tbuckley/cabot-search huggingface dataset:
In Vivo Calcium Detection by Comparing Optical Coherence Tomography, Intravascular Ultrasound, and Angiography
Authors: Xiao Wang, Mitsuaki Matsumura, Gary S Mintz, Tetsumin Lee, Wenbin Zhang, Yang Cao, Akiko Fujino, Yongqing Lin, Eisuke Usui, Yoshihisa Kanaji, Tadashi Murai, Taishi Yonetsu, Tsunekazu Kakuta, Akiko Maehara
Journal: JACC. Cardiovascular imaging (2017)
Methodological Standards for Meta-Analyses and Qualitative Systematic Reviews of Cardiac Prevention and Treatment Studies: A Scientific Statement From the American Heart Association
Authors: Goutham Rao, Francisco Lopez-Jimenez, Jack Boyd, Frank D’Amico, Nefertiti H. Durant, Mark A. Hlatky, George Howard, Katherine Kirley, Christopher Masi, Tiffany M. Powell-Wiley, Anthony E. Solomonides, Colin P. West, Jennifer Wessel
Journal: Circulation (2017)

Meta-analyses are becoming increasingly popular, especially in the fields of cardiovascular disease prevention and treatment. They are often considered to be a reliable source of evidence for making healthcare decisions. Unfortunately, problems among meta-analyses such as the misapplication and misinterpretation of statistical methods and tests are long-standing and widespread. The purposes of this statement are to review key steps in the development of a meta-analysis and to provide recommendations that will be useful for carrying out meta-analyses and for readers and journal editors, who must interpret the findings and gauge methodological quality. To make the statement practical and accessible, detailed descriptions of statistical methods have been omitted. Based on a survey of cardiovascular meta-analyses, published literature on methodology, expert consultation, and consensus among the writing group, key recommendations are provided. Recommendations reinforce several current practices, including protocol registration; comprehensive search strategies; methods for data extraction and abstraction; methods for identifying, measuring, and dealing with heterogeneity; and statistical methods for pooling results. Other practices should be discontinued, including the use of levels of evidence and evidence hierarchies to gauge the value and impact of different study designs (including meta-analyses) and the use of structured tools to assess the quality of studies to be included in a meta-analysis. We also recommend choosing a pooling model for conventional meta-analyses (fixed effect or random effects) on the basis of clinical and methodological similarities among studies to be included, rather than the results of a test for statistical heterogeneity.
Abstract 29: Heme Levels Are Increased in the Hearts of Patients with End-Stage Heart Failure
Authors: Arineh Khechaduri, Marina Bayeva, Hossein Ardehali
Journal: Circulation Research (2012)

Introduction: Diseases of iron imbalance can cause cardiomyopathy, as observed in hereditary hemochromatosis or Friedreich’s ataxia. However, the iron status of a failing heart has not been systematically examined. Results: The iron levels were quantified in ten hearts from human patients with end-stage cardiomyopathy and ten unmatched healthy control hearts. Total cellular and cytosolic non-heme iron levels were significantly reduced in failing hearts; however, there was a 2-fold increase in cytosolic heme levels in heart failure, as measured by the total protoporphyrin IX (PPIX) content. The amount of iron-free PPIX was low and did not differ between the two groups, suggesting that the majority of PPIX is complexed with iron to form heme, and thus our assay accurately estimates heme levels in the heart. To study the mechanism for the increased heme content in failing hearts, we examined the expression of genes involved in heme and iron homeostasis. Consistent with elevated heme, there was a decrease in the levels of the cellular iron importer (transferrin receptor 1 orTfR1) and the first enzyme in heme synthesis (δ-aminolevulinic acid synthase 1 or ALAS1), both of which are negatively regulated by heme. Other genes involved in heme synthesis, iron incorporation into PPIX, and heme degradation were not affected. However, we noted a significant increase in the mRNA and protein levels of ALAS2 in the failing hearts. ALAS2 is normally expressed in hemoatopoietic cells and displays very low expression in the heart. Its induction in the setting of heart failure provides a possible explanation for increased heme levels. We then assessed whether increase in ALA and heme in failing hearts is associated with generation of reactive oxygen species (ROS). Addition of exogenous ALA led to a four-fold increase in ROS, while incubation with hemin have doubled ROS levels in these cells, suggesting that augmentation of heme synthesis may exacerbate heart failure by increasing the oxidative stress. Conclusions: Our results suggest that heme levels are increased in human hearts with end-stage cardiomyopathy, possibly through the induction of ALAS2 expression. The elevated heme levels may exacerbate heart failure by increased production of ROS.
KINEMATIC ANALYSIS OF PRESSING MOVEMENTS IN WOMEN'S SOCCER COMPETITIONS
Authors: Shogo Sasaki, Hideyuki Koga, Tron Krosshaug, Toru Fukubayashi
Journal: British Journal of Sports Medicine (2017)

Background The most common movements that occur during anterior cruciate ligament (ACL) injuries in soccer are “pressing” movements. There are currently no accurate kinematic descriptions of joint kinematics in pressing movements in defensive situations. Objective To describe the knee and hip joint kinematics during pressing actions in soccer in order to identify kinematic patterns in high-risk situations for ACL injuries. Design Case study Setting Competitive level, division-1 amateur female soccer league in Japan. Participants Five video sequences involving 4 collegiate soccer players. Assessment of Risk Factors The high-risk pressing situations were determined by the large distance between trunk and foot placements in the sagittal plane. Main Outcome Measurements The knee and hip joint kinematics using model-based image-matching technique. Results The mean knee flexion angle at initial contact (IC) was 13°; it had increased by 11° (95% CI: 3°–14°) 40 ms after IC. As for knee adduction and rotation angles, the knee positions were close to neutral at IC, and only minor knee angular changes occurred later in the sequences. The mean hip flexion was 25° at IC, and had increased by 22° (95% CI: 11°–32°) 100 ms later. The hip was also externally rotated 7° at IC, and gradually rotated internally, reaching 10° of internal rotation 100 ms after IC. Conclusions In contrast with previously reported injury-causing situations, the present knee did not experience rapid knee valgus and increased internal rotation. The hip displayed a smooth transition after IC, which contrasted with previously reported hip kinematics of substantial internal rotation and static hip flexion in injury situations. This study suggests that the observed sudden changes in knee valgus and rotation, as well as the static hip flexion seen in ACL injury situations are unique to such situations, supporting the view that these characteristics likely contribute to the injury mechanism.
Abstract 3466: Potential Effects of 3-Hydroxy-3-Methylglutaryl Coenzyme a Reductase Inhibition on G Protein-Mediated Cardiac Hypertrophy
Authors: Eui-Young Choi, Woochul Chang, Soyeon Lim, Byeong-Wook Song, Hye-Jung Kim, Min-Ji Cha, Eunju Choi, Yangsoo Jang, Ki-Chul Hwang, Namsik Chung
Journal: Circulation (2008)

Statins have recently been shown to produce anti-cardiac hypertrophic effects via the regulation of small GTPases. We sought to evaluate whether statin treatment directly suppresses cardiac hypertr...
RELATIONSHIP BETWEEN MOTOR CONTROL ASYMMETRIES AND MOTOR PERFORMANCE ASYMMETRIES
Authors: Kornelius Kraus, Markus Heffels, Denise Rahn, Nicole Stukenbröker, Hans-Georg Scherer
Journal: British Journal of Sports Medicine (2017)

Background The in-line lunge (ILL) is used to determine muscle sling behavior and possible unilateral motor control asymmetries (UMCA). Though, its validity remains unclear. Objective The aim of this analysis was to explore the relationship between UMCA and unilateral motor performance asymmetries (UMPA). Design Correlational-study. To reduce bias of circadian effects we executed the testing sessions within a timeframe of ±1 h. A crossover design was used in order to avoid sequence effects. Setting Collegiate athletes Participants 54 healthy sportsmen were enrolled in the study, whereas 50 (43 men and 7 women; 22.3±1.6 yrs) completed the study. Interventions The participants visited the laboratory twice. In session 1 they performed the FMS, followed by a warm-up including a treadmill run (10 min at 10 km/h) and 5 free split squats at 40% load of their bodyweight (FSS40). Thereafter, the participants performed 3 sets of 5 repetitions of the FSS40 intermitted by a recovery period of 1 minute. In session 2 the sportsmen underwent the same warm-up and FSS40 assessment, however the starting leg was switched. Kinetic data were recorded with a linear power encoder. Main Outcome Measurements Correlational-Analysis. The criterion for a UMPA was determined by a weighted TEM based on Cohens d. Results The relationship between UMCA and UMPA is low (r=0.2; p&gt;0.05). In general, we identified 17 UMCAs and 13 UMPAs (8 weak, 4 moderate,1 strong). The ICCs of kinetic parameters were &gt;0.9. TEMs were &lt;7.5%. Conclusions The data indicates that the association between UMCA and UMPA is low. Based on that evidence it seems that asymmetries are task specific. However, on the methodological level the scoring procedure could be a confounder for our result. Within a physiological context there are different factors that possibly explain the result, like different motor unit recruitment strategies, different muscle fibre distribution or connective tissue properties.
Some concerns and improvements from Turkey
Authors: Olgu Erkin Cinar, Abdulsamet Erden, Alper Sari, Berkan Armagan, Levent Kilic
Journal: Annals of the Rheumatic Diseases (2017)

First, thank you for this article which tries to answer a difficult clinical problem about anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis remission phase treatment.1 We believe that the study will be a milestone in ANCA-associated vasculitis maintenance treatment paradigm. To improve clinical implications, we wanted to ask about some important points in the study.

As seen in the literature,2 the Five Factor Score (FFS) is an easily …
アップコンバージョン光学/磁気共鳴画像ガイド下小腫りゅう検出と高速発光ナノロッドに基づくin vivo三モードバイオイメージング【Powered by NICT】
Authors: Xue Zhenluan, Yi Zhigao, Li Xiaolong, Li Youbin, Jiang Mingyang, Liu Hongrong, Zeng Songjun
Journal: Biomaterials (2017)
08.13 Understanding aberrant il-6 mediated cd4+ t-cell signalling in early rheumatoid arthritis
Authors: Laura Ridgley, Amy Anderson, Andrew Skelton, David Young, John Isaacs, Ruaidhrí Carmody, Arthur Pratt
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a heterogeneous disease of immune dysregulation. Transcriptional profiling of circulating CD4<sup>+</sup> T-cells identified a 12 gene signature which could distinguish untreated early arthritis patients from disease controls. This signature was enriched for STAT-3 target genes whose expression correlated with circulating IL-6 levels. We hypothesise that pre-exposure of naïve CD4<sup>+</sup> T-cells to circulating IL-6 mediates STAT-3 activation and subsequent aberrant effector function following T-cell receptor (TCR) stimulation, providing a mechanism of antigen non-specific immune dysfunction in early RA. <h3>Materials and methods</h3> Naïve (CD45RA+) and antigen experienced (CD45RA-) CD4<sup>+</sup> T-cells from healthy donors were cultured with IL-6 and equimolar concentrations of soluble IL-6R for 3 days to mimic chronic exposure, before being washed thoroughly and stimulated with anti-CD3/anti-CD28 for 6 days. Activation and proliferation were assessed by flow cytometry measuring cell surface markers and CFSE. RNA was extracted from cells at multiple experimental time points and global gene expression profiling undertaken using an Illumina microarray. <h3>Results</h3> Aside from downregulation of IL-6β receptor, no change in the activation of naïve CD4<sup>+</sup> T-cells following culture with IL-6 was observed. Pre-exposure of naïve CD4<sup>+</sup> T-cells to IL-6 and subsequent TCR stimulation enhanced proliferative capacity and cell activation, in a dose-dependent manner. Interestingly, physiological levels of IL-6, mirroring those found in the serum of RA patient's strongly enhanced naïve CD4<sup>+</sup> T-cell proliferation. This effect was less pronounced in memory CD4<sup>+</sup> T-cells. In addition pre-exposure of CD4<sup>+</sup> T-cells to IL-6 resulted in altered cytokine profiles and T-helper cell differentiation. Pre-exposure of healthy control naïve CD4<sup>+</sup> T-cells to physiological levels of IL-6 caused significant STAT-3 activated gene induction which mirror genes previously found to distinguish RA patients from disease controls. These genes were less pronounced and unsustained in memory CD4<sup>+</sup> T-cells. <h3>Conclusions</h3> In the proinflammatory early RA disease state our data imply that pre-exposure of cells to IL-6 causes increased proliferative capacity and activation status as well as differential gene expression, most prominently in naïve CD4<sup>+</sup> T-cells. This highlights that cytokine 'pre-priming' during this critical phase may have consequences for naïve CD4<sup>+</sup> T-cell effector function impacting the transition to disease chronicity.
Local IL‐25 contributes to Th2‐biased inflammatory profiles in nasal polyps
Authors: H.‐Y. Hong, F.‐H. Chen, Y.‐Q. Sun, X.‐T. Hu, Y. Wei, Y.‐P. Fan, J. Zhang, D.‐H. Wang, R. Xu, H.‐B. Li, J.‐B. Shi
Journal: Allergy (2017)

Abstract Background IL ‐25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps ( CRS w NP ). This study aimed to evaluate the association of IL ‐25 with the Th2‐biased inflammatory profiles in CRS w NP . Methods Nasal polyp ( NP ) tissues and control uncinate process tissues were collected from 92 patients with CRS w NP , 20 patients with chronic rhinosinusitis without nasal polyps ( CRS s NP ), and 16 normal control subjects. IL ‐25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT ‐ qPCR , and ELISA . The inflammatory profiles and clinical characteristics of 2 NP subtypes ( IL ‐25 high and IL ‐25 low ) were evaluated, and the effects of IL ‐25 on Th2 cytokine production in cultured dispersed polyp cells were examined in vitro. Results The mRNA and protein levels of IL ‐25 were significantly increased in the polyp tissues compared with the control uncinate process tissues. The IL ‐25 high subtype showed greater computed tomography scores, endoscopic scores, and Th2 response. Exposure to IL ‐25 activated type 2 innate lymphoid cells and Th2 cells in NP simultaneously which further increased Th2 cytokine production in vitro. Conclusions Local IL ‐25 plays a crucial role in promoting Th2‐biased inflammatory profiles in NP and may serve as a promising therapeutic target in CRS w NP patients.
A prospective, randomized, double-blinded, split-face/chest study of prophylactic topical dapsone 5% gel versus moisturizer for the prevention of cetuximab-induced acneiform rash
Authors: Viswanath R. Belum, Michael A. Marchetti, Stephen W. Dusza, Andrea Cercek, Nancy E. Kemeny, Mario E. Lacouture
Journal: Journal of the American Academy of Dermatology (2017)
Genomic epidemiology of methicillin-susceptible Staphylococcus aureus across colonisation and skin and soft tissue infection
Authors: Alex Grinberg, Patrick J. Biggs, Ji Zhang, Stephen Ritchie, Zachary Oneroa, Charlotte O'Neill, Ali Karkaba, Niluka S. Velathanthiri, Geoffrey W. Coombs
Journal: Journal of Infection (2017)
Abstract 18: Synoviolin, an E3 Ubiquitin Ligase, Modulates Cardiac Myocyte Size and Restores Heart Function in Hypertrophic Cardiomyopathy
Authors: Shirin Doroudgar, Mirko Völkers, Donna J Thuerauf, Ashley Bumbar, Mohsin Khan, Sadia Mohsin, Wei Wang, Jonathan L Respress, Natalie Gude, Oliver J Müller, Xander H Wehrens, Mark A Sussman, Christopher C Glembotski
Journal: Circulation Research (2012)

The endoplasmic reticulum (ER) is essential for protein homeostasis, or proteostasis, which governs the balance of the proteome. In addition to secreted and membrane proteins, proteins bound for many other cellular locations are also made on ER-bound ribosomes, emphasizing the importance of protein quality and quantity control in the ER. Unlike cytosolic E3 ubiquitin ligases studied in the heart, synoviolin/Hrd1, which has not been studied in the heart, is an ER transmembrane E3 ubiquitin ligase, which we found to be upregulated upon protein misfolding in cardiac myocytes. Given the strategic location of synoviolin in the ER membrane, we addressed the hypothesis that synoviolin is critical for regulating the balance of the proteome, and accordingly, myocyte size. We showed that in vitro, adenovirus-mediated overexpression of synoviolin decreased cardiac myocyte size and protein synthesis, but unlike atrophy-related ubiquitin ligases, synoviolin did not increase global protein degradation. Furthermore, targeted gene therapy using adeno-associated virus 9 (AAV9) showed that overexpression of synoviolin in the left ventricle attenuated maladaptive cardiac hypertrophy and preserved cardiac function in mice subjected to trans-aortic constriction (AAV9-control TAC = 22.5 ± 6.2% decrease in EF vs. AAV9-synoviolin TAC at 6 weeks post TAC; P&lt;0.001), and decreased mTOR activity. Since calcium is a major regulator of cardiac myocyte size, we examined the effects of synoviolin gain- or loss-of-function, using AAV9-synoviolin, or an miRNA designed to knock down synoviolin, respectively. While synoviolin gain-of-function did not affect calcium handling in isolated adult myocytes, synoviolin loss-of-function increased calcium transient amplitude (P&lt;0.01), prolonged spark duration (P&lt;0.001), and increased spark width (P&lt;0.001). Spark frequency and amplitude were unaltered upon synoviolin gain- or loss-of-function. Whereas SR calcium load was unaltered by synoviolin loss-of-function, SERCA-mediated calcium removal was reduced (P&lt;0.05). In conclusion, our studies suggest that in the heart, synoviolin is 1) a critical component of proteostasis, 2) a novel determinant of cardiac myocyte size, and 3) necessary for proper calcium handling.
Abstract #2754: Phosphatase of regenerating liver-3 as prominent factor for lymph node metastasis downstream of EGFR pathway in esophageal squamous cell carcinoma
Authors: Ooki Akira, Keishi Yamashita, Masahiko Watanabe
Journal: Cancer Research (2009)

Introduction : The phosphatase of regenerating liver-3 (PRL-3) plays crucial roles in metastasis through augmented invasion and angiogenesis, and is significantly associated with lymph node metastasis (LNM) in various malignant tumors including esophageal squamous cell carcinoma (ESCC). The aim of this study is to elucidate the clinical relevance and therapeutic potential to target PRL-3 in ESCC.  Methods : We first examined correlation of PRL-3 expression with its gene amplification using real-time PCR and, partly, fluorescence in situ hybridization (FISH) in 88 primary ESCC tissues and mechanisms of PRL-3 over-expression were then evaluated using oncogenic inhibitors (epidermal growth factor receptor: EGFR, PI3K, MAPK, MET, TGF-beta inhibitor) in 10 ESCC cell lines.  Results : In ESCC tissues, PRL-3 overexpression was detected in 68 (77 %) of 88 patients by immunohistochemistry and closely associated with LNM independent of other clinical factors on multivariate logistic regression analysis (odds ratio=18.70,  P =0.0005). The exclusive gene amplification of PRL-3 or EGFR was detected in 3 (7.9%) and 6 (15.8%) of the 38 ESCC with LNM showing PRL-3 overexpression, while none of 10 with no PRL-3 expression showed gene amplification, suggesting that EGFR is on the same pathway of PRL-3. Any ESCC did not also have EGFR mutation in exon19 to 21. PRL-3 gene amplification was observed in 2 (TE8 and TE10) out of 7 cell lines with PRL-3 overexpression, and the EGFR inhibitors, AG1478 or gefitinib, robustly repressed endogenous PRL-3 expression in TE11 cells with EGFR gene amplification, while not in cell lines without EGFR gene amplification. Moreover, EGFR ligands, EGF or transforming growth factor-\#945; (TGF-\#945;), actually up-regulated PRL-3 in TE15 constitutively expressing low level of PRL-3.  Conclusion : PRL-3 is the prominent molecule for lymph node metastasis of ESCC and its overexpression is accounted for by either its gene amplification or EGFR regulation, and therefore genomic information of both genes may facilitate an attractive therapeutic strategy by their use as biomarkers and targeting inhibition.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2754.
Epiregulin and EGFR interactions are involved in pain processing
Authors: Loren J. Martin, Shad B. Smith, Arkady Khoutorsky, Claire A. Magnussen, Alexander Samoshkin, Robert E. Sorge, Chulmin Cho, Noosha Yosefpour, Sivaani Sivaselvachandran, Sarasa Tohyama, Tiffany Cole, Thang M. Khuong, Ellen Mir, Dustin G. Gibson, Jeffrey S. Wieskopf, Susana G. Sotocinal, Jean Sebastien Austin, Carolina B. Meloto, Joseph H. Gitt, Christos Gkogkas, Nahum Sonenberg, Joel D. Greenspan, Roger B. Fillingim, Richard Ohrbach, Gary D. Slade, Charles Knott, Ronald Dubner, Andrea G. Nackley, Alfredo Ribeiro-da-Silva, G. Gregory Neely, William Maixner, Dmitri V. Zaykin, Jeffrey S. Mogil, Luda Diatchenko
Journal: Journal of Clinical Investigation (2017)

The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREG-mediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9. Moreover, EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons. Both the EGFR and EREG genes displayed a genetic association with the development of chronic pain in several clinical cohorts of temporomandibular disorder. Thus, EGFR and EREG may be suitable therapeutic targets for persistent pain conditions.
Trends in Neoadjuvant Approaches in Pancreatic Cancer
Authors: Lingling Du, Andrea Wang-Gillam
Journal: Journal of the National Comprehensive Cancer Network (2017)

Pancreatic cancer (PDAC) is an aggressive tumor type associated with development of micrometastasis at an early stage. In attempt to eradicate disseminated disease, neoadjuvant therapy has been explored in patients with resectable and borderline resectable PDAC. In large retrospective studies, neoadjuvant therapy was associated with better survival compared with upfront surgery. Previously, trials more commonly used radiotherapy (RT) with small doses of chemotherapy as radiosensitizers. Recent studies, however, have incorporated full systemic doses of chemotherapy with or without RT before surgery with the hope of achieving adequate systemic chemotherapy coverage and improving survival. Several phase II trials have shown encouraging clinical benefits using the neoadjuvant approach. Large cooperative group studies are exploring the role of neoadjuvant treatment with newer combination chemotherapy regimens and modern RT techniques, which will provide more evidence regarding the utility of this approach.