bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Arthroscopic Surgical Skill Evaluation Tool (ASSET)
Authors: Koehler Ryan J. , Amsdell Simon , Arendt Elizabeth A. , Bisson Leslie J. , Bramen Jonathan P. , Butler Aaron , Cosgarea Andrew J. , Harner Christopher D. , Garrett William E. , Olson Tyson , Warme Winston J. , Nicandri Gregg T. 
Published: April 2013

Background: Surgeries employing arthroscopic techniques are among the most commonly performed in orthopaedic clinical practice; however, valid and reliable methods of assessing the arthroscopic skill of orthopaedic surgeons are lacking. Hypothesis: The Arthroscopic Surgery Skill Evaluation Tool (ASSET) will demonstrate content validity, concurrent criterion-oriented validity, and reliability when used to assess the technical ability of surgeons performing diagnostic knee arthroscopic surgery on cadaveric specimens. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Content validity was determined by a group of 7 experts using the Delphi method. Intra-articular performance of a right and left diagnostic knee arthroscopic procedure was recorded for 28 residents and 2 sports medicine fellowship–trained attending surgeons. Surgeon performance was assessed by 2 blinded raters using the ASSET. Concurrent criterion-oriented validity, interrater reliability, and test-retest reliability were evaluated. Results: Content validity: The content development group identified 8 arthroscopic skill domains to evaluate using the ASSET. Concurrent criterion-oriented validity: Significant differences in the total ASSET score ( P < .05) between novice, intermediate, and advanced experience groups were identified. Interrater reliability: The ASSET scores assigned by each rater were strongly correlated ( r = 0.91, P < .01), and the intraclass correlation coefficient between raters for the total ASSET score was 0.90. Test-retest reliability: There was a significant correlation between ASSET scores for both procedures attempted by each surgeon ( r = 0.79, P < .01). Conclusion: The ASSET appears to be a useful, valid, and reliable method for assessing surgeon performance of diagnostic knee arthroscopic surgery in cadaveric specimens. Studies are ongoing to determine its generalizability to other procedures as well as to the live operating room and other simulated environments.
Breaking the ice in systemic lupus erythematosus: belimumab, a promising new therapy
Authors: Mosak J , Furie R 
Published: April 2013

B lymphocyte stimulator (BLyS), a protein discovered in the 1990s that induces B cell proliferation and differentiation, promotes B cell survival, and is important in immunoglobulin class switching, was the target of a drug development program launched by Human Genome Sciences in the early part of the last decade. Belimumab, a human monoclonal antibody specific for soluble BLyS, was ultimately approved by the United States Food and Drug Administration (FDA) in March 2011 for active autoantibody patients with systemic lupus erythematosus (SLE) despite standard therapy. This program, whose studies spanned approximately 10 years from phase I through phase III, was founded on sound biology and advanced on logic and perseverance. Pre-clinical experimentation in murine models of SLE as well as observational studies in human SLE provided sufficient evidence to support the use of an inhibitor of BLyS as a novel therapy to reduce SLE disease activity. Progressing from phase I through a robust phase III program was no easy task given the complexities of SLE trial design. These challenges were overcome with the implementation of strict study entry requirements, the development of a novel responder index, and rigorous rules regarding background therapies. The success of two phase III studies and the approval of belimumab by the US Food and Drug Administration represent an unprecedented milestone in the history of SLE drug development. Belimumab was the first drug approved in SLE in over 50 years and was the first drug ever approved in SLE through the conventional route of randomized controlled trials. This article reviews the biology of BLyS, clinical trial results, and some of the emerging data from the robust phase II and III datasets.
A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese
Authors: Huang Jian , Yoshimura Satoshi , Isobe Noriko , Matsushita Takuya , Yonekawa Tomomi , Sato Shinya , Yamasaki Ryo , Kira Jun-ichi ,   the South Japan Multiple Sclerosis Genetics Consortium, Miyamoto Katsuichi , Kusunoki Susumu , Nakatsuji Yuji , Mochizuki Hideki , Ochi Kazuhide , Matsumoto Masayasu , Kanda Takeshi , Ochi Hirofumi , Miki Tetsuro , Okada Kazumasa , Tsuji Sadatoshi 
Published: April 2013

Background: The G allele of NOTCH4 rs422951 is protective against demyelinating disease in Japanese. Objectives: The purpose of this study was to assess the relation of the G allele to neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) and multiple sclerosis (MS) and the interaction between the G allele and HLA-DRB1 alleles, and to clarify any association of the G allele with clinical features. Methods: DNA sequencing was used to genotype 106 NMO/NMOSD patients, 118 MS patients and 152 healthy controls (HCs) for rs422951. Results: G allele frequency in MS patients, but not that in NMO/NMOSD patients, was lower than that in HCs (8.9% vs 21.7%, p<0.0001, odds ratio (OR)=0.35). HLA-DRB1*0405 was positively associated with MS (OR=2.22, pcorr=0.0380) while DRB1*0901 was negatively associated (OR=0.32, pcorr =0.0114). Logistic regression analyses revealed that, after adjusting for gender and either HLA-DRB1*0405 or DRB1*0901, rs422951 was associated with MS in the dominant model (OR=0.37, 95% confidence interval (CI)= 0.20–0.66, p=0.0012). Haplotype analyses identified two susceptible and three resistant haplotypes formed from rs422951 and either HLA-DRB1*0405 or DRB1*0901. There were no statistically significant differences in clinical features between G allele carriers and non-G allele carriers. Conclusion: This NOTCH4 missense mutation decreased the risk for developing MS in Japanese, but did not affect clinical features of those who had already developed the disease.
Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank samples
Authors: Salzer Jonatan , Nyström Maria , Hallmans Göran , Stenlund Hans , Wadell Göran , Sundström Peter 
Published: April 2013

Background: The antibody reactivity against Epstein-Barr nuclear antigen-1 (EBNA-1), and 25-hydroxyvitamin D (25(OH)D) status have been associated with multiple sclerosis (MS) risk. Interaction between these two factors has been proposed. Objectives: The objective of this paper is to examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk of MS, and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples. Methods: Antibody reactivity and 25(OH)D levels were measured using ELISAs in n = 192 MS cases and n = 384 matched controls. The risk of MS was analysed using matched logistic regression. Interaction on the additive scale was assessed. Results: The risk of MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trends < 0.001. In young individuals (below median age at sampling, < 26.4 years), these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains. No statistical interaction was found. Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor of MS. 25(OH)D status might influence the immune response towards Epstein-Barr virus in young subjects, and thereby modulate MS risk.
Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia
Authors: Klepin Heidi D. , Geiger Ann M. , Tooze Janet A. , Kritchevsky Stephen B. , Williamson Jeff D. , Pardee Timothy S. , Ellis Leslie R. , Powell Bayard L. 
Published: April 2013

Key Points
Geriatric assessment, with a focus on cognitive and physical function, improves prediction of survival among older adults treated for AML. Use of geriatric assessment may inform trial design and interventions to improve outcomes for older adults with AML.
Extensive circadian and light regulation of the transcriptome in the malaria mosquito Anopheles gambiae
Authors: Rund Samuel SC , Gentile James E , Duffield Giles E 
Published: April 2013

Abstract

Background
Mosquitoes exhibit 24 hr rhythms in flight activity, feeding, reproduction and development. To better understand the molecular basis for these rhythms in the nocturnal malaria vector Anopheles gambiae, we have utilized microarray analysis on time-of-day specific collections of mosquitoes over 48 hr to explore the coregulation of gene expression rhythms by the circadian clock and light, and compare these with the 24 hr rhythmic gene expression in the diurnal Aedes aegypti dengue vector mosquito.

Results
In time courses from An. gambiae head and body collected under light:dark cycle (LD) and constant dark (DD) conditions, we applied three algorithms that detect sinusoidal patterns and an algorithm that detects spikes in expression. This revealed across four experimental conditions 393 probes newly scored as rhythmic. These genes correspond to functions such as metabolic detoxification, immunity and nutrient sensing. This includes glutathione S-transferase GSTE5, whose expression pattern and chromosomal location are shared with other genes, suggesting shared chromosomal regulation; and pulsatile expression of the gene encoding CYP6M2, a cytochrome P450 that metabolizes pyrethroid insecticides. We explored the interaction of light and the circadian clock and highlight the regulation of odorant binding proteins (OBPs), important components of the olfactory system. We reveal that OBPs have unique expression patterns as mosquitoes make the transition from LD to DD conditions. We compared rhythmic expression between An. gambiae and Ae. aegypti heads collected under LD conditions using a single cosine fitting algorithm, and report distinct similarities and differences in the temporal regulation of genes involved in tRNA priming, the vesicular-type ATPase, olfaction and vision between the two species.

Conclusions
These data build on our previous analyses of time-of-day specific regulation of the An. gambiae transcriptome to reveal additional rhythmic genes, an improved understanding of the co-regulation of rhythms in gene expression by the circadian clock and by light, and an understanding of the time-of-day specific regulation of some of these rhythmic processes in comparison with a different species of mosquito. Improved understanding of biological timing at the molecular level that underlies key physiological aspects of mosquito vectors may prove to be important to successful implementation of established and novel insect control methods.
Genomic imbalances in patients with a clinical presentation in the spectrum of Cornelia de Lange syndrome
Authors: Gervasini Cristina , Picinelli Chiara , Azzollini Jacopo , Rusconi Daniela , Masciadri Maura , Cereda Anna , Marzocchi Cinzia , Zampino Giuseppe , Selicorni Angelo , Tenconi Romano , Russo Silvia , Larizza Lidia , Finelli Palma 
Published: April 2013

Abstract

Background
Cornelia de Lange syndrome (CdLS) is a rare autosomal-dominant disorder characterised by facial dysmorphism, growth and psychomotor developmental delay and skeletal defects. To date, causative mutations in the NIPBL (cohesin regulator) and SMC1A (cohesin structural subunit) genes account for > 50% and 6% of cases, respectively.

Methods
We recruited 50 patients with a CdLS clinical diagnosis or with features that overlap with CdLS, who were negative for mutations at NIPBL and SMC1A at molecular screening. Chromosomal rearrangements accounting for the clinical diagnosis were screened for using array Comparative Genomic Hybridisation (aCGH).

Results
Four patients were shown to carry imbalances considered to be candidates for having pathogenic roles in their clinical phenotypes: patient 1 had a 4.2 Mb de novo deletion at chromosome 20q11.2-q12; patient 2 had a 4.8 Mb deletion at chromosome 1p36.23-36.22; patient 3 carried an unbalanced translocation, t(7;17), with a 14 Mb duplication of chromosome 17q24.2-25.3 and a 769 Kb deletion at chromosome 7p22.3; patient 4 had an 880 Kb duplication of chromosome 19p13.3, for which his mother, who had a mild phenotype, was also shown to be a mosaic.

Conclusions
Notwithstanding the variability in size and gene content of the rearrangements comprising the four different imbalances, they all map to regions containing genes encoding factors involved in cell cycle progression or genome stability. These functional similarities, also exhibited by the known CdLS genes, may explain the phenotypic overlap between the patients included in this study and CdLS. Our findings point to the complexity of the clinical diagnosis of CdLS and confirm the existence of phenocopies, caused by imbalances affecting multiple genomic regions, comprising 8% of patients included in this study, who did not have mutations at NIPBL and SMC1A. Our results suggests that analysis by aCGH should be recommended for CdLS spectrum cases with an unexplained clinical phenotype and included in the flow chart for diagnosis of cases with a clinical evaluation in the CdLS spectrum.
Dynamical behaviors of a discrete SIS epidemic model with standard incidence and stage structure
Authors: Teng Zhidong , Nie Linfei , Xu Jiabo 
Published: April 2013

AbstractA discrete SIS epidemic model with stage structure and standard incident rate which is governed by Beverton-Holt type is studied. The sufficient conditions on the permanence and extinction of disease are established. The existence of the endemic equilibrium is obtained. Further, by using the method of linearization, the local asymptotical stability of the endemic equilibrium is also studied. Lastly, the examples and numerical simulations carried out to illustrate the feasibility of the main results and revealed the far richer dynamical behaviors of the discrete epidemic model compared with the corresponding continuous epidemic models.MSC:39A30, 92D30.
Limited cross-border infections in patients newly diagnosed with HIV in Europe
Authors: Frentz Dineke , Wensing Annemarie M J , Albert Jan , Paraskevis Dimitrios , Abecasis Ana B , Hamouda Osamah , Jørgensen Louise B , Kücherer Claudia , Struck Daniel , Schmit Jean-Claude , Åsjö Birgitta , Balotta Claudia , Beshkov Danail , Camacho Ricardo J , Clotet Bonaventura , Coughlan Suzie , De Wit Stéphane , Griskevicius Algirdas , Grossman Zehava , Horban Andrzej , Kolupajeva Tatjana , Korn Klaus , Kostrikis Leondios G , Liitsola Kirsi , Linka Marek , Nielsen Claus , Otelea Dan , Paredes Roger , Poljak Mario , Puchhammer-Stöckl Elisabeth , Sönnerborg Anders , Stanekova Danica , Stanojevic Maja , Vandamme Anne-Mieke , Boucher Charles A B , Van de Vijver David A M C ,   SPREAD Programme
Published: April 2013

Abstract

Background
International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe.

Results
Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002–2007 were included.
We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value <0.0001), in men who have sex with men (P-value <0.0001), and in recently infected patients (P-value =0.045).

Conclusions
Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics.
Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation
Authors: González-Ramos Daniel , van den Broek Marcel , van Maris Antonius JA , Pronk Jack T , Daran Jean-Marc G 
Published: April 2013

Abstract

Background

n-Butanol and isobutanol produced from biomass-derived sugars are promising renewable transport fuels and solvents. Saccharomyces cerevisiae has been engineered for butanol production, but its high butanol sensitivity poses an upper limit to product titers that can be reached by further pathway engineering. A better understanding of the molecular basis of butanol stress and tolerance of S. cerevisiae is important for achieving improved tolerance.

Results
By combining a screening of the haploid S. cerevisiae knock-out library, gene overexpression, and genome analysis of evolutionary engineered n-butanol-tolerant strains, we established that protein degradation plays an essential role in tolerance. Strains deleted in genes involved in the ubiquitin-proteasome system and in vacuolar degradation of damaged proteins showed hypersensitivity to n- butanol. Overexpression of YLR224W, encoding the subunit responsible for the recognition of damaged proteins of an ubiquitin ligase complex, resulted in a strain with a higher n-butanol tolerance. Two independently evolved n-butanol-tolerant strains carried different mutations in both RPN4 and RTG1, which encode transcription factors involved in the expression of proteasome and peroxisomal genes, respectively. Introduction of these mutated alleles in the reference strain increased butanol tolerance, confirming their relevance in the higher tolerance phenotype. The evolved strains, in addition to n-butanol, were also more tolerant to 2-butanol, isobutanol and 1-propanol, indicating a common molecular basis for sensitivity and tolerance to C3 and C4 alcohols.

Conclusions
This study shows that maintenance of protein integrity plays an essential role in butanol tolerance and demonstrates new promising targets to engineer S. cerevisiae for improved tolerance.
The pea aphid uses a version of the terminal system during oviparous, but not viviparous, development
Authors: Bickel Ryan D , Cleveland Hillary C , Barkas Joanna , Jeschke Caitlin C , Raz Amelie A , Stern David L , Davis Gregory K 
Published: April 2013

Abstract

Background
In most species of aphid, female nymphs develop into either sexual or asexual adults depending on the length of the photoperiod to which their mothers were exposed. The progeny of these sexual and asexual females, in turn, develop in dramatically different ways. The fertilized oocytes of sexual females begin embryogenesis after being deposited on leaves (oviparous development) while the oocytes of asexual females complete embryogenesis within the mother (viviparous development). Compared with oviparous development, viviparous development involves a smaller transient oocyte surrounded by fewer somatic epithelial cells and a smaller early embryo that comprises fewer cells. To investigate whether patterning mechanisms differ between the earliest stages of the oviparous and viviparous modes of pea aphid development, we examined the expression of pea aphid orthologs of genes known to specify embryonic termini in other insects.

Results
Here we show that pea aphid oviparous ovaries express torso-like in somatic posterior follicle cells and activate ERK MAP kinase at the posterior of the oocyte. In addition to suggesting that some posterior features of the terminal system are evolutionarily conserved, our detection of activated ERK in the oocyte, rather than in the embryo, suggests that pea aphids may transduce the terminal signal using a mechanism distinct from the one used in Drosophila. In contrast with oviparous development, the pea aphid version of the terminal system does not appear to be used during viviparous development, since we did not detect expression of torso-like in the somatic epithelial cells that surround either the oocyte or the blastoderm embryo and we did not observe restricted activated ERK in the oocyte.

Conclusions
We suggest that while oviparous oocytes and embryos may specify posterior fate through an aphid terminal system, viviparous oocytes and embryos employ a different mechanism, perhaps one that does not rely on an interaction between the oocyte and surrounding somatic cells. Together, these observations provide a striking example of a difference in the fundamental events of early development that is both environmentally induced and encoded by the same genome.
Classification of Hungarian medieval silver coins using x-ray fluorescent spectroscopy and multivariate data analysis
Authors: Rácz Anita , Héberger Károly , Rajkó Róbert , Elek János 
Published: April 2013

Abstract

Background
A set of silver coins from the collection of Déri Museum Debrecen (Hungary) was examined by X-ray fluorescent elemental analysis with the aim to assign the coins to different groups with the best possible precision based on the acquired chemical information and to build models, which arrange the coins according to their historical periods.

Results
Principal component analysis, linear discriminant analysis, partial least squares discriminant analysis, classification and regression trees and multivariate curve resolution with alternating least squares were applied to reveal dominant pattern in the data and classify the coins into several groups. We also identified those chemical components, which are present in small percentages, but are useful for the classification of the coins. With the coins divided into two groups according to adequate historical periods, we have obtained a correct classification (76-78%) based on the chemical compositions.

Conclusions
X-ray fluorescent elemental analysis together with multivariate data analysis methods is suitable to group medieval coins according to historical periods.
Analytical pyrolysis with in-situ silylation, Py(HMDS)-GC/MS, for the chemical characterization of archaeological and historical amber objects
Authors: Colombini Maria Perla , Ribechini Erika , Rocchi Marco , Selleri Paola 
Published: April 2013

Abstract

Introduction
An optimised analytical technique based on pyrolysis coupled with gas chromatography/mass spectrometry (Py-GC/MS) and derivatisation in situ with hexamethyldisilazane (HMDS) was used to study several archaeological and artistic amber objects. The aim was to verify the authenticity of the objects and to provide historical information regarding the geographical origin of the ambers, and thus reveal the trade routes between different ancient civilizations.

Results
Py-GC/MS using HMDS as a silylating agent enabled us not only to identify the geographical origin of the archaeological and artistic ambers as succinites, but also highlighted the degradation of amber objects revealing a lower abundance of free diterpenes on the surface.

Conclusion
This work demonstrates the capability of Py-GC/MS with silylation in situ to identify the geographical origin of archaeological ambers and to provide crucial information regarding their degradation process. The porous and rough appearance of the outer layer can be correlated with the higher lixiviation and to the evaporation of free diterpenes from the surface. The knowledge of the amber degradation mechanisms is crucial to select proper conservation-restoration methods.