bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphino‐amine (PN) Ligands for Rapid Catalyst Discovery in Ruthenium‐Catalyzed Hydrogen‐Borrowing Alkylation of Anilines: A Proof of Principle
Authors: Broomfield Lewis Marc , Wu Yichen , Martin Eddy , Shafir Alexandr 
Published: November 2015

AbstractA general synthetic protocol for the synthesis of simple phosphino‐amine (PN) ligands is described with 19 ligands being isolated in good yields. High‐throughput ligand screening uncovered the success of two of these ligands for aromatic amine alkylations via ruthenium‐catalyzed hydrogen borrowing reactions. The combination of N,N′‐bis(diphenylphosphino)‐N,N′‐dimethylpropylenediamine with a ruthenium(II) source and potassium hydroxide (15 mol%) is the optimal system for selective monobenzylations of aromatic amines (method A). Over 70% isolated yields have been achieved for the formation of 14 secondary aromatic amines under mild reaction conditions (120 °C and 1.05 equivalents of benzyl alcohol). On the other hand, N,N‐bis(diphenylphosphino)‐isopropylamine was the ligand utilized for both selective monomethylation and monoethylation reactions of aromatic amines (method B). Here the alcohol is charged as both the reaction medium and substrate and 9 examples are disclosed with all isolated yields exceeding 70%. These methods have been applied to the synthesis of important synthetic building blocks based on aminoferrocene.magnified image
Aminocatalyzed Cascade Synthesis of Enantioenriched 1,7‐Annulated Indoles from Indole‐7‐Carbaldehyde Derivatives and α,β‐Unsaturated Aldehydes
Authors: Giardinetti Maxime , Moreau Xavier , Coeffard Vincent , Greck Christine 
Published: November 2015

AbstractWe report herein a new cascade strategy for the enantioselective synthesis of 1,7‐annulated indoles based on iminium‐enamine activation. A careful study of the indole substitution pattern revealed that a chloro substituent at the C‐3 position was important to the implementation of the reaction. Employing a diphenylprolinol silyl ether catalyst, a range of 3‐chloro‐1H‐indole‐7‐carbaldehyde derivatives reacted with α,β‐unsaturated aldehydes to afford the corresponding 1,7‐annulated indoles in good yields (62–99%) and enantioselectivities (62–92%). Besides the fluorescence properties of the 1,7‐ring fused indoles prepared following our methodology, these compounds contain a useful set of functional groups which undergo various synthetic transformations.magnified image
Developmental patterns of bilateral asymmetry in ancestral puebloans
Authors: Waxenbaum Erin B. , Sirak Kendra A. 
Published: November 2015

ObjectivesProducing and maintaining a bilaterally symmetric phenotype throughout the lifespan is energetically demanding. Over the course of an individual's life, various intrinsic and external stressors impact the growth trajectory. These perturbations can compromise the allocation of energetic resources to processes that maintain developmental precision, potentially resulting in bilateral asymmetry (BA). Because different stressors are present during the lifespan, BA is a valuable tool for examining the unique factors impacting symmetrical growth and development. This study examines BA in paired long bones across a developmental skeletal series.MethodsThe humeri, radii, femora, and tibiae of 198 individuals from Ancestral Puebloan New Mexico (919–1670 CE) are analyzed to explore BA across development. Individuals are separated into five age categories, and by sex when possible, to explore patterns of BA.ResultsSignificant BA is found in the bones of the upper limb when the interaction between bone and age is examined. Results suggest that BA in the humerus and radius becomes more right‐biased with age. These directional trends are not observed in the lower limbs. Division into age categories illuminates patterns of asymmetry associated with age‐related activities and physiological maturity, indicating that BA is differentially affected by varying environmental stressors across development.ConclusionsOur findings support the hypothesis that BA in long bones is influenced by environmental stressors that impact an individual's ability to produce symmetric morphological traits over the lifespan. Right‐biased BA in the upper limb bones indicates that this variation from a symmetric ideal is strongly influenced by handedness resulting from habitual manual activities. Am. J. Hum. Biol. 28:421–430, 2016. © 2015 Wiley Periodicals, Inc.
Occupational exposures and chronic kidney disease: Possible associations with endotoxin and ultrafine particles
Authors: Sponholtz Todd R. , Sandler Dale P. , Parks Christine G. , Applebaum Katie M. 
Published: November 2015

BackgroundChronic kidney disease (CKD) carries a high public health burden yet there is limited research on occupational factors, which are examined in this retrospective case‐control study.MethodsNewly diagnosed cases of CKD (n = 547) and controls (n = 508) from North Carolina provided detailed work histories in telephone interviews. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThere was heterogeneity in the association of CKD and agricultural work, with crop production associated with increased risk and work with livestock associated with decreased risk. Work with cutting/cooling/lubricating oils was associated with a reduced risk. CKD risk was increased for working in dusty conditions.ConclusionsCKD risk was reduced in subjects with occupational exposures previously reported to involve endotoxin exposure. Further, exposure to dusty conditions was consistently associated with increased risk of glomerulonephritis across industry, suggesting that research on CKD and ultrafine particulates is needed. Am. J. Ind. Med. 59:1–11, 2016. © 2015 Wiley Periodicals, Inc.
Reduced sinonasal levels of 1α‐hydroxylase are associated with worse quality of life in chronic rhinosinusitis with nasal polyps
Authors: Schlosser Rodney J. , Carroll William W. , Soler Zachary M. , Pasquini Whitney N. , Mulligan Jennifer K. 
Published: November 2015

BackgroundPatients with chronic rhinosinusitis with nasal polyps (CRSwNP) have deficiencies in circulating and sinonasal levels of the inactive form of vitamin D3, 25‐hydroxycholecalciferol (25VD3). Moreover, CRSwNP patients have reduced epithelial cell–specific expression of 1α‐hydroxylase; the enzyme responsible for the conversion of 25VD3 to its metabolically active form, 1α,25‐dihydroxyvitamin D3 (1,25VD3). The objective of this work was to determine the impact of sinonasal 1α‐hydroxylase levels combined from all cellular sources on subjective disease severity and to identify variables influencing its expression.MethodsBlood and sinus tissue explants were collected at the time of surgery from control, chronic rhinosinusitis without nasal polyps (CRSsNP), CRSwNP, and allergic fungal rhinosinusitis (AFRS) patients. 1α‐Hydroxylase was measured by immunostaining with flow cytometric analysis. Subjective disease severity was measured by the 22‐item Sino‐Nasal Outcomes Test (SNOT‐22). 1,25VD3 and 25VD3 were measured by enzyme‐linked immunosorbent assay (ELISA).ResultsPatients with CRSwNP or AFRS have reduced 1α‐hydroxylase and 1,25VD3 compared to controls or CRSsNP. Circulating 1,25VD3 levels were the same among all groups. No differences in sinonasal 1α‐hydroxylase or 1,25VD3 were found between CRSwNP and AFRS. Gender, age, race, atopy, and systemic 25VD3 had no impact on sinonasal 1α‐hydroxylase levels in any group. However, CRSwNP patients with asthma had higher 1α‐hydroxylase than those without asthma. Total 1α‐hydroxylase levels inversely correlated with SNOT‐22 in CRSwNP, but not CRSsNP.ConclusionPatients with CRSwNP and AFRS both have reduced sinonasal 1α‐hydroxylase and 1,25VD3 compared to controls or CRSsNP. Reductions in intracellular 1α‐hydroxylase combined from all sinonasal cell types were associated with more severe subjective disease severity in CRSwNP.
Mometasone furoate nasal spray in the treatment of nasal polyposis in Chinese patients: a double‐blind, randomized, placebo‐controlled trial
Authors: Zhou Bing , He Gang , Liang Jianping , Cheng Lei , Mehta Anish , Liu Shu , Yu Wenbo , Wang Zaiqi , Han Demin 
Published: November 2015

BackgroundAlthough mometasone furoate nasal spray (MFNS) has demonstrated efficacy in nasal polyposis (NP) in Western populations, data in Asian populations is limited.MethodsThis randomized, double‐blind study evaluated MFNS 200 μg twice per day (BID) vs placebo in Chinese adults with bilateral nasal polyps (graded as 1, 2, or 3 by the investigator). A 14‐day placebo run‐in period was followed by a 16‐week treatment period with MFNS 200 μg BID vs placebo (1:1 ratio). The co‐primary endpoints were change from baseline in nasal congestion/obstruction averaged over the first 4 weeks of treatment and change from baseline in the total polyp size score (sum of scores from the left and right nasal fossa) at week 16. Secondary endpoints included other sinonasal symptoms scores and safety outcomes such as monitoring laboratory measurements, vital signs, and adverse events (AEs).ResultsThere were 748 patients randomized, 375 received MFNS 200 μg BID and 373 received placebo. The between‐treatment difference in least squares (LS) mean change from baseline in nasal congestion/obstruction over 4 weeks of treatment was −0.14 (95% confidence interval [CI], −0.22 to −0.06) for MFNS vs placebo (p = 0.0007). The between‐treatment difference in LS mean change from baseline in total polyp size score at week 16 was −0.30 (95% CI, −0.45 to −0.15) for MFNS vs placebo (p < 0.0001). Serious AEs were rare (0.5% and 0.8% in MFNS and placebo groups, respectively) and considered not drug‐related. There were significantly more AEs of epistaxis with MFNS vs placebo (p = 0.009).ConclusionThis study demonstrated that MFNS was effective and well tolerated in this population of adult, Chinese patients with NP.
The effects of house dust mite sublingual immunotherapy in patients with allergic rhinitis according to duration
Authors: Lin Zhibin , Liu Qihong , Li Tianying , Chen Dong , Chen Dehua , Xu Rui 
Published: November 2015

BackgroundThe safety and efficacy of sublingual immunotherapy (SLIT) have been demonstrated in the recent 2 decades. However, the data is still mixed regarding the efficacy of house dust mite (HDM) SLIT. The objective of this work was to evaluate the different clinical efficacy SLIT in patients with allergic rhinitis (AR) according to different durations of treatment.MethodsA total of 500 subjects with HDM‐induced AR were randomized to receive SLIT with Dermatophagoides farinae (Der.f) drops or pharmacotherapy with oral antihistamines. Patients in the SLIT group were further divided into SLIT1, SLIT2, and SLIT3 subgroups. After SLIT completion, a yearly follow‐up visit was given to patients in the SLIT1 and SLIT2 subgroups. The total nasal symptom score (TNSS), the proportion of medication withdrawal, the visual analogue scale (VAS) score, and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were assessed at each monthly visit.ResultsComparing with the baseline value, TNSS, VAS, and RQLQ were significantly improved in 3 SLIT subgroups after treatment (p < 0.05). In addition, patients in SLIT3 subgroup achieved the highest proportion of medication withdrawal compared to the SLIT1 and SLIT2 subgroups (p < 0.05). After 1‐year follow‐up, no significant differences were observed in TNSS, VAS scores, and the proportion of medication withdrawal of SLIT1 and SLIT2 subgroups (p > 0.05) with respect to the completion value. No severe systemic adverse events (AEs) were reported.ConclusionThe randomized study suggested that 3‐year courses of SLIT in patients with AR was more efficacious than 1‐year or 2‐year courses. Furthermore, patients achieved 1‐year long‐term clinical benefits from HDM SLIT.
Anatomic variants of the paranasal sinuses in patients with recurrent acute rhinosinusitis
Authors: Loftus Patricia Anne , Lin Juan , Tabaee Abtin 
Published: November 2015

BackgroundThe incidence and potential disease impact of paranasal sinus anatomic variants in patients with recurrent acute rhinosinusitis (RARS) has important implications for management, including surgery, but is incompletely defined.MethodsA retrospective review of 26 patients with RARS who had undergone computed tomography (CT) was performed. Patient demographics, RARS severity and comorbidities were reviewed. CT scans were reviewed for the incidence of anatomic variants in all patients. The pattern of inflammatory changes was explored in the subset of patients with acute rhinosinusitis at the time of CT. Potential correlation between the presence of anatomic variants and disease severity were investigated.ResultsIn the patient cohort who met inclusion criteria, the most common variants included agger nasi cell (88.5%), concha bullosa (53.8%), infraorbital cell (50%), and deviated nasal septum with middle meatus obstruction (42%). In exploring correlations with RARS severity, type 2 frontal cells correlated with a greater number of years with RARS (0.0363). In the 23 patients who underwent CT at the time of an acute infection, no statistically significant correlation was found between severity or location of inflammatory changes and the presence of anatomic variants.ConclusionThis study describes the incidence of anatomic variants in a cohort of patients with RARS. A correlation between the presence of anatomic variants and the pattern of inflammatory changes was not identified.
Subepithelial inflammatory load and basement membrane thickening in refractory chronic rhinosinusitis with nasal polyposis: a histopathological study
Authors: Bassiouni Ahmed , Ou Judy , Rajiv Sukanya , Cantero Daniel , Vreugde Sarah , Wormald Peter‐John 
Published: November 2015

BackgroundA subgroup of chronic rhinosinusitis with nasal polyps (CRSwNP) patients is refractory to optimal surgical therapy and requires multiple revision sinus operations. Studies have shown that mucosal eosinophilia correlates with disease severity. We hypothesized that a high‐grade tissue inflammatory load is associated with these refractory patients.MethodsA single‐surgeon, retrospective case‐control study comparing 20 CRSwNP patients requiring a second surgery during follow‐up (refractory group) vs a matched cohort of 20 CRSwNP patients without needing further revision surgery (control group). Hematoxylin and eosin (H&E)‐stained tissue harvested intraoperatively (×2 for the refractory group) were recalled for histopathological examination of subepithelial inflammation and basement membrane (BM) thickness.ResultsThe refractory group had a significantly higher average eosinophil count (49 vs 18), relative eosinophilia (55% vs 32%) as well as total inflammatory cell count (86 vs 49) than the control group (p < 0.05). However within the refractory group, the eosinophil‐lymphocyte ratio was reduced from their first to their second (revision) surgeries whereas the total averaged inflammatory cell count remained unchanged. No significant difference in BM thickness was found between the groups.ConclusionThese findings suggest that a higher inflammatory and eosinophilic load is associated with refractory disease and thus may be useful in predicting need for future revision surgery in CRSwNP.
The role for human nasal epithelial nuclear factor kappa B activation in histamine‐induced mucin 5 subtype B overproduction
Authors: Wang Weiwei , Shao Shengwen , Wang Sha 
Published: November 2015

BackgroundMucin 5 subtype B (MUC5B) is 1 of the major mucins secreted by airway epithelial cells. We sought to determine the effect of histamine on MUC5B expression in human nasal epithelial cells.MethodsHuman nasal epithelial cells from allergic rhinitis patients were cultured, and stimulated with 4 concentrations of histamine, or pretreated with a specific nuclear factor‐kappa B (NF‐κB) inhibitor (Bay11‐7082) before histamine stimulation. Immunocytochemistry and Western blotting were used to detect phosphorylated inhibitor of kappa B alpha (p‐IκBα), NF‐κBp65 and MUC5B protein. MUC5B content in supernatants was assayed by enzyme‐linked immunosorbent assay (ELISA).ResultsHistamine promoted IκBα phosphorylation and NF‐κBp65 nuclear translocation. A concentration‐dependent histamine‐induced increase of MUC5B protein was observed, and its content in supernatants was upregulated in a concentration‐dependent fashion, but these effects were attenuated by Bay11‐7082.ConclusionHistamine activated the IκBα/NF‐κB pathway by promoting IκBα phosphorylation and inducing NF‐κBp65 nuclear translocation, contributing to MUC5B overproduction and secretion.
Gender‐specific differences in chronic rhinosinusitis patients electing endoscopic sinus surgery
Authors: Lal Devyani , Rounds Alexis B. , Divekar Rohit 
Published: November 2015

BackgroundThe objective of this study was to investigate gender‐specific differences in chronic rhinosinusitis (CRS) patients electing endoscopic sinus surgery (ESS).MethodsThis study was a retrospective review of CRS patients electing ESS (2011–2013) at a tertiary‐care center.ResultsESS was elected by 272 patients (mean age 54.6 years; 48.5% female). Mean Lund‐Mackay computed tomography (CT) score was 10.9; total 22‐item Sino‐Nasal Outcome Test (SNOT‐22) score was 41.8. Compared to men, women electing ESS had lower CT score (10.1 vs 11.7; p = 0.01) but higher total SNOT‐22 score (44.9 vs 39; p = 0.02). Women reported significantly worse postnasal drainage (p < 0.0001) and embarrassment (p = 0.0021). SNOT‐22 scores declined with advancing age (women, p = 0.003; men, p = 0.0005). Reduction in CT scores with age was seen only in males (p = 0.03). Stratifying by age, females aged 61 to 80 years had higher SNOT‐22 scores compared to male counterparts (p = 0.04), whereas CT scores were similar. More women underwent surgery for CRS without nasal polyps (CRSsNP) (54.9%) whereas more men underwent surgery for CRS with nasal polyps (CRSwNP) (57.4%), but this difference missed statistical significance (p = 0.052). Women with CRSwNP had higher SNOT‐22 scores than men (p = 0.02) for similar CT scores. Men electing ESS for CRSsNP had higher CT scores than women (p = 0.02). Women with CRSsNP aged 18 to 40 years reported higher SNOT‐22 scores than men (p = 0.003), even though CT scores were lower (p = 0.005).ConclusionEquivalent numbers of men and women underwent ESS for CRS. Overall, women electing ESS had higher total SNOT‐22 scores and lower Lund‐Mackay CT scores than men. Women reported more problems with postnasal drainage (CRS overall, CRSsNP, and CRSwNP), embarrassment (CRS overall and CRSwNP), and facial pain (CRSwNP). Gender differences in CRS are poorly understood and merit further study.
Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy
Authors: Mendell Jerry R. , Goemans Nathalie , Lowes Linda P. , Alfano Lindsay N. , Berry Katherine , Shao James , Kaye Edward M. , Mercuri Eugenio ,   for the Eteplirsen Study Group and Telethon Foundation DMD Italian Network
Published: November 2015

ObjectiveTo continue evaluation of the long‐term efficacy and safety of eteplirsen, a phosphorodiamidate morpholino oligomer designed to skip DMD exon 51 in patients with Duchenne muscular dystrophy (DMD). Three‐year progression of eteplirsen‐treated patients was compared to matched historical controls (HC).MethodsAmbulatory DMD patients who were ≥7 years old and amenable to exon 51 skipping were randomized to eteplirsen (30/50mg/kg) or placebo for 24 weeks. Thereafter, all received eteplirsen on an open‐label basis. The primary functional assessment in this study was the 6‐Minute Walk Test (6MWT). Respiratory muscle function was assessed by pulmonary function testing (PFT). Longitudinal natural history data were used for comparative analysis of 6MWT performance at baseline and months 12, 24, and 36. Patients were matched to the eteplirsen group based on age, corticosteroid use, and genotype.ResultsAt 36 months, eteplirsen‐treated patients (n = 12) demonstrated a statistically significant advantage of 151m (p < 0.01) on 6MWT and experienced a lower incidence of loss of ambulation in comparison to matched HC (n = 13) amenable to exon 51 skipping. PFT results remained relatively stable in eteplirsen‐treated patients. Eteplirsen was well tolerated. Analysis of HC confirmed the previously observed change in disease trajectory at age 7 years, and more severe progression was observed in patients with mutations amenable to exon skipping than in those not amenable. The subset of patients amenable to exon 51 skipping showed a more severe disease course than those amenable to any exon skipping.InterpretationOver 3 years of follow‐up, eteplirsen‐treated patients showed a slower rate of decline in ambulation assessed by 6MWT compared to untreated matched HC. Ann Neurol 2016;79:257–271
Katalytische elektrophile C‐H‐Silylierung von Pyridinen ermöglicht durch vorübergehende Aufhebung der Aromatizität
Authors: Wübbolt Simon , Oestreich Martin 
Published: November 2015

AbstractEine C‐H‐Silylierung von Pyridinen wurde entwickelt, die scheinbar dem Mechanismus einer elektrophilen aromatischen Substitution (SEAr) folgt. Reaktionen von 2‐ und 3‐substituierten Pyridinen mit Hydrosilanen in Gegenwart eines Katalysators, welcher die Si‐H‐Bindung in ein Hydrid und ein Siliciumelektrophil spaltet, ergeben die entsprechenden 5‐silylierten Pyridine. Diese formale Silylierung einer aromatischen C‐H‐Bindung ist das Ergebnis einer dreistufigen Reaktionssequenz bestehend aus einer Pyridinhydrosilylierung, einer dehydrierenden C‐H‐Silylierung der Enaminzwischenstufe und einer Retro‐Hydrosilylierung des 1,4‐Dihydropyridins. Die Schlüsselzwischenstufen wurden 1H‐NMR‐spektroskopisch nachgewiesen und schrittweise einzeln hergestellt. Dieses komplexe Wechselspiel elektrophiler Silylierungen, Hydridübertragungen und Protonenabstraktionen wird durch einen einzigen Katalysator vermittelt.
Catalytic Electrophilic CH Silylation of Pyridines Enabled by Temporary Dearomatization
Authors: Wübbolt Simon , Oestreich Martin 
Published: November 2015

AbstractA CH silylation of pyridines that seemingly proceeds through electrophilic aromatic substitution (SEAr) is reported. Reactions of 2‐ and 3‐substituted pyridines with hydrosilanes in the presence of a catalyst that splits the SiH bond into a hydride and a silicon electrophile yield the corresponding 5‐silylated pyridines. This formal silylation of an aromatic CH bond is the result of a three‐step sequence, consisting of a pyridine hydrosilylation, a dehydrogenative CH silylation of the intermediate enamine, and a 1,4‐dihydropyridine retro‐hydrosilylation. The key intermediates were detected by 1H NMR spectroscopy and prepared through the individual steps. This complex interplay of electrophilic silylation, hydride transfer, and proton abstraction is promoted by a single catalyst.