tbuckley/cabot-search huggingface dataset:
INVESTIGATION OF THE LOWER EXTREMITY STATIC POSTURES PREDICTING VALGUS COLLAPSE DURING DROP LANDING IN KOREAN MALE AND FEMALE – LOGICAL ANALYSIS OF DATA (LAD) APPROACH
Authors: Sae Yong Lee, Seok Gi Lee, Yuncheol Kang, Young Min Chun, Chang-Young Kim, In Deok Kong
Journal: British Journal of Sports Medicine (2017)

Background The result of 2002∼2012 National Health Insurance Sharing Service (NHISS) data analysis demonstrated that the gender's odds ratio of ACL was as low as 1.06, which is different from other studies. The static posture measures (SPM) of Asian may not be strongly associated with valgus collapse during landing. Objective To investigate SPMs that account for valgus collapse in Korean male and female using the LAD approach. Design Cross-sectional study. Setting Controlled laboratory. Patients (or Participants) Forty-four active male (age: 22.2±3.6 yrs; Height: 176±6.6 cm; Weight: 73.3±9.7 kg) and 43 female (age: 21.9±2.5 yrs; Height: 163±5.3 cm; Weight: 56.5±5.1 kg) with no history of lower extremity injury were recruited. Interventions (or Assessment of Risk Factors) Gender. Main Outcome Measurements Joint kinematics associated with valgus collapse during drop landing were extracted (Vicon Inc, Oxford, UK) during drop landing task. Thirteen lower extremity SPMs were collected. LAD was implemented using the machine learning software, Weka 3.7.10 (U of Waikato, Hamilton, New Zealand) to generate male and female patterns that characterize features of SPM and its association with valgus collapse. Results A total of eight and 33 distinct male and female patterns respectively could be generated (&gt;10% relative prevalence (RP)). Interestingly, Joint kinematics associated with valgus collapse were not shown in patterns, but only six SPMs were included. The most relevant pattern that represents male (RP 25.00%) was tibiofemoral angle less than or equal to 9.5° and leg length discrepancy greater than −3.5 cm. The most relevant pattern that represents female (RP 34.88%) was Q-angle greater than 17.5°, genu recurvatum greater than −1.5°, femoral anteversion greater than 5.5°, and leg length discrepancy less than or equal to 2.5 cm. Conclusions SPMs of Korean male and female were not associated with valgus collapse during drop jump. It seemed that the Korean female demonstrated similar neuromuscular control characteristics as male to avoid valgus collapse.
05.03 Differential methylation profile of tnf-signalling genes in t-cells and monocytes
Authors: Joshua H Rogers, Agata N Burska, Rujiraporn Pitaksalee, Rekha Parmar, Paul Emery, Richard Hodgett, Frederique Ponchel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Recently, epigenetics has become an important field of research, with several diseases related to alteration in methylation patterns. Whether these epimutations are early events due to a local perturbation causing the initial epigenetic event and then leading to pathogenesis, or a later consequence of the pathology itself remains open for discussion. The objective of this study is to assess the methylation patterns of CpG islands in naïve and memory T-cells and monocytes from drug-naïve, early Rheumatoid arthritis (RA) patients. <h3>Materials and methods</h3> The methylation patterns of 480,000 CpGs were measured in 6 healthy controls and 10 RA patients using an Illumina methylation genome-wide array (EWAS). T-tests were used to calculate the significance of the methylation differences at each CpG site. A p-value of 1 × 10<sup>–4</sup> was used to elucidate highly specific differences. Methylation patterns of individual promoters were then reconstructed using the Human genome database for the position and length of CpG islands. The genes with 3 or more differentially methylated CpGs clustered over a short distance and localised in potentially regulatory regions of the gene were deemed relevant. <h3>Results</h3> Analysis of the EWAS data showed 4123 CpG sites differently methylated in naïve T-cells, 2672 in memory T-cells and 904 in monocytes. Of the relevant genes, TNFR1 appeared particularly interesting. We therefore focused our next analysis on the TNF-α signalling pathway as this has proven pivotal in early disease. Results highlight 9 genes implicated in the 3 TNF-signalling cascades: TNFR1, LTBR, TRAF1, BCL2, UACA, RNF36, MIR21, DAXX and MAP3K14-AS1. These 9 loci exhibited different methylation patterns in naïve T-cells. Each had between 3 and 10 CpGs with differential methylation over short DNA regions (&lt;250 bp) suggesting a potential effect the 3-dimentional structure of the DNA possibly affecting gene expression. These patterns were highly specific to naïve T-cells and were not observed in memory T-cells or monocytes in RA. <h3>Conclusion</h3> Naïve T-cells have been implicated in RA pathogenesis through activation/differentiation by cytokine rather than antigen.<sup>1</sup> This data confirms the selective role of naïve T-cells in early RA primarily linked to differences in up- and down-regulation of elements involved in the TNF-signalling pathway. <h3>Reference</h3> Blood, 2002;100:4550–6.
Hundreds of Chinese researchers are sanctioned after mass retraction
Authors: Owen Dyer
Journal: BMJ (2017)

China’s regulatory authorities have taken disciplinary action against 486 researchers found to have committed misconduct in a peer review scandal that rocked Chinese science.

The publisher Springer Nature announced in April that one of its journals, Tumor Biology , was retracting 107 papers because of fake peer reviews.1 Springer’s investigation found that some authors, who were allowed to suggest potential reviewers and forward their email addresses, had provided addresses leading to companies that offered fake peer reviews.

China’s ministry of science and technology, alarmed that the incident had “seriously harmed the international reputation of our country’s scientific profession and the dignity of …
Construction of a five-marker protein-based model for stage-independent assessment of prognosis in breast cancer
Authors: J. M. Giltnane, J. Rapp, C. Moeder, R. L. Camp, H. Kluger, A. Molinaro, D. Rimm
Journal: Journal of Clinical Oncology (2009)

11013 Background: While the TNM method for assessment of stage in breast cancer is simple and robust, molecular methods for limited patient subsets are gaining popularity (i.e Oncotype Dx or Mammaprint). We hypothesized that multiplexed quantitative measurement of proteins known to be involved in breast cancer signaling pathways of growth, proliferation, survival, and metastasis can enhance clinical methods of predicting prognosis in all patients. Methods: We assessed the expression of twenty-three proteins (ER, PR, EGFR, HER2, HER3, HER4, ERK, PTEN, PI3Kp85α, PI3Kp110α, p27/Kip1,EIF4E, FOXO3,AKT1, AKT2, AKT3, MYC, cyclinD1, FOXO1, mTOR, p70S6Kb, NFkB and BCL2) in four subcellular compartments by automated quantitative analysis of protein expression (AQUA) on tissue microarrays of the archival Yale breast cancer cohort (n=676). To project future performance of these markers including clinicopathological parameters, we constructed univariate and multivariate logistic regression models using leave-one-out cross-validation and calculated prediction error (PE) estimates of each model's value to predict a binary endpoint of 10 year survival. In addition, we constructed univariate and multivariate Cox models of ten year disease specific survival (DSS). Results: By Cox univariate analysis, ER, PR, PTEN, and BCL2 were directly correlated with DSS, while FOXO1, HER2, HER3, and PI3Kp110α were inversely correlated with DSS. A five-variable logistic regression model of 10 year survival including nuclear AKT1, BCL2, nuclear FOXO1, cytoplasmic mTOR, and nuclear p70S6Kb (prediction error= .274) surpasses performance of TNM staging (PE=.367) and the Nottingham Prognostic Index (PE=.326). The same model is associated with 10-year DSS by Cox proportional hazard (p=&lt;.00001) independent of TNM stage and NPI. Conclusions: Our protein-based, multiplexed approach to prognostic classification was superior to traditional methods (TNM or NPI) and single biomarkers in this retrospective cohort. Current outcomes are influenced by modern therapies, limiting the direct impact of this analysis. However, molecular profiling of primary tumor linked to outcome paves the way for the incorporation of new prognostic models into prospective studies. [Table: see text]
Final Results of Northern Italy Leukemia Group (NILG) Trial 10/07 Combining Pediatric-Type Therapy with Minimal Residual Disease Study and Risk-Oriented Hematopoietic Cell Transplantation in Adult Acute Lymphoblastic Leukemia (ALL)
Authors: Renato Bassan, Arianna Masciulli, Tamara Intermesoli, Orietta Spinelli, Manuela Tosi, Chiara Pavoni, Ernesta Audisio, Giuseppe Rossi, Monica Fumagalli, Vincenzo Cassibba, Daniele Mattei, Claudio Romani, Agostino Cortelezzi, Fabio Ciceri, Anna Maria Scattolin, Umberto Vitolo, Erika Borlenghi, Sergio Cortelazzo, Andrea Gallamini, Lorella Depaoli, Leonardo Campiotti, Monica Tajana, Monica Bocchia, Antonella Vitale, Marco Ladetto, Eros Di Bona, Elena Oldani, Alessandro Rambaldi
Journal: Blood (2016)
The immune reconstitution of the skin following sex‐mismatched allogeneic haematopoietic stem cell transplant: a prospective case series utilizing fluorescence <i>in situ</i> hybridization and immunohistochemistry
Authors: C.L. Stewart, C.M. Cornejo, K.A. Wanat, I. Sander, S. Samimi, S. Prouty, J. Seykora, P. Zhang, M. Rosenbach, E.J. Kim, R.G. Micheletti
Journal: British Journal of Dermatology (2017)

Graft versus host disease (GVHD) is a common, morbid, and potentially fatal complication of allogeneic hematopoietic stem cell transplantation (aHSCT).1-3 The exact timing of the arrival of donor-derived immune cells and their profile in the skin have not been well described in humans.4-6 Fluorescent in situ hybridization (FISH) is a technique that has been used to distinguish host versus donor-derived immune cells in patients who have undergone sex-mismatched aHSCT.7

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Preclinical Development of Gene Therapy for X-Linked Severe Combined Immunodeficiency (SCID-X1)
Authors: Valentina Poletti, Sabine Charrier, Samia Martin, Bernard Gjata, Alban Vignaud, Fang Zhang, Karen Buckland, Michael Rothe, Axel Schambach, Sung-Yun Pai, David A. Williams, H. Bobby Gaspar, Adrian J Thrasher, Fulvio Mavilio
Journal: Blood (2016)
Cardiovascular Event Prediction by Machine Learning
Authors: Bharath Ambale-Venkatesh, Xiaoying Yang, Colin O. Wu, Kiang Liu, W. Gregory Hundley, Robyn McClelland, Antoinette S. Gomes, Aaron R. Folsom, Steven Shea, Eliseo Guallar, David A. Bluemke, João A.C. Lima
Journal: Circulation Research (2017)

Rationale: Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. Objective: To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. Methods and Results: We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%–25%). Conclusions: Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00005487.
Task Demands Predict a Dynamic Switch in the Content of Awake Hippocampal Replay
Authors: H. Freyja Ólafsdóttir, Francis Carpenter, Caswell Barry
Journal: Neuron (2017)

Reactivation of hippocampal place cell sequences during behavioral immobility and rest has been linked with both memory consolidation and navigational planning. Yet it remains to be investigated whether these functions are temporally segregated, occurring during different behavioral states. During a self-paced spatial task, awake hippocampal replay occurring either immediately before movement toward a reward location or just after arrival at a reward location preferentially involved cells consistent with the current trajectory. In contrast, during periods of extended immobility, no such biases were evident. Notably, the occurrence of task-focused reactivations predicted the accuracy of subsequent spatial decisions. Additionally, during immobility, but not periods preceding or succeeding movement, grid cells in deep layers of the entorhinal cortex replayed coherently with the hippocampus. Thus, hippocampal reactivations dynamically and abruptly switch between operational modes in response to task demands, plausibly moving from a state favoring navigational planning to one geared toward memory consolidation.
Optimization of storage conditions for formalin-fixed paraffin-embedded tissue sections to be used in molecular testing.
Authors: Jill Detmer, Xiaolei Qiu, Madeleine Matias, Zhen Wang, Mark Baumeister, Monalisa Ray, Erik Sudin, Arejas James Uzgiris
Journal: Journal of Clinical Oncology (2016)

e23137 Background: FFPE tissue sections are routinely stored at ambient temperature in pathology departments for histology staining, immunohistochemistry, and in situ hybridization. These specimens are also utilized for mutation detection and gene expression tests. The RNA degradation and modification during formalin fixation, and additional deterioration that may occur during storage, diminish the utility of these valuable samples for quantitative molecular analysis. This study was designed to determine the impact of storage conditions and times on the integrity of FFPE samples by analyzing the RNA extracted from well-characterized paraffin-embedded cell pellets. Methods: H460, a large cell lung carcinoma cell line, was cultured. Cells were then harvested, fixed, and embedded in paraffin. Storage at 35°C, ambient temperature (20–25°C), and 4°C was tested for a period of 6 months. RNA was evaluated for total yield, intactness, and functional RT-qPCR performance. Six replicate sections for each condition were tested at each time point. Results: Although total yield of RNA was consistent across all time points, the quality of RNA, as measured by RIN score, decreased over time when stored at ambient temperature and 35°C. Cq values from two reference gene-expression assays increased for ambient temperature and 35°C storage conditions. HPRT1 mean Cq after 6 months was 26.27 at 4°C, 26.71 at ambient temperature, and 28.09 at 35°C. GAPDH mean Cq after 6 months was 18.56 at 4°C, 19.25 at ambient temperature, and 21.06 at 35°C. In pair-wise comparisons, the results were significantly better for 4°C storage in all cases (at 95% confidence level). Conclusions: For use with molecular testing, we found refrigerated FFPE tissue sections were more suitable than those stored at ambient temperature for extended periods. Intact tissue blocks were found to be equally stable at ambient temperature and 4°C during the 6 months of testing. These results established optimal sample-storage conditions during the development of several prototype companion diagnostic assays to be used in upcoming clinical trials. *© 2016, Siemens Healthcare Diagnostics Inc. All rights reserved.
ニコチン中毒に対する次世代免疫療法戦略としてのハイブリッドナノ粒子に基づくニコチンnanovaccineのエンジニアリング:ハプテン密度に焦点を当てて【Powered by NICT】
Authors: Zhao Zongmin, Powers Kristen, Hu Yun, Raleigh Michael, Pentel Paul, Zhang Chenming
Journal: Biomaterials (2017)
OP0241 Erap1 is a susceptibility factor for early axial spondyloarthritis meeting the asas classification criteria: results from the desir and space cohorts
Authors: A de Koning, M Hameetman, C Micelli, M Dougados, D van der Heijde, F Kurreeman, FA van Gaalen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Genetic research in axSpA is performed in patients with longstanding ankylosing spondylitis (AS). Early axial spondyloarthritis (axSpA) is a diverse patient group in which a minority of the patients have AS. Therefore, it is not known if recently identified genetic risk factors for AS are also risk factors for early axSpA. <h3>Objectives</h3> To evaluate if ERAP1 and HLA-B*4001 are susceptibility factors for early axSpA. <h3>Methods</h3> Patients with early axSpA meeting the ASAS classification criteria from the SPACE cohort (inclusion criteria: back pain for ≥3 months, ≤2 years, onset &lt;45 years) and the DESIR cohort (inclusion criteria: inflammatory back pain for ≥3 months, ≤3 years, age &lt;50) were typed for two well established AS genetic risk factors: ERAP1 SNPs rs30187 (susceptibility), rs17482078 (protective) and rs10050860 (neutral) and HLA-B*4001. Analysis of weaker AS risk factors was limited by sample size. For ERAP1, genotyped Dutch healthy controls (n=1085) and published French controls<sup>1</sup> were used as controls. For HLA-B*4001 healthy blood bank donors from the Netherlands (n=5584) and France (n=10177) were used as controls. <h3>Results</h3> In 486 DESIR patients (mean age 32.5 (SD 8.6); 50% male; 84% HLA-B27+; 18% X-SI+) and 144 SPACE patients (mean age 29.5 (SD 8); 51% male; 88% HLA-B27+; 24% X-SI+) ERAP1 SNP rs30187 was more common than in controls (OR 1.2, p=0.01 in meta-analysis; table 1). rs17482078 and rs10050860 were negatively associated with early axSpA (both 0.7 (0.6–0.9) p&lt;0.01 in meta-analysis). Although both cohorts were sufficiently powered, HLA-B*4001 was not positively associated with early axSpA (OR 0.6 (0.4–0.9) in meta-analysis). <h3>Conclusions</h3> ERAP1 rs30187 is a genetic risk factor for early axSpA. To our knowledge this is the first report of genetic risk factor research in early axSpA patients meeting the ASAS criteria. Larger cohorts are needed to study additional AS risk factors. <h3>References</h3> Kadi A, Izac B, Said-Nahal R, Leboime A, Van Praet L, de Vlam K, et al. Investigating the genetic association between ERAP1 and spondyloarthritis. Ann Rheum Dis. 2013;72(4):608–13. <h3>Disclosure of Interest</h3> None declared
AB0991 Prevalence of fibromyalgia and depression in patients with autoimmune /inflammatory syndrome induced by adjuvants compared to patients with systemic sclerosis
Authors: O Vera-Lastra, P Blas Hernadez, A Sánchez-Rodríguez, LJ Jara
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been associated with previous exposure to various agents such as mineral oil, silicone and vaccines, which act as adjuvants eliciting chronic stimulation of the immune system and manifestation of autoimmune diseases. There is little information about fibromyalgia (FM), depression and the deterioration of the quality of life in ASIA patients. <h3>Objectives</h3> To determine the prevalence of FM, depression and both in ASIA patients associated to mineral oil versus systemic sclerosis (SSc) patients. <h3>Methods</h3> A comparative cross-sectional study was performed in patients with ASIA according to Shoenfeld9s criteria associated to injection of mineral oil with cosmetic purposes. The prevalence of fibromyalgia according to criteria of ACR, depression by Beck questionnaire and quality of life with FS-36 in patients with ASIA versus patients with systemic sclerosis matched by age were evaluated. <h3>Results</h3> There were 100 women, 50 ASIA patients (mean age 49±9.7 years) compared to 50 SSc patients (mean age 49±10 years). Of patients with ASIA, 40 patients had non-specific rheumatic disease and 10 met ACR criteria for SSc in 4 patients, SLE 3 and overlap syndrome 1 (SLE plus SSc) and rheumatoid arthritis 2. In ASIA vs. SSc we found depression in 72% vs 46% respectively, p&lt;0.005, fibromyalgia in 66 vs 48%, p&lt;0.008 and fibromyalgia plus depression in 56% vs. 28, p&lt;0.005. Patients with ASIA had a worse quality of life than SSc by SF36 and the most affected parameter was the emotional one. <h3>Conclusions</h3> ASIA patients associated to injection of mineral oild had higher prevalence of depression, fibromyalgia and greater deterioration of quality of life compared to SSc patients. There is a possible link between ASIA, depression and FM. <h3>References</h3> Agmon-Levin N et al. Chronic fatigue syndrome and fibromyalgia following immunization with hepatitis Bvaccine:another angle of autpimmune (auto-inflammatory)syndrome induced by adjuvants (ASIA). Immunol Res 2014;60:376–82. Vera Lastra o, et al. Autoimmune /Inflammatory syndrome induced by adjuvants (Shoenfeld9s syndrome):clinical and immunological spectrum. Expert Rev Clibn Immunol 2013;9:361–73. Jara LJ; et al. Severe manifestation of autoimmune syndrome induced by adjuvants (shoenfeld9s syndrome. Immunol Res 2016 Jul 13. <h3>Disclosure of Interest</h3> None declared
ラット脳におけるNa + /ミオイノシトール共輸送体(SMIT)の局在と調節
Authors: Yamauchi A, Minami Y, Inoue K, Shimada S, Morimura H, Miyai A, Tanaka K, Imai E, Matsunaga T, Tohyama M
Journal: Journal of the American Society of Nephrology (1995)
New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification
Authors: Joakim Crona, David Taïeb, Karel Pacak
Journal: Endocrine Reviews (2017)

A molecular biology–based taxonomy has been proposed for pheochromocytoma and paraganglioma (PPGL). Data from the Cancer Genome Atlas revealed clinically relevant prognostic and predictive biomarkers and stratified PPGLs into three main clusters. Each subgroup has a distinct molecular–biochemical–imaging signature. Concurrently, new methods for biochemical analysis, functional imaging, and medical therapies have also become available. The research community now strives to match the cluster biomarkers with the best intervention. The concept of precision medicine has been long awaited and holds great promise for improved care. Here, we review the current and future PPGL classifications, with a focus on hereditary syndromes. We discuss the current strengths and shortcomings of precision medicine and suggest a condensed manual for diagnosis and treatment of both adult and pediatric patients with PPGL. Finally, we consider the future direction of this field, with a particular focus on how advanced molecular characterization of PPGL can improve a patient's outcome, including cures and, ultimately, disease prevention.
Clinical and Genetic Implications of DNA Mismatch Repair Deficiency in Patients With Pancreatic Ductal Adenocarcinoma
Authors: Jordan M. Cloyd, Matthew H. G. Katz, Huamin Wang, Amanda Cuddy, Y. Nancy You
Journal: JAMA Surgery (2017)

This cohort study examines the behavior and outcomes of deficient DNA mismatch repair in patients at elevated risk for malignant neoplasms, including pancreatic ductal adenocarcinoma.