof Saskia M. , Radstake Timothy R. D. J. , de Boer Joke H. 
Published: February 2016

ObjectiveChildhood uveitis is a vision‐threatening inflammatory eye disease commonly attributed to juvenile idiopathic arthritis (JIA). The pathogenesis is poorly understood, which makes clinical management challenging. We analyzed soluble mediators in ocular fluid (aqueous humor [AqH]) and serum from children with JIA‐associated uveitis and common childhood uveitis to identify potential biomarkers and investigate the ocular microenvironment of this sight‐threatening eye disease.MethodsAqH (n = 73) and paired serum (n = 66) samples were analyzed for 51 soluble mediators of inflammation by multiplex immunoassay. Twenty‐one children with JIA‐associated uveitis were compared to 15 children with chronic anterior uveitis without arthritis, 29 children with noninfectious idiopathic uveitis, and 8 children with noninflammatory conditions (controls). For visualization of the joint effect of multiple mediators, we used the radial coordinate visualization (Radviz) method. Optimal biomarker level cutoffs were also determined.ResultsThe levels of interleukin‐29 (IL‐29)/interferon‐λ1 (IFNλ1) were decreased (P < 0.001) and the levels of latency‐associated peptide and osteoprotegerin were increased (P = 0.002 andP = 0.001, respectively) in samples of AqH, but not serum, from patients with JIA‐associated uveitis. Multivariate analysis correcting for disease activity and treatment revealed that intraocular levels of IL‐29/IFNλ1 were specifically decreased in patients with JIA‐associated uveitis as compared to those with idiopathic uveitis. Indeed, JIA‐associated uveitis patients and idiopathic uveitis patients showed distinct profiles of intraocular soluble mediators. IL‐29/IFNλ1 showed a high area under the curve value (0.954), with 23.5 pg/ml as the optimal cutoff value.ConclusionWe identified IL‐29/IFNλ1 as an intraocular biomarker for JIA‐associated uveitis, which suggests that aberrant IFNλ signaling might be important in JIA‐associated uveitis and distinct from other forms of childhood uveitis.
Development of Biomarker Models to Predict Outcomes in Lupus Nephritis
Authors: Wolf Bethany J. , Spainhour John C. , Arthur John M. , Janech Michael G. , Petri Michelle , Oates Jim C. 
Published: February 2016

ObjectiveThe American College of Rheumatology guidelines for the treatment of lupus nephritis recommend change in induction therapy when response to therapy has not occurred within 6 months. Response is not defined, and renal fibrosis can occur while waiting for this end point. Therefore, a decision support tool to better define response is needed to guide clinicians when starting patients on therapy. This study was undertaken to identify biomarker models with sufficient predictive power to develop such a tool.MethodsUrine samples from 140 patients with biopsy‐proven lupus nephritis who had not yet started induction therapy were analyzed for a panel of urinary biomarkers. Univariate receiver operating characteristic (ROC) curves were generated for each individual biomarker and compared to the ROC area under the curve values from machine learning models developed using random forest algorithms. Biomarker models of outcome developed with novel markers in addition to clinical markers were compared to those developed with traditional clinical markers alone.ResultsModels developed with the combined traditional and novel biomarker panels demonstrated clinically meaningful predictive power. Markers most predictive of response were chemokines, cytokines, and markers of cellular damage.ConclusionThis is the first study to demonstrate the power of low‐abundance biomarker panels and machine learning algorithms for predicting lupus nephritis outcomes. This is a critical first step in research to develop clinically meaningful decision support tools.
Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis
Authors: Munters Li Alemo , Loell Ingela , Ossipova Elena , Raouf Joan , Dastmalchi Maryam , Lindroos Eva , Chen Yi‐Wen , Esbjörnsson Mona , Korotkova Marina , Alexanderson Helene , Nagaraju Kanneboyina , Crofford Leslie J. , Jakobsson Per‐Johan , Lundberg Ingrid E. 
Published: February 2016

ObjectiveEndurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12‐week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM.MethodsFifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12‐week follow‐up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry–based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise.ResultsCompared to the control group, the exercise group improved in minutes of cycling time (P < 0.01) and Vo2 max (P < 0.05). The exercise group also had reduced disease activity (P < 0.05) and reduced lactate levels at exhaustion (P < 0.05). Genes related to capillary growth, mitochondrial biogenesis, protein synthesis, cytoskeletal remodeling, and muscle hypertrophy were up‐regulated in the exercise group, while genes related to inflammation/immune response and endoplasmic reticulum stress were down‐regulated. Mitochondrial pathways including the oxidative phosphorylation metabolic pathway were most affected by the endurance exercise, as demonstrated by proteomics analysis. The exercise group also showed a higher number of capillaries per mm2 in follow‐up biopsy samples (P < 0.05).ConclusionOur data indicate that endurance exercise in patients with established PM and DM may activate an aerobic phenotype and promote muscle growth and simultaneously suppress the inflammatory response in these patients’ muscles, as supported by a combination of data on gene expression, proteomics, and capillary density in repeated muscle biopsies.
Brief Report: Predicting Functional Disability: One‐Year Results From the Scottish Early Rheumatoid Arthritis Inception Cohort
Authors: Kronisch Caroline , McLernon David J. , Dale James , Paterson Caron , Ralston Stuart H. , Reid David M. , Tierney Ann , Harvie John , McKay Neil , Wilson Hilary E. , Munro Robin , Saunders Sarah , Richmond Ruth , Baxter Derek , McMahon Mike , Kumar Vinod , McLaren John , Siebert Stefan , McInnes Iain B. , Porter Duncan , Macfarlane Gary J. , Basu Neil 
Published: February 2016

ObjectiveTo identify baseline prognostic indicators of disability at 1 year within a contemporary early inflammatory arthritis inception cohort and then develop a clinically useful tool to support early patient education and decision‐making.MethodsThe Scottish Early Rheumatoid Arthritis (SERA) inception cohort is a multicenter, prospective study of patients with newly presenting RA or undifferentiated arthritis. SERA data were analyzed to determine baseline predictors of disability (defined as a Health Assessment Questionnaire [HAQ] score of ≥1) at 1 year. Clinical and psychosocial baseline exposures were entered into a forward stepwise logistic regression model. The model was externally validated using newly accrued SERA data and subsequently converted into a prediction tool.ResultsOf the 578 participants (64.5% female), 36.7% (n = 212) reported functional disability at 1 year. Functional disability was independently predicted by baseline disability (odds ratio [OR] 2.67 [95% confidence interval (95% CI) 1.98, 3.59]), depression (OR 2.52 [95% CI 1.18, 5.37]), anxiety (OR 2.37 [95% CI 1.33, 4.21]), being in paid employment with absenteeism during the last week (OR 1.19 [95% CI 0.63, 2.23]), not being in paid employment (OR 2.36 [95% CI 1.38, 4.03]), and being overweight (OR 1.61 [95% CI 1.04, 2.50]). External validation (using 113 newly acquired patients) evidenced good discriminative performance with a C statistic of 0.74, and the calibration slope showed no evidence of model overfit (P = 0.31).ConclusionIn the context of modern early inflammatory arthritis treatment paradigms, predictors of disability at 1 year appear to be dominated by psychosocial rather than more traditional clinical measures. This indicates the potential benefit of early access to nonpharmacologic interventions targeting key psychosocial factors, such as mental health and work disability.
Association of Increased Treg Cell Levels With Elevated Indoleamine 2,3‐Dioxygenase Activity and an Imbalanced Kynurenine Pathway in Interferon‐Positive Primary Sjögren's Syndrome
Authors: Maria Naomi I. , van Helden‐Meeuwsen Cornelia G. , Brkic Zana , Paulissen Sandra M. J. , Steenwijk Eline C. , Dalm Virgil A. , van Daele Paul L. , Martin van Hagen P. , Kroese Frans G. M. , van Roon Joel A. G. , Harkin Andrew , Dik Willem A. , Drexhage Hemmo A. , Lubberts Erik , Versnel Marjan A. 
Published: February 2016

ObjectiveIndoleamine 2,3‐dioxygenase (IDO), the rate‐limiting enzyme that converts tryptophan to kynurenine, is driven in part by type I and type II interferons (IFNs). Naive T cells are polarized into FoxP3+ Treg cells upon exposure to either IDO+ cells or kynurenine. Recent studies have suggested that the kynurenine pathway reflects a crucial interface between the immune and nervous system. The aims of the present study were to evaluate whether Treg cell levels are elevated, in conjunction with increased IDO activity, in patients with primary Sjögren's syndrome (SS) who are positive for the IFN gene expression signature, and to investigate the downstream kynurenine pathway in these patients.MethodsSerum from 71 healthy controls, 58 IFN‐negative patients with primary SS, and 66 IFN‐positive patients with primary SS was analyzed using high‐performance liquid chromatography to measure the levels of tryptophan and kynurenine. Expression levels of messenger RNA (mRNA) for IDO and downstream enzymes in the kynurenine pathway were assessed in CD14+ monocytes using real‐time quantitative polymerase chain reaction. CD4+CD45RO+ T helper memory cell populations were analyzed by flow cytometry.ResultsSignificantly increased levels of IDO activity (assessed as the kynurenine:tryptophan ratio) (P = 0.0054) and percentages of CD25highFoxP3+ Treg cells (P = 0.039) were observed in the serum from IFN‐positive patients with primary SS, and these parameters were significantly correlated with one another (r = 0.511, P = 0.002). In circulating monocytes from IFN‐positive patients with primary SS, the expression of IDO1 mRNA was up‐regulated (P < 0.0001), and this was correlated with the IFN gene expression score (r = 0.816, P < 0.0001). Interestingly, the proapoptotic and neurotoxic downstream enzyme kynurenine 3‐monooxygenase was up‐regulated (P = 0.0057), whereas kynurenine aminotransferase I (KATI) (P = 0.0003), KATIII (P = 0.016), and KATIV (P = 0.04) were down‐regulated in IFN‐positive patients with primary SS compared to healthy controls.ConclusionThese findings demonstrate enhanced IDO activity in conjunction with increased percentages of CD25highFoxP3+ Treg cells in primary SS patients who carry the IFN signature. In addition, IFN‐positive patients with primary SS exhibit an imbalanced kynurenine pathway, with evidence of a shift toward potentially more proapoptotic and neurotoxic metabolites. Intervening in these IFN‐ and IDO‐induced immune system imbalances may offer a new array of possibilities for therapeutic interventions in patients with primary SS.
Associations of Smoking and Age With Inflammatory Joint Signs Among Unaffected First‐Degree Relatives of Rheumatoid Arthritis Patients: Results From Studies of the Etiology of Rheumatoid Arthritis
Authors: Sparks Jeffrey A. , Chang Shun‐Chiao , Deane Kevin D. , Gan Ryan W. , Kristen Demoruelle M. , Feser Marie L. , Moss LauraKay , Buckner Jane H. , Keating Richard M. , Costenbader Karen H. , Gregersen Peter K. , Weisman Michael H. , Mikuls Ted R. , O'Dell James R. , Michael Holers V. , Norris Jill M. , Karlson Elizabeth W. 
Published: February 2016

ObjectiveTo examine whether genetic, environmental, and serologic rheumatoid arthritis (RA) risk factors are associated with inflammatory joint signs in a cohort of first‐degree relatives (FDRs) of RA patients.MethodsWe evaluated RA risk factors and inflammatory joint signs in a prospective cohort of FDRs without RA in the Studies of the Etiology of RA. Genetic factors included 5 HLA–DRB1 shared epitope alleles and 45 RA‐associated single‐nucleotide polymorphisms; loci were combined using genetic risk scores weighted by RA risk. Environmental factors (smoking, body mass index, education, and parity) and RA‐related autoantibodies were assessed at baseline. Physical examination was performed at baseline and 2‐year follow‐up, by observers who were blinded with regard to autoantibody status, to assess inflammatory joint signs as tender or swollen joints at sites typical for RA. Logistic regression was performed to evaluate associations of genetic, environmental, and serologic factors with inflammatory joint signs.ResultsWe analyzed 966 non‐Hispanic white FDRs at baseline and 262 at 2‐year follow‐up after excluding those with inflammatory joint signs at baseline. The mean ± SD age was 47.2 ± 15.5 years, 71% were female, and 55% were shared epitope positive. Smoking >10 pack‐years was associated with inflammatory joint signs at baseline (odds ratio [OR] 1.89 [95% confidence interval (95% CI) 1.26–2.82]) and at 2 years (OR 2.66 [95% CI 1.01–7.03]), compared to never smokers. There was a significant interaction between smoking and age with regard to risk of inflammatory joint signs (P = 0.02). FDRs younger than 50 years with >10 pack‐years had the highest risk of inflammatory joint signs (OR 4.39 [95% CI 2.22–8.66], compared to never smokers younger than 50 years).ConclusionIn a high‐risk cohort of FDRs, smoking and age were associated with both prevalent and incident inflammatory joint signs at sites typical for RA. Further prospective investigations of the factors affecting the transitions between preclinical RA phases are warranted.
Amine‐bis(phenolate) Iron(III)‐Catalyzed Formal Hydroamination of Olefins
Authors: Zhu Kailong , Shaver Michael P. , Thomas Stephen P. 
Published: February 2016

AbstractA practical synthesis of highly functionalized amines by the formal hydroamination reaction of alkenes with nitroarenes catalyzed by an air stable amine‐bis(phenolate) iron(III) complex is reported. The reaction uses an easily handled silane, low catalyst loadings, and mild reaction conditions. A wide range of substrates are transformed with synthetically useful yields (21 examples).
An Enantioselective Assembly of Dihydropyranones through an NHC/LiCl‐Mediated in situ Activation of α,β‐Unsaturated Carboxylic Acids
Authors: Que Yonglei , Lu Yinan , Wang Wenjing , Wang Yuhong , Wang Haotian , Yu Chenxia , Li Tuanjie , Wang Xiang‐Shan , Shen Shide , Yao Changsheng 
Published: February 2016

AbstractA straightforward N‐heterocyclic carbene (NHC)/LiCl‐mediated synthesis of dihydropyranones from α,β‐unsaturated carboxylic acids and 1,3‐dicarbonyl compounds was realized through the in situ activation strategy. The key advantages of this protocol include ready availability and high stability of starting materials, good yields, and excellent enantioselectivity.
Structure‐Triggered High Quantum Yield Luminescence and Switchable Dielectric Properties in Manganese(II) Based Hybrid Compounds
Authors: Wang Zhong‐Xia , Li Peng‐Fei , Liao Wei‐Qiang , Tang Yuanyuan , Ye Heng‐Yun , Zhang Yi 
Published: February 2016

AbstractTwo new manganese(II) based organic–inorganic hybrid compounds, C11H21Cl3MnN2 (1) and C11H22Cl4MnN2 (2), with prominent photoluminescence and dielectric properties were synthesized by solvent modulation. Compound 1 with novel trigonal bipyramidal geometry exhibits bright red luminescence with a lifetime of 2.47 ms and high quantum yield of 35.8 %. Compound 2 with tetrahedral geometry displays intense long‐lived (1.54 ms) green light emission with higher quantum yield of 92.3 %, accompanied by reversible solid‐state phase transition at 170 K and a distinct switchable dielectric property. The better performance of 2 results from the structure, including a discrete organic cation moiety and inorganic metal anion framework, which gives the cations large freedom of motion.
Reactions of a Ruthenium Complex with Substituted N‐Propargyl Pyrroles
Authors: Chia Pi‐Yeh , Huang Shou‐Ling , Liu Yi‐Hong , Lin Ying‐Chih 
Published: February 2016

AbstractIn an investigation into the chemical reactions of N‐propargyl pyrroles 1 a–c, containing aldehyde, keto, and ester groups on the pyrrole ring, with [Ru]−Cl ([Ru]=Cp(PPh3)2Ru; Cp=C5H5), an aldehyde group in the pyrrole ring is found to play a crucial role in stimulating the cyclization reaction. The reaction of 1 a, containing an aldehyde group, with [Ru]−Cl in the presence of NH4PF6 yields the vinylidene complex 2 a, which further reacts with allyl amine to give the carbene complex 6 a with a pyrrolizine group. However, if 1 a is first reacted with allyl amine to yield the iminenyne 8 a, then the reaction of 8 a with [Ru]−Cl in the presence of NH4PF6 yields the ruthenium complex 9 a, containing a cationic pyrrolopyrazinium group, which has been fully characterized by XRD analysis. These results can be adequately explained by coordination of the triple bond of the propargyl group to the ruthenium metal center first, followed by two processes, that is, formation of a vinylidene intermediate or direct nucleophilic attack. Additionally, the deprotonation of 2 a by R4NOH yields the neutral acetylide complex 3 a. In the presence of NH4PF6, the attempted alkylation of 3 a resulted in the formation the Fischer‐type amino–carbene complex 5 a as a result of the presence of NH3, which served as a nucleophile. With KPF6, the alkylation of 3 a with ethyl and benzyl bromoacetates afforded the disubstituted vinylidene complexes 10 a and 11 a, containing ester groups, which underwent deprotonation reactions to give the furyl complexes 12 a and 13 a, respectively. For 13 a, containing an O‐benzyl group, subsequent 1,3‐migration of the benzyl group was observed to yield product 14 a with a lactone unit. Similar reactivity was not observed for the corresponding N‐propargyl pyrroles 1 b and 1 c, which contained keto and ester groups, respectively, on the pyrrole ring.
Solution and Solid‐State Analysis of Binding of 13‐Substituted Berberine Analogues to Human Telomeric G‐quadruplexes
Authors: Ferraroni Marta , Bazzicalupi Carla , Papi Francesco , Fiorillo Gaetano , Guamán‐Ortiz Luis Miguel , Nocentini Alessio , Scovassi Anna Ivana , Lombardi Paolo , Gratteri Paola 
Published: February 2016

AbstractThe interaction between 13‐phenylalkyl and 13‐diphenylalkyl berberine derivatives (NAX) and human telomeric DNA G4 structures has been investigated by both spectroscopic and crystallographic methods. NAX042 and NAX053 are the best compounds improving the performance of the natural precursor berberine. This finding is in agreement with the X‐ray diffraction result for the NAX053‐Tel12 adduct, showing the ligand which interacts via π‐stacking, sandwiched at the interface of two symmetry‐related quadruplex units, with its benzhydryl group contributing to the overall stability of the adduct by means of additional π‐stacking interactions with the DNA residues. The berberine derivatives were also investigated for their cytotoxic activity towards a panel of human cancer cell lines. Compounds NAX042 and NAX053 affect the viability of cancer cell lines in a dose‐dependent manner.