Showing papers by "Stephen J. O'Brien published in 2017"
Pontifícia Universidade Católica do Rio Grande do Sul1, Texas A&M University2, Oswaldo Cruz Foundation3, University College Dublin4, Saint Petersburg State University5, University of Porto6, University of California, Berkeley7, California Institute for Quantitative Biosciences8, Escola Superior de Agricultura Luiz de Queiroz9, Sao Paulo State University10, Pompeu Fabra University11, Instituto de Biología y Medicina Experimental12, Catalan Institution for Research and Advanced Studies13
TL;DR: Findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages.
Abstract: The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages.
121 citations
TL;DR: The 3-Pack examination for biceps-labrum complex (BLC) disease has excellent inter-rater reliability, sensitivity, and NPV and is a critical screening tool for BLC disease in all zones.
Abstract: Purpose To determine the diagnostic value of the 3-Pack examination for biceps-labrum complex (BLC) disease, assess interobserver reliability, and generate an evidence-based diagnostic and therapeutic algorithm. Methods A total of 145 consecutive patients were enrolled in this prospective comparative study. The study included 116 chronically symptomatic patients indicated for arthroscopic subdeltoid transfer of the long head of the biceps tendon to the conjoint tendon and 29 asymptomatic comparison subjects. Each patient underwent examination that included the 3-Pack (active compression test [O'Brien sign], throwing test, and bicipital tunnel palpation) and traditional examination (Speed test; Yergason test; full can test; empty can test) in a blinded, randomized fashion by 3 investigators. Intraoperative BLC disease was prospectively categorized by location (inside, junctional, or bicipital tunnel). Results 3-Pack tests were highly sensitive (73% to 98%), but less specific (46% to 79%) for BLC in all 3 locations than some of the traditional tests, which were less sensitive (20% to 67%), but more specific (83% to 100%) for BLC disease in all 3 locations. With regard to hidden bicipital tunnel lesions, palpation and O'Brien sign were highly sensitive (97.8% and 95.7% respectively) and revealed high negative predictive value (NPV, 96.4% and 92.6% respectively). Speed and Yergason tests, conversely, were poorly sensitive but had high specificities (86.7% and 97.9%, respectively) and positive predictive value (76% and 92.3%, respectively). Inter-rater reliabilities were substantial to almost perfect for the 3-Pack examination (kappa 70% to 85%) and fair to moderate for the 4 traditional examinations (kappa 25% to 56%). Conclusions The 3-Pack has excellent inter-rater reliability, sensitivity, and NPV and is a critical screening tool for BLC disease in all zones. Hidden extra-articular bicipital tunnel disease can reliably be excluded based on negative tenderness to palpation or a negative O'Brien sign (NPV 93% to 96%). Level of Evidence Level III, case control study.
58 citations
TL;DR: Higher reoperation rates at 1 year were seen in patients who had concomitant bicepsTenodesis, whereas dislocation, nerve injury, and surgical site infection were more common in tenodesis patients.
Abstract: Purpose To determine if reoperation rates are higher for patients who underwent isolated rotator cuff repair (RCR) than those who underwent RCR with concomitant biceps tenodesis using a large private-payer database. Methods A national insurance database was queried for patients who underwent arthroscopic RCR between the years 2007 and 2014 (PearlDiver, Warsaw, IN). The Current Procedural Terminology (CPT) 29,827 (arthroscopy, shoulder, surgical; with RCR) identified RCR patients who were subdivided into 3 groups—group 1: RCR without biceps tenodesis; group 2: RCR with concomitant arthroscopic biceps tenodesis (CPT 29827 and 29,828); group 3: RCR with concomitant open biceps tenodesis (CPT 29827 and 23,430). Reoperation rates (revision RCR, subsequent biceps surgeries) and complications at 30 days, 90 days, 6 months, and 1 year were analyzed. Multivariate logistic regression was used to compare reoperations and complications between groups. Rotator cuff tear size, whether the biceps was ruptured and whether a biceps tenotomy was performed, was not available. Results Group 1: 27,178 patients. Group 2: 4,810 patients. Group 3: 1,493 patients. More patients underwent concomitant arthroscopic than concomitant open tenodesis ( P P Conclusions Higher reoperation rates at 1 year were seen in patients who had concomitant biceps tenodesis. Level of Evidence Level III, case-control database review study.
39 citations
TL;DR: The proportion of patients requiring revision at five years is lower than that generally reported for UKA, adding support for the use of the cementless OUKA outside the design centre.
Abstract: Aims Our aim was to examine the clinical and radiographic outcomes in 257 consecutive Oxford unicompartmental knee arthroplasties (OUKAs) (238 patients), five years post-operatively.
Patients and Methods A retrospective evaluation was undertaken of patients treated between April 2008 and October 2010 in a regional centre by two non-designing surgeons with no previous experience of UKAs. The Oxford Knee Scores (OKSs) were recorded and fluoroscopically aligned radiographs were assessed post-operatively at one and five years.
Results The median age of the 238 patients was 65.0 years (interquartile range (IQR) 59.0 to 73.0), the median body mas index was 30.0 (IQR 27.5 to 33.0) and 51.7% were male. There were no intra-operative complications. There was a significant improvement in the median OKS at six weeks (34, IQR 31.0 to 37.0), one year (38, IQR 29.0 to 43.0) and five years (37, IQR 27.0 to 42.0) when compared with the pre-operative scores (16, IQR 13.0 to 19.0) (all p = < 0.01). No patient had progressive radiolucent lines or loosening.
A total of 16 patients had died by five years. The cumulative survival at five years was 98.8% and the mean survival time was 5.8 years (95% confidence interval 5.6 to 5.9). A total of seven OUKAs (2.7%) were revised; three within five years and four thereafter, between 5.1 and 5.7 years post-operatively. Five (1.9%) had re-operations within five years.
Conclusion The proportion of patients requiring revision at five years is lower than that generally reported for UKA. These findings add support for the use of the cementless OUKA outside the design centre. Longer follow-up is required.
Cite this article: Bone Joint J 2017;99-B:623–31.
32 citations
TL;DR: It was found that the ALDH1 isoform showed high aldehyde dehydrogenase activity, which was protective for HCCs with multiple nodules and high serum alpha–fetoprotein (AFP) level.
Abstract: Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)-related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV-related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57-month recurrence-free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha-fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.
32 citations
TL;DR: A synthesis of 3 decades of data, interpretation, and controversy, capped by whole genome sequence analysis of cheetahs, provides a compelling tale of conservation relevance and action to protect this species and other threatened wildlife.
Abstract: The dwindling wildlife species of our planet have become a cause celebre for conservation groups, governments, and concerned citizens throughout the world The application of powerful new genetic technologies to surviving populations of threatened mammals has revolutionized our ability to recognize hidden perils that afflict them We have learned new lessons of survival, adaptation, and evolution from viewing the natural history of genomes in hundreds of detailed studies A single case history of one species, the African cheetah, Acinonyx jubatus, is here reviewed to reveal a long-term story of conservation challenges and action informed by genetic discoveries and insights A synthesis of 3 decades of data, interpretation, and controversy, capped by whole genome sequence analysis of cheetahs, provides a compelling tale of conservation relevance and action to protect this species and other threatened wildlife
30 citations
TL;DR: Risk factors for revision surgery after SLAP repair include age >40 years, female sex, obesity, smoking, and diagnosis of biceps tendinitis or long head of the biceps tearing.
Abstract: Background:Data regarding risk factors for revision surgery after superior labral anterior-posterior (SLAP) repair are limited to institutional series.Purpose:To define risk factors for revision su...
27 citations
TL;DR: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients.
Abstract: Background/Aims: Hepatocellular carcinoma (HCC) is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of prolifer
27 citations
TL;DR: The recently described phenomenon of the evolutionary new centromere emergence has taken place in the X chromosome evolution of Cetartiodactyla at least five times and the structure of the putative ancestral cetartodactyl X chromosome is proposed by reconstructing the order of syntenic segments and centreromere position for key groups.
Abstract: The phenomenon of a remarkable conservation of the X chromosome in eutherian mammals has been first described by Susumu Ohno in 1964. A notable exception is the cetartiodactyl X chromosome, which varies widely in morphology and G-banding pattern between species. It is hypothesized that this sex chromosome has undergone multiple rearrangements that changed the centromere position and the order of syntenic segments over the last 80 million years of Cetartiodactyla speciation. To investigate its evolution we have selected 26 evolutionarily conserved bacterial artificial chromosome (BAC) clones from the cattle CHORI-240 library evenly distributed along the cattle X chromosome. High-resolution BAC maps of the X chromosome on a representative range of cetartiodactyl species from different branches: pig (Suidae), alpaca (Camelidae), gray whale (Cetacea), hippopotamus (Hippopotamidae), Java mouse-deer (Tragulidae), pronghorn (Antilocapridae), Siberian musk deer (Moschidae), and giraffe (Giraffidae) were obtained by fluorescent in situ hybridization. To trace the X chromosome evolution during fast radiation in specious families, we performed mapping in several cervids (moose, Siberian roe deer, fallow deer, and Pere David’s deer) and bovid (muskox, goat, sheep, sable antelope, and cattle) species. We have identified three major conserved synteny blocks and rearrangements in different cetartiodactyl lineages and found that the recently described phenomenon of the evolutionary new centromere emergence has taken place in the X chromosome evolution of Cetartiodactyla at least five times. We propose the structure of the putative ancestral cetartiodactyl X chromosome by reconstructing the order of syntenic segments and centromere position for key groups.
20 citations
TL;DR: Adequate correction of valgus knee deformity was successfully achieved using this modified technique with satisfactory medium-term outcome and avoidance of instability.
Abstract: The author would like to correct the following errors in the publication of the original article.
14 citations
TL;DR: A mitogenomic phylogeny confirmed the basal position of solenodons relative to shrews and moles, with solenodon mitogenomes estimated to have diverged from those of other mammals ca.
Abstract: Solenodons are insectivores found only in Hispaniola and Cuba, with a Mesozoic divergence date versus extant mainland mammals. Solenodons are the oldest lineage of living eutherian mammal for which a mitogenome sequence has not been reported. We determined complete mitogenome sequences for six Hispaniolan solenodons (Solenodon paradoxus) using next-generation sequencing. The solenodon mitogenomes were 16,454–16,457 bp long and carried the expected repertoire of genes. A mitogenomic phylogeny confirmed the basal position of solenodons relative to shrews and moles, with solenodon mitogenomes estimated to have diverged from those of other mammals ca. 78 Mya. Control region sequences of solenodons from the northern (n = 3) and southern (n = 5) Dominican Republic grouped separately in a network, with FST = 0.72 (p = 0.036) between north and south. This regional genetic divergence supports previous morphological and genetic reports recognizing northern (S. p. paradoxus) and southern (S. p. woodi) subspe...
TL;DR: This study uncovered two genetic regions that are significant and have specific effects on HIV-1C acquisition or progression in sub-Saharan Africans, and the result suggested new potential targets for AIDS prevention and treatment.
Abstract: Sub-Saharan Africans infected with HIV-1C make up the largest AIDS patient population in the world and exhibit large heterogeneity in disease progression before initiating antiretroviral therapy. To identify host variants associated with HIV disease progression, we performed genome-wide association studies on a total of 556 treatment-naive HIV-infected individuals in Botswana. We characterized the pattern of HIV disease progression using a novel functional principal component analysis, which can better capture longitudinal CD4 and viral load (VL) trajectories. Two single-nucleotide polymorphisms (SNPs) near HCG22 (chr6, peak variant rs2535307, combined p = 3.72 × 10−7, minor allele as risky allele) and CCNG1 (chr5, peak variant kgp22385164, combined p = 1.88 × 10−6, minor allele as risky allele) were significantly associated with CD4 and VL dynamics. Inspection of SNPs in these gene regions in a third Botswana cohort (using GWATCH) also revealed a strong association of HCG22 with HIV-1C acquisiti...
TL;DR: MUA is an effective treatment for reduced flexion following TKA and should be the first line of management after failed physiotherapy and it can still have benefit beyond 6 months but the gains become less effective with time.
Abstract: Background Reduced flexion following knee arthroplasty (TKA) may compromise patient’s function and outcome. The timing of manipulation under anaesthesia (MUA) has been controversial. We present our experience in a high volume practice and analyse the impact of timing. Methods All TKA patients requiring MUA from February 1996 to June 2015 under the care of a single surgeon were analysed. MUA was offered to patients who had ≤ 75° of flexion post-op, providing that they had 30° more flexion preoperatively. To address the impact of timing from primary surgery to MUA on flexion gain we looked at 3 groups: Group I ≤ 90 days, Group II 91-180 days and Group III > 180 days. Results Sixty two out of 7,423 (0.84%) underwent MUA. The MUA patients were significantly younger than the overall TKA cohort 61.2 vs 70.5 years (p = 180 days) both at 6 weeks and 1 year following MUA but not better than group II (90-180 days). Conclusions MUA is an effective treatment for reduced flexion following TKA and should be the first line of management after failed physiotherapy. It can still have benefit beyond 6 months but the gains become less effective with time.
Journal Article•
TL;DR: The differences in the healing biology of biceps tenodesis performed on either bone or soft tissue in a rat model is reported on to provide further insight into what may be the optimal strategy for managing biceps-labrum complex disease.
Abstract: In this article, we report on the differences in the healing biology of biceps tenodesis performed on either bone or soft tissue in a rat model. This work provides further insight into what may be the optimal strategy for managing biceps-labrum complex disease.
TL;DR: The string-graph based assembly strategy seems a better choice compared to the conventional de Brujn graph approach, due to the high levels of homozygosity within the Hispaniolan solenodon, which is often a hallmark of endemic or endangered species.
Abstract: Solenodons are insectivores living on the Caribbean islands, with few surviving related taxa. The genus occupies one of the most ancient branches among the placental mammals. The history, unique biology and adaptations of these enigmatic venomous species, can be greatly advanced given the availability of genome data, but the whole genome assembly for solenodons has never been previously performed, partially due to the difficulty in obtaining samples from the field. Island isolation has likely resulted in extreme homozygosity within the Hispaniolan solenodon ( Solenodon paradoxus ), thus we tested the performance of several assembly strategies for performance with genetically impoverished species9 genomes. The string-graph based assembly strategy seems a better choice compared to the conventional de Brujn graph approach, due to the high levels of homozygosity, which is often a hallmark of endemic or endangered species. A consensus reference genome was assembled from sequences of five individuals from the southern subspecies ( S. p. woodi ). In addition, we obtained one additional sequence of the northern subspecies ( S. p. paradoxus ). The resulting genome assemblies were compared to each other, and annotated for genes, with a specific emphasis on the venomous genes, repeats, variable microsatellite loci and other genomic variants. Phylogenetic positioning and selection signatures were inferred based on 4,416 single copy orthologs from 10 other mammals. Patterns of SNP variation allowed us to infer population demography, which indicated a subspecies split within the species at least 300 Kya.
TL;DR: A new approach for statistical association signal identification by extending the well‐known signal detection and signal identification methods applicable to the multiple testing problem and applying average statistics and the localization method to GWAS to discover better gene influences of regulating loci in a Chinese cohort developed for risk of nasopharyngeal carcinoma.
Abstract: A new approach for statistical association signal identification is developed in this paper. We consider a strategy for nonprecise signal identification by extending the well-known signal detection and signal identification methods applicable to the multiple testing problem. Collection of statistical instruments under the presented approach is much broader than under the traditional signal identification methods, allowing more efficient signal discovery. Further assessments of maximal value and average statistics in signal discovery are improved. While our method does not attempt to detect individual predictors, it instead detects sets of predictors that are jointly associated with the outcome. Therefore, an important application would be in genome wide association study (GWAS), where it can be used to detect genes which influence the phenotype but do not contain any individually significant single nucleotide polymorphism (SNP). We compare power of the signal identification method based on extremes of single p-values with the signal localization method based on average statistics for logarithms of p-values. A simulation analysis informs the application of signal localization using the average statistics for wide signals discovery in Gaussian white noise process. We apply average statistics and the localization method to GWAS to discover better gene influences of regulating loci in a Chinese cohort developed for risk of nasopharyngeal carcinoma (NPC).
TL;DR: Mitochondrial genomes encode genes essential for electron transport, and data provided here will complement ongoing investigations of genome-to-phenome maps for teleost respiration and metabolism.
Abstract: Sculpins are predominantly benthic sit-and-wait predators that inhabit marine and freshwaters of the Northern Hemisphere. In striking contrast to riverine relatives, sculpins endemic to Lake Baikal have diversified in both form and function, with multiple taxa having adaptations for pelagic and bathyal niches within the world's deepest lake. Baikal Oilfishes (Comephorus spp.) represent a highly apomorphic taxon with unique skeletal morphology, soft anatomy, and reproductive ecology. Selection for novel behavior and life history may be evident in genes responsible for organismal energy balance, including those encoding subunits of the electron transport chain. Complete mitochondrial genomes were sequenced for the Big Baikal Oilfish (Comephorus baicalensis) and Little Baikal Oilfish (Comephorus dybowskii). Mitochondrial genomes encode genes essential for electron transport, and data provided here will complement ongoing investigations of genome-to-phenome maps for teleost respiration and metabolism. Phylogenetic analyses including oilfish mitogenomes and all publicly available cottoid representative sequences are largely concordant with previous studies.
TL;DR: It is suggested that preoperative TAC might postpone postoperative HCC relapse within 1 year via suppression of tumor cells by induction of high levels of oxidative stress.
Abstract: // Hao Su 1, * , Guangzhi Zhu 1, * , Ketut Indra Djaja P 1, * , Yi Lin 1 , Yizhen Gong 1 , Xiaoguang Liu 1 , Jiaquan Li 2 , Zhiming Liu 1 , Xiao Qin 1 , Lequn Li 1 , Tangwei Liu 1 , Zili Lu 3 , Minyi Wei 3 , Lunan Yan 4 , Cheryl Ann Winkler 5 , Stephen J. O’Brien 5 , Jing Li 6 , Kaiyin Xiao 1 and Tao Peng 1, 5 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China 2 Experimental Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China 3 Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China 4 Department of General Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, China 5 Laboratory of Genomic Diversity, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA 6 Department of Physiology and Pathophysiology, College of Basic Medical Science, Peking University, Health Science Center, Beijing, 100191, China * These authors contributed equally to this work Correspondence to: Tao Peng, email: pengtaogmu@163.com Kaiyin Xiao, email: xiaokaiyin@163.com Keywords: transcatheter arterial chemotherapy, hepatocellular carcinoma, TP53, p21 waf1/cip1 , oxidative stress Received: August 12, 2016 Accepted: April 21, 2017 Published: May 07, 2017 ABSTRACT In this study, we aim to investigate oxidative stress in hepatocellular carcinoma (HCC) tissues in patients receiving preoperative transcatheter arterial chemotherapy (TAC) and its association with prognosis. A total of 89 HCC patients enrolled in this study, 39 received preoperative TAC 1 week before surgery (pTAC group) and 50 did not (non-pTAC group). All patients underwent hepatectomy and postoperative TAC and were followed up to 400 weeks. Samples of liver tissue without HCC and hepatitis ( n = 15) served as normal controls. Cellular levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), TP53, and p21 waf1/cip1 were measured in both cancer and surrounding tissues using an immunohistochemistry assay. Taken together, our data suggested that preoperative TAC might postpone postoperative HCC relapse within 1 year via suppression of tumor cells by induction of high levels of oxidative stress.
TL;DR: A novel role for CEAR gene in the regulation of colorectal cancer cell Invasiveness and progression is revealed and targeted suppression of endogenous CEAR in tumor cells resulted in changes in cell invasiveness.
Abstract: Clinical and experimental data suggest that carcinoembryonic antigen (CEA, CD66e, CEACAM-5) plays a key role in the formation of hepatic metastasis from colorectal and other types of epithelial cancers. The molecular events involved in CEA-induced metastasis have yet to be defined. Our group first cloned the gene (CEAR) for CEA-binding protein from the surface of fixed liver macrophages, (Kupffer cells). In this study to further elucidate the role of CEAR in colorectal cancer progression, its expression in colorectal cancer cells was suppressed by short hairpin RNAs (shRNAs) in CEA-overexpressing and CEA - negative MIP-101 colorectal cancer cell lines. The data show that targeted suppression of endogenous CEAR in tumor cells resulted in changes in cell invasiveness. RT-PCR data indicated reduced levels of E-cadherin, Snail, MMP-2, and Oct-4 in the clones with suppressed CEAR suggesting a role in the epithelial mesenchymal transition. The comparative analysis of tumorigenic activity to the liver of the cell lines with suppressed CEAR has also been conducted using an intrasplenic injection model in immuno-deficient mice. This data shows a decrease in tumor progression associated with CEAR suppression. In summary the results of this study revealed a novel role for CEAR gene in the regulation of colorectal cancer cell invasiveness and progression.