bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of Kidney Motion under Free, Deep and Forced-Shallow Breathing Conditions: Implications for Stereotactic Ablative Body Radiotherapy Treatment
Authors: Pham D. , Kron T. , Foroudi F. , Schneider M. , Siva S.
Published: December 2013

Motion management strategies are important during stereotactic ablative body radiotherapy for abdominal targets. The kidney is a mobile retroperitoneal organ that moves with respiration. A review of the literature was performed to investigate the reported degree of kidney motion associated with various breathing conditions. A structured search was performed using Medline from January 1970 to May 2013 for all publications describing cranial-caudal kidney motion. Relevance to radiotherapy practice was reviewed based on any breathing instructions and/or immobilization equipment that could affect breathing pattern. Studies were categorized under three types of breathing conditions: Forced-shallow, breath-hold/deep and free. A total of 25 publications were identified describing cranial-caudal kidney motion with a combined total of 415 participants. Three publications described forced-shallow breathing using prone positioning or abdominal compression plates. Prone positioning, compared to supine positioning, did little to minimise kidney motion, however use of compression plates can result in kidney motion of less than 5 mm. Eight publications described deep breathing/breath hold techniques that showed average kidney motion ranging between 10 mm-40 mm. Fifteen publications investigated kidney motion under free breathing with the majority reporting mean motion of less than 10 mm. Kidney movement of up to 8.1 mm in the anterior posterior direction and 6.2 mm laterally were reported with no indications that breathing technique can influence the extent of this motion. In summary, kidney movement is complex and consideration should be made to ensure that motion management strategies provide the desired radiotherapy benefit. There are limited publications on the effectiveness of abdominal compression on reducing kidney motion which warrant further investigation in this area.
Combination of Cetuximab and Rapamycin Enhances the Therapeutic Efficacy in Hepatocellular Carcinoma
Authors: Geng Jing , Li Xinying , Lang Xiaoling , Qiao Chunxia , Hu Meiyun , Yang Jing , Feng Jiannan , Lv Ming
Published: December 2013

Hepatocellular carcinoma (HCC) is one of the most deadly cancers worldwide. It is well known that the activation of PI3K/AKT/mTOR and the Ras/MAPK signaling pathway plays a critical role in cellular metabolism, growth and proliferation, and its inhibitors have been used as therapeutic drugs for hepatocellular carcinoma. Cetuximab, a chimerical monoclonal EGFR lgG1 antibody, can block the binding of EGF or other ligands to EGFR and thus inhibit ligands-induced receptor phosphorylation. In the present study, we found that rapamycin could enhance the antiproliferation effect of cetuximab in both HepG2 cells and Huh-7 cells and arrest the cell cycle. Cetuximab in combination with rapamycin had synergistic effects on inhibiting the phosphrylation of proteins in PI3K/AKT/mTOR and Ras/MAPK signaling pathway. Combination of cetuximab with rapamycin treatment significantly suppressed the HCC development in HepG2 cells-xenografted mice and improved the survival. Cetuximab and rapamycin inhibited the growth of HCC both in vitro and in vivo. These results suggest that the combination therapy using the inhibitors for both EGFR and PI3K/AKT/mTOR signaling pathways may be a novel therapeutic approach for HCC.
Optimized PET Imaging for 4D Treatment Planning in Radiotherapy: the Virtual 4D PET Strategy
Authors: Gianoli Chiara , Riboldi Marco , Fontana Giulia , Giri Maria G. , Grigolato Daniela , Ferdeghini Marco , Cavedon Carlo , Baroni Guido
Published: December 2013

The purpose of the study is to evaluate the performance of a novel strategy, referred to as “virtual 4D PET”, aiming at the optimization of hybrid 4D CT-PET scan for radiotherapy treatment planning. The virtual 4D PET strategy applies 4D CT motion modeling to avoid time-resolved PET image acquisition. This leads to a reduction of radioactive tracer administered to the patient and to a total acquisition time comparable to free-breathing PET studies. The proposed method exploits a motion model derived from 4D CT, which is applied to the free-breathing PET to recover respiratory motion and motion blur. The free-breathing PET is warped according to the motion model, in order to generate the virtual 4D PET. The virtual 4D PET strategy was tested on images obtained from a 4D computational anthropomorphic phantom. The performance was compared to conventional motion compensated 4D PET. Tests were also carried out on clinical 4D CT-PET scans coming from seven lung and liver cancer patients. The virtual 4D PET strategy was able to recover lesion motion, with comparable performance with respect to the motion compensated 4D PET. The compensation of the activity blurring due to motion was successfully achieved in terms of spill out removal. Specific limitations were highlighted in terms of partial volume compensation. Results on clinical 4D CT-PET scans confirmed the efficacy in 4D PET count statistics optimization, as equal to the free-breathing PET, and recovery of lesion motion. Compared to conventional motion compensation strategies that explicitly require 4D PET imaging, the virtual 4D PET strategy reduces clinical workload and computational costs, resulting in significant advantages for radiotherapy treatment planning.
Influence of the Atlantic Meridional Overturning Circulation on the monsoon rainfall and carbon balance of the American tropics
Authors: Parsons Luke A. , Yin Jianjun , Overpeck Jonathan T. , Stouffer Ronald J. , Malyshev Sergey
Published: December 2013

We examine the response of the American Tropics to changes in Atlantic Meridional Overturning Circulation (AMOC) strength using a set of water‐hosing experiments with an Earth system model that explicitly simulates the global and regional carbon cycle. We find that a moderate weakening (27%) of the AMOC, induced by a 0.1 Sv (1 Sv ≡ 106 m3 s−1) freshwater addition in the northern North Atlantic, drives small but statistically significant drying in the South American monsoon region. By contrast, a complete shutdown of the AMOC, induced by a 1.0 Sv freshwater addition, acts to considerably shift the ITCZ southward, which changes the seasonal cycle of precipitation over Amazonia. Our results indicate that AMOC weakening can have a significant impact on the terrestrial primary productivity and carbon storage of the American Tropics.
Atmospheric tides in the low‐latitude E and F regions and their responses to a sudden stratospheric warming event in January 2010
Authors: Gong Yun , Zhou Qihou , Zhang Shaodong
Published: December 2013

An extensive analysis of atmospheric tides in the low‐latitude thermosphere and their responses to a major sudden stratospheric warming (SSW) event (18–23 January 2010) is presented. The analysis is based on observational data from the Arecibo dual‐beam incoherent scatter radar. Important findings of the present study are as follows. (1) The diurnal tide with an evanescent phase structure dominates the F region meridional wind field. The diurnal tide has a peak amplitude of 45 m/s occurring at about 245 km, and it is very stable throughout the nine consecutive days' observation. Below 114 km, the vertical structures of the diurnal tide in the meridional and zonal components are consistent, which resemble the classical solar S1, 1 tidal mode. (2) The F region semidiurnal tide is much weaker and has larger day‐to‐day variability than the diurnal tide. In the E region, the semidiurnal amplitudes in the meridional and zonal components grow continuously in the altitude ranges from 106 to 121 km and from 100 to 115 km, respectively. The vertical wavelength of the zonal component is estimated to be 45 km above 100 km, which is close to the solar S2, 4 and S2, 5 tidal modes. (3) The semidiurnal and terdiurnal tides respond strongly to the SSW while the impact that the SSW has on the diurnal tide in the meridional wind is limited. During the SSW event, the amplitudes of the semidiurnal and terdiurnal tides are enhanced in the F region but reduced in the upper E region.
Magnetosphere‐ionosphere energy interchange in the electron diffuse aurora
Authors: Khazanov G. V. , Glocer A. , Himwich E. W.
Published: December 2013

The diffuse aurora has recently been shown to be a major contributor of energy flux into the Earth's ionosphere. Therefore, a comprehensive theoretical analysis is required to understand its role in energy redistribution in the coupled ionosphere‐magnetosphere system. In previous theoretical descriptions of precipitated magnetospheric electrons (E∼ 1 keV), the major focus has been the ionization and excitation rates of the neutral atmosphere and the energy deposition rate to thermal ionospheric electrons. However, these precipitating electrons will also produce secondary electrons via impact ionization of the neutral atmosphere. This paper presents the solution of the Boltzman‐Landau kinetic equation that uniformly describes the entire electron distribution function in the diffuse aurora, including the affiliated production of secondary electrons (E< 600 eV) and their ionosphere‐magnetosphere coupling processes. In this article, we discuss for the first time how diffuse electron precipitation into the atmosphere and the associated secondary electron production participate in ionosphere‐magnetosphere energy redistribution.
Topographic effects on current variability in the Caspian Sea
Authors: Ghaffari P. , Isachsen P. E. , LaCasce J. H.
Published: December 2013

Satellite‐derived surface height fields reveal that variability in the central and southern basins of the Caspian Sea is correlated with topography. Consistently, empirical orthogonal functions from current meter data from the southern basin are aligned with the isobaths. In addition, the gravest mode, which accounts for over 80% of the variance, has an equivalent barotropic structure in the vertical. To what extent this variability can be modeled using a linear analytical model is examined. The latter assumes equivalent barotropic flow aligned with the geostrophic contours, which in turn are dominated by the topography. With ECMWF winds and ETOPO2 topography, the model yields surface height deviations which are significantly correlated with satellite‐derived estimates on seasonal and longer time scales in the central basin. The model is somewhat less successful in the southern basin, where the stratification is stronger. Nevertheless, the results are encouraging, given the extreme simplicity of the model.
Burden of Systemic Lupus Erythematosus on Employment and Work Productivity: Data From a Large Cohort in the Southeastern United States
Authors: Drenkard Cristina , Bao Gaobin , Dennis Greg , Kan Hong J. , Jhingran Priti M. , Molta Charles T. , Lim S. Sam
Published: December 2013

Objective

To examine the burden of systemic lupus erythematosus (SLE) on work loss, unemployment, and work productivity impairment in an SLE cohort from the southeastern US.

Methods

We examined 689 SLE patients ages 18–64 years from the Georgians Organized Against Lupus (GOAL) cohort. GOAL is a longitudinal cohort predominantly derived from the Georgia Lupus Registry, a population‐based registry established in metropolitan Atlanta. We used the Kaplan‐Meier method to assess the proportion of patients who self‐reported work loss since diagnosis. We compared unemployment between SLE patients and the general population from the same geographic area, calculating the standardized unemployment ratio (SUR) within demographic and disease strata. We also calculated the percentage of work productivity impairment by disease outcomes.

Results

Of 511 patients employed at diagnosis, 249 (49%) experienced work loss within an average disease duration of 13 years. The proportion of patients who lost their jobs since diagnosis was almost twice for African Americans than for whites. However, the SURs were similar across demographic characteristics, including race. Patients with severe disease activity and severe organ damage had the highest SUR at 4.4 and 5.6, respectively. Among those that remained employed, patients with severe fatigue, neurocognitive symptoms, and musculoskeletal symptoms had the highest impairment of work productivity.

Conclusion

SLE imposes a substantial toll on individuals and burden on society. Major factors that negatively impact work outcomes are fatigue, disease activity, and organ damage. More effective treatments along with coping strategies at the workplace are needed to reduce the burden of SLE on work outcomes.
Validation of Relapse Risk Biomarkers for Routine Use in Patients With Juvenile Idiopathic Arthritis
Authors: Rothmund Friederike , Gerss Joachim , Ruperto Nicolino , Däbritz Jan , Wittkowski Helmut , Frosch Michael , Wulffraat Nico M. , Wedderburn Lucy R. , Holzinger Dirk , Gohar Faekah , Vastert Sebastiaan J. , Brik Riva , Job Deslandre Chantal , Melo‐Gomes Jose Antonio , Saad Magalhães Claudia , Barcellona Roberto , Russo Ricardo , Gattorno Marco , Martini Alberto , Roth Johannes , Foell Dirk ,   for the Paediatric Rheumatology International Trials Organisation (PRINTO)
Published: December 2013

Objective

The myeloid‐related proteins 8 and 14 (MRP‐8/MRP‐14) and neutrophil‐derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping antiinflammatory treatment. In this study, we tested the performance of different enzyme‐linked immunosorbent assays (ELISAs) in order to validate systems available for routine use.

Methods

MRP‐8/MRP‐14 and S100A12 serum concentrations of 188 JIA patients in remission were analyzed. Commercially available test systems were compared to experimental ELISAs established in house. The ability of the assays to identify JIA patients at risk for relapse was analyzed.

Results

For MRP‐8/MRP‐14, the PhiCal Calprotectin and Bühlmann MRP8/14 Calprotectin ELISAs revealed hazard ratios of 2.3 and 2.1, respectively. For S100A12, the CircuLex S100A12/EN‐RAGE ELISA revealed a hazard ratio of 3.1. The commercial assays allowed a JIA relapse prediction that was at least comparable to the experimental ELISAs.

Conclusion

For the prediction of JIA relapse after stopping medication, the biomarkers MRP‐8/MRP‐14 and S100A12 can be determined by using assays that are available for routine use. The tested commercial MRP‐8/MRP‐14 and S100A12 ELISAs showed a performance comparable to well‐established experimental ELISA protocols when assay‐specific cutoffs for the indication of relapse prediction are thoroughly applied.
Impact of Psychological Factors on Subjective Disease Activity Assessments in Patients With Severe Rheumatoid Arthritis
Authors: Cordingley Lis , Prajapati Rita , Plant Darren , Maskell Deborah , Morgan Catharine , Ali Faisal R. , Morgan Ann W. , Wilson Anthony G. , Isaacs John D. ,   the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS), Barton Anne
Published: December 2013

Objective

The Disease Activity Score in 28 joints (DAS28), used to assess disease activity in rheumatoid arthritis (RA), is a composite score comprising clinical, biochemical, and patient self‐report measures. We hypothesized that psychological factors (cognitions and mood) would be more strongly associated with patient‐reported components of the DAS28 than clinical or biochemical components.

Methods

A cross‐sectional, observational study of 322 RA patients with active disease (mean DAS28 6.0) awaiting therapy with a biologic agent was undertaken. Patients' illness beliefs, treatment beliefs, and mood were measured using the Brief Illness Perception Questionnaire (IPQ), the Beliefs about Medicines Questionnaire (BMQ), and the Hospital Anxiety and Depression Scale (HADS), respectively. Relationships between psychological factors and 1) total DAS28 and 2) individual components of the DAS28 were analyzed using linear regression.

Results

Total DAS28 produced significant but weak associations with 2 of the Brief IPQ items, but no associations with BMQ or HADS scores. There were larger significant associations between the patient‐reported visual analog scale (VAS) with 5 items of the Brief IPQ and with HADS depression. Low illness coherence was associated with higher tender joint count. Three Brief IPQ items and HADS anxiety scores were significantly associated with C‐reactive protein level or erythrocyte sedimentation rate. No psychological factors were associated with the swollen joint count.

Conclusion

One of the subjective components of the DAS28, patient VAS, was highly correlated with cognitive factors and depression in those with severe RA. By reporting individual DAS28 components, clinicians may be better able to assess the impact of therapies on each component, adjusting approaches according to patients' needs.
Are Older Adults Missing From Low Back Pain Clinical Trials? A Systematic Review and Meta‐Analysis
Authors: Paeck Tatjana , Ferreira Manuela L. , Sun Clive , Lin Chung‐Wei Christine , Tiedemann Anne , Maher Chris G.
Published: December 2013

Objective

There is evidence to suggest that older adults are underrepresented in randomized controlled trials of health interventions. The aim of this review was to systematically examine the age‐related inclusion criteria distribution of participants in randomized controlled trials (RCTs) of low back pain (LBP) interventions and to investigate if this distribution pattern changes over time.

Methods

We identified, in PubMed, 1,047 RCTs on nonspecific LBP published since 1992, of which a random sample of 400 was assessed for inclusion in the review. Included studies were grouped according to treatment type. Data were extracted on year of publication, types of treatment, total number of participants, age inclusion criteria, and age of included participants.

Results

A total of 274 RCTs published between 1992 and 2010 met the inclusion criteria. A total of 41.6% (n = 114) of the included trials excluded people ages >65 years. The pooled mean age of participants was 44.3 years (95% confidence interval 42.4–46.3); the pooled minimum age for inclusion was 19.8 years and the pooled maximum age for inclusion was 65.4 years. We found no trend of including older participants in RCTs on LBP over time.

Conclusion

Despite an aging population around the globe, older adults are largely excluded from RCTs evaluating management of LBP, and there is no evidence of change in this practice over the last 2 decades.
Patients' Willingness to Trade Off Between the Duration and Frequency of Rheumatoid Arthritis Treatments
Authors: Poulos Christine , Hauber A. Brett , González Juan Marcos , Turpcu Adam
Published: December 2013

Objective

Biologic treatments for rheumatoid arthritis (RA) vary widely in both the time required to administer treatment and treatment frequency. This study aimed to quantify the rate at which RA patients are willing to trade off between the time required to administer treatment (duration) and treatment frequency.

Methods

Respondents with a self‐reported physician diagnosis of moderate to severe RA completed an online discrete choice experiment survey (also known as conjoint analysis). Respondents were presented with a series of treatment‐choice questions. Each hypothetical treatment included 6 attributes: response rate, mode of administration, treatment duration, treatment frequency, and the risks of immediate mild and serious treatment reactions. Preference weights, also called marginal utilities or relative importances, were estimated using mixed‐logit methods and then used to calculate the marginal rates of substitution between attributes, including treatment duration and treatment frequency.

Results

Among the 901 respondents, 505 were in the RA Information, Service, and Education group (www.risesupport.com) and 396 were members of an online panel. The marginal utility of changes in treatment features was largest for a 1‐hour change in treatment duration, while a 1‐unit change in the annual frequency of treatment was the second least important change. The marginal utility of changes in annual treatment frequency depends on the treatment duration and vice versa.

Conclusion

Respondents would accept treatments with lower efficacy and greater risk to achieve lower duration and frequency. Previous studies have linked patient preferences to treatment adherence, suggesting that reductions in duration or frequency could improve adherence and health outcomes.
Rheological modeling of carbon nanotube suspensions with rod–rod interactions
Authors: Natale G. , Heuzey M. C. , Carreau P. J. , Ausias G. , Férec J.
Published: December 2013

To explain the shear‐thinning behavior of untreated carbon nanotube (CNT) suspensions in a Newtonian matrix, a new set of rheological equations is developed. The CNTs are modeled as rigid rods dispersed in a Newtonian matrix and the evolution of the system is controlled by hydrodynamic and rod–rod interactions. The particle–particle interactions is modeled by a nonlinear lubrication force, function of the relative velocity at the contact point, and weighted by the contact probability. The stress tensor is calculated from the known fourth‐order orientation tensor and a new fourth‐order interaction tensor. The Fokker‐Planck equation is numerically solved for steady simple shear flows using a finite volume method. The model predictions show a good agreement with the steady shear data of CNTs dispersed in a Newtonian epoxy matrix as well as for suspensions of glass fibers in polybutene,1 demonstrating its ability to describe the behavior of micro‐ and nanoscale particle suspensions. © 2013 American Institute of Chemical Engineers AIChE J, 60: 1476–1487, 2014
Brief communication: Emergence chronology of permanent teeth in Nigerian children
Authors: Oziegbe Elizabeth O. , Esan Temitope A. , Oyedele Titus A.
Published: December 2013

This study measured the mean age, duration, and sequence of the emergence of permanent dentition in Nigerian children and compared the findings with other population groups. The cross‐sectional study involved 1,078 Nigerian children, aged 4–16 years old, from selected primary and secondary schools in the Ife Central local government area in Ile‐Ife, Osun State. In general, compared to boys, girls had an earlier mean age of emergence of all the permanent teeth. Children from high socioeconomic class had an earlier mean age of emergence for the maxillary incisors (6.43 and 7.58 years) and mandibular incisors (5.28 and 6.44 years) compared to children from middle and low socioeconomic classes, although socioeconomic effects were more mixed for premolars and molars. Compared to their counterparts in the USA, Australia, Belgium, and Iran, Nigerian children showed an earlier mean age of emergence of all the permanent teeth studied except for Pakistani boys, who had an earlier mean age of emergence of the maxillary premolars and second molar. Poorer economic status has been associated with delayed dental development; however, when compared to other populations, the Nigerian children in this study have earlier mean emergence ages than children from wealthier countries such as the USA and Australia. Am J Phys Anthropol 153:506–511, 2014. © 2013 Wiley Periodicals, Inc.
Endogenous Myeloperoxidase Is a Mediator of Joint Inflammation and Damage in Experimental Arthritis
Authors: Odobasic Dragana , Yang Yuan , Muljadi Ruth C. M. , O'Sullivan Kim M. , Kao Wenping , Smith Malcolm , Morand Eric F. , Holdsworth Stephen R.
Published: December 2013

Objective

Myeloperoxidase (MPO) is implicated as a local mediator of tissue damage when released extracellularly in many chronic inflammatory diseases. The purpose of this study was to explore the role of endogenous MPO in experimental rheumatoid arthritis (RA).

Methods

K/BxN serum–transfer arthritis was induced in C57BL/6 wild‐type (WT) and MPO knockout (MPO−/−) mice, and disease development was assessed. MPO activity was measured in joint tissues from mice with or without K/BxN arthritis. Collagen‐induced arthritis (CIA) was induced in WT and MPO−/− mice, and disease development and immune responses were examined. MPO expression was assessed in synovial biopsy samples from patients with active RA, and the effect of MPO on synovial fibroblasts was tested in vitro.

Results

MPO was up‐regulated in the joints of mice with K/BxN arthritis, and MPO deficiency attenuated the severity of the disease without affecting circulating cytokine levels. In CIA, MPO−/− mice had enhanced CD4+ T cell responses and reduced frequency of regulatory T cells in the lymph nodes and spleen, as well as augmented interleukin‐17A and diminished interferon‐γ secretion by collagen‐stimulated splenocytes, without an effect on circulating anticollagen antibody levels. Despite enhanced adaptive immunity in secondary lymphoid organs, CIA development was attenuated in MPO−/− mice. Intracellular and extracellular MPO was detected in the synovium of patients with active RA, and human MPO enhanced the proliferation and decreased the apoptosis of synovial fibroblasts in vitro.

Conclusion

MPO contributes to the development of arthritis despite suppressing adaptive immunity in secondary lymphoid organs. This suggests distinct effects of local MPO on arthritogenic effector responses.
Assessment of Osteoarthritis Candidate Genes in a Meta‐Analysis of Nine Genome‐Wide Association Studies
Authors: Rodriguez‐Fontenla Cristina , Calaza Manuel , Evangelou Evangelos , Valdes Ana M. , Arden Nigel , Blanco Francisco J. , Carr Andrew , Chapman Kay , Deloukas Panos , Doherty Michael , Esko Tõnu , Garcés Aletá Carlos M. , Gomez‐Reino Carnota Juan J. , Helgadottir Hafdis , Hofman Albert , Jonsdottir Ingileif , Kerkhof Hanneke J. M. , Kloppenburg Margreet , McCaskie Andrew , Ntzani Evangelia E. , Ollier William E. R. , Oreiro Natividad , Panoutsopoulou Kalliope , Ralston Stuart H. , Ramos Yolande F. , Riancho Jose A. , Rivadeneira Fernando , Slagboom P. Eline , Styrkarsdottir Unnur , Thorsteinsdottir Unnur , Thorleifsson Gudmar , Tsezou Aspasia , Uitterlinden André G. , Wallis Gillian A. , Wilkinson J. Mark , Zhai Guangju , Zhu Yanyan ,   the arcOGEN Consortium, Felson David T. , Ioannidis John P. A. , Loughlin John , Metspalu Andres , Meulenbelt Ingrid , Stefansson Kari , van Meurs Joyce B. , Zeggini Eleftheria , Spector Timothy D. , Gonzalez Antonio
Published: December 2013

Objective

To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA.

Methods

A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single‐nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed‐effects meta‐analysis of 9 genome‐wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta‐analysis. After correction for the number of independent tests, P values less than 1.58 × 10−5 were considered significant.

Results

SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta‐analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10−5, odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06−1.17) and rs1241164 (P = 1.47 × 10−5, OR 0.82, 95% CI 0.74−0.89). The sex‐stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10−5, OR 0.87, 95% CI 0.82−0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10−5, OR 0.85, 95% CI 0.79−0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened.

Conclusion

Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta‐analysis. The remaining candidate genes were not associated.
Long Noncoding RNA Related to Cartilage Injury Promotes Chondrocyte Extracellular Matrix Degradation in Osteoarthritis
Authors: Liu Qiang , Zhang Xin , Dai Linghui , Hu Xiaoqing , Zhu Jingxian , Li La , Zhou Chunyan , Ao Yingfang
Published: December 2013

Objective

Long noncoding RNAs (lncRNAs) play crucial regulatory roles in diverse biologic processes, but knowledge of lncRNAs in osteoarthritis (OA) is limited. The aim of this study was to identify lncRNA expression in articular cartilage and to explore the function of cartilage injury–related lncRNAs (lncRNA‐CIR) in OA.

Methods

To identify lncRNAs specifically expressed in OA cartilage, we compared the expression of lncRNAs in OA cartilage with that in normal cartilage using microarray and quantitative polymerase chain reaction (qPCR) analyses. In OA cartilage, lncRNA‐CIR was specifically, differentially, and highly expressed. The function of lncRNA‐CIR was determined by silencing and overexpression in vitro. Extracellular matrix (ECM)–related molecules were detected by qPCR, Western blot, and immunofluorescence analyses.

Results

Up to 152 lncRNAs were found to be differentially expressed (>8‐fold) in OA and normal cartilage (82 lncRNAs more highly expressed and 70 less highly expressed in OA cartilage than in normal cartilage). A specific differentially expressed lncRNA‐CIR was selected according to the results of the higher expression in OA cartilage and OA chondrocytes. The expression of lncRNA‐CIR increased in chondrocytes with in vitro treatment with interleukin‐1β and tumor necrosis factor α. Silencing of lncRNA‐CIR by small interfering RNA promoted the formation of collagen and aggrecan and reduced the expression of matrix‐degrading enzymes, such as MMP13 and ADAMTS5. The expression of collagen and aggrecan was reduced, whereas the expression of matrix‐degrading enzymes was increased, after overexpression of lncRNA‐CIR.

Conclusion

The results indicate that lncRNA‐CIR contributes to ECM degradation and plays a key role in the pathogenesis of OA. We propose that lncRNA‐CIR could be used as a potential target in OA therapy.
Halofuginone Ameliorates Autoimmune Arthritis in Mice by Regulating the Balance Between Th17 and Treg Cells and Inhibiting Osteoclastogenesis
Authors: Park Mi‐Kyung , Park Jin‐Sil , Park Eun‐Mi , Lim Mi‐Ae , Kim Sung‐Min , Lee Dong‐Gun , Baek Seung‐Ye , Yang Eun‐Ji , Woo Jung‐Won , Lee Jennifer , Kwok Seung‐Ki , Kim Ho‐Youn , Cho Mi‐La , Park Sung‐Hwan
Published: December 2013

Objective

The small molecule halofuginone has been shown to inhibit fibrosis, angiogenesis, and tumor progression. This study was undertaken to evaluate the effects of halofuginone in preventing autoimmune arthritis in mice.

Methods

The effects of halofuginone on joint diseases were assessed by clinical scoring and histologic analysis. Protein expression levels were confirmed by immunohistochemistry, enzyme‐linked immunosorbent assay, flow cytometry, and/or Western blotting. The expression levels of messenger RNA (mRNA) for various molecules were determined by real‐time polymerase chain reaction (PCR). Proliferation of osteoclast precursors was assessed by bromodeoxyuridine uptake. Osteoclast differentiation and activity were determined by quantifying tartrate‐resistant acid phosphatase (TRAP)–positive multinucleated cells and area of resorbed bone.

Results

Treatment with halofuginone suppressed the development of autoimmune arthritis and reciprocally regulated Th17 cells and FoxP3+ Treg cells. These effects of halofuginone on Th17 differentiation involved increased signaling of ERK and reduction of STAT‐3 and NF‐ATc1 expression. Furthermore, halofuginone induced the expression of indoleamine 2,3‐dioxygenase (IDO) in dendritic cells, leading to reduced production of Th17 cells. In addition, halofuginone prevented the formation and activity of osteoclasts through suppression of transcription factors, such as activator protein 1 and NF‐ATc1, and inhibited cell cycle arrest by the committed osteoclast precursors via expression of Ccnd1 encoding cyclin D1.

Conclusion

Taken together, our results suggest that halofuginone is a promising therapeutic agent for the treatment of Th17 cell–mediated inflammatory diseases and bone diseases.
The Dynamic Feedback Matrix Control for Multidimensional Chaotic Systems
Authors: Zhang Fangfang , Liu Shutang
Published: December 2013

Multidimensional chaotic systems are difficult to control because of their nonlinearity and coupling relationship among state variables. We present the error feedback matrix for nonlinear systems, which contains coupling information of state variables and updates online according to the gradient descent method. The error feedback matrix is similar to the state feedback matrix for linear systems, however, the former is time‐varying and converges to a constant matrix. Using the coupling relationship, we give a simple controller only by a few elements of the matrix and present whole matrix control and partial matrix control. Finally, we apply these schemes to a three‐dimensionalHenon system and make mathematical analysis and simulation experiments, which verify the effectiveness of the proposed controllers.
Two‐step transpeptidation of the insulin precursor expressed in Pichia pastoris to insulin ester via trypsin‐catalyzed cleavage and coupling
Authors: Liu Haifeng , Zhou Xiangshan , Tian Shousheng , Hao Xianghui , You Jinhua , Zhang Yuanxing
Published: December 2013

Insulin precursor fusion protein expressed in Pichia pastoris is a single‐chain protein with a spacer peptide (EEAEAEAEPK) localized at its N‐terminal. Currently, the one‐step transpeptidation reaction with low yield and high cost is generally employed to convert the insulin precursor fusion protein into human insulin ester. In this study, a two‐step transpeptidation reaction was proposed separating the cleavage step from the coupling step so that each reaction was performed under its optimal conditions. Using this method, the total efficiency doubled and the reaction time was shortened compared with the one‐step method. In addition, the amount of O‐t‐butyl‐l‐threonine t‐butyl ester and trypsin dosages were reduced by 50% and 75%, respectively. This two‐step transpeptidation strategy was simple and efficient and could be used for the pharmaceutical production of human insulin.
Exploiting CRISPR/Cas systems for biotechnology
Authors: Sampson Timothy R. , Weiss David S.
Published: December 2013

The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA‐directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site‐specific transcriptional repression or activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering.
Endogenous microRNA clusters outperform chimeric sequence clusters in Chinese hamster ovary cells
Authors: Klanert Gerald , Jadhav Vaibhav , Chanoumidou Konstantina , Grillari Johannes , Borth Nicole , Hackl Matthias
Published: December 2013

MicroRNAs (miRNAs) are small non‐coding RNAs (∼22 nucleotides) which regulate gene expression by silencing mRNA translation. MiRNAs are transcribed as long primary transcripts, which are enzymatically processed by Drosha/Dgcr8, in the nucleus, and by Dicer in the cytoplasm, into mature miRNAs. The importance of miRNAs for coordinated gene expression is commonly accepted. Consequentially, there is a growing interest in the application of miRNAs to improve phenotypes of mammalian cell factories such as Chinese hamster ovary (CHO) cells. Few studies have reported the targeted over‐expression of miRNAs in CHO cells using vector‐based systems. These approaches were hampered by limited sequence availability, and required the design of “chimeric” miRNA genes, consisting of the mature CHO miRNA sequence encompassed by murine flanking and loop sequences. Here we show that the substitution of chimeric sequences with CHO‐specific sequences for expression of miRNA clusters yields significantly higher expression levels of the mature miRNA in the case of miR–221/222 and miR–15b/16. Our data suggest that the Drosha/Dgcr8‐mediated excision from primary transcripts is reduced for chimeric miRNA sequences compared to the endogenous sequence. Overall, this study provides important guidelines for the targeted over‐expression of clustered miRNAs in CHO cells.

See accompanying commentary by Baik and Lee DOI: 10.1002/biot.201300503
Splenic vein thrombosis and pancreatic fistula after minimally invasive distal pancreatectomy
Authors: Kang C M , Chung Y E , Jung M J , Hwang H K , Choi S H , Lee W J
Published: December 2013

Background

This study aimed to investigate the clinical relevance of splenic vein thrombosis (SVT) in the splenic vein remnant following minimally invasive distal pancreatosplenectomy (DPS).

Methods

Medical records of patients who underwent laparoscopic or robotic distal pancreatectomy (DP) with or without splenectomy between January 2006 and August 2012 were reviewed. Rates of SVT and clinically relevant postoperative pancreatic fistula (POPF) were compared in a group of patients undergoing DPS and a group having spleen-preserving DP.

Results

Seventy-nine patients had minimally invasive DP, of whom 38 (48 per cent) developed SVT in the splenic vein remnant. DPS was associated with POPF (P = 0·001) and SVT (P < 0·001). SVT length was closely related to the amount of peripancreatic fluid collection (P = 0·025) and POPF (P = 0·045). In a comparison of splenic vessel-sacrificing, spleen-preserving DP and DPS, postoperative platelet count was significantly higher in the DPS group (P < 0·001). In addition, grade of SVT (P = 0·092) and POPF (P = 0·065) tended to be associated with DPS, suggesting that SVT may be related to both splenectomy and POPF.

Conclusion

Minimally invasive DPS is associated with SVT and POPF. Preservation of the spleen should be considered when treating patients with benign and borderline malignant tumours of the distal pancreas.
Patient exposure to X‐rays during coronary angiography and percutaneous transluminal coronary intervention: Results of a multicenter national survey
Authors: Georges Jean‐Louis , Belle Loic , Ricard Cécile , Cattan Simon , Albert Franck , Hirsch Jean‐Lou , Monsegu Jacques , Dibie Alain , Khalife Khalife , Caussin Christophe , Maccia Carlo , Livarek Bernard , Hanssen Michel ,   on behalf of the RAY'ACT investigators
Published: December 2013

Objectives

To evaluate practices for the protection from radiation of patients during coronary angiography (CA) and percutaneous coronary intervention (PCI), and to update reference values for the main radiation dose parameters.

Background

Few multicenter data from large populations exist on radiation doses to patients during CA and PCI.

Methods

RAY'ACT is a multicenter, nationwide French survey, with retrospective analysis of radiation parameters routinely registered in professional software from 33,937 CAs and 27,826 PCIs performed at 44 centers from January 1, through December 31, 2010.

Results

Kerma‐area product (KAP) was registered in 91.7% (44/48) of centers and in 91.5% of procedures for CA (median, 27.2 Gy·cm2, interquartile range [IQR], 15.5–45.2) and 91.1% for PCI (median, 56.8 Gy·cm2, IQR, 32.8–94.6). Fluoroscopy time was registered in 87.5% (42/48) of centers and in 83.1% of procedures (median, 3.7 min, IQR, 2.3–6.3 for CA; 10.3 min, 6.7–16.2 for PCI). Variability across centers was high. Old equipment and routine left ventriculography were more common and number of registered frames and frame rate were higher in centers delivering high doses. The radial route was associated with lower doses than the femoral route (median KAP 26.8 Gy·cm2 [15.1–44.25] vs. 28.1 [16.4–46.9] for CA, respectively; and 55.6 Gy·cm2 [32.2–92.1] vs. 59.4 [24.6–99.9] for PCI, respectively; P < 0.01).

Conclusions

This survey showed a very high rate of compliance with dose registration during CA and PCI in French nonacademic hospitals. Updated diagnostic reference values are established for the main dose parameters (KAP, 45 Gy·cm2 for CA, 95 Gy·cm2 for PCI). © 2013 Wiley Periodicals, Inc.
Balloon aortic valvuloplasty in high risk aortic stenosis patients with left ventricular ejection fractions <20%
Authors: Pedersen Wes R. , Goldenberg Irvin F. , Pedersen Christopher W. , Lesser Andrew , Harris Kevin M. , Lesser John R. , Garberich Ross F. , Schwartz Jonathan G. , Shank Emily , Schwartz Robert S.
Published: December 2013

Objectives

To determine outcomes following balloon aortic valvuloplasty (BAV) in aortic stenosis (AS) patients with a left ventricular ejection fraction (LVEF) <20%.

Background

Severe AS patients with a LVEF <20% are excluded from United States (U.S.) transcatheter aortic valve replacement (TAVR) trials and often surgical aortic valve replacement (AVR). The role for BAV to enhance LVEF is unclear.

Methods

Our BAV database of 270 consecutive patients extending from 2005 through 2010 was queried for a preoperative LVEF <20%. Demographics, echocardiograms, procedural technique, and outcomes were analyzed. Pre‐ and postoperative echocardiograms were used to determine improvement in aortic valve area (AVA) and LVEF.

Results

Sixteen patients were identified with a median age of 82 years. The composite Society of Thoracic Surgeons' (STS) mortality risk was 16.4%. The median preoperative AVA and LVEF were 0.60 cm2 and 16%, respectively, and postoperative AVA and LVEF were 0.77 cm2 and LVEF 19%, respectively. About 15 of the 16 patients had postoperative echocardiograms available for comparison. And 7 of these 15 (47%) demonstrated improvement in LVEF to ≥20% (median LVEF 25%). The absence of coronary disease and improvement in AVA of ≥0.2 cm2 was associated with postoperative LVEF of ≥20%. Procedural mortality was 0%. The 30‐day, 6‐month, and 1‐year survival was 69%, 56%, and 29%. STS's mortality risk score ≥15% was associated with short‐term mortality.

Conclusion

With appropriate technique, BAV can be reasonably safe in patients with LVEF <20%. Roughly half of these patients demonstrated improvement in LVEF to ≥20%. © 2013 Wiley Periodicals, Inc.
Percutaneous edge‐to‐edge repair of the mitral valve in patients with degenerative versus functional mitral regurgitation
Authors: Braun Daniel , Lesevic Hasema , Orban Martin , Michalk Fabian , Barthel Petra , Hoppe Katharina , Sonne Carolin , Pache Jürgen , Mehilli Julinda , Kastrati Adnan , Hausleiter Jörg , Massberg Steffen
Published: December 2013

Objectives

To prospectively assess the outcome of percutaneous edge‐to‐edge repair in patients with degenerative versus functional mitral regurgitation (MR).

Background

The optimal patient population eligible for percutaneous edge‐to‐edge repair has yet to be defined.

Methods

We analyzed 119 patients treated by percutaneous edge‐to‐edge repair for symptomatic MR, 72 patients with degenerative and 47 patients with functional MR. The primary endpoints were defined as procedural success (MR grade reduction ≥1 grade) as well as a composite endpoint defined as freedom from MR 3+ or 4+, mitral valve reintervention and death 12 months after clip implantation. In patients with successful clip placement we further analyzed MR grade, New York Heart Association (NYHA) functional class, distance in the 6 min walking test and left ventricular volumes 12 months after clip implantation.

Results

The primary success rate of all intended clipping procedures was 83.3% for degenerative and 89.4% for functional MR (P = 0.42). Regarding the composite endpoint we observed an event free survival of 59.7% in patients treated for degenerative MR and 63.8% in patients treated for functional MR (P = 0.73). We observed a highly significant reduction in MR grade as well as improvement in NYHA functional status in both groups 12 months after clip implantation. However, there was a more pronounced MR grade reduction in patients treated for degenerative MR compared with patients treated for functional MR.

Conclusions

Percutaneous edge‐to‐edge repair of the mitral valve is feasible and comparably effective in patients with degenerative and functional MR. © 2013 Wiley Periodicals, Inc.
Transcatheter closure of large patent ductus arteriosus using custom made devices
Authors: Rohit Manoj Kumar , Gupta Ankur
Published: December 2013

There has been a paradigm shift in the transcatheter closure of patent ductus arteriosus (PDA) over the last 45 years. With the availability of various coils, plugs and occluders, PDA of almost all shapes and sizes are amenable to transcatheter closure. However, very large PDA diagnosed late in life are being referred for surgical closure in the absence of availability of large size devices, especially in developing countries. In this case series, we have described four patients with large PDA, three of which were closed by transcatheter custom made PDA occluders. © 2014 Wiley Periodicals, Inc.
Detailed Mathematical Analysis of Solute Transport in Armfield's Liquid Diffusion Apparatus
Authors: Ramírez Carlos A.
Published: December 2013

A solute's diffusivity is a key property in the design and analysis of mass transfer systems. A simple method to determine such coefficients in aqueous media is Armfield's diffusion apparatus, in which reservoir (donor) and bath (receiver) compartments are separated by a honeycomb array of liquid‐filled cylindrical pores. The solute of interest, i.e., NaCl, diffuses from the reservoir and pores into the bath. The electrical conductivity of the bath solution, which is proportional to the NaCl molarity, is tracked as a function of time at constant temperature. A comprehensive mathematical model is presented which combines simultaneous solute transport in the three compartments, allowing estimation of the aqueous NaCl diffusivity from experimental data. The model improves existing theoretical analyses of such data and can be adapted to study other challenging systems.
A Magnetic Ionic Liquid Based on Tetrachloroferrate Exhibits Three‐Dimensional Magnetic Ordering: A Combined Experimental and Theoretical Study of the Magnetic Interaction Mechanism
Authors: García‐Saiz Abel , Migowski Pedro , Vallcorba Oriol , Junquera Javier , Blanco Jesús Angel , González Jesús Antonio , Fernández‐Díaz María Teresa , Rius Jordi , Dupont Jairton , Rodríguez Fernández Jesús , de Pedro Imanol
Published: December 2013

A new magnetic ionic liquid (MIL) with 3D antiferromagnetic ordering has been synthetized and characterized. The information obtained from magnetic characterization was supplemented by analysis of DFT calculations and the magneto‐structural correlations. The result gives no evidence for direct iron‐iron interactions, corroborating that the 3D magnetic ordering in MILs takes place via super‐exchange coupling containing two diamagnetic atoms intermediaries.