bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contradictory Role of CD97 in Basal and Tumor Necrosis Factor–Induced Osteoclastogenesis In Vivo
Authors: Won Hee Yeon , Mun Se Hwan , Shin Bongjin , Lee Sun‐Kyeong 
Published: December 2015

ObjectiveCD97, a member of the 7‐transmembrane epidermal growth factor family of adhesion G protein–coupled receptors, is expressed on various cell types. This study was undertaken to elucidate the functions of CD97 in bone and inflammation in an experimental mouse model, by examining the effect of CD97 on osteoclastogenesis in vitro, characterizing the skeletal phenotype of CD97‐deficient (CD97‐knockout [KO]) mice, and assessing the responses to tumor necrosis factor (TNF) treatment.MethodsFemoral tissue and bone marrow (BM)–derived cells from CD97‐KO and wild‐type (WT) mice were assessed using histomorphometric analyses, in vitro cultures, and reverse transcription–polymerase chain reaction. Serum cytokine and chemokine levels in the presence or absence of TNF challenge were analyzed by multiplex assay.ResultsIn cultures of mouse BM‐derived macrophages in vitro, RANKL induced the expression of CD97. In vivo, the trabecular bone volume of the femurs of female CD97‐KO mice was increased, and this was associated with a decrease in the number of osteoclasts. Compared to WT mice, CD97‐KO mice had a reduced potential to form osteoclast‐like cells in vitro. Furthermore, TNF treatment augmented the formation of osteoclasts in the calvaria of CD97‐KO mice in vivo, by increasing the production of RANKL and other cytokines and chemokines and by reducing the production of osteoprotegerin by calvarial cells.ConclusionThese findings demonstrate that CD97 is a positive regulator of osteoclast‐like cell differentiation, a mechanism that influences bone homeostasis. However, the presence of CD97 may be essential to suppress the initial osteoclastogenesis that occurs in response to acute and local inflammatory stimuli.
Brief Report: Influence of HLA–DRB1 Susceptibility Alleles on the Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans
Authors: Bang So‐Young , Choi Ji‐Young , Park Songree , Choi Jeongim , Hong Seung‐Jae , Lee Hye‐Soon , Choi Chan‐Bum , Bae Sang‐Cheol 
Published: December 2015

ObjectiveTo investigate the association between HLA–DRB1 alleles and systemic lupus erythematosus (SLE) susceptibility and features of SLE, such as clinical manifestations and autoantibody profiles, in a Korean population.MethodsWe tested the genetic associations between HLA–DRB1 alleles and SLE susceptibility and clinical subphenotypes in 1,089 patients with SLE and 2,161 control subjects, including a discovery set (475 patients and 1,119 controls) and a replication set (614 patients and 1,042 controls). We used a relative predispositional effects (RPEs) method to examine the independent effect of each allele associated with SLE or its subphenotypes.ResultsWe identified 4 HLA–DRB1 alleles that were associated with increased susceptibility to SLE, 2 of which had been detected previously (*15:01; P for RPE = 1.11 × 10−13, odds ratio [OR] 1.88) and *09:01 (P for RPE = 1.59 × 10−5, OR 1.46), and 2 of which were novel alleles (*08:03 [P for RPE = 8.80 × 10−8, OR 1.62]) and *07:01 (P for RPE = 1.14 × 10−6, OR 1.57)]. In addition, protective effects on the development of SLE were observed for 2 novel alleles (HLA–DRB1*12:02 [P for RPE = 6.35 × 10−4, OR 0.49]) and *11:01 [P for RPE = 1.24 × 10−3, OR 0.59]). The SLE risk alleles had an additive genetic effect, as demonstrated by the finding that double copies of these alleles (OR 3.38) had larger risk effects size compared with single copies (OR 1.95) and no copy (OR 1 [reference]). In a subphenotype analysis, various HLA–DRB1 alleles (including SLE risk alleles) were observed to have significant predispositional effects on diverse clinical manifestations. In particular, HLA–DRB1*15:01 (OR 2.30), *09:01 (OR 2.46), *07:01 (OR 2.61), and *08:03 (OR 2.97) were strongly associated with the risk of anti‐Sm antibody production.ConclusionWe detected 6 HLA–DRB1 alleles that were associated with SLE in Koreans. The SLE risk alleles promoted the production of autoantibodies, including anti‐Sm, and diverse clinical manifestations.
Thigh Muscle Strength Predicts Knee Replacement Risk Independent of Radiographic Disease and Pain in Women: Data From the Osteoarthritis Initiative
Authors: Culvenor Adam G. , Wirth Wolfgang , Ruhdorfer Anja , Eckstein Felix 
Published: December 2015

ObjectiveTo determine whether thigh muscle strength predicts the risk of undergoing knee replacement surgery, independent of radiographic severity of osteoarthritis and pain.MethodsParticipants in the Osteoarthritis Initiative study who had received a knee replacement between the 12‐month and 60‐month follow‐up visits (cases) were each matched with 1 control subject (who did not receive a knee replacement over 60 months) for age, sex, height, body mass index, baseline radiographic stage, and location of joint space narrowing. Isometric knee extensor and flexor strength was recorded biennially. The strength examination prior to knee replacement (≤2 years) was termed time 0, that 2 years prior to time 0 was termed time −2, and that 4 years prior to time 0 was termed time −4. Muscle strength in patients and controls was compared using paired t‐tests and conditional logistic regression analysis adjusted for pain.Results. One hundred thirty‐six participants (60% women, mean ± SD age 65 ± 9 years, body mass index 29 ± 4 kg/m2) received a knee replacement during follow‐up, had strength data for at least time 0, and had a matched control. Knee extensor strength at time 0 (primary outcome measure) was significantly lower in female patients compared with controls (P < 0.001, pain‐adjusted odds ratio [ORadj] 1.72, 95% confidence interval 1.16–2.56), but no significant difference was observed in men. Results were similar for knee flexor strength at time 0 and for longitudinal change in extensor and flexor strength between time −2 and time 0. Thigh muscle strength at time −2 or time −4, or change between time −4 and time −2, did not predict the risk of undergoing knee replacement surgery in men or women.ConclusionThigh muscle strength predicted the risk of undergoing knee replacement surgery in women, but not in men. The results of this study may identify a window during which the risk of undergoing knee replacement surgery in women can be modified.
Identification of Cyclin‐Dependent Kinase 1 as a Novel Regulator of Type I Interferon Signaling in Systemic Lupus Erythematosus
Authors: Wu Lingling , Qin Yuting , Xia Shiwei , Dai Min , Han Xiao , Wu Yanfang , Zhang Xiaoyan , Ma Jianyang , Wang Yan , Tang Yuanjia , Liu Zheng , Zhu Wei , Jallal Bahija , Yao Yihong , Qu Bo , Shen Nan 
Published: December 2015

ObjectiveType I interferon (IFN) signaling is regarded as a central pathogenic pathway in systemic lupus erythematosus (SLE). Specific inhibition of this pathway is a core area for the development of new therapies for SLE. This study was undertaken to clarify the pathogenic mechanism involved and to identify new therapeutic targets, using a high‐throughput screening platform to determine novel regulators that contribute to the overactivation of the type I IFN signaling pathway in SLE.MethodsA high‐throughput IFN‐stimulated response element (ISRE)–luciferase assay was used to screen for candidate genes that regulate the IFN signaling pathway. Western blotting was used to confirm the regulatory function of CDK1. SYBR Green quantitative reverse transcriptase–polymerase chain reaction was used to detect the expression of individual IFN‐stimulated genes (ISGs). The differential expression of CDK1 and ISGs in SLE patients and healthy controls was analyzed using RNA sequencing data and a microarray.ResultsThe high‐throughput ISRE‐luciferase assay revealed that CDK1 enhanced type I IFN signaling. Consistent with this finding, CDK1 promoted the type I IFN–induced phosphorylation of STAT‐1 and the up‐regulated expression of ISGs. CDK1 expression was elevated in peripheral blood mononuclear cells (PBMCs) and kidney biopsy specimens from SLE patients and correlated positively with their IFN scores. A CDK1 inhibitor reduced the expression of ISGs in PBMCs from SLE patients and in renal cells from mice with lupus.ConclusionOur findings indicate that CDK1 is a positive regulator of the IFN signaling pathway. The overexpression of CDK1 might contribute to the abnormally amplified type I IFN signaling in SLE, and the inhibition of CDK1 could be used to down‐regulate type I IFN signaling in SLE.
Whole Exome Sequencing Identifies Rare Protein‐Coding Variants in Behçet's Disease
Authors: Ognenovski Mikhail , Renauer Paul , Gensterblum Elizabeth , Kötter Ina , Xenitidis Theodoros , Henes Jörg C. , Casali Bruno , Salvarani Carlo , Direskeneli Haner , Kaufman Kenneth M. , Sawalha Amr H. 
Published: December 2015

ObjectiveBehçet's disease (BD) is a systemic inflammatory disease with an incompletely understood etiology. Despite the identification of multiple common genetic variants associated with BD, rare genetic variants have been less explored. We undertook this study to investigate the role of rare variants in BD by performing whole exome sequencing in BD patients of European descent.MethodsWhole exome sequencing was performed in a discovery set comprising 14 German BD patients of European descent. For replication and validation, Sanger sequencing and Sequenom genotyping were performed in the discovery set and in 2 additional independent sets of 49 German BD patients and 129 Italian BD patients of European descent. Genetic association analysis was then performed in BD patients and 503 controls of European descent. Functional effects of associated genetic variants were assessed using bioinformatic approaches.ResultsUsing whole exome sequencing, we identified 77 rare variants (in 74 genes) with predicted protein‐damaging effects in BD. These variants were genotyped in 2 additional patient sets and then analyzed to reveal significant associations with BD at 2 genetic variants detected in all 3 patient sets that remained significant after Bonferroni correction. We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and between BD and NEIL1 (rs5745908), involved in base excision DNA repair (P = 3.22 × 10−4 and P = 5.16 × 10−4, respectively). The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis (Bonferroni‐corrected P = 5.63 × 10−14, P = 7.29 × 10−6, P = 1.15 × 10−5, and P = 6.40 × 10−3, respectively). The genetic association in NEIL1 is a predicted splice donor variant that may introduce a deleterious intron retention and result in a noncoding transcript variant.ConclusionWe used whole exome sequencing in BD for the first time and identified 2 rare putative protein‐damaging genetic variants associated with this disease. These genetic variants might influence cytoskeletal regulation and DNA repair mechanisms in BD and might provide further insight into increased leukocyte tissue infiltration and the role of oxidative stress in BD.
Adaptation of CHO cells in serum‐free conditions for erythropoietin production: Application of EVOP technique for process optimization
Authors: Jukić Suzana , Bubenik Dijana , Pavlović Nediljko , Tušek Ana Jurinjak , Srček Višnja Gaurina 
Published: December 2015

AbstractMammalian cell cultures are the preferred expression systems for the production of biopharmaceuticals requiring posttranslational processing. Usually, cell cultures are cultivated in medium supplemented with serum, which supports cell proliferation, viability, and productivity. However, due to scientific and regulatory concerns, serum‐free conditions are required in recombinant protein production. Cell lines that are intended for commercial recombinant protein production have to adapt to serum‐ or protein‐free conditions early in their development. This is a labor‐ and time‐consuming process because of the specific cell requirements related to their adaptation in new microenvironment. In the present study, a Chinese hamster ovary (CHO) cell line producing glycosylated recombinant human erythropoietin (rhEPO) was adapted for growth and rhEPO production in serum‐ and protein‐free conditions. The physiology, growth parameters, and morphology of the CHO cells and rhEPO biosynthesis and structure were closely monitored during the adaptation process to avoid unwanted selection of cell subpopulations. The results showed that the CHO cells were successfully adapted to suspension growth and rhEPO production in the protein‐free conditions and that the structure of rhEPO remained nearly unchanged. In addition, during rhEPO production in the protein‐free suspension conditions, the agitation rate seem to be significant for optimal process performance in contrast to the initial cell concentration, evaluated through evolutionary operation method.
Functionalization of poly(amidoamine) dendrimer‐based nano‐architectures using a naphthalimide derivative and their fluorescent, dyeing and antimicrobial properties on wool fibers
Authors: Sadeghi‐Kiakhani Mousa , Safapour Siyamak 
Published: December 2015

AbstractNovel naphthalimide–poly(amidoamine) dendrimer fluorescent dyes were synthesized, and their structures were identified and confirmed using different characterization methods such as Fourier transform infrared, 1H NMR, 13C NMR, differential scanning calorimetry, elemental analysis and UV–vis spectroscopy. The spectrophotometric studies demonstrated absorption maxima (λmax) and extinction coefficient (εmax) values in the ranges of 429–438 nm and 25,635–88,618 L/mol/cm, respectively. The dyeing, fastness and antimicrobial properties of dyed wool fibers were examined. Colorimetric measurements demonstrated a greenish‐yellow hue with remarkable fluorescence intensity on dyed wool. Although the fastness properties of naphthalimide dye on wool fibers were poor/moderate, color fastness was appreciably improved through modification of the dye using dendrimers. The results revealed that the newly synthesized dyes are potent antimicrobial agents on wool fibers. Overall, it was deduced that poly(amidoamine) (PAMAM) dendrimers could be exploited as a promising tool in tailoring the different properties of naphthalimide dyes, being suitable for dyeing and antimicrobial finishing agents for wool fibers. Copyright © 2015 John Wiley & Sons, Ltd.
Randomized clinical trial of 940- versus 1470-nm endovenous laser ablation for great saphenous vein incompetence
Authors: Malskat W S J , Giang J , De Maeseneer M G R , Nijsten T E C , van den Bos R R 
Published: December 2015

Abstract

Background
The independent effect of wavelength used for endovenous laser ablation (EVLA) on patient-reported outcomes, health-related quality of life (HRQoL), treatment success and complications has not yet been established in a randomized clinical trial. The aim was to compare two different wavelengths, with identical energy level and laser fibres, in patients undergoing EVLA.

Methods
Patients with great saphenous vein incompetence were randomized to receive 940- or 1470-nm EVLA. The primary outcome was pain at 1 week. Secondary outcomes were: patient satisfaction, duration of analgesia use and time without normal activities assessed at 1 week; HRQoL after 12 weeks; treatment success after 12 and 52 weeks; change in Venous Clinical Severity Score (VCSS) after 12 weeks; and adverse events at 1 and 12 weeks.

Results
A total of 142 legs were randomized (940-nm EVLA, 70; 1470-nm EVLA, 72). Patients in the 1470-nm laser group reported significantly less pain on a visual analogue scale than those in the 940-nm laser group: median (i.q.r.) score 3 (2–7) versus 6 (3–8) (P = 0·004). Duration of analgesia use was significantly shorter after 1470-nm EVLA: median (i.q.r.) 1 (0–3) versus 2 (0–5) days (P = 0·037). HRQoL and VCSS improved equally in both groups. There was no difference in treatment success rates. Complications were comparable in both groups, except for more superficial vein thrombosis 1 week after 1470-nm EVLA.

Conclusion
EVLA using a 1470-nm wavelength fibre was associated with improved postoperative pain and a reduction in analgesia use in the first week after surgery compared with use of a 940-nm fibre. Treatment success and adverse event rates were similar. Registration number: NCT01637181 (http://www.clinicaltrials.gov).
Problems and solutions in delivering global surgery in the 21st century
Authors: McDermott F D , Kelly M E , Warwick A , Arulampalam T , Brooks A J , Gaarder T , Cotton B A , Winter D C 
Published: December 2015

Abstract

Background
Surgery has had low priority in global health planning, so the delivery of surgical care in low- and middle-income countries is often poorly resourced. A recent Lancet Commission on Global Surgery has highlighted the need for change.

Methods
A consensus view of the problems and solutions was identified by individual surgeons from high-income countries, familiar with surgical care in remote and poorer environments, based on recent publications related to global surgery.

Results
The major issues identified were: the perceived unimportance of surgery, shortage of personnel, lack of appropriate training and failure to establish surgical standards, failure to appreciate local needs and poor coordination of service delivery.

Conclusion
Surgery deserves a higher priority in global health resource allocation. Lessons learned from participation in humanitarian crises should be considered in surgical developments.
No‐Regret Solutions – Modular Production Concepts for Times of Complexity and Uncertainty
Authors: Mothes Helmut 
Published: December 2015

AbstractGlobal competition, shorter product cycles, individualized products, and faster technology innovation lead to more complex production systems. For the product life cycle, forecast of product demand, resource availability, and technology chances becomes a mission impossible. Applying a modularization strategy, future production systems are designed as no‐regret‐solutions that add risk minimization to profit maximization. Additive manufacturing and the Internet of Things will significantly improve economics of modular designs for the chemical‐pharmaceutical Industry.
Chemical Programming of the Domain of Existence of Liquid Crystals
Authors: Dutronc Thibault , Terazzi Emmanuel , Guénée Laure , Buchwalder Kerry‐Lee , Floquet Sébastien , Piguet Claude 
Published: December 2015

AbstractThis work illustrates how enthalpy and entropy changes responsible for successive phase transitions of cyanobiphenyl‐based liquid crystals can be combined to give cohesive free energy densities. These new parameters are able to rationalize and quantify the demixing of the melting and clearing processes that occur in thermotropic liquid crystals. Minor structural variations at the molecular level can be understood as pressure increments that alter either the melting or clearing temperatures in a predictable way. This assessment of microsegregation operating in amphiphilic molecules paves the way for the chemical programming of the domain of existence of liquid‐crystalline phases.
On the Orthogonality of Two Thiol‐Based Modular Ligations
Authors: Turgut Hatice , Delaittre Guillaume 
Published: December 2015

AbstractThe chemoselectivity of two thiol‐based modular ligations operating under mild conditions is assessed. For this purpose, a macromolecular scaffold possessing allyl and pentafluorophenyl groups in two distinct parts is employed, which enables facile characterization by NMR spectroscopy (1H and 19F) and size‐exclusion chromatography. By using appropriate triggers (introduction of a base or light irradiation), it is possible to direct thiols to an arbitrarily chosen part of the scaffold, without any change to the other part and with no involvement of protecting group chemistry. Dual functionalization experiments are achieved by applying these triggers consecutively with no consideration of the reaction sequence order, evidencing full bidirectionality. A set of one‐pot, purification‐free procedures that enable near‐quantitative to full dual functionalization in (very) short reaction times (17–180 min) is also presented.
Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART‐1) trial design
Authors: Bartunek Jozef , Davison Beth , Sherman Warren , Povsic Thomas , Henry Timothy D. , Gersh Bernard , Metra Marco , Filippatos Gerasimos , Hajjar Roger , Behfar Atta , Homsy Christian , Cotter Gad , Wijns William , Tendera Michal , Terzic Andre 
Published: December 2015

AbstractAimsCardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient‐derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART‐1 is designed as a large randomized, sham‐controlled multicentre study aimed to validate cardiopoietic stem cell therapy.MethodsPatients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (<35%), and at high risk for recurrent HF‐related events, despite optimal medical therapy, will be randomized 1:1 to receive 600 × 106 bone marrow‐derived and lineage‐directed autologous cardiopoietic stem cells administered via a retention‐enhanced intramyocardial injection catheter or a sham procedure. The primary efficacy endpoint is a hierarchical composite of mortality, worsening HF, Minnesota Living with Heart Failure Questionnaire score, 6 min walk test, LV end‐systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months.ConclusionThe CHART‐1 clinical trial is powered to examine the therapeutic impact of lineage‐directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART‐1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF.Trial registration: NCT01768702
Electronic Structure Evaluation of an Oxidized Tris(methoxy)‐Substituted Ni Salen Complex
Authors: Chiang Linus , Clarke Ryan M. , Herasymchuk Khrystyna , Sutherland Mathew , Prosser Kathleen E. , Shimazaki Yuichi , Storr Tim 
Published: December 2015

AbstractThe Ni salen complex N,N′‐bis(2,3,4‐trimethoxysalicylidene)‐1,2‐cyclohexane‐(1R,2R)‐diamine nickel(II) (1), containing ortho‐, meta‐, and para‐methoxy‐substituted phenolate moieties, was prepared. Electrochemical studies revealed that the first oxidation of 1 occurs at a similar potential to a previously reported Ni salen complex NiSaltBu,OMe, employing an ortho‐tBu and para‐methoxy substitution pattern (M. Orio et al., Angew. Chem. Int. Ed. 2010, 49, 4989), demonstrating the counteracting effects of the methoxy substituent depending on ring location (ortho/para vs. meta). The second oxidation occurred at a much lower potential (E1/22 – E1/21 = 0.11 V) for 1, in comparison to NiSaltBu,OMe, suggesting significant localization of the ligand radical. The one‐electron oxidized form was prepared and studied using a number of experimental and theoretical methods. A localized ligand radical electronic structure was confirmed by the shape and intensity of the NIR bands, which was further verified by the presence of both phenolate and phenoxyl signatures in the resonance Raman spectrum. Theoretical calculations provided insight into the degree of ligand radical localization, and the nature of the low energy bands observed in the Vis/NIR experiment. Overall, the oxidation of 1 results in a localized ligand radical complex, with further oxidation processes easily accessible due to resonance stabilization afforded by the methoxy substituents.