bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability of a New Stabilized Dynamometer System for the Evaluation of Hip Strength
Authors: Tourville Timothy W. , Smith Helen C. , Shultz Sandra J. , Vacek Pamela M. , Slauterbeck James R. , Johnson Robert J. , Beynnon Bruce D. 
Published: September 2012

Background: Hip strength is associated with numerous orthopaedic and neuromuscular injuries and/or pathologies and may be assessed with a variety of anatomic testing positions and techniques. Isokinetic dynamometers are generally too cumbersome and intricate for efficient use in mass screenings (for prognostic studies of risk for injury) as well as with special populations. The reliability of isometric testing devices has demonstrated varied reliability, generally examining only 1 or 2 motions of the hip and reporting values of force, not torque. Consequently, there is a need for an efficient hip strength-testing device to quantify torque that tests subjects in 1 anatomic position, while evaluating multiple hip motions. Hypothesis: Evaluation of supine hip abduction, adduction, flexion, and extension torque using a new stabilized dynamometer system will produce good to excellent intra- and interexaminer reliability results. Study Design: A blinded, randomized, repeated-measures study design was used in this descriptive laboratory investigation. Methods: Supine isometric hip flexion, extension, abduction, and adduction torques were evaluated with a cage-stabilized dynamometer in 19 collegiate and professional-level ice hockey athletes by 2 investigators at 3 time intervals. Inter- and intrarater reliability was assessed. Results: Supine hip flexion, extension, abduction, and adduction torque was performed with good to excellent inter- and intrarater reliability (intraclass correlation coefficients ranging from 0.74 to 0.92 and 0.78 to 0.92, respectively) for all motions tested. Conclusions: We have developed an isometric hip strength-testing device that can be assembled around an examination table to efficiently and reliably evaluate torque developed for multiple motions of the hip. Clinical Relevance: This device and testing protocol may be used to efficiently evaluate hip strength in numerous settings; it allows decreased subject burden and increased comfort (which may be important following an injury in case-control investigations); and it may be well tolerated when testing athletes as well as special populations in the clinical setting.
Glenohumeral Joint Injections
Authors: Gross Christopher , Dhawan Aman , Harwood Daniel , Gochanour Eric , Romeo Anthony 
Published: September 2012

Context: Intra-articular injections into the glenohumeral joint are commonly performed by musculoskeletal providers, including orthopaedic surgeons, family medicine physicians, rheumatologists, and physician assistants. Despite their frequent use, there is little guidance for injectable treatments to the glenohumeral joint for conditions such as osteoarthritis, adhesive capsulitis, and rheumatoid arthritis. Evidence Acquisition: We performed a comprehensive review of the available literature on glenohumeral injections to help clarify the current evidence-based practice and identify deficits in our understanding. We searched MEDLINE (1948 to December 2011 [week 1]) and EMBASE (1980 to 2011 [week 49]) using various permutations of intra-articular injections AND ( corticosteroid OR hyaluronic acid) and ( adhesive capsulitis OR arthritis). Results: We identified 1 and 7 studies that investigated intra-articular corticosteroid injections for the treatment of osteoarthritis and adhesive capsulitis, respectively. Two and 3 studies investigated the use of hyaluronic acid in osteoarthritis and adhesive capsulitis, respectively. One study compared corticosteroids and hyaluronic acid injections in the treatment of osteoarthritis, and another discussed adhesive capsulitis. Conclusion: Based on existing studies and their level of evidence, there is only expert opinion to guide corticosteroid injection for osteoarthritis as well as hyaluronic acid injection for osteoarthritis and adhesive capsulitis.
Investigational agent MLN9708/2238 targets tumor-suppressor miR33b in MM cells
Authors: Tian Ze , Zhao Jian-jun , Tai Yu-Tzu , Amin Samir B. , Hu Yiguo , Berger Allison J. , Richardson Paul , Chauhan Dharminder , Anderson Kenneth C. 
Published: September 2012

Abstract
miRs play a critical role in tumor pathogenesis as either oncogenes or tumor-suppressor genes. However, the role of miRs and their regulation in response to proteasome inhibitors in multiple myeloma (MM) is unclear. In the current study, miR profiling in proteasome inhibitor MLN2238-treated MM.1S MM cells shows up-regulation of miR33b. Mechanistic studies indicate that the induction of miR33b is predominantly via transcriptional regulation. Examination of miR33b in patient MM cells showed a constitutively low expression. Overexpression of miR33b decreased MM cell viability, migration, colony formation, and increased apoptosis and sensitivity of MM cells to MLN2238 treatment. In addition, overexpression of miR33b or MLN2238 exposure negatively regulated oncogene PIM-1 and blocked PIM-1 wild-type, but not PIM-1 mutant, luciferase activity. Moreover, PIM-1 overexpression led to significant abrogation of miR33b- or MLN2238-induced cell death. SGI-1776, a biochemical inhibitor of PIM-1, triggered apoptosis in MM. Finally, overexpression of miR33b inhibited tumor growth and prolonged survival in both subcutaneous and disseminated human MM xenograft models. Our results show that miR33b is a tumor suppressor that plays a role during MLN2238-induced apoptotic signaling in MM cells, and these data provide the basis for novel therapeutic strategies targeting miR33b in MM.
Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke
Authors: Gelderblom Mathias , Weymar Anna , Bernreuther Christian , Velden Joachim , Arunachalam Priyadharshini , Steinbach Karin , Orthey Ellen , Arumugam Thiruma V. , Leypoldt Frank , Simova Olga , Thom Vivien , Friese Manuel A. , Prinz Immo , Hölscher Christoph , Glatzel Markus , Korn Thomas , Gerloff Christian , Tolosa Eva , Magnus Tim 
Published: September 2012

AbstractThe devastating effect of ischemic stroke is attenuated in mice lacking conventional and unconventional T cells, suggesting that inflammation enhances tissue damage in cerebral ischemia. We explored the functional role of αβ and γδ T cells in a murine model of stroke and distinguished 2 different T cell–dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced by CD4+ T cells induced TNF-α production in macrophages, whereas IL-17A secreted by γδ T cells led to neutrophil recruitment. The synergistic effect of TNF-α and IL-17A on astrocytes resulted in enhanced secretion of CXCL-1, a neutrophil chemoattractant. Application of an IL-17A–blocking antibody within 3 hours after stroke induction decreased infarct size and improved neurologic outcome in the murine model. In autoptic brain tissue of patients who had a stroke, we detected IL-17A–positive lymphocytes, suggesting that this aspect of the inflammatory cascade is also relevant in the human brain. We propose that selective targeting of IL-17A signaling might provide a new therapeutic option for the treatment of stroke.
Disentangling evolutionary signals: conservation, specificity determining positions and coevolution. Implication for catalytic residue prediction
Authors: Teppa Elin , Wilkins Angela D , Nielsen Morten , Buslje Cristina Marino 
Published: September 2012

Abstract

Background
A large panel of methods exists that aim to identify residues with critical impact on protein function based on evolutionary signals, sequence and structure information. However, it is not clear to what extent these different methods overlap, and if any of the methods have higher predictive potential compared to others when it comes to, in particular, the identification of catalytic residues (CR) in proteins. Using a large set of enzymatic protein families and measures based on different evolutionary signals, we sought to break up the different components of the information content within a multiple sequence alignment to investigate their predictive potential and degree of overlap.

Results
Our results demonstrate that the different methods included in the benchmark in general can be divided into three groups with a limited mutual overlap. One group containing real-value Evolutionary Trace (rvET) methods and conservation, another containing mutual information (MI) methods, and the last containing methods designed explicitly for the identification of specificity determining positions (SDPs): integer-value Evolutionary Trace (ivET), SDPfox, and XDET. In terms of prediction of CR, we find using a proximity score integrating structural information (as the sum of the scores of residues located within a given distance of the residue in question) that only the methods from the first two groups displayed a reliable performance. Next, we investigated to what degree proximity scores for conservation, rvET and cumulative MI (cMI) provide complementary information capable of improving the performance for CR identification. We found that integrating conservation with proximity scores for rvET and cMI achieved the highest performance. The proximity conservation score contained no complementary information when integrated with proximity rvET. Moreover, the signal from rvET provided only a limited gain in predictive performance when integrated with mutual information and conservation proximity scores. Combined, these observations demonstrate that the rvET and cMI scores add complementary information to the prediction system.

Conclusions
This work contributes to the understanding of the different signals of evolution and also shows that it is possible to improve the detection of catalytic residues by integrating structural and higher order sequence evolutionary information with sequence conservation.
Diversity and evolution of multiple orc/cdc6-adjacent replication origins in haloarchaea
Authors: Wu Zhenfang , Liu Hailong , Liu Jingfang , Liu Xiaoqing , Xiang Hua 
Published: September 2012

AbstractBackgroundWhile multiple replication origins have been observed in archaea, considerably less is known about their evolutionary processes. Here, we performed a comparative analysis of the predicted (proved in part)orc/cdc6-associated replication origins in 15 completely sequenced haloarchaeal genomes to investigate the diversity and evolution of replication origins in halophilic Archaea.ResultsMultipleorc/cdc6-associated replication origins were predicted in all of the analyzed haloarchaeal genomes following the identification of putative ORBs (origin recognition boxes) that are associated withorc/cdc6genes. Five of these predicted replication origins inHaloarcula hispanicawere experimentally confirmed via autonomous replication activities. Strikingly, several predicted replication origins inH. hispanicaandHaloarcula marismortuiare located in the distinct regions of their highly homologous chromosomes, suggesting that these replication origins might have been introduced as parts of new genomic content. A comparison of the origin-associated Orc/Cdc6 homologs and the corresponding predicted ORB elements revealed that the replication origins in a given haloarchaeon are quite diverse, while different haloarchaea can share a few conserved origins. Phylogenetic and genomic context analyses suggested that there is an original replication origin (oriC1) that was inherited from the ancestor of archaea, and several other origins were likely evolved and/or translocated within the haloarchaeal species.ConclusionThis study provides detailed information about the diversity of multipleorc/cdc6-associated replication origins in haloarchaeal genomes, and provides novel insight into the evolution of multiple replication origins in Archaea.
Computational identification of transcriptionally co-regulated genes, validation with the four ANT isoform genes
Authors: Dupont Pierre-Yves , Guttin Audrey , Issartel Jean-Paul , Stepien Georges 
Published: September 2012

Abstract

Background
The analysis of gene promoters is essential to understand the mechanisms of transcriptional regulation required under the effects of physiological processes, nutritional intake or pathologies. In higher eukaryotes, transcriptional regulation implies the recruitment of a set of regulatory proteins that bind on combinations of nucleotide motifs. We developed a computational analysis of promoter nucleotide sequences, to identify co-regulated genes by combining several programs that allowed us to build regulatory models and perform a crossed analysis on several databases. This strategy was tested on a set of four human genes encoding isoforms 1 to 4 of the mitochondrial ADP/ATP carrier ANT. Each isoform has a specific tissue expression profile linked to its role in cellular bioenergetics.

Results
From their promoter sequence and from the phylogenetic evolution of these ANT genes in mammals, we constructed combinations of specific regulatory elements. These models were screened using the full human genome and databases of promoter sequences from human and several other mammalian species. For each of transcriptionally regulated ANT1, 2 and 4 genes, a set of co-regulated genes was identified and their over-expression was verified in microarray databases.

Conclusions
Most of the identified genes encode proteins with a cellular function and specificity in agreement with those of the corresponding ANT isoform. Our in silico study shows that the tissue specific gene expression is mainly driven by promoter regulatory sequences located up to about a thousand base pairs upstream the transcription start site. Moreover, this computational strategy on the study of regulatory pathways should provide, along with transcriptomics and metabolomics, data to construct cellular metabolic networks.
Modified endoscopic submucosal dissection with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer
Authors: Chu Yin-Yi , Lien Jau-Min , Tsai Ming-Hung , Chiu Cheng-Tang , Chen Tse-Ching , Yang Kuo-Ching , Ng Soh-Ching 
Published: September 2012

Abstract

Background
Gastric subepithelial tumors are usually asymptomatic and observed incidentally during endoscopic examination. Although most of these tumors are considered benign, some have a potential for malignant transformation, particularly those originating from the muscularis propria layer. For this type of tumor, surgical resection is the standard treatment of choice. With recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative way of treatment. The aim of this study is to demonstrate the feasibility of a modified ESD technique with enucleation for removal of gastric subepithelial tumors originating from the muscularis propria layer, and to evaluate its efficacy and safety.

Methods
From November 2009 to May 2011, a total of 16 patients received a modified ESD with enucleation for their subepithelial tumors. All tumors were smaller than 5 cm and originated from the muscularis propria layer of the stomach, as shown by endoscopic ultrasonography (EUS). The procedure was conducted with an insulated-tip knife 2. Patient’s demographics, tumor size and pathological diagnosis, procedure time, procedure-related complication, and treatment outcome were reviewed.

Results
Fifteen of the sixteen tumors were successful complete resection. The mean tumor size measured by EUS was 26.1 mm (range: 20–42 mm). The mean procedure time was 52 minutes (range: 30–120 minutes). Endoscopic features of the 4 tumors were pedunculated and 12 were sessile. Their immunohistochemical diagnosis was c-kit (+) stromal tumor in 14 patients and leiomyoma in 2 patients. There was no procedure-related perforation or overt bleeding. During a mean follow up duration of 14.8 months (range: 6–22 months), there was no tumor recurrence or metastasis.

Conclusions
Using a modified ESD with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer and larger than 2 cm, complete resection can be successfully performed without serious complication. It is a safe and effective alternative to surgical therapy for these tumors of 2 to 5 cm in size.
High yield of culture-based diagnosis in a TB-endemic setting
Authors: Demers Anne-Marie , Verver Suzanne , Boulle Andrew , Warren Robin , van Helden Paul , Behr Marcel A , Coetzee David 
Published: September 2012

AbstractBackgroundIn most of the world, microbiologic diagnosis of tuberculosis (TB) is limited to microscopy. Recent guidelines recommend culture-based diagnosis where feasible.MethodsIn order to evaluate the relative and absolute incremental diagnostic yield of culture-based diagnosis in a high-incidence community in Cape Town, South Africa, subjects evaluated for suspected TB had their samples processed for microscopy and culture over a 21 month period.ResultsFor 2537 suspect episodes with 2 smears and 2 cultures done, 20.0% (508) had at least one positive smear and 29.9% (760) had at least one positive culture. One culture yielded 1.8 times more cases as 1 smear (relative yield), or an increase of 12.0% (absolute yield). Based on the latter value, thenumber of culturesneeded todiagnose (NND) one extra case of TB was 8, compared to 19 if second specimens were submitted for microscopy.ConclusionIn a high-burden setting, the introduction of culture can markedly increase TB diagnosis over microscopy. The concept of number needed to diagnose can help in comparing incremental yield of diagnosis methods. Although new promising diagnostic molecular methods are being implemented, TB culture is still the gold standard.
A missense founder mutation in VLDLR is associated with Dysequilibrium Syndrome without quadrupedal locomotion
Authors: Ali Bassam R , Silhavy Jennifer L , Gleeson Matthew J , Gleeson Joseph G , Al-Gazali Lihadh 
Published: September 2012

Abstract

Background
Dysequilibrium syndrome is a genetically heterogeneous condition that combines autosomal recessive, nonprogressive cerebellar ataxia with mental retardation. The condition has been classified into cerebellar ataxia, mental retardation and disequilibrium syndrome types 1 (CAMRQ1), 2 (CAMRQ2) and 3 (CAMRQ3) and attributed to mutations in VLDLR, CA8 and WDR81 genes, respectively. Quadrupedal locomotion in this syndrome has been reported in association with mutations in all three genes.

Methods
SNP mapping and candidate gene sequencing in one consanguineous Omani family from the United Arab Emirates with cerebellar hypoplasia, moderate mental retardation, delayed ambulation and truncal ataxia was used to identify the mutation. In a second unrelated consanguineous Omani family, massively parallel exonic sequencing was used.

Results
We identified a homozygous missense mutation (c.2117 G > T, p.C706F) in the VLDLR gene in both families on a shared affected haplotype block.This is the first reported homozygous missense mutation in VLDLR and it occurs in a highly conserved residue and predicted to be damaging to protein function.

Conclusions
We have delineated the phenotype associated with dysequilibrium syndrome in two Omani families and identified the first homozygous missense pathogenic mutation in VLDLR gene with likely founder effect in the southeastern part of the Arabian Peninsula.
PNPLA 3I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection
Authors: Rembeck Karolina , Maglio Cristina , Lagging Martin , Christensen Peer Brehm , Färkkilä Martti , Langeland Nina , Buhl Mads Rauning , Pedersen Court , Mørch Kristine , Norkrans Gunnar , Hellstrand Kristoffer , Lindh Magnus , Pirazzi Carlo , Burza Maria Antonella , Romeo Stefano , Westin Johan ,   for the NORDynamIC group
Published: September 2012

Abstract

Background
Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients.

Methods
Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients.

Results
In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients.

Conclusions
Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.
A predictive tool for an effective use of 18F-FDG PET in assessing activity of sarcoidosis
Authors: Mostard Rémy LM , Kuijk Sander MJ Van , Verschakelen Johny A , Kroonenburgh Marinus JPG van , Nelemans Patty J , Wijnen Petal AHM , Drent Marjolein 
Published: September 2012

Abstract

Background

18F-FDG PET/CT (PET) is useful in assessing inflammatory activity in sarcoidosis. However, no appropriate indications are available. The aim of this study was to develop a prediction rule that can be used to identify symptomatic sarcoidosis patients who have a high probability of PET-positivity.

Methods
We retrospectively analyzed a cohort of sarcoidosis patients with non organ specific persistent disabling symptoms (n = 95). Results of soluble interleukin-2 receptor (sIL-2R) assessment and high-resolution computed tomography (HRCT) were included in the predefined model. HRCT scans were classified using a semi-quantitative scoring system and PET findings as positive or negative, respectively. A prediction model was derived based on logistic regression analysis. We quantified the model’s performance using measures of discrimination and calibration. Finally, we constructed a prediction rule that should be easily applicable in clinical practice.

Results
The prediction rule showed good calibration and good overall performance (goodness-of-fit test, p = 0.78, Brier score 20.1%) and discriminated between patients with positive and negative PET findings (area under the receiver-operating characteristic curve, 0.83). If a positive predictive value for the presence of inflammatory activity of ≥90% is considered acceptable for clinical decision-making without referral to PET, PET would be indicated in only 29.5% of the patients. Using a positive predictive value of 98%, about half of the patients (46.3%) would require referral to PET.

Conclusions
The derived and internally validated clinical prediction rule, based on sIL-2R levels and HRCT scoring results, appeared to be useful to identify sarcoidosis patients with a high probability of inflammatory activity. Using this rule may enable a more effective use of PET scan for assessment of inflammatory activity in sarcoidosis.