bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrantly expressed long noncoding RNAs in human intervertebral disc degeneration: a microarray related study
Authors: Wan Zhong-Yuan , Song Fang , Sun Zhen , Chen Yu-Fei , Zhang Wei-Lin , Samartzis Dino , Ma Chi-Jiao , Che Lu , Liu Xu , Ali M-Azam , Wang Hai-Qiang , Luo Zhuo-Jing 
Published: October 2014

Abstract
Introduction
In addition to the well-known short noncoding RNAs such as microRNAs (miRNAs), increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, little is known regarding the role of lncRNAs with regards to intervertebral disc degeneration (IDD). In the present study we aimed to determine whether lncRNAs are differentially expressed in IDD.

Methods
An lncRNA-mRNA microarray analysis of human nucleus pulposus (NP) was employed. Bioinformatics prediction was also applied to delineate the functional roles of the differentially expressed lncRNAs. Several lncRNAs and mRNAs were chosen for quantitative real-time PCR (qRT-PCR) validation.

Results
Microarray data profiling indicated that 116 lncRNAs (67 up and 49 down) and 260 mRNAs were highly differentially expressed with an absolute fold change greater than ten. Moreover, 1,052 lncRNAs and 1,314 mRNAs were differentially expressed in the same direction in at least four of the five degenerative samples with fold change greater than two. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated a number of pathways, such as extracellular matrix (ECM)-receptor interaction. A coding-noncoding gene co-expression (CNC) network was constructed for the ten most significantly changed lncRNAs. Annotation terms of the coexpressed mRNAs were related to several known degenerative alterations, such as chondrocyte differentiation. Moreover, lncRNAs belonging to a particular subgroup were identified. Functional annotation for the corresponding nearby coding genes showed that these lncRNAs were mainly associated with cell migration and phosphorylation. Interestingly, we found that Fas-associated protein factor-1 (FAF1), which potentiates the Fas-mediated apoptosis and its nearby enhancer-like lncRNA RP11-296A18.3, were highly expressed in the degenerative discs. Subsequent qRT-PCR results confirmed the changes.

Conclusions
This is the first study to demonstrate that aberrantly expressed lncRNAs play a role in the development of IDD. Our study noted that up-regulated RP11-296A18.3 highly likely induced the over-expression of FAF1, which eventually promoted the aberrant apoptosis of disc cells. Such findings further broaden the understanding of the etiology of IDD.
Loss of Tropomodulin4 in the zebrafish mutant träge causes cytoplasmic rod formation and muscle weakness reminiscent of nemaline myopathy
Authors: Berger Joachim , Tarakci Hakan , Berger Silke , Li Mei , Hall Thomas E. , Arner Anders , Currie Peter D. 
Published: October 2014

Abstract
Nemaline myopathy is an inherited muscle disease that is mainly diagnosed by the presence of nemaline rods in muscle biopsies. Of the nine genes associated with the disease, 5 encode for components of striated muscle sarcomeres. In a genetic zebrafish screen the mutant träge (trg) was isolated based on its reduction in muscle birefringence, indicating muscle damage. Myofibres in trg appeared disorganized and showed inhomogeneous cytoplasmic eosin staining alongside malformed nuclei. Linkage analysis of trg combined with sequencing identified a nonsense mutation in tropomodulin4 (tmod4), a regulator of thin filament length and stability. Accordingly, although actin monomers polymerise to form thin filaments in the skeletal muscle of tmod4trg mutants, thin filaments often appeared to be dispersed throughout myofibres. Organised myofibrils with the typical striation rarely assemble, leading to severe muscle weakness, impaired locomotion, and early death. Myofibrils of tmod4trg mutants often featured thin filaments of various lengths, widened Z-disks, undefined H-zones, and electron-dense aggregations of various shapes and sizes. Importantly, Gomori trichrome staining and the lattice pattern of the detected cytoplasmic rods together with the reactivity of rods with phalloidin and an antibody against actinin is reminiscent of nemaline rods found in nemaline myopathy, suggesting that misregulation of thin filament length causes cytoplasmic rod formation in tmod4trg mutants. Although Tropomodulin4 has not been associated with myopathy, the results presented here implicate TMOD4 as a novel candidate for unresolved nemaline myopathies and suggest that the tmod4trg mutant will be a valuable tool to study human muscle disorders.
An integrated transcriptomic and comparative genomic analysis of differential gene expression in Arctic charr (Salvelinus alpinus) following seawater exposure
Authors: Norman Joseph D. , Ferguson Moira M. , Danzmann Roy G. 
Published: October 2014

Abstract
High-throughput RNA sequencing was employed to compare expression profiles in two Arctic charr (Salvelinus alpinus) families post seawater exposure to identify genes and biological processes involved in hypo-osmoregulation and regulation of salinity tolerance. To further understand the genetic architecture of hypo-osmoregulation, the genomic organization of differentially expressed (DE) genes was also analysed. Using a de novo gill transcriptome assembly we found over 2300 contigs to be DE. Major transporters from the seawater mitochondrion-rich cell (MRC) complex were up-regulated in seawater. Expression ratios for 257 differentially expressed contigs were highly correlated between families, suggesting they are strictly regulated. Based on expression profiles and known molecular pathways we inferred that seawater exposure induced changes in methylation states and elevated peroxynitrite formation in gill. We hypothesized that concomitance between DE immune genes and the transition to a hypo-osmoregulatory state could be related to Cl- sequestration by antimicrobial defence mechanisms. Gene Ontology analysis revealed that cell division genes were up-regulated, which could reflect the proliferation of ATP1α1b-type seawater MRCs. Comparative genomics analyses suggest that hypo-osmoregulation is influenced by the relative proximities among a contingent of genes on Arctic charr linkage groups AC-4 and AC-12 that exhibit homologous affinities with a region on stickleback chromosome Ga-I. This supports the hypothesis that relative gene location along a chromosome is a property of the genetic architecture of hypo-osmoregulation. Evidence of non-random structure between hypo-osmoregulation candidate genes was found on AC-1/11 and AC-28, suggesting that interchromosomal rearrangements played a role in the evolution of hypo-osmoregulation in Arctic charr.
Validation of a model-based measurement of the minimum insert thickness of knee prostheses
Authors: van IJsseldijk E. A. , Harman M. K. , Luetzner J. , Valstar E. R. , Stoel B. C. , Nelissen R. G. H. H. , Kaptein B. L. 
Published: October 2014

Introduction Wear of polyethylene inserts plays an important role in failure of total knee replacement and can be monitored in vivo by measuring the minimum joint space width in anteroposterior radiographs. The objective of this retrospective cross-sectional study was to compare the accuracy and precision of a new model-based method with the conventional method by analysing the difference between the minimum joint space width measurements and the actual thickness of retrieved polyethylene tibial inserts. Method Before revision, the minimum joint space width values and their locations on the insert were measured in 15 fully weight-bearing radiographs. These measurements were compared with the actual minimum thickness values and locations of the retrieved tibial inserts after revision. Results The mean error in the model-based minimum joint space width measurement was significantly smaller than the conventional method for medial condyles (0.50 vs 0.94 mm, p < 0.01) and for lateral condyles (0.06 vs 0.34 mm, p = 0.02). The precision (standard deviation of the error) of the methods was similar (0.84 vs 0.79 mm medially and both 0.46 mm laterally). The distance between the true minimum joint space width locations and the locations from the model-based measurements was less than 10 mm in the medial direction in 12 cases and less in the lateral direction in 13 cases. Conclusion The model-based minimum joint space width measurement method is more accurate than the conventional measurement with the same precision. Cite this article: Bone Joint Res 2014;3:289–96
Precision and Reliability of 5 Platelet Function Tests in Healthy Volunteers and Donors on Daily Antiplatelet Agent Therapy
Authors: Karon Brad S , Tolan Nicole V , Koch Christopher D , Wockenfus Amy M , Miller Randall S , Lingineni Ravi K , Pruthi Rajiv K , Chen Dong , Jaffe Allan S 
Published: October 2014

Abstract

BACKGROUND
Anticoagulation protocols used during mechanical circulatory support call for titration of antiplatelet agents. We compared the precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet therapy to distinguish their efficacy for titrating antiplatelet therapy.

METHODS
We assessed arachidonic acid–induced platelet function by light transmission aggregometry (LTA), Multiplate impedance aggregometry, VerifyNow, and platelet mapping by thromboelastography (TEG PM). We assessed ADP-induced platelet function by the same methods and flow cytometry. Forty healthy volunteers and 10–13 volunteers on daily aspirin and/or clopidogrel therapy were evaluated. We compared tests for intraassay precision, interassay precision (samples from 2 separate blood draws), and reliability coefficient.

RESULTS
For arachidonic acid–induced platelet aggregation in healthy volunteers, intra- and interassay CVs were ≤10% for all methods. Intra- and interassay precision among donors on daily aspirin was ≤30% for all methods except LTA (38% interassay CV) and TEG PM (95% intraassay and 104% interassay CV). For ADP-induced platelet function, intra- and interassay precision was ≤10% and ≤30% for all methods. Only Multiplate demonstrated moderate or greater (R &gt; 0.40) reliability coefficients for arachidonic acid–induced platelet function among all subjects. All methods of ADP-induced platelet function, except TEG PM, demonstrated substantial or greater (R &gt; 0.60) reliability among all subjects.

CONCLUSIONS
TEG PM is least suited to monitor effects of antiplatelet agents. Multiplate impedance aggregometry was the only method to demonstrate an acceptable reliability coefficient among healthy volunteers and donors on both aspirin and clopidogrel therapy.
THERAPY OF ENDOCRINE DISEASE: Effects of chronic use of phosphodiesterase inhibitors on endothelial markers in type 2 diabetes mellitus: a meta-analysis
Authors: Santi Daniele , Giannetta Elisa , Isidori Andrea M , Vitale Cristiana , Aversa Antonio , Simoni Manuela 
Published: October 2014

ObjectiveDiabetes mellitus (DM) is associated with endothelial dysfunction, reducing nitric oxide-dependent vasodilation, and increasing production of pro-inflammatory factors, leading to an increased risk of long-term cardiovascular disease. As the effects of phosphodiesterase 5 inhibitors (PDE5i) on endothelial function have not been systematically investigated, we conducted a meta-analysis of available randomized clinical trials (RCTs).DesignA thorough search of the literature was carried out. Relevant studies were considered according to RCT study design, enrollment of men with type 2 DM, chronic administration of PDE5i, and evaluation of endothelial function through both hemodynamic and endothelial inflammation-related parameters.ResultsFifteen studies fulfilled the eligibility criteria but only six RCTs met the inclusion criteria and were analyzed for 476 diabetic men, 239 randomized to Sildenafil, and 237 to placebo respectively. Four RCTs evaluated flow-mediated dilation (FMD), demonstrating a weighted mean increase of 2.19% (95% CI 0.48 to 3.90). This result showed a high heterogeneity (I2: 98%). Thus, a further sub-group meta-analysis was performed and this analysis confirmed a significant, Sildenafil-related FMD improvement. Sildenafil improved endothelin 1 and high sensitivity C-reactive protein by ∼−0.94 pg/ml and −0.36 mg/l, respectively, not reaching statistical significance (P=0.69 andP=0.22 respectively). Finally, Sildenafil administration significantly reduced serum levels of interleukin 6 (IL6, −0.82 pg/ml; 95% CI −1.58 to −0.07).ConclusionThis meta-analysis suggests a beneficial effect of chronic PDE5i administration on endothelial function. Chronic Sildenafil administration seems to improve hemodynamic (FMD) and serum pro-inflammatory makers (IL6) in diabetic men. Larger studies are needed to confirm the effects of chronic PDE5i on endothelial function.
Does Cardiac Rehabilitation After an Acute Cardiac Syndrome Lead to Changes in Physical Activity Habits? Systematic Review
Authors: ter Hoeve Nienke , Huisstede Bionka M.A. , Stam Henk J. , van Domburg Ron T. , Sunamura Madoka , van den Berg-Emons Rita J.G. 
Published: October 2014

BackgroundOptimal physical activity levels have health benefits for patients with acute coronary syndrome (ACS) and are an important goal of cardiac rehabilitation (CR).PurposeThe purpose of this study was to systematically review literature regarding short-term effects (&lt;6 months after completion of CR) and long-term effects (≥6 months after completion) of standard CR on physical activity levels in patients with ACS.Data SourcesPubMed, EMBASE, CINAHL, and PEDro were systematically searched for relevant randomized clinical trials (RCTs) published from 1990 until 2012.Study SelectionRandomized clinical trials investigating CR for patients with ACS reporting physical activity level were reviewed.Data ExtractionTwo reviewers independently selected articles, extracted data, and assessed methodological quality. Results were summarized with a best evidence synthesis. Results were categorized as: (1) center-based/home-based CR versus no intervention, (2) comparison of different durations of CR, and (3) comparison of 2 types of CR.Data SynthesisA total of 26 RCTs were included. Compared with no intervention, there was, at most, conflicting evidence for center-based CR and moderate evidence for home-based CR for short-term effectiveness. Limited evidence and no evidence were found for long-term maintenance for center-based and home-based CR, respectively. When directly compared with center-based CR, moderate evidence showed that home-based CR has better long-term effects. There was no clear evidence that increasing training volume, extending duration of CR, or adding an extra intervention to CR is more effective.LimitationsBecause of the variety of CR interventions in the included RCTs and the variety of outcome measures in the included RCTs, pooling of data was not possible. Therefore, a best evidence synthesis was used.ConclusionsIt would appear that center-based CR is not sufficient to improve and maintain physical activity habits. Home-based programs might be more successful, but the literature on these programs is limited. More research on finding successful interventions to improve activity habits is needed.
Prognostic value of intrathecal heme oxygenase–1 concentration in patients with Fisher Grade III aneurysmal subarachnoid hemorrhage
Authors: Wang Kuo-Chuan , Tang Sung-Chun , Lee Jing-Er , Lai Dar-Ming , Huang Sheng-Jean , Hsieh Sung-Tsang , Jeng Jiann-Shing , Tu Yong-Kwang 
Published: October 2014

Object
Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients.

Methods
Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase–1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed.

Results
The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age > 60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883–0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 μM, with higher values predicting unfavorable outcome (82.4% accuracy).

Conclusions
The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.
Trends and outcome predictors after traumatic brain injury surgery: a nationwide population-based study in Taiwan
Authors: Shi Hon-Yi , Hwang Shiuh-Lin , Lee I-Chen , Chen I-Te , Lee King-Teh , Lin Chih-Lung 
Published: October 2014

Object
The authors sought to analyze trends in hospital resource utilization and mortality rates in a population of patients who had received traumatic brain injury (TBI) surgery.

Methods
This nationwide population-based cohort study retrospectively analyzed 18,286 patients who had received surgical treatment for TBI between 1998 and 2010. The multiple linear regression model and Cox proportional hazards model were used for multivariate assessment of outcome predictors.

Results
The prevalence rate of surgical treatment for patients with TBI gradually but significantly (p < 0.001) increased by 47.6% from 5.0 per 100,000 persons in 1998 to 7.4 per 100,000 persons in 2010. Age, sex, Deyo-Charlson comorbidity index score, hospital volume, and surgeon volume were significantly associated with TBI surgery outcomes (p < 0.05). Over the 12-year period analyzed, the estimated mean hospital treatment cost increased 19.06%, whereas the in-hospital mortality rate decreased 10.9%. The estimated mean time of overall survival after TBI surgery (± SD) was 83.0 ± 4.2 months, and the overall in-hospital and 1-, 3-, and 5-year survival rates were 74.5%, 67.3%, 61.1%, and 57.8%, respectively.

Conclusions
These data reveal an increased prevalence of TBI, especially in older patients, and an increased hospital treatment cost but a decreased in-hospital mortality rate. Health care providers and patients should recognize that attributes of the patient and of the hospital may affect hospital resource utilization and the mortality rate. These results are relevant not only to other countries with similar population sizes but also to countries with larger populations.
The impact of dynamic factors on surgical outcomes after double-door laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine
Authors: Maruo Keishi , Moriyama Tokuhide , Tachibana Toshiya , Inoue Shinichi , Arizumi Fumihiro , Daimon Takashi , Yoshiya Shinichi 
Published: October 2014

Object
Laminoplasty is the preferred operation for most patients with cervical myelopathy due to multilevel ossification of the posterior longitudinal ligament (OPLL). Recent studies have demonstrated several significant risk factors for poor clinical outcomes after laminoplasty, including older age, lower preoperative Japanese Orthopaedic Association (JOA) score, postoperative change in cervical alignment, cervical kyphosis, and high occupying ratio of the OPLL (that is, the ratio of the greatest anteroposterior thickness of the OPLL to the anteroposterior diameter of the spinal canal at the same level on a lateral image). However, the impact of dynamic factors on clinical outcomes is unclear. The purpose of this study is to assess the impact of dynamic factors on the clinical outcome after laminoplasty for cervical myelopathy due to OPLL.

Methods
A consecutive series of patients who underwent laminoplasty for cervical myelopathy due to OPLL between 2003 and 2009 was retrospectively reviewed. The indication for laminoplasty at the authors' hospital included preoperative straight or lordotic alignment of the cervical spine and an occupying ratio of OPLL less than 60%. The JOA score and recovery rate were used to evaluate clinical outcomes. A poor clinical outcome was defined as a recovery rate of less than 50%. Patient factors examined along with outcome included age, preoperative JOA score, preoperative somatosensory evoked potentials, preoperative motor evoked potentials, body mass index, and presence of high intensity on MRI. Radiographic measures included the preoperative C2–7 lordotic angle, preoperative C2–7 range of motion (ROM), preoperative segmental ROM at the level of myelopathy, and the occupying ratio of OPLL.

Results
There were 45 patients (33 males and 12 females). The mean follow-up period was 4 years (range 2–6.8 years). The mean patient age was 66.9 years (range 50–85 years). The mean JOA score significantly increased from 9.1 before surgery to 13.1 at the final follow-up. The mean recovery rate was 51.2%. Nineteen patients (42%) had a recovery rate of less than 50%. Patient factors were not associated with surgical outcomes. Only the preoperative C2–7 ROM was significantly greater in the poor surgical outcome group (23.1° vs 14.1°). Receiver operating characteristic curve analysis showed that the optimal preoperative C2–7 ROM cutoff was 20°. Logistic regression analysis revealed that patients with a preoperative C2–7 ROM of greater than 20° had a 4.6 times higher risk (p = 0.021) of a poor clinical outcome, indicating that dynamic factors may have an impact on the surgical outcome of laminoplasty.

Conclusions
Fusion surgery may be a useful strategy in patients with preoperative hypermobility of the cervical spine.