bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review
Authors: Desai Rishi J. , Thaler Kylie J. , Mahlknecht Peter , Gartlehner Gerald , McDonagh Marian S. , Mesgarpour Bita , Mazinanian Alireza , Glechner Anna , Gopalakrishnan Chandrasekar , Hansen Richard A. 
Published: December 2015

ObjectiveTo systematically compare the risk of adverse events (AEs) for 13 targeted immunomodulators (TIMs) indicated for ankylosing spondylitis (AS), inflammatory bowel diseases, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis (PsA), or rheumatoid arthritis (RA).MethodsWe searched electronic databases through July 2015 to retrieve randomized controlled trials (RCTs) and observational studies comparing AEs between 2 or more TIMs head‐to‐head. We reported on the following outcomes: number of AEs, discontinuation due to AEs, serious AEs, mortality, serious infections, tuberculosis, herpes zoster, and malignancies. We qualitatively synthesized the literature and conducted random‐effects meta‐analyses if 3 or more studies provided data for an outcome.ResultsTen head‐to‐head RCTs and 51 observational studies were included in this systematic review. A majority of the studies (70%) were conducted in RA patients. Risk of treatment discontinuation due to AEs was higher with infliximab than with adalimumab or etanercept in RA, PsA, and AS. A higher risk for serious infections was noted with infliximab than with abatacept, adalimumab, or etanercept in RA. Risk for treatment discontinuation due to AEs, serious infections, and tuberculosis was lower with etanercept than with adalimumab in RA. Limited evidence suggested no comparative differences in risk for mortality, malignancies, and herpes zoster for adalimumab, etanercept, and infliximab in RA.ConclusionImportant differences were noted in the safety profile of TIMs in RA, generally favoring abatacept, adalimumab, and etanercept over infliximab. Head‐to‐head comparative evidence for other TIMs and non‐RA populations was insufficient to draw conclusions for most of the safety outcomes.
Symptomatic and Electrodiagnostic Features of Peripheral Neuropathy in Scleroderma
Authors: Paik Julie J. , Mammen Andrew L. , Wigley Fredrick M. , Shah Ami A. , Hummers Laura K. , Polydefkis Michael 
Published: December 2015

ObjectiveTo determine the prevalence of peripheral neuropathy in scleroderma.MethodsThe prevalence of length‐dependent peripheral neuropathy was rigorously assessed using signs and symptoms of neuropathy derived from the Total Neuropathy Score (TNS), and standardized nerve conduction study (NCS). All subjects underwent TNS and NCS. Those who were symptomatic or had NCS evidence of peripheral neuropathy underwent laboratory evaluation for secondary causes of neuropathy.ResultsA total of 130 subjects were approached for participation and 60 enrolled. Of the 60 subjects, 50 (83.3%) were female and 37 (61.7%) were of the limited cutaneous subtype. The mean ± SD age was 55 ± 11.1 years, and mean ± SD disease duration was 15.3 ± 10.1 years. A total of 17 of 60 (28%) had evidence of a peripheral neuropathy as defined by the presence of neuropathic symptoms on the TNS (12 of 60) and/or electrophysiologic evidence of neuropathy (5 subjects with neuropathic symptoms and 5 without neuropathic symptoms). Subjects with neuropathy were more likely to be male (60% versus 40%; P = 0.02), African American (41% versus 4.6%; P = 0.001), have diabetes mellitus (17.7% versus 0%; P = 0.02), have limited cutaneous scleroderma (82.3% versus 53.5%; P = 0.04), and have anti‐U1 RNP antibodies (23.5% versus 0%; P = 0.009) than those without neuropathy. A potential nonscleroderma etiology for the peripheral neuropathy such as diabetes mellitus was found in 82.3% (14 of 17) of subjects with neuropathy.ConclusionWhile symptoms or objective evidence of peripheral neuropathy are common among patients with scleroderma, the cause may often be attributed to comorbid nonscleroderma‐related conditions.
N‐Bromosuccinimide‐Mediated Thiocyanation of Cyclohexene‐Fused Isoxazoline N‐Oxides
Authors: Ichake Sachin S. , Rajawinslin R. R. , Kavala Veerababurao , Villuri Bharath Kumar , Yang Huei‐Ting , Kuo Chun‐Wei , Yao Ching‐Fa 
Published: December 2015

AbstractAn efficient, metal‐free, NBS‐mediated thiocyanation protocol has been developed for the synthesis of (6‐(hydroxyimino)‐2‐thiocyanatocyclohex‐1‐en‐1‐yl)(phenyl)methanone derivatives from cyclohexene‐fused isoxazoline N‐oxides under mild conditions. This rapid, one‐pot transformation is achieved in acetonitrile, and provides access to diverse SCN‐containing compounds bearing a wide range of functional groups in good to excellent yields. Moreover, an SCN containing product was further utilized for the synthesis of cyclohexanone ring‐fused isothiazole derivatives.
An Ethyne‐Bridged Porphyrin‐Hexaphyrin‐Porphyrin Triad That Undergoes a Thermal Transannular Cyclization
Authors: Honjo Kazuma , Mori Hirotaka , Osuka Atsuhiro 
Published: December 2015

AbstractAn ethyne‐bridged Ni2+ porphyrin‐[26]hexaphyrin‐Ni2+ porphyrin triad (4) has been prepared and shown to adopt a dumbbell‐like conformation despite the two bulky porphyrinylethynyl groups at the hinge positions of the hexaphyrin. The 1H NMR and UV/vis/NIR spectra of 4 revealed that the aromatic nature of the [26]hexaphyrin unit was significantly mitigated via conjugative interaction with the porphyrinylethynyl substituents. Thermal transannular cyclization of 4 proceeded smoothly to give vinylene‐bridged triad 12, in which the π‐systems of the Ni2+ porphyrins and [26]hexaphyrin are not conjugated and the aromatic character of the latter is enhanced.
Platinfreie Nanomaterialien für die Sauerstoffreduktion
Authors: Xia Wei , Mahmood Asif , Liang Zibin , Zou Ruqiang , Guo Shaojun 
Published: December 2015

AbstractDer Ersatz von Platin (Pt) durch billigere, unedle Elemente in Elektrokatalysatoren für die Sauerstoffreduktionsreaktion (ORR) ist für die Entwicklung nachhaltiger, leistungsfähiger Brennstoffzellen zur Energieumwandlung von größtem Interesse. Platinfreie Materialien bergen jedoch eine Reihe von Herausforderungen, wie eine geringe intrinsische katalytische Aktivität, eine begrenzte Zahl aktiver Zentren und schlechte Stofftransporteigenschaften. Jüngste Fortschritte in den Materialwissenschaften und der Nanotechnologie ermöglichen nun ein rationales Design von neuen Materialien mit unedlen Elementen mit optimierter Zusammensetzung und präziser Nanostruktur. Dies eröffnet neue Möglichkeiten zur Verbesserung der ORR‐Leistung auf molekularer Ebene. Dieser Aufsatz beleuchtet die aktuellen Durchbrüche bei der Entwicklung von Nanokatalysatoren für die ORR.
Controlling the Assembly of Coiled–Coil Peptide Nanotubes
Authors: Thomas Franziska , Burgess Natasha C. , Thomson Andrew R. , Woolfson Derek N. 
Published: December 2015

AbstractAn ability to control the assembly of peptide nanotubes (PNTs) would provide biomaterials for applications in nanotechnology and synthetic biology. Recently, we presented a modular design for PNTs using α‐helical barrels with tunable internal cavities as building blocks. These first‐generation designs thicken beyond single PNTs. Herein we describe strategies for controlling this lateral association, and also for the longitudinal assembly. We show that PNT thickening is pH sensitive, and can be reversed under acidic conditions. Based on this, repulsive charge interactions are engineered into the building blocks leading to the assembly of single PNTs at neutral pH. The building blocks are modified further to produce covalently linked PNTs via native chemical ligation, rendering ca. 100 nm‐long nanotubes. Finally, we show that small molecules can be sequestered within the interior lumens of single PNTs.
Brook Rearrangement as a Trigger for the Ring Opening of Strained Carbocycles
Authors: Zhang Fa‐Guang , Eppe Guillaume , Marek Ilan 
Published: December 2015

AbstractThe combined regio‐ and stereoselective carbometalation of cyclopropenyl amides, followed by the addition of an acyl silane, led to the formation of polysubstituted cyclopropyl derivatives as unique diastereoisomers. Upon warming of the reaction mixture to room temperature, a Brook rearrangement proceeded with inversion of configuration to provide ready access to δ‐ketoamides possessing a quaternary carbon center with high enantiomeric ratios through selective CC bond cleavage of the ring.
What a Difference an OH Makes: Conformational Dynamics as the Basis for the Ligand Specificity of the Neomycin‐Sensing Riboswitch
Authors: Duchardt‐Ferner Elke , Gottstein‐Schmidtke Sina R. , Weigand Julia E. , Ohlenschläger Oliver , Wurm Jan‐Philip , Hammann Christian , Suess Beatrix , Wöhnert Jens 
Published: December 2015

AbstractTo ensure appropriate metabolic regulation, riboswitches must discriminate efficiently between their target ligands and chemically similar molecules that are also present in the cell. A remarkable example of efficient ligand discrimination is a synthetic neomycin‐sensing riboswitch. Paromomycin, which differs from neomycin only by the substitution of a single amino group with a hydroxy group, also binds but does not flip the riboswitch. Interestingly, the solution structures of the two riboswitch–ligand complexes are virtually identical. In this work, we demonstrate that the local loss of key intermolecular interactions at the substitution site is translated through a defined network of intramolecular interactions into global changes in RNA conformational dynamics. The remarkable specificity of this riboswitch is thus based on structural dynamics rather than static structural differences. In this respect, the neomycin riboswitch is a model for many of its natural counterparts.
Enantioselective Catalysts for the Synthesis of α‐Substituted Allylboronates—An Accelerated Approach towards Isomerically Pure Homoallylic Alcohols
Authors: Brauns Marcus , Muller Frédéric , Gülden Daniel , Böse Dietrich , Frey Wolfgang , Breugst Martin , Pietruszka Jörg 
Published: December 2015

AbstractThe use of a convenient protecting group for boronates allows a selective, catalyzed SN2′ reaction to generate allylboronates which are applied for the synthesis of enantiomerically pure homoallylic alcohols. Depending on the configuration of both catalyst and the protecting group any of the four possible stereoisomers can be formed. The rationale behind the selective addition is supported by density functional theory calculations.
Identification of a Systemic Lupus Erythematosus Risk Locus Spanning ATG16L2, FCHSD2, and P2RY2 in Koreans
Authors: Lessard Christopher J. , Sajuthi Satria , Zhao Jian , Kim Kwangwoo , Ice John A. , Li He , Ainsworth Hannah , Rasmussen Astrid , Kelly Jennifer A. , Marion Miranda , Bang So‐Young , Bin Joo Young , Choi Jeongim , Lee Hye‐Soon , Mo Kang Young , Suh Chang‐Hee , Tae Chung Won , Lee Soo‐Kon , Choe Jung‐Yoon , Cheol Shim Seung , Hee Oh Ji , Jin Kim Young , Han Bok‐Ghee , Shen Nan , Siew Howe Hwee , Wakeland Edward K. , Li Quan‐Zhen , Wook Song Yeong , Gaffney Patrick M. , Alarcón‐Riquelme Marta E. , Criswell Lindsey A. , Jacob Chaim O. , Kimberly Robert P. , Vyse Timothy J. , Harley John B. , Sivils Kathy L. , Bae Sang‐Cheol , Langefeld Carl D. , Tsao Betty P. 
Published: December 2015

ObjectiveSystemic lupus erythematosus (SLE) is a chronic autoimmune disorder whose etiology is incompletely understood, but likely involves environmental triggers in genetically susceptible individuals. Using an unbiased genome‐wide association (GWA) scan and replication analysis, we sought to identify the genetic loci associated with SLE in a Korean population.MethodsA total of 1,174 SLE cases and 4,246 population controls from Korea were genotyped and analyzed with a GWA scan to identify single‐nucleotide polymorphisms (SNPs) significantly associated with SLE, after strict quality control measures were applied. For select variants, replication of SLE risk loci was tested in an independent data set of 1,416 SLE cases and 1,145 population controls from Korea and China.ResultsEleven regions outside the HLA exceeded the genome‐wide significance level (P = 5 × 10−8). A novel SNP–SLE association was identified between FCHSD2 and P2RY2, peaking at rs11235667 (P = 1.03 × 10−8, odds ratio [OR] 0.59) on a 33‐kb haplotype upstream of ATG16L2. In the independent replication data set, the SNP rs11235667 continued to show a significant association with SLE (replication meta‐analysis P = 0.001, overall meta‐analysis P = 6.67 × 10−11; OR 0.63). Within the HLA region, the SNP–SLE association peaked in the class II region at rs116727542, with multiple independent effects observed in this region. Classic HLA allele imputation analysis identified HLA–DRB1*1501 and HLA–DQB1*0602, each highly correlated with one another, as most strongly associated with SLE. Ten previously established SLE risk loci were replicated: STAT1–STAT4, TNFSF4, TNFAIP3, IKZF1, HIP1, IRF5, BLK, WDFY4, ETS1, and IRAK1–MECP2. Of these loci, previously unreported, independent second risk effects of SNPs in TNFAIP3 and TNFSF4, as well as differences in the association with a putative causal variant in the WDFY4 region, were identified.ConclusionFurther studies are needed to identify true SLE risk effects in other loci suggestive of a significant association, and to identify the causal variants in the regions of ATG16L2, FCHSD2, and P2RY2.
Computational Characterization of the Origin of Selectivity in Cycloaddition Reactions Catalyzed by Phosphoric Acid Derivatives
Authors: Liu Chunhui , Besora Maria , Maseras Feliu 
Published: December 2015

AbstractThe mechanism of the organocatalyzed [4+2] cycloaddition of ο‐hydroxybenzaldimines to 2,3‐dihydro‐2 H‐furan (DHF) to form furanobenzopyrans has been investigated by using computational methods. Experiments have shown that this reaction produces different products (trans‐fused or cis‐fused) if different phosphoric acid derivatives are applied. Our study shows the reaction proceeds through a mechanism in which the imine re‐arranges into an amine, which subsequently reacts with DHF with mediation from the catalyst. The rate‐limiting step in this process is the formation of two new bonds, which is also the key step in determining the reaction selectivity. The selectivity is controlled by a balance of noncovalent interactions between the catalyst and the substrates. The discriminating factor between the two catalysts is the presence of a triflyl substituent on one of catalysts, which constraints the relative orientations of the substrates.
2D l‐Di‐toluoyl‐tartaric acid Lanthanide Coordination Polymers: Toward Single‐component White‐Light and NIR Luminescent Materials
Authors: Niu Wan‐Ying , Sun Jing‐Wen , Yan Peng‐Fei , Li Yu‐Xin , An Guang‐Hui , Li Guang‐Ming 
Published: December 2015

AbstractA series of five l‐di‐p‐toluoyl‐tartaric acid (l‐DTTA) lanthanide coordination polymers, namely {[Ln4K4 L6(H2O)x]⋅yH2O}n, [Ln=Dy (1), x=24, y=12; Ln=Ho (2), x=23, y=12; Ln=Er (3), x=24, y=12; Ln=Yb (4), x=24, y=11; Ln=Lu (5), x=24, y=12] have been isolated by simple reactions of H2L (H2L= L‐DTTA) with LnCl3⋅6 H2O at ambient temperature. X‐ray crystallographic analysis reveals that complexes 1–5 feature two‐dimensional (2D) network structures in which the Ln3+ ions are bridged by carboxylate groups of ligands in two unique coordinated modes. Luminescent spectra demonstrate that complex 1 realizes single‐component white‐light emission, while complexes 2–4 exhibit a characteristic near‐infrared (NIR) luminescence in the solid state at room temperature.
Elevated body mass index and decreased diet quality among women and risk of birth defects in their offspring
Authors: Carmichael Suzan L. , Yang Wei , Gilboa Suzanne , Ailes Elizabeth , Correa Adolfo , Botto Lorenzo D. , Feldkamp Marcia L. , Shaw Gary M. ,   the National Birth Defects Prevention Study
Published: December 2015

BackgroundWe examined whether risks of 32 birth defects were higher than expected in the presence of overweight or obese body mass index (BMI) and low diet quality, based on estimating individual and joint effects of these factors and calculating relative excess risk due to interaction.MethodsAnalyses included mothers of 20,250 cases with birth defects and 8617 population‐based controls without birth defects born from 1997 to 2009 and interviewed for the National Birth Defects Prevention Study. We used logistic regression to generate adjusted odds ratios (AORs) reflecting the combined effects of BMI and diet quality. We focused analyses on 16 birth defects (n = 11,868 cases, 8617 controls) for which initial results suggested an association with BMI or diet quality.ResultsRelative to the reference group (normal weight women with not low diet quality, i.e., >lowest quartile), AORs for low diet quality among normal weight women tended to be >1, and AORs for overweight and obese women tended to be stronger among women who had low diet quality than not low diet quality. For 9/16 birth defects, AORs for obese women who had low diet quality—the group we hypothesized to have highest risk—were higher than other stratum‐specific AORs. Most relative excess risk due to interactions were positive but small (<0.5), with confidence intervals that included zero.ConclusionThese findings provide evidence for the hypothesis of highest birth defect risks among offspring to women who are obese and have low diet quality but insufficient evidence for an interaction of these factors in their contribution to risk. Birth Defects Research (Part A) 106:164–171, 2016. © 2015 Wiley Periodicals, Inc.
Metabolic engineering of acid resistance elements to improve acid resistance and propionic acid production of Propionibacterium jensenii
Authors: Guan Ningzi , Li Jianghua , Shin Hyun‐dong , Du Guocheng , Chen Jian , Liu Long 
Published: December 2015

ABSTRACTPropionic acid (PA) and its salts are widely used in the food, pharmaceutical, and chemical industries. Microbial production of PA by propionibacteria is a typical product‐inhibited process, and acid resistance is crucial in the improvement of PA titers and productivity. We previously identified two key acid resistance elements—the arginine deaminase and glutamate decarboxylase systems—that protect propionibacteria against PA stress by maintaining intracellular pH homeostasis. In this study, we attempted to improve the acid resistance and PA production of Propionibacterium jensenii ATCC 4868 by engineering these elements. Specifically, five genes (arcA, arcC, gadB, gdh, and ybaS) encoding components of the arginine deaminase and glutamate decarboxylase systems were overexpressed in P. jensenii. The activities of the five enzymes in the engineered strains were 26.7–489.0% higher than those in wild‐type P. jensenii. The growth rates of the engineered strains decreased, whereas specific PA production increased significantly compared with those of the wild‐type strain. Among the overexpressed genes, gadB (encoding glutamate decarboxylase) increased PA resistance and yield most effectively; the PA resistance of P. jensenii‐gadB was more than 10‐fold higher than that of the wild‐type strain, and the production titer, yield, and conversion ratio of PA reached 10.81 g/L, 5.92 g/g cells, and 0.56 g/g glycerol, representing increases of 22.0%, 23.8%, and 21.7%, respectively. We also investigated the effects of introducing these acid resistance elements on the transcript levels of related enzymes. The results showed that the expression of genes in the engineered pathways affected the expression of the other genes. Additionally, the intracellular pools of amino acids were altered as different genes were overexpressed, which may further contribute to the enhanced PA production. This study provides an effective strategy for improving PA production in propionibacteria; this strategy may be useful for the production of other organic acids. Biotechnol. Bioeng. 2016;113: 1294–1304. © 2015 Wiley Periodicals, Inc.
A novel strategy for selective gene delivery by using the inhibitory effect of blue light on jetPRIME‐mediated transfection
Authors: Dateki Minori , Imamura Osamu , Arai Masaaki , Shimizu Hidehisa , Takishima Kunio 
Published: December 2015

ABSTRACTPhotodynamic control of gene delivery is a new technology with growing applications in gene therapy and basic cell research. Main approaches of light‐selective gene delivery rely on the light‐dependent enhancement of transfection efficiency. Studies focused on light‐stimulated inhibitory regulation of transfection have rarely been reported. Here, we tried to establish a novel procedure of light‐dependent inhibition of transfection. Our experiments, conducted with several types of commercial transfection reagents, revealed that jetPRIME‐mediated transfection was strongly inhibited by blue light. Although the uptake of reagent–DNA complex was drastically reduced, preliminary exposure of cells or reagent–DNA complex to blue light had no inhibitory effect on the transfection efficiency. The inhibitory effect was wavelength‐dependent and mediated by reactive oxygen species. Partial exposure of a culture vessel to blue light resulted in selective gene delivery into cells grown on the unexposed area of the vessel. By using this approach, different types of plasmid DNA were delivered into different areas in the culture vessel. This novel approach to the inhibitory control of transfection provides practical options for research and therapeutics. Biotechnol. Bioeng. 2016;113: 1560–1567. © 2015 Wiley Periodicals, Inc.
Kidney and liver transplantation in the elderly
Authors: Sutherland A I , IJzermans J N M , Forsythe J L R , Dor F J M F 
Published: December 2015

Abstract

Background
Transplant surgery is facing a shortage of deceased donor organs. In response, the criteria for organ donation have been extended, and an increasing number of organs from older donors are being used. For recipients, the benefits of transplantation are great, and the growing ageing population has led to increasing numbers of elderly patients being accepted for transplantation.

Methods
The literature was reviewed to investigate the impact of age of donors and recipients in abdominal organ transplantation, and to highlight aspects of the fine balance in donor and recipient selection and screening, as well as allocation policies fair to young and old alike.

Results
Overall, kidney and liver transplantation from older deceased donors have good outcomes, but are not as good as those from younger donors. Careful donor selection based on risk indices, and potentially biomarkers, special allocation schemes to match elderly donors with elderly recipients, and vigorous recipient selection, allows good outcomes with increasing age of both donors and recipients. The results of live kidney donation have been excellent for donor and recipient, and there is a trend towards inclusion of older donors. Future strategies, including personalized immunosuppression for older recipients as well as machine preservation and reconditioning of donor organs, are promising ways to improve the outcome of transplantation between older donors and older recipients.

Conclusion
Kidney and liver transplantation in the elderly is a clinical reality. Outcomes are good, but can be optimized by using strategies that modify donor risk factors and recipient co-morbidities, and personalized approaches to organ allocation and immunosuppression.