bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early, Incomplete, or Preclinical Autoimmune Systemic Rheumatic Diseases and Pregnancy Outcome
Authors: Spinillo Arsenio , Beneventi Fausta , Locatelli Elena , Ramoni Vèronique , Caporali Roberto , Alpini Claudia , Albonico Giulia , Cavagnoli Chiara , Montecucco Carlomaurizio 
Published: May 2016

ObjectiveTo evaluate the impact of preclinical systemic autoimmune rheumatic disorders on pregnancy outcome.MethodsIn this longitudinal cohort study, patients were enrolled during the first trimester of pregnancy if they reported having had connective tissue disorder symptoms, were found to be positive for circulating autoantibodies, and on clinical evaluation were judged to have a preclinical or incomplete rheumatic disorder. The incidence of fetal growth restriction (FGR), preeclampsia, and adverse pregnancy outcomes in patients with preclinical rheumatic disorders was compared with that in selected controls, after adjustment for confounders by penalized logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsOf 5,232 women screened, 150 (2.9%) were initially diagnosed as having a suspected rheumatic disorder. After a mean ± SD postpartum follow‐up of 16.7 ± 5.5 months, 64 of these women (42.7%) had no clinically apparent rheumatic disease and 86 (57.3%) had persistent symptoms and positive autoantibody results, including 10 (6.7%) who developed a definitive rheumatic disease. The incidences of preeclampsia/FGR and of small for gestational age (SGA) infants were 5.1% (23 of 450) and 9.3% (42 of 450), respectively, among controls, 12.5% (8 of 640) (OR 2.7 [95% CI 1.1–6.4]) and 18.8% (12 of 64) (OR 2.2 [95% CI 1.1–4.5]), respectively, among women with no clinically apparent disease, and 16.3% (14 of 86) (OR 3.8 [95% CI 1.9–7.7]) and 18.6% (16 of 86) (OR 2.3 [95% CI 1.2–4.3]), respectively, among those with persisting symptoms at follow‐up. Mean ± SD umbilical artery Doppler pulsatility indices were higher among women with no clinically apparent disease (0.95 ± 0.2) and those with persisting symptoms (0.96 ± 0.21) than in controls (0.89 ± 0.12) (P = 0.01 and P < 0.001, respectively).ConclusionIn our study population, preclinical rheumatic disorders were associated with an increased risk of FGR/preeclampsia and SGA. The impact of these findings and their utility in screening for FGR/preeclampsia need to be confirmed in population studies.
Association Between Breast Cancer Recurrence and Immunosuppression in Rheumatoid Arthritis and Inflammatory Bowel Disease: A Cohort Study
Authors: Mamtani Ronac , Clark Amy S. , Scott Frank I. , Brensinger Colleen M. , Boursi Ben , Chen Lang , Xie Fenglong , Yun Huifeng , Osterman Mark T. , Curtis Jeffrey R. , Lewis James D. 
Published: May 2016

ObjectiveBreast cancer recurrence may be promoted by immunosuppression due to decreased immune surveillance. The aim of this study was to examine the rates of breast cancer recurrence in patients with immune‐mediated disease and treated breast cancer who received therapy with methotrexate, thiopurines, or anti–tumor necrosis factor (anti‐TNF).MethodsThree retrospective cohort studies within Medicare (2000–2012) included women with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) who underwent surgery for primary breast cancer. Recurrent or second primary breast cancers occurring more than 365 days after the initial surgery were identified. Separate Cox regression models were used to examine the risk of cancer recurrence in patients treated with methotrexate, thiopurines, or anti‐TNF agents after surgery, each compared with no use. Analyses were matched for type of breast surgery and receipt and type of adjuvant therapy.ResultsAcross all medication groups, 107 women experienced breast cancer recurrence during 5,196 person‐years. The incidence rates were 20.3 and 19.6 per 1,000 person‐years in methotrexate users and nonusers, respectively, 32.3 and 17.6 in thiopurine users and nonusers, respectively, and 22.3 and 19.5 in anti‐TNF users and nonusers, respectively. There was no significantly increased risk of breast cancer recurrence with use of methotrexate (adjusted hazard ratio [HR] 1.07, 95% confidence interval [95% CI] 0.67–1.69), anti‐TNF therapy (HR 1.13, 95% CI 0.65–1.97), or thiopurines (HR 2.10, 95% CI 0.62–7.14).ConclusionThe risk of breast cancer recurrence in patients who received methotrexate, thiopurine, or anti‐TNF therapy was not statistically significantly increased, although we cannot rule out a 2‐fold or greater increased risk in those treated with thiopurines. These data provide reassurance to clinicians choosing to start methotrexate or anti‐TNF therapy in RA or IBD patients with treated breast cancer.
Pin1‐Targeted Therapy for Systemic Lupus Erythematosus
Authors: Wei Shuo , Yoshida Nobuya , Finn Greg , Kozono Shingo , Nechama Morris , Kyttaris Vasileios C. , Zhen Zhou Xiao , Tsokos George C. , Ping Lu Kun 
Published: May 2016

ObjectiveSystemic lupus erythematosus (SLE) is a debilitating autoimmune disease affecting multiple organs in the body, but therapeutic options are still very limited and often come with adverse effects. Increasing evidence has underlined an important role of the Toll‐like receptor 7 (TLR‐7)/TLR‐9/interleukin‐1 receptor–associated kinase 1 (IRAK‐1)/interferon regulatory factor 7 (IRF‐7) pathway in the development and progression of SLE. Notably, the prolyl isomerase Pin1 is an essential regulator of IRAK‐1 in TLR‐7/TLR‐9 signaling, but its role in SLE is unknown. We undertook this study to determine whether Pin1 is activated and plays any role in the development and treatment of SLE.MethodsActivation of Pin1 and TLR‐7/TLR‐9/IRAK‐1/IRF‐7 signaling was determined in various cell types among peripheral blood mononuclear cells from healthy controls and SLE patients. The effects of Pin1 and TLR signaling on SLE development were determined using validated Pin1 short hairpin RNA (shRNA), Pin1 genetic knockout, and the small‐molecule Pin1 inhibitor all‐trans‐retinoic acid (ATRA) in immune cells and in several strains of lupus‐prone mice.ResultsWe found abnormal activation of Pin1 and its downstream targets IRAK‐1 and IRF‐7 in SLE patients. Furthermore, inhibition of Pin1 using either validated Pin1 shRNA or ATRA blocked TLR‐7–induced activation of IRAK‐1 and IRF‐7 in SLE patient–derived immune cells. Moreover, in multiple lupus‐prone animals, both Pin1 knockout and ATRA strikingly attenuated the expression of autoimmunity, including skin lesions, lymphadenopathy, splenomegaly, glomerulonephritis, proteinuria, and production of anti–double‐stranded DNA antibodies and CD4−CD8− T cells, and also prolonged overall survival in MRL/lpr and B6.lpr mice.ConclusionPin1 plays a critical role in the development of SLE, and Pin1‐targeted therapy offers a promising new strategy for treating SLE.
Enrichment of Scleroderma Vascular Disease–Associated Autoantigens in Endothelial Lineage Cells
Authors: McMahan Zsuzsanna H. , Cottrell Tricia R. , Wigley Fredrick M. , Antiochos Brendan , Zambidis Elias T. , Soon Park Tea , Halushka Marc K. , Gutierrez‐Alamillo Laura , Cimbro Raffaello , Rosen Antony , Casciola‐Rosen Livia 
Published: May 2016

ObjectiveScleroderma patients with autoantibodies to CENPs and/or interferon‐inducible protein 16 (IFI‐16) are at increased risk of severe vascular complications. This study was undertaken to determine whether these autoantigens are enriched in cells of the vasculature.MethodsSuccessive stages of embryoid bodies (EBs) as well as vascular progenitors were used to evaluate the expression of scleroderma autoantigens IFI‐16 and CENP by immunoblotting. CD31 was included to mark early blood vessels. IFI‐16 and CD31 expression were defined in paraffin‐embedded skin sections from scleroderma patients and from healthy controls. IFI‐16 expression was determined by flow cytometric analysis in circulating endothelial cells (CECs) and circulating hematopoietic progenitor cells.ResultsExpression of CENP‐A, IFI‐16, and CD31 was enriched in EBs on days 10 and 12 of differentiation, and particularly in cultures enriched in vascular progenitors (IFI‐16, CD31, and CENPs A and B). This pattern was distinct from that of comparator autoantigens. Immunohistochemical staining of paraffin‐embedded skin sections showed enrichment of IFI‐16 in CD31‐positive vascular endothelial cells in biopsy specimens from scleroderma patients and normal controls. Flow cytometric analysis revealed IFI‐16 expression in circulating hematopoietic progenitor cells but minimal expression in CECs.ConclusionOur findings indicate that expression of the scleroderma autoantigens IFI‐16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage‐enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens.
Bcl‐2 as a Therapeutic Target in Human Tubulointerstitial Inflammation
Authors: Ko Kichul , Wang Jianing , Perper Stuart , Jiang Yulei , Yanez Denisse , Kaverina Natalya , Ai Junting , Liarski Vladimir M. , Chang Anthony , Peng Yahui , Lan Li , Westmoreland Susan , Olson Lisa , Giger Maryellen L. , Chun Wang Li , Clark Marcus R. 
Published: May 2016

ObjectiveIn lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ adaptive immune cell networks that amplify local tissue damage. Since conventional therapy appears ineffective for severe TII, and these patients often progress to renal failure, understanding in situ mechanisms might reveal new therapeutic targets. This study was undertaken to assess whether dysregulated apoptotic regulators maintain local adaptive immunity and drive inflammation in TII.MethodsThis study utilized novel computational approaches that, when applied to multicolor confocal images, quantified apoptotic regulator protein expression in selected lymphocyte subsets. This approach was validated using laser‐capture microdissection (LCM) coupled to quantitative polymerase chain reaction (qPCR). Furthermore, the consequences of dysregulated apoptotic mediator expression were explored in a murine model of lupus nephritis.ResultsAnalyses of renal biopsy tissue from patients with lupus nephritis and those with mixed cellular renal allograft rejection revealed that the B cell lymphoma 2 protein (Bcl‐2) was frequently expressed in infiltrating lymphocytes, whereas expression of myeloid cell leukemia 1 was low. In contrast, the reciprocal pattern of expression was observed in tonsil germinal centers. These results were consistent with RNA expression data obtained using LCM and qPCR. Bcl‐2 was also highly expressed in tubulointerstitial infiltrates in (NZB × NZW)F1 (NZB/NZW) mice. Furthermore, treatment of NZB/NZW mice with ABT‐199, a selective oral inhibitor of Bcl‐2, prolonged survival and prevented proteinuria and development of TII in a lupus prevention model. Interestingly, glomerular immune complexes were partially ameliorated by ABT‐199 treatment, and serum anti–double‐stranded DNA antibody titers were unaffected.ConclusionThese data demonstrate that Bcl‐2 is an attractive therapeutic target in patients with lupus nephritis who manifest TII.
Accelerated homology‐directed targeted integration of transgenes in Chinese hamster ovary cells via CRISPR/Cas9 and fluorescent enrichment
Authors: Lee Jae Seong , Grav Lise Marie , Pedersen Lasse Ebdrup , Lee Gyun Min , Kildegaard Helene Faustrup 
Published: May 2016

ABSTRACTTargeted gene integration into site‐specific loci can be achieved in Chinese hamster ovary (CHO) cells via CRISPR/Cas9 genome editing technology and the homology‐directed repair (HDR) pathway. The low efficiency of HDR often requires antibiotic selection, which limits targeted integration of multiple genes at multiple sites. To improve HDR‐mediated targeted integration, while avoiding the use of selection markers, chemical treatment for increased HDR, and fluorescent enrichment of genome‐edited cells was assessed in CHO cells. Chemical treatment did not improve HDR‐mediated targeted integration. In contrast, fluorescent markers in Cas9 and donor constructs enable FACS enrichment, resulting in a threefold increase in the number of cells with HDR‐mediated genome editing. Combined with this enrichment method, large transgenes encoding model proteins (including an antibody) were successfully targeted integrated. This approach provides a simple and fast strategy for targeted generation of stable CHO production cell lines in a rational way. Biotechnol. Bioeng. 2016;113: 2518–2523. © 2016 Wiley Periodicals, Inc.
Construction of plasmids with tunable copy numbers in Saccharomyces cerevisiae and their applications in pathway optimization and multiplex genome integration
Authors: Lian Jiazhang , Jin Run , Zhao Huimin 
Published: May 2016

ABSTRACTThe CEN/ARS‐based low‐copy plasmids and 2 μ‐based high‐copy plasmids have been broadly used for both fundamental studies and practical applications in Saccharomyces cerevisiae. However, the relative low copy numbers and narrow dynamic range limit their applications in many cases. In this study, the expression level of the selection marker proteins was engineered to increase the plasmid copy numbers. A series of plasmids with step‐wise increased copy numbers were constructed. The copy number of the plasmids with engineered dominant markers (5–100 copies per cell) showed a positive correlation with the concentration of antibiotics supplemented to the growth media. Based on this finding, we developed a simple yet highly efficient strategy, named Pathway Optimization by Tuning Antibiotic Concentrations (POTAC) to rapidly balance the flux of multi‐gene pathways at the DNA level in S. cerevisiae. As proof of concept, POTAC was used to optimize the lycopene and n‐butanol biosynthetic pathways, increasing the production of lycopene and n‐butanol by 10‐ and 100‐fold, respectively. Additionally, multiplex genome integration with controllable copy numbers was attempted by combining the engineered dominant markers with the CRISPR/Cas9 system. Biotechnol. Bioeng. 2016;113: 2462–2473. © 2016 Wiley Periodicals, Inc.
Mold‐casted non‐degradable, islet macro‐encapsulating hydrogel devices for restoration of normoglycemia in diabetic mice
Authors: Rios Peter Daniel , Zhang Xiaomin , Luo Xunrong , Shea Lonnie D. 
Published: May 2016

ABSTRACTIslet transplantation is a potential cure for diabetic patients, however this procedure is not widely adopted due to the high rate of graft failure. Islet encapsulation within hydrogels is employed to provide a three‐dimensional microenvironment conducive to survival of transplanted islets to extend graft function. Herein, we present a novel macroencapsulation device, composed of PEG hydrogel, that combines encapsulation with lithography techniques to generate polydimethylsiloxane (PDMS) molds. PEG solutions are mixed with islets, which are then cast into PDMS molds for subsequent crosslinking. The molds can also be employed to provide complex architectures, such as microchannels that may allow vascular ingrowth through pre‐defined regions of the hydrogel. PDMS molds allowed for the formation of stable gels with encapsulation of islets, and in complex architectures. Hydrogel devices with a thickness of 600 μm containing 500 islets promoted normoglycemia within 12 days following transplantation into the epididymal fat pad, which was sustained over the two‐month period of study until removal of the device. The inclusion of microchannels, which had a similar minimum distance between islets and the hydrogel surface, similarly promoted normoglycemia. A glucose challenge test indicated hydrogel devices achieved normoglycemia 90 min post‐dextrose injections, similar to control mice with native pancreata. Histochemical staining revealed that transplanted islets, identified as insulin positive, were viable and isolated from host tissue at 8 weeks post‐transplantation, yet devices with microchannels had tissue and vascular ingrowth within the channels. Taken together, these results demonstrate a system for creating non‐degradable hydrogels with complex geometries for encapsulating islets capable of restoring normoglycemia, which may expand islet transplantation as a treatment option for diabetic patients. Biotechnol. Bioeng. 2016;113: 2485–2495. © 2016 Wiley Periodicals, Inc.
Parental bonding and neuropsychological performance are associated with episodic simulation of future events in trauma‐exposed patients with major depressive disorder
Authors: Parlar Melissa , Lee Alex , Haqqee Zeeshan , Rhooms Latisha , Lanius Ruth A. , McKinnon Margaret C. 
Published: May 2016

AbstractIntroductionMajor depressive disorder (MDD) and trauma‐related disorders are associated with deficits in remembering the past and imagining the future (i.e., episodic simulation). We examined parental bonding and neuropsychological performance in relation to episodic simulation in trauma‐exposed patients with recurrent MDD.MethodsTrauma‐exposed patients with MDD (n = 21) and matched controls (n = 20) completed a future‐oriented Autobiographical Interview, the Parental Bonding Instrument, and a standardized neuropsychological battery.ResultsPatients with major depressive disorder generated fewer episodic details for future neutral events compared to controls. Although higher reported levels of maternal care were associated with increased specificity of negative future events among the patient group, higher maternal overprotection was related to decreased specificity of negative and positive future events. Higher levels of performance on measures of intelligence, verbal memory, executive functioning, and sustained attention were associated with increased specificity of future events.ConclusionsMaternal relations during childhood and neuropsychological performance are related to the specificity of episodic simulation in adult patients with MDD. Childhood experience continues to influence memory performance into adulthood.
Expanding an Efficient, Electrically Driven and CNT‐Tagged P450 System into the Third Dimension: A Nanowired CNT‐Containing and Enzyme‐Stabilising 3 D Sol–Gel Electrode
Authors: Llaudet Enrique C. , Darimont Dominique , Samba Ramona , Matiychyn Ilona , Stelzle Martin , Weissenborn Martin J. , Hauer Bernhard 
Published: May 2016

AbstractAlthough electrochemically catalysed P450 reactions have been described, their efficiency and applicability remained limited. This is mostly due to low enzyme activity, laborious protein immobilisation and the small electrode surface. We established a novel protein immobilisation method for a determined orientation and electrical wiring of the enzyme without post‐expression modification. By genetic introduction of an anchor‐peptide our method is applicable for screening medium to large mutant libraries and detection by an electrode system. The system was expanded by using wired carbon nanotubes within a sol‐gel matrix to create a three dimensional electrode.
Ligand‐Mediated G‐Quadruplex Induction in a Double‐Stranded DNA Context by Cyclic Imidazole/Lysine Polyamide
Authors: Asamitsu Sefan , Li Yue , Bando Toshikazu , Sugiyama Hiroshi 
Published: May 2016

AbstractG‐quadruplex (G4) DNA is often observed as a DNA secondary structure in guanine‐rich sequences, and is thought to be relevant to pharmacological and biological events. Therefore, G4 ligands have attracted great attention as potential anticancer therapies or in molecular probe applications. Here, we designed cyclic imidazole/lysine polyamide (cIKP) as a new class of G4 ligand. It was readily synthesized without time‐consuming column chromatography. cIKP selectively recognized particular G4 structures with low nanomolar affinity. Moreover, cIKP exhibited the ability to induce G4 formation of the promoter of G4‐containing DNA in the context of stable double‐stranded DNA (dsDNA) under molecular crowding conditions. This cIKP might be applicable as a molecular probe for the detection of potential G4‐forming sequences in dsDNA.
Polyaniline Nanorods Grown on Hollow Carbon Fibers as High‐Performance Supercapacitor Electrodes
Authors: Gao Shuangyan , He Shuyue , Zang Peiyu , Dang Liqin , Shi Feng , Xu Hua , Liu Zonghuai , Lei Zhibin 
Published: May 2016

AbstractHollow carbon fibers (aCFs) with a high specific surface area are applied as conductive scaffolds for polyaniline (PANi) growth. aCFs oxidized by HNO3 treatment have more surface negative charges, which interact with protonated aniline molecules in acidic media. The subsequent chemical oxidative polymerization assisted by (NH4)2S2O8 yields aCF–PANi composites with PANi nanorod arrays strongly coupled on both the external and internal surfaces of the aCFs. Serving as binder‐free supercapacitor electrode, the aCF–PANi composite with 31 wt % PANi exhibits a specific capacitance of 364 F g−1, and retains 70 % of this value at 20 A g−1. More interestingly, it exhibits excellent cycling stability with 92.5 % capacitance retention, and outstanding reversibility with 98.6 % coulombic efficiency, even after 5000 continuous cycles; this performance is far superior to that of both aCF and PANi electrodes. The strongly coupled PANi arrays on the aCF surface greatly reduce the interface resistance, thus facilitating both ion and electron transport for enhanced capacitive performance.
The Electric Double Layer in an Ionic Liquid Incorporated with Water Molecules: Atomic Force Microscopy Force Curve Study
Authors: Zhong Yunxin , Yan Jiawei , Li Miangang , Chen Li , Mao Bingwei 
Published: May 2016

AbstractElectrochemical techniques and atomic force microscopy based force curve measurements under potential control are combined to investigate the effect of small amounts of water on the structure of the electric double layer of an Au(111)/1‐butyl‐1‐methylpyrrolidinium bis(trifluoromethylsulfonyl)amide (BMPTFSA) interface. Three to five layering structures, including two charged layers, are observed at the Au(111)/BMPTFSA interface at potentials more negative than the point of zero charge. With an increase in the water concentration, the stiffness values for both the first and second layers decrease, which demonstrates that more water molecules adsorb on the Au(111) surface or interact with the ionic liquid, and thus weaken the interactions between cations, anions, and the electrode surface and lower the stability of the layering structures. The thicknesses of the charged interior layers (the first and second layers in this system) increase with an increase in the water concentration and the thicknesses of neutral exterior layers (the next one to three layers in this system) remain almost unchanged. The structure of the first layer of the interface varies dramatically with the change in the water concentration.
Towards Uniform Iodine Catalysis: Intramolecular C−H Amination of Arenes under Visible Light
Authors: Martínez Claudio , Bosnidou Alexandra E. , Allmendinger Simon , Muñiz Kilian 
Published: May 2016

AbstractA photochemical catalytic amination of arenes is presented. The reaction proceeds under benign iodine catalysis in the presence of visible light as the initiator and provides access to a range of differently substituted arylamines. A total of 29 examples demonstrate the broad applicability of this mild oxidation method. The scope of the reaction could further be expanded to silyl‐tethered derivatives, which undergo intramolecular amination upon formation of seven‐membered heterocycles. Cleavage of the silicon tether provides access to the corresponding 3‐substituted anilines.
ChemInform Abstract: ELECTRON‐TRANSFER QUENCHING OF THE LUMINESCENCE OF RUTHENIUM AND OSMIUM POLYPYRIDINE COMPLEXES BY COBALT(III) COMPLEXES
Authors: SANDRINI D. , GANDOLFI M. T. , MAESTRI M. , BOLLETTA F. , BALZANI V. 
Published: May 2016

AbstractDie Lumineszenzlöschung der Komplexe (I) und (II) durch 17 Co(III)‐Komplexe wird in wäßriger Lösung untersucht.