Incidence and outcomes of intraoperative periprosthetic acetabular fractures during cementless total hip arthroplasty: a prospective three-dimensional computer tomography-based study.

PURPOSE: Unlike periprosthetic femoral fractures, periprosthetic acetabular fractures during total hip arthroplasty (THA) have not been evaluated in detail. We prospectively evaluated the incidence, patterns, risk factors, and clinical outcomes of intraoperative periprosthetic acetabular fractures using pre- and postoperative computer tomography (CT). METHODS: In this prospective single-centre study, we evaluated 234 consecutive patients (250 hips) who underwent THA and three-dimensional CT before and after the surgery. We assessed the incidence, pattern of fractures, outcomes for each fracture pattern, reoperation and revision rates, Harris hip score, and visual analog scale (VAS) for pain. Multivariate regression models were used to identify risk factors for periprosthetic acetabular fractures. RESULTS: In total, 43 periprosthetic acetabular fractures (17.2%) were identified via CT. Fractures occurred most frequently at the superolateral wall. Early cup migration occurred in three hips. None of the patients underwent revision surgery for acetabular loosening. Regression modeling showed that rheumatoid arthritis was a significant predictor of periprosthetic acetabular fractures. CONCLUSIONS: Periprosthetic acetabular fractures are not infrequent during cementless THA and are more common in patients with rheumatoid arthritis.

An Exosome-based Transcriptomic Signature for Noninvasive, Early Detection of Patients With Pancreatic Ductal Adenocarcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising worldwide, and most patients present with an unresectable disease at initial diagnosis. Measurement of carbohydrate antigen 19-9 (CA19-9) levels lacks adequate sensitivity and specificity for early detection; hence, there is an unmet need to develop alternate molecular diagnostic biomarkers for PDAC. Emerging evidence suggests that tumor-derived exosomal cargo, particularly micro RNAs (miRNAs), offer an attractive platform for the development of cancer-specific biomarkers. Herein, genomewide profiling in blood specimens was performed to develop an exosome-based transcriptomic signature for noninvasive and early detection of PDAC. METHODS: Small RNA sequencing was undertaken in a cohort of 44 patients with an early-stage PDAC and 57 nondisease controls. Using machine-learning algorithms, a panel of cell-free (cf) and exosomal (exo) miRNAs were prioritized that discriminated patients with PDAC from control subjects. Subsequently, the performance of the biomarkers was trained and validated in independent cohorts (n = 191) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. RESULTS: The sequencing analysis initially identified a panel of 30 overexpressed miRNAs in PDAC. Subsequently using qRT-PCR assays, the panel was reduced to 13 markers (5 cf- and 8 exo-miRNAs), which successfully identified patients with all stages of PDAC (area under the curve [AUC] = 0.98 training cohort; AUC = 0.93 validation cohort); but more importantly, was equally robust for the identification of early-stage PDAC (stages I and II; AUC = 0.93). Furthermore, this transcriptomic signature successfully identified CA19-9 negative cases (<37 U/mL; AUC = 0.96), when analyzed in combination with CA19-9 levels, significantly improved the overall diagnostic accuracy (AUC = 0.99 vs AUC = 0.86 for CA19-9 alone). CONCLUSIONS: In this study, an exosome-based liquid biopsy signature for the noninvasive and robust detection of patients with PDAC was developed.

Regulation of Synapse Weakening through Interactions of the Microtubule Associated Protein Tau with PACSIN1.

Hyperphosphorylation of the microtubule associated protein tau (tau) is inextricably linked to several neurodegenerative diseases, collectively termed tauopathies, in which synapse dysfunction occurs through largely unidentified mechanisms. Our research aimed to uncover molecular mechanisms by which phosphorylation of tau (pTau) affects synapse function. Using combined molecular and electrophysiological analysis with in vitro genetic knock-in of phosphorylation mutant human tau in male rat CA1 hippocampal neurons, we show an interplay between tau and protein kinase C and casein kinase substrate in neurons protein 1 (PACSIN1) that regulates synapse function. pTau at serine residues 396/404 decreases tau:PACSIN1 binding and evokes PACSIN1-dependent functional and structural synapse weakening. Knock-down of tau or PACSIN1 increases AMPA receptor (AMPAR)-mediated current at extrasynaptic regions, supporting a role for these proteins in affecting AMPAR trafficking. The pTau-induced PACSIN1 dissociation may represent a pathophysiological regulator of synapse function that underlies tauopathy-associated synapse defects.SIGNIFICANCE STATEMENT Knowledge is still lacking for how hyperphosphorylation of tau and its effectors lead to synaptic and neuronal dysfunction. Our results provide crucial insight for this mechanistic understanding; we show that specific tau phosphorylation events modulate its protein interaction with PACSIN1 and thus elicits synapse weakening likely through PACSIN1-dependent regulation of AMPA receptor (AMPAR) trafficking. These findings develop our understanding of molecular events that may be relevant to cellular changes underpinning tauopathy-associated neurodegenerative diseases.

Cathelicidin-related antimicrobial peptide promotes neuroinflammation through astrocyte-microglia communication in experimental autoimmune encephalomyelitis.

Cathelicidin-related antimicrobial peptide (CRAMP) is an effector molecule of the innate immune system with direct antimicrobial and immunomodulatory activities; however, its role in neuroinflammatory responses and related diseases is not clearly understood. In particular, the expression of CRAMP and its functional role has not been previously studied in experimental autoimmune encephalomyelitis (EAE) or multiple sclerosis (MS). Here, we investigated the role of CRAMP in neuroinflammation, using an EAE mouse model of MS and postmortem patient tissues. We found that the CRAMP expression was increased in the spinal cords of EAE-induced mice. Immunofluorescence analysis revealed that CRAMP is mainly induced in reactive astrocytes in the inflamed spinal cord of EAE mice. A similar pattern of the LL-37 (human CRAMP) expression was observed in the brain and spinal cord tissues of patients with MS. An intrathecal injection of the CRAMP peptide in EAE mice accelerated the onset of symptoms and increased disease severity with augmented expression of inflammatory mediators, glial activation, infiltration of inflammatory cells, and demyelination. In addition, shRNA-mediated knockdown of Cramp in the spinal cord resulted in a milder disease course with less inflammation in EAE mice. We identified FPR2 on microglia as a CRAMP receptor and demonstrated that CRAMP potentiates IFN-γ-induced microglial activation via the STAT3 pathway. Taken together, our findings suggest that CRAMP is a novel mediator of astrocyte-microglia interactions in neuroinflammatory conditions such as EAE. Thus, CRAMP could be exploited as a biomarker or therapeutic target for the diagnosis or treatment of MS.

Gamma subunit of complement component 8 is a neuroinflammation inhibitor.

The complement system is part of the innate immune system that comprises several small proteins activated by sequential cleavages. The majority of these complement components, such as components 3a (C3a) and C5a, are chemotactic and pro-inflammatory. However, in this study, we revealed an inhibitory role of complement component 8 gamma (C8G) in neuroinflammation. In patients with Alzheimer's disease, who exhibit strong neuroinflammation, we found higher C8G levels in brain tissue, CSF, and plasma. Our novel findings also showed that the expression level of C8G increases in the inflamed mouse brain, and that C8G is mainly localized to brain astrocytes. Experiments using recombinant C8G protein and shRNA-mediated knockdown showed that C8G inhibits glial hyperactivation, neuroinflammation, and cognitive decline in acute and chronic animal models of Alzheimer's disease. Additionally, we identified sphingosine-1-phosphate receptor 2 (S1PR2) as a novel interaction protein of C8G and demonstrated that astrocyte-derived C8G interacts with S1PR2 to antagonize the pro-inflammatory action of S1P in microglia. Taken together, our results reveal the previously unrecognized role of C8G as a neuroinflammation inhibitor. Our findings pave the way towards therapeutic containment of neuroinflammation in Alzheimer's disease and related neurological diseases.

Matrix stiffening induces a pathogenic QKI-miR-7-SRSF1 signaling axis in pulmonary arterial endothelial cells.

Pulmonary arterial hypertension (PAH) refers to a set of heterogeneous vascular diseases defined by elevation of pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), leading to right ventricular (RV) remodeling and often death. Early increases in pulmonary artery stiffness in PAH drive pathogenic alterations of pulmonary arterial endothelial cells (PAECs), leading to vascular remodeling. Dysregulation of microRNAs can drive PAEC dysfunction. However, the role of vascular stiffness in regulating pathogenic microRNAs in PAH is incompletely understood. Here, we demonstrated that extracellular matrix (ECM) stiffening downregulated miR-7 levels in PAECs. The RNA-binding protein quaking (QKI) has been implicated in the biogenesis of miR-7. Correspondingly, we found that ECM stiffness upregulated QKI, and QKI knockdown led to increased miR-7. Downstream of the QKI-miR-7 axis, the serine and arginine-rich splicing factor 1 (SRSF1) was identified as a direct target of miR-7. Correspondingly, SRSF1 was reciprocally upregulated in PAECs exposed to stiff ECM and was negatively correlated with miR-7. Decreased miR-7 and increased QKI and SRSF1 were observed in lungs from patients with PAH and PAH rats exposed to SU5416/hypoxia. Lastly, miR-7 upregulation inhibited human PAEC migration, whereas forced SRSF1 expression reversed this phenotype, proving that miR-7 depended upon SRSF1 to control migration. In aggregate, these results define the QKI-miR-7-SRSF1 axis as a mechanosensitive mechanism linking pulmonary arterial vascular stiffness to pathogenic endothelial function. These findings emphasize implications relevant to PAH and suggest the potential benefit of developing therapies that target this miRNA-dependent axis in PAH.

Long-Term Results of Total Hip Arthroplasty in Young Patients With Osteonecrosis After Allogeneic Bone Marrow Transplantation for Hematological Disease: A Multicenter, Propensity-Matched Cohort Study With a Mean 11-Year Follow-Up.

BACKGROUND: The number of young patients with hematological disease requiring total hip arthroplasty (THA) is expected to increase. We aimed to investigate the long-term THA outcomes in patients with osteonecrosis of the femoral head (ONFH) following allogeneic bone marrow transplantation (BMT) for hematological disease. METHODS: All patients who underwent THA for osteonecrosis after BMT from 1997 to 2012 were identified at 2 institutions. Using propensity scores, 75 THAs in 45 patients were matched for age, gender, body mass index, American Society of Anesthesiologists score, and year of surgery with 75 THAs in 58 patients with idiopathic ONFH without a history of hematological disease (1:1 ratio). The mean age at surgery was 36.7 years and 52% were men. Clinical and radiographic evaluations were performed and clinical scores were obtained at last follow-up. Kaplan-Meier analyses were used to compare survivorship. RESULTS: At a mean follow-up of 10.6 ± 3.5 years, clinical, radiographic, and survivorship outcomes, and the Harris hip scores were similar between both groups. The 13-year survivorship for all-cause revision was 93.4% for the BMT group and 95% for the control group (P = .928). No significant differences were observed between groups in the rates of reoperation (4% vs 5.3%, P = 1.000), 90-day readmission (all 5.3%), or overall mortality (4.4% vs 1.7%, P = .681). No hips had periprosthetic joint infection or septic loosening in either group. Osteolysis occurred in none of the BMT patients and in 2 hips (2.7%) of the control patients (P = .497). CONCLUSION: This large cohort multicenter survey at 11-year follow-up shows that contemporary cementless THA in young hematological disease patients after allogeneic BMT is not associated with a higher risk for surgical complications, revision, reoperation, readmission, and mortality compared to a matched cohort of idiopathic ONFH.

Recognition of Fine-Grained Walking Patterns Using a Smartwatch with Deep Attentive Neural Networks.

Generally, people do various things while walking. For example, people frequently walk while looking at their smartphones. Sometimes we walk differently than usual; for example, when walking on ice or snow, we tend to waddle. Understanding walking patterns could provide users with contextual information tailored to the current situation. To formulate this as a machine-learning problem, we defined 18 different everyday walking styles. Noting that walking strategies significantly affect the spatiotemporal features of hand motions, e.g., the speed and intensity of the swinging arm, we propose a smartwatch-based wearable system that can recognize these predefined walking styles. We developed a wearable system, suitable for use with a commercial smartwatch, that can capture hand motions in the form of multivariate timeseries (MTS) signals. Then, we employed a set of machine learning algorithms, including feature-based and recent deep learning algorithms, to learn the MTS data in a supervised fashion. Experimental results demonstrated that, with recent deep learning algorithms, the proposed approach successfully recognized a variety of walking patterns, using the smartwatch measurements. We analyzed the results with recent attention-based recurrent neural networks to understand the relative contributions of the MTS signals in the classification process.

Astrocytic AEG-1 regulates expression of TREK-1 under acute hypoxia.

TREK-1 (TWIK-related K+ channel), a member of the two-pore domain K+ (K2P) channel family, is highly expressed in astrocytes, where it plays a key role in glutamate release and passive conductance. In addition, TREK-1 is induced to protect neurons under pathological conditions such as hypoxia. However, the upstream regulation of TREK-1 remains poorly understood. In this study, we found that AEG-1 (astrocyte elevated gene-1) regulates the expression of astrocytic TREK-1 under hypoxic conditions. Upregulation of AEG-1 increased expression of TREK-1 in astrocytes, and knockdown of AEG-1 dramatically decreased the mRNA and protein levels of TREK-1, which were restored by expression of shRNA-insensitive AEG-1. In addition, expression of TREK-1 was not regulated in the absence of AEG-1, even when HIF1α was present. Together, these results suggest that AEG-1 acts as a major upstream regulator of TREK-1 channels in astrocytes under hypoxia. SIGNIFICANCE OF THE STUDY: Previous studies have reported that hypoxia increases the expression of astrocytic TREK-1 and that increased TREK-1 expression protects neuronal cells from apoptosis. However, its cellular mechanism is not clear. In this study we first showed that AEG-1 is a major mediator of hypoxic-regulated TREK-1 expression in normal astrocytes independently of HIF-1α.

Knocking and Listening: Learning Mechanical Impulse Response for Understanding Surface Characteristics.

Inspired by spiders that can generate and sense vibrations to obtain information regarding a substrate, we propose an intelligent system that can recognize the type of surface being touched by knocking the surface and listening to the vibrations. Hence, we developed a system that is equipped with an electromagnetic hammer for hitting the ground and an accelerometer for measuring the mechanical responses induced by the impact. We investigate the feasibility of sensing 10 different daily surfaces through various machine-learning techniques including recent deep-learning approaches. Although some test surfaces are similar, experimental results show that our system can recognize 10 different surfaces remarkably well (test accuracy of 98.66%). In addition, our results without directly hitting the surface (internal impact) exhibited considerably high test accuracy (97.51%). Finally, we conclude this paper with the limitations and future directions of the study.

Systems Analysis of the Human Pulmonary Arterial Hypertension Lung Transcriptome.

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary artery pressure and vascular resistance, typically leading to right heart failure and death. Current therapies improve quality of life of the patients but have a modest effect on long-term survival. A detailed transcriptomics and systems biology view of the PAH lung is expected to provide new testable hypotheses for exploring novel treatments. We completed transcriptomics analysis of PAH and control lung tissue to develop disease-specific and clinical data/tissue pathology gene expression classifiers from expression datasets. Gene expression data were integrated into pathway analyses. Gene expression microarray data were collected from 58 PAH and 25 control lung tissues. The strength of the dataset and its derived disease classifier was validated using multiple approaches. Pathways and upstream regulators analyses was completed with standard and novel graphical approaches. The PAH lung dataset identified expression patterns specific to PAH subtypes, clinical parameters, and lung pathology variables. Pathway analyses indicate the important global role of TNF and transforming growth factor signaling pathways. In addition, novel upstream regulators and insight into the cellular and innate immune responses driving PAH were identified. Finally, WNT-signaling pathways may be a major determinant underlying the observed sex differences in PAH. This study provides a transcriptional framework for the PAH-diseased lung, supported by previously reported findings, and will be a valuable resource to the PAH research community. Our investigation revealed novel potential targets and pathways amenable to further study in a variety of experimental systems.

Fourth-generation ceramic-on-ceramic THA results in improvements in midterm outcomes compared to third-generation THA but does not resolve noise problems: a cohort study of a single-hip system.

BACKGROUND: Using data from the Korean Hip Registry, we aimed to investigate mid-term clinical and radiographic outcomes, including the prevalence of periprosthetic joint infection (PJI), osteolysis, and component loosening or dislocation, and to analyze the incidence of bearing-related complications following modern ceramic-on-ceramic (COC) total hip arthroplasty (THA) using a single cementless hip system. METHODS: Four hundred eighty-two patients (602 hips) who underwent Forte or Delta COC THAs with a single hip system and had a minimum 5-year follow-up were identified. The sample included 243 (50.4%) women and 239 (49.6%) men with a mean age of 50.6 years (range: 18-83 years). The Forte group comprised 310 hips, and the Delta group comprised 292 hips. The mean follow-up was 6.1 years (range: 5-10.2 years). RESULTS: Cup orientation did not differ between groups. No hip had a PJI or osteolysis in either group. All acetabular components and all but two femoral components (in the Delta group) were well fixed. Dislocations occurred in six (1.9%) hips in the Forte group and one (0.3%) hip in the Delta group (p = 0.124). A total of nine (1.5%) revisions were performed. The 5-year survival rates for all-cause revisions were 98.4 and 98.6%, respectively. One (0.3%) ceramic head fracture occurred in the Forte group. Sixteen (5%) hips exhibited clicking and 6 (2%) hips had squeaking in the Forte group; 16 (6%) hips exhibited clicking and 5 (2%) hips had squeaking in the Delta group. Multiple regression analysis revealed that noise generation was unassociated with any factor. CONCLUSIONS: From the Korean Hip Registry data, THA with modern ceramic bearings showed encouraging results, with lower risks of PJI, osteolysis, and component loosening. In particular, Delta COC THA resulted in no PJI or ceramic fracture and had a reduced dislocation risk. However, associated noise remains a concern.

Context-Aware Winter Sports Based on Multivariate Sequence Learning.

In this paper, we present an intelligent system that is capable of estimating the status of a player engaging in winter activities based on the sequence analysis of multivariate time-series sensor signals. Among the winter activities, this paper mainly focuses on downhill winter sports such as alpine skiing and snowboarding. Assuming that the mechanical vibrations generated by physical interaction between the ground surface and ski/snowboard in motion can describe the ground conditions and playing contexts, we utilize inertial and vibration signals to categorize the motion context. For example, the proposed system estimates whether the player is sitting on a ski lift or standing on the escalator, or skiing on wet or snowy ground, etc. To measure the movement of a player during a game or on the move, we develop a custom embedded system comprising a motion sensor and piezo transducer. The captured multivariate sequence signals are then trained in a supervised fashion. We adopt artificial neural network approaches (e.g., 1D convolutional neural network, and gated recurrent neural networks, such as long short-term memory and gated recurrent units). The experimental results validate the feasibility of the proposed approach.

The Knockdown of TREK-1 in Hippocampal Neurons Attenuate Lipopolysaccharide-Induced Depressive-Like Behavior in Mice.

TWIK-related potassium channel-1 (TREK-1) is broadly expressed in the brain and involved in diverse brain diseases, such as seizures, ischemia, and depression. However, the cell type-specific roles of TREK-1 in the brain are largely unknown. Here, we generated a Cre-dependent TREK-1 knockdown (Cd-TREK-1 KD) transgenic mouse containing a gene cassette for Cre-dependent TREK-1 short hairpin ribonucleic acid to regulate the cell type-specific TREK-1 expression. We confirmed the knockdown of TREK-1 by injecting adeno-associated virus (AAV) expressing Cre into the hippocampus of the mice. To study the role of hippocampal neuronal TREK-1 in a lipopolysaccharide (LPS)-induced depression model, we injected AAV-hSyn-BFP (nCTL group) or AAV-hSyn-BFP-Cre (nCre group) virus into the hippocampus of Cd-TREK-1 KD mice. Interestingly, the immobility in the tail suspension test after LPS treatment did not change in the nCre group. Additionally, some neurotrophic factors (BDNF, VEGF, and IGF-1) significantly increased more in the nCre group compared to the nCTL group after LPS treatment, but there was no difference in the expression of their receptors. Therefore, our data suggest that TREK-1 in the hippocampal neurons has antidepressant effects, and that Cd-TREK-1 KD mice are a valuable tool to reveal the cell type-specific roles of TREK-1 in the brain.

Contextualization of drug-mediator relations using evidence networks.

BACKGROUND: Genomic analysis of drug response can provide unique insights into therapies that can be used to match the "right drug to the right patient." However, the process of discovering such therapeutic insights using genomic data is not straightforward and represents an area of active investigation. EDDY (Evaluation of Differential DependencY), a statistical test to detect differential statistical dependencies, is one method that leverages genomic data to identify differential genetic dependencies. EDDY has been used in conjunction with the Cancer Therapeutics Response Portal (CTRP), a dataset with drug-response measurements for more than 400 small molecules, and RNAseq data of cell lines in the Cancer Cell Line Encyclopedia (CCLE) to find potential drug-mediator pairs. Mediators were identified as genes that showed significant change in genetic statistical dependencies within annotated pathways between drug sensitive and drug non-sensitive cell lines, and the results are presented as a public web-portal (EDDY-CTRP). However, the interpretability of drug-mediator pairs currently hinders further exploration of these potentially valuable results. METHODS: In this study, we address this challenge by constructing evidence networks built with protein and drug interactions from the STITCH and STRING interaction databases. STITCH and STRING are sister databases that catalog known and predicted drug-protein interactions and protein-protein interactions, respectively. Using these two databases, we have developed a method to construct evidence networks to "explain" the relation between a drug and a mediator.  RESULTS: We applied this approach to drug-mediator relations discovered in EDDY-CTRP analysis and identified evidence networks for ~70% of drug-mediator pairs where most mediators were not known direct targets for the drug. Constructed evidence networks enable researchers to contextualize the drug-mediator pair with current research and knowledge. Using evidence networks, we were able to improve the interpretability of the EDDY-CTRP results by linking the drugs and mediators with genes associated with both the drug and the mediator. CONCLUSION: We anticipate that these evidence networks will help inform EDDY-CTRP results and enhance the generation of important insights to drug sensitivity that will lead to improved precision medicine applications.

Surgical accuracy, function, and quality of life of simultaneous versus staged bilateral Total hip Arthroplasty in patients with Osteonecrosis of the femoral head.

BACKGROUND: The optimal surgical option for patients requiring bilateral hip replacement remains controversial. The purpose of this study was to compare surgical accuracy; functional outcome and health-related quality of life; and prosthetic-related complications and revision surgery of a simultaneous bilateral total hip arthroplasty (THA) with those of a staged bilateral THA with an interval between procedures <12 months. METHODS: A total of 123 unselected consecutive patients (mean age, 43.3 years) who underwent bilateral THAs for osteonecrosis of the femoral head (ONFH) with a minimum follow-up of two years (mean, 60.2 months) were studied retrospectively; 63 simultaneous procedures served as a test group and 60 staged procedures served as a control group. RESULTS: The mean postoperative leg-length discrepancy (LLD) and the percentage of patients who had an LLD >3 mm were significantly lower in the simultaneous group (P < 0.001 and P = 0.001, respectively). A higher number of cups within the safe zones, a higher correction rate, and a lower failure rate for the cup placement in the second-operated hip were also identified in the simultaneous group. The mean Harris hip score, EuroQol-5D index, and EuroQol-visual analogue scale score were all better in the simultaneous group at the latest follow-up (P < 0.001, in all comparisons). We found that the simultaneous procedure was associated with a lower incidence of postoperative prosthetic-related complications and revision surgery. CONCLUSIONS: We suggest that bilateral ONFH could be treated with a simultaneous THA rather than a staged THA to achieve a better surgical outcome.

EDDY: a novel statistical gene set test method to detect differential genetic dependencies.

Identifying differential features between conditions is a popular approach to understanding molecular features and their mechanisms underlying a biological process of particular interest. Although many tests for identifying differential expression of gene or gene sets have been proposed, there was limited success in developing methods for differential interactions of genes between conditions because of its computational complexity. We present a method for Evaluation of Dependency DifferentialitY (EDDY), which is a statistical test for differential dependencies of a set of genes between two conditions. Unlike previous methods focused on differential expression of individual genes or correlation changes of individual gene-gene interactions, EDDY compares two conditions by evaluating the probability distributions of dependency networks from genes. The method has been evaluated and compared with other methods through simulation studies, and application to glioblastoma multiforme data resulted in informative cancer and glioblastoma multiforme subtype-related findings. The comparison with Gene Set Enrichment Analysis, a differential expression-based method, revealed that EDDY identifies the gene sets that are complementary to those identified by Gene Set Enrichment Analysis. EDDY also showed much lower false positives than Gene Set Co-expression Analysis, a method based on correlation changes of individual gene-gene interactions, thus providing more informative results. The Java implementation of the algorithm is freely available to noncommercial users. Download from: http://biocomputing.tgen.org/software/EDDY.

Comparative Analysis of Radiographic Hip Joint Geometry Using Measurement Tools on Picture Archiving and Communication System: A Prospective Study of 100 Pelvic Radiographs of Koreans.

BACKGROUND: A contralateral normal hip joint has been often used as a reference standard in preoperative planning and intraoperative assessment of hip arthroplasty, with the assumption that bilateral hip joint geometries have no significant differences. However, one previous study using analog measurements on hardcopy films reported significant bilateral variation in hip joint geometry. We therefore investigated the level of agreement between the right and left hips for each measurement and determined index values and the range of normal bilateral variations. METHODS: We assessed 100 standard anteroposterior radiographs of the pelvis in this study. Two independent observers measured the actual value of femoral head diameter, location of the femoral head center, acetabular offset, femoral offset, hip offset, greater trochanteric height, neck-shaft angle, medullary canal diameter, and proximal femoral diameter. Intraclass correlation coefficients (ICCs) and values of mean difference were calculated for each measurement. RESULTS: The results demonstrated perfect agreement (ICC >0.8) between the right and left hips for most parameters and substantial agreement for greater trochanteric height (ICC = 0.735) and femoral offset (ICC = 0.773). The mean difference and standard deviation in the measurement between the right and left hips for the location of the femoral head center and the acetabular offset were 0.60 ± 0.48 mm and 0.42 ± 0.30 mm, respectively. CONCLUSION: Hip joint geometry is not influenced by side. In hip arthroplasty, a contralateral normal hip can be reliably used as a guide for preoperative planning using measurement tools on a picture archiving and communication system.

Identification of extracellular miRNA in human cerebrospinal fluid by next-generation sequencing.

There has been a growing interest in using next-generation sequencing (NGS) to profile extracellular small RNAs from the blood and cerebrospinal fluid (CSF) of patients with neurological diseases, CNS tumors, or traumatic brain injury for biomarker discovery. Small sample volumes and samples with low RNA abundance create challenges for downstream small RNA sequencing assays. Plasma, serum, and CSF contain low amounts of total RNA, of which small RNAs make up a fraction. The purpose of this study was to maximize RNA isolation from RNA-limited samples and apply these methods to profile the miRNA in human CSF by small RNA deep sequencing. We systematically tested RNA isolation efficiency using ten commercially available kits and compared their performance on human plasma samples. We used RiboGreen to quantify total RNA yield and custom TaqMan assays to determine the efficiency of small RNA isolation for each of the kits. We significantly increased the recovery of small RNA by repeating the aqueous extraction during the phenol-chloroform purification in the top performing kits. We subsequently used the methods with the highest small RNA yield to purify RNA from CSF and serum samples from the same individual. We then prepared small RNA sequencing libraries using Illumina's TruSeq sample preparation kit and sequenced the samples on the HiSeq 2000. Not surprisingly, we found that the miRNA expression profile of CSF is substantially different from that of serum. To our knowledge, this is the first time that the small RNA fraction from CSF has been profiled using next-generation sequencing.