tbuckley/cabot-search huggingface dataset:
SAT0063 A prospective study on comparison of composite indices with ultrasound for detecting remission and prediction of flare in 2 years
Authors: MO Olmez, EK Gunal, SB Ureyen, H Keskin, AB Ozturk, HG Yeter, E Cobanoglu, SZ Aydin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Treat-to-target (T2T) approach suggests using a composite index when following patients with rheumatoid arthritis (RA) without identifying which one to use. <h3>Objectives</h3> In this prospective study we aimed to compare the accuracy of different indices for RA patients in remission taking Ultrasound Global Synovitis Score (GLOESS) as a gold standard and their predictive value for flares in 2 years. <h3>Methods</h3> RA patients who were considered to be in clinical remission according to the clinician were recruited. Disease activity was assessed using DAS28-CRP, CDAI, SDAI and RAPID-3 and 38 joints per patient were scanned by US and scored according to GLOESS. The total GLOESS scores were calculated for 38 joints and also for 28 joints by excluding the MTP joints. The number of joints with ≥2 GLOESS was calculated. Flare data was collected in 3 subsequent visits in the following 2 years, whenever available. <h3>Results</h3> Ninety-six consecutive patients (80.2% females) were recruited. Patients were more frequently categorized as being in remission using DAS28 (80%) compared to CDAI (50%), SDAI (45.2%) and RAPID 3 (37.5%). Patients that were in remission according to CDAI had lower GLOESS scores on 28 joints (p=0.05) and had less joints with ≥2 signals (p=0.04) (table). For SDAI patients in remission had significantly less number of joints with grade 3 signals (p=0.03) and tend to have lower GLOESS scores on 28 joints as well as lower number of joints with ≥2 signals (p=0.06). None of the US scores were able to differentiate different disease states according to DAS28-CRP or RAPID. Flare data was available in 76 patients, 22 of whom had flares. Patients that had flare had higher GLOESS scores on 28 joints at baseline (p=0.05) and tend to have higher number of joints with grade 3 signals (p=0.06). Although numerically higher, none of the clinical indices were able to predict flares based on remission status (remission vs non remission: CDAI: 22.5% vs 36.1, p=0.2; SDAI: 22.9 vs 36.8, p=0.2; DAS28: 25.4% vs 50%, p=0.1; RAPID3: 20% vs 34.8%, p=0.2). <h3>Conclusions</h3> Our results show that CDAI is superior then other clinical indices to assess remission in RA. US has the superiority over clinical indices to predict flares and 28 joint GLOESS is superior to 38 joints. <h3>Disclosure of Interest</h3> None declared
Evaluation of GalNAc-siRNA Conjugate Activity in Pre-clinical Animal Models with Reduced Asialoglycoprotein Receptor Expression
Authors: Jennifer L.S. Willoughby, Amy Chan, Alfica Sehgal, James S. Butler, Jayaprakash K. Nair, Tim Racie, Svetlana Shulga-Morskaya, Tuyen Nguyen, Kun Qian, Kristina Yucius, Klaus Charisse, Theo J.C. van Berkel, Muthiah Manoharan, Kallanthottathil G. Rajeev, Martin A. Maier, Vasant Jadhav, Tracy S. Zimmermann
Journal: Molecular Therapy (2017)

The hepatocyte-specific asialoglycoprotein receptor (ASGPR) is an ideal candidate for targeted drug delivery to the liver due to its high capacity for substrate clearance from circulation together with its well-conserved expression and function across species. The development of GalNAc-siRNA conjugates, in which a synthetic triantennary N-acetylgalactosamine-based ligand is conjugated to chemically modified siRNA, has enabled efficient, ASGPR-mediated delivery to hepatocytes. To investigate the potential impact of variations in receptor expression on the efficiency of GalNAc-siRNA conjugate delivery, we evaluated the pharmacokinetics and pharmacodynamics of GalNAc-siRNA conjugates in multiple pre-clinical models with reduced receptor expression. Despite greater than 50% reduction in ASGPR levels, GalNAc conjugate activity was retained, suggesting that the remaining receptor capacity was sufficient to mediate efficient uptake of potent GalNAc-siRNAs at pharmacologically relevant dose levels. Collectively, our data support a broad application of the GalNAc-siRNA technology for hepatic targeting, including disease states where ASGPR expression may be reduced.
Abstract 264: Nitrite Therapy Ameliorates Myocardial Injury via H2S and Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2)-Dependent Signaling in Chronic Heart Failure
Authors: Kazi N Islam, Erminia Donnarumma, Shashi Bhushan, David J Lefer
Journal: Circulation Research (2015)

Background: Nitric oxide (NO) and hydrogen sulfide (H 2 S) are reduced in congestive heart failure. Recent studies suggest cross-talk between NO and H 2 S signaling. We previously reported that sodium nitrite (NaNO 2 ) significantly ameliorates myocardial ischemia-reperfusion injury and heart failure. Nrf2 regulates the expression of antioxidant protein genes and is upregulated by H 2 S. We examined the effects of NaNO 2 therapy on endogenous H 2 S bioavailability and Nrf2 activation in mice subjected to ischemia-induced heart failure. Materials and Methods: Mice underwent 60 min. of left coronary artery occlusion and 4 weeks (WKS) of reperfusion. NaNO 2 (165 μg/kg) or saline vehicle (VEH) was administered at reperfusion and then in drinking water (100 mg/L) for 4 wks. Left ventricular ejection fraction (LVEF) was determined at baseline and 4 wks of reperfusion. Myocardial tissue was collected and analyzed for oxidative stress status and respective gene/protein levels. Results: NaNO 2 therapy preserved LVEF (47 ± 4% vs. 32 ± 4%, p &lt; 0.01) and LV diastolic and systolic dimensions (LVEDD/LVESD; 4.0/3.1 mm vs. 4.5/3.9 mm, p &lt; 0.05) at 4 wks. MDA and protein carbonyl contents were significantly reduced in NaNO 2 treated mice as compared to VEH. NaNO 2 markedly increased expression of CuZn-superoxide dismutase and catalase at 4 wks. Furthermore, NaNO 2 increased mRNA levels of H 2 S producing enzymes and H 2 S bioavailabilty. Cardiac Nrf2 activation was also observed with NaNO 2 therapy. Conclusions: Our results demonstrate that NaNO 2 therapy significantly improves left ventricular function via by increasing H 2 S bioavailability, activation of Nrf2, and increased antioxidant defenses.1
T <sub>fr</sub> cells lack IL-2Rα but express decoy IL-1R2 and IL-1Ra and suppress the IL-1–dependent activation of T <sub>fh</sub> cells
Authors: Paul-Gydeon G. Ritvo, Guillame Churlaud, Valentin Quiniou, Laura Florez, Faustine Brimaud, Gwladys Fourcade, Encarnita Mariotti-Ferrandiz, David Klatzmann
Journal: Science Immunology (2017)

Follicular regulatory T cells suppress B cell activation by expression of decoy IL-1R2 and IL-1Ra.
ソラフェニブは,5T33MMマウスモデルにおける多発性骨髄腫In Vitro,Ex VivoおよびIn Vivoに対する強力な抗腫瘍活性を有する
Authors: Kharaziha Pedram, DE Raeve Hendrik, Fristedt Charlotte, Li Qiao, Gruber Astrid, Johnsson Per, Kokaraki Georgia, Panzar Maria, Laane Edward, Oesterborg Anders, Zhivotovsky Boris, Jernberg-Wiklund Helena, Grander Dan, Celsing Fredrik, Bjoerkholm Magnus, Vanderkerken Karin, Panaretakis Theocharis
Journal: Cancer Research (2012)
Administrative Codes for Capturing In-Hospital Cardiac Arrest
Authors: Rohan Khera, John A. Spertus, Monique A. Starks, Yuanyuan Tang, Steven M. Bradley, Saket Girotra, Paul S. Chan
Journal: JAMA Cardiology (2017)

This study uses linked data from Get With the Guidelines–Resuscitation and Medicare claims to assess the challenges of using administrative billing data to conduct research on 56678 patients with confirmed in-hospital cardiac arrest.
FRI0742-HPR Does the use of technological devices improve the reliability of measuring the active cervical range of motion in patients with neck pain? a systematic review with meta-regression
Authors: A Rondoni, G Rossettini, M Strobe, F Gallo, D Ristori, M Testa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Economic impact of neck pain shows an increasing trend. In order to limit the costs of spine disorders management, it is important to assess clinical efficacy and the cost-worthiness of new technological devices, recently introduced in physical therapist9s clinical practice <h3>Objectives</h3> This systematic review compares, in patients with non-specific neck pain, the reliability of measures of Active Cervical Range of Motion (ACROM) detected with technological devices with those assessed with low cost, common-use devices. As secondary outcomes, it was investigated if ACROM reliability depends on the plane on which the measured movement is performed <h3>Methods</h3> The literature search was carried out in Medline, Scopus, Embase, The Cochrane Library, CINHAL, PEDro and grey literature until August 2016. Inclusion criteria were: reliability design, population of adults with nonspecific neck pain, examiners of any level of experience, measures repeated at least twice and statistics indexes on reliability. Exclusion criteria were: other study designs, asymptomatic population or mixed population, single or none ACROM measure, inadequate statistics. The risk of bias was assessed by QAREL. It was considered inexpensive a device that costs at maximum 500 euros. A Univariate, and a Multivariate Analysis, were performed by using the Linear Mixed-Effect Model <h3>Results</h3> Searching the databases yielded 35,151 records. Nine studies met all eligibility criteria. The QAREL mean score of the selected studies was 3.7 out of 11. No significant effect of the type of device (inexpensive versus expensive) on ICC was observed for intra-rater (ICC=0.93vs0.91 p-value&gt;0.99) and inter-rater reliability (ICC=0.80vs0.87 p-value&gt;0.99) [Table 1]. The plane of movement did not affect inter-rater reliability (p-value=0.11) while significantly influenced the intra-rater reliability (p-value=0.0001) assessed with low-cost devices. Intra-rater reliability significantly decreases (p-value=0.0129) in frontal plane movements (side bending) compared with movement on the sagittal plane (flexion-extension). <h3>Conclusions</h3> The use of expensive devices to measure ACROM in adults with nonspecific neck pain does not seem to improve the reliability of the assessment. The assessment of side bending showed the lowest level of inter-raters reliability. Since the quality of the analysed studies is low, the conclusion of the present study should be taken cautiously <h3>Disclosure of Interest</h3> None declared
Supplemental oxygen does not reduce mortality in patients with suspected myocardial infarction, finds study
Authors: Susan Mayor
Journal: BMJ (2017)

Routine use of supplemental oxygen in patients with suspected myocardial infarction (MI) who are not hypoxic is associated with no reduction in mortality at one year, a randomised trial has found.1

Supplemental oxygen has been used routinely in patients with suspected MI for more than a century and is recommended in clinical guidelines. The rationale behind …
Modeling Long-Term Survival in Chemotherapy-Only Versus Combined Modality Therapy in Patients with Early Stage Unfavorable Hodgkin Lymphoma Involving the Mediastinum
Authors: Scott Tuttle, John Plastaras, Lauren E. Strelec, Reid F. Thompson, Amit Maity, Wei-Ting Hwang, Sunita Dwivedy Nasta, Anthony R. Mato, Daniel J. Landsburg, Stephen J. Schuster, Jakub Svoboda
Journal: Blood (2016)
Cut Points for Identifying Clinically Significant Diabetes Distress in Adolescents With Type 1 Diabetes Using the PAID-T: Results From Diabetes MILES Youth–Australia
Authors: Virginia Hagger, Christel Hendrieckx, Fergus Cameron, Frans Pouwer, Timothy C. Skinner, Jane Speight
Journal: Diabetes Care (2017)

To establish cut point(s) for the Problem Areas in Diabetes-teen version (PAID-T) scale to identify adolescents with clinically meaningful, elevated diabetes distress.Data were available from the Diabetes Management and Impact for Long-term Empowerment and Success (MILES) Youth-Australia Study, a national survey assessing various psychosocial indicators among self-selected National Diabetes Services Scheme registrants. Participants in the current study (n = 537) were (mean ± SD) 16 ± 2 years old, had type 1 diabetes for 6 ± 4 years, and 62% (n = 334) were girls. They completed measures of diabetes distress (PAID-T) and depressive symptoms (Patient Health Questionnaire for Adolescents) and self-reported their most recent HbA1c and frequency of self-monitoring of blood glucose (SMBG). Relationships between the PAID-T and the psychological and clinical variables were examined to identify a clinically meaningful threshold for elevated diabetes distress. ANOVA was used to test whether these variables differed by levels of distress.Two cut points distinguished none-to-mild (<70), moderate (70-90), and high (>90) diabetes distress. Moderate distress was experienced by 18% of adolescents and high distress by 36%. Mean depressive symptoms, self-reported HbA1c, and SMBG differed significantly across the three levels of diabetes distress (all P < 0.001), with moderate-to-large effect sizes.Using the PAID-T, this study defined two clinically meaningful cut points to distinguish none-to-mild, moderate, and high diabetes distress in adolescents (aged 13-19). Based on these cut points, most respondents experienced at least moderate diabetes distress, which was clinically significant. Establishing thresholds for elevated diabetes distress will aid clinicians and researchers to interpret PAID-T scores, prompt discussion and intervention for those with unmet needs, and enable the effectiveness of interventions to be evaluated.
Mesenchymal Stromal Cell Exosomes Ameliorate Experimental Bronchopulmonary Dysplasia and Restore Lung Function through Macrophage Immunomodulation
Authors: Gareth R. Willis, Angeles Fernandez-Gonzalez, Jamie Anastas, Sally H. Vitali, Xianlan Liu, Maria Ericsson, April Kwong, S. Alex Mitsialis, Stella Kourembanas
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Mesenchymal stem/stromal cell (MSC) therapies have shown promise in preclinical models of pathologies relevant to newborn medicine, such as bronchopulmonary dysplasia (BPD). We have reported that the therapeutic capacity of MSCs is comprised in their secretome, and demonstrated that the therapeutic vectors are exosomes produced by MSCs (MSC-exos).To assess efficacy of MSC-exo treatment in a preclinical model of BPD and to investigate mechanisms underlying MSC-exo therapeutic action.Exosomes were isolated from media conditioned by human MSC cultures. Newborn mice were exposed to hyperoxia (HYRX; 75% O2), treated with exosomes on Postnatal Day (PN) 4 and returned to room air on PN7. Treated animals and appropriate controls were harvested on PN7, -14, or -42 for assessment of pulmonary parameters.HYRX-exposed mice presented with pronounced alveolar simplification, fibrosis, and pulmonary vascular remodeling, which was effectively ameliorated by MSC-exo treatment. Pulmonary function tests and assessment of pulmonary hypertension showed functional improvements after MSC-exo treatment. Lung mRNA sequencing demonstrated that MSC-exo treatment induced pleiotropic effects on gene expression associated with HYRX-induced inflammation and immune responses. MSC-exos modulate the macrophage phenotype fulcrum, suppressing the proinflammatory "M1" state and augmenting an antiinflammatory "M2-like" state, both in vitro and in vivo.MSC-exo treatment blunts HYRX-associated inflammation and alters the hyperoxic lung transcriptome. This results in alleviation of HYRX-induced BPD, improvement of lung function, decrease in fibrosis and pulmonary vascular remodeling, and amelioration of pulmonary hypertension. The MSC-exo mechanism of action is associated with modulation of lung macrophage phenotype.
A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin’s lymphoma (NHL): CALGB 50803 (Alliance)
Authors: P. Martin, S.-H. Jung, B. Pitcher, N.L. Bartlett, K.A. Blum, T. Shea, E.D. Hsi, J. Ruan, S.E. Smith, J.P. Leonard, B.D. Cheson
Journal: Annals of Oncology (2017)
Immuno-oncology Trial Endpoints: Capturing Clinically Meaningful Activity
Authors: Valsamo Anagnostou, Mark Yarchoan, Aaron R. Hansen, Hao Wang, Franco Verde, Elad Sharon, Deborah Collyar, Laura Q.M. Chow, Patrick M. Forde
Journal: Clinical Cancer Research (2017)

Abstract Immuno-oncology (I-O) has required a shift in the established paradigm of toxicity and response assessment in clinical research. The design and interpretation of cancer clinical trials has been primarily driven by conventional toxicity and efficacy patterns observed with chemotherapy and targeted agents, which are insufficient to fully inform clinical trial design and guide therapeutic decisions in I-O. Responses to immune-targeted agents follow nonlinear dose–response and dose–toxicity kinetics mandating the development of novel response evaluation criteria. Biomarker-driven surrogate endpoints may better capture the mechanism of action and biological response to I-O agents and could be incorporated prospectively in early-phase I-O clinical trials. While overall survival remains the gold standard for evaluation of clinical efficacy of I-O agents in late-phase clinical trials, exploration of potential novel surrogate endpoints such as objective response rate and milestone survival is to be encouraged. Patient-reported outcomes should also be assessed to help redefine endpoints for I-O clinical trials and drive more efficient drug development. This paper discusses endpoints used in I-O trials to date and potential optimal endpoints for future early- and late-phase clinical development of I-O therapies. Clin Cancer Res; 23(17); 4959–69. ©2017 AACR. See all articles in this CCR Focus section, “Clinical Trial Design Considerations in the Immuno-oncology Era.”
Abstract 88: Small Molecule Inhibition of Mixed Lineage Kinase 3 Attenuates Cardiac Fibroblast Activation and Pathologic Cardiac Remodeling
Authors: Melissa L Martin, Stephen Dewhurst, Harris A Gelbard, Val Goodfellow, Burns C Blaxall
Journal: Circulation Research (2012)

Heart failure (HF) is a manifestation of most cardiovascular diseases whose increasing prevalence highlights the need for novel therapeutics. The extent of pathologic cardiac remodeling is correlated with clinical outcome. Importantly, cardiac injury enhances cardiac fibroblast (CF) activation, producing myofibroblasts that release pro-fibrotic/inflammatory mediators which target cardiomyocytes (CM), CFs, and local inflammatory cells to exacerbate remodeling. Mixed Lineage Kinases (MLKs) are a family of stress-activated MAPKKKs whose functional role(s) in the heart remain largely unknown. MLK3 has been implicated in HIV-associated neurocognitive disorder (HAND), where it mediates deleterious cross-talk between microglia and neurons, suggesting an analogous mechanism of pathologic intercellular CF-CM communication in HF. We hypothesize that MLK3 exacerbates cardiac remodeling through enhanced CF activation that contributes to pathologic cardiac intercellular communication. We have synthesized a series of MLK3-specific small molecule inhibitors, one of which (URMC-099) was found to attenuate microglial-mediated neurotoxicity in murine models of HAND. To investigate the role of MLK3 in CF activation, neonatal rat ventricular CFs were stimulated with isoproterenol (Iso) or angiotensin II (AngII). Concurrent treatment with URMC-099 attenuated both α-smooth muscle actin expression, indicative of myofibroblast transition, and proinflammatory cytokine production. Further, therapeutic efficacy and specificity of URMC-099 were tested in iso-infused and myocardial infarction (MI) models of HF using wild-type (WT) and MLK3-/- mice (shown to have no overt cardiac phenotype). URMC-099 significantly attenuated cardiac hypertrophy (HW:BW) and reduced interstitial fibrosis (assessed by Masson's Trichrome staining) in an acute iso-pump model of HF in WT mice. Current echocardiographic data post-MI suggest cardioprotection in the MLK3-/- and URMC-099 treated mice. In conclusion, our collaborative data not only suggest a role for MLK3 in cardiac remodeling through pathologic CF activation but indicate a possibly novel paradigm of pathologic intercellular communication in multiple disease states.
天然胸腺細胞外マトリックスはin vivoで胸腺器官T細胞出力を改善し,in vitroでの胸腺上皮細胞分化を駆動する【Powered by NICT】
Authors: Hun Michael, Barsanti Marco, Wong Kahlia, Ramshaw John, Werkmeister Jerome, P Chidgey Ann
Journal: Biomaterials (2017)
SMAC mimetic combined with conventional chemotherapy agents yields synergy in the treatment of non-small cell lung cancer
Authors: Rachel Greer, Michael Peyton, Sunny Zachariah, Noelle Williams, Patrick Harran, Xiaodong Wang, John Minna
Journal: Cancer Research (2007)

4884   Standard chemotherapy for non-small cell lung cancer often uses doublet combinations of cisplatin or carboplatin with gemcitabine, paclitaxel, docetaxel, vinorelbine, or etoposide. While clinical responses and survival benefits are seen these are very modest and new more effective therapies are needed. As one approach to this problem we recently developed a small molecule mimetic of SMAC, a mitochondrial protein that inhibits the inhibitors of apoptosis proteins (IAPs) as a potential new chemotherapy agent (Li L, et. al. Science. (2004) 305: 1471-1474). Here we explore SMAC mimetic as a potential therapy for NSCLC, as well as the benefits of using it in conjunction with traditional chemotherapies. We tested 50 non-small cell lung cancer lines (NSCLCs) for their in vitro sensitivity to the SMAC mimetic or combined with other chemotherapy agents in a 96 hour MTS assay. Most NSCLC lung cancer lines were completely resistant to treatment with the SMAC mimetic alone (IC50 >>10μM). However, 10/50 NSCLC lines were killed by the SMAC mimetic alone at IC50s
A New Monoclonal Protein Detected in a Patient With Myeloma Undergoing Elotuzumab Therapy
Authors: Felicia Tang, Christine Schmotzer, Rose C. Beck
Journal: JAMA Oncology (2017)

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Clonal Evolution Pattern of Leukemia Progression and Richter Transformation in Ibrutinib-Relapsed CLL Patients
Authors: Sabah Kadri, Jimmy Lee, Carrie Fitzpatrick, Natalie Galanina, Madina Sukhanova, Girish Venkataraman, Shruti Sharma, Bradley Long, Megan Theissen, Mei Ming, Yuri Kobzev, Kang Wenjun, Ailin Guo, Weige V Wang, Nifang Niu, Howie Lawrence Weiner, Michael J. Thirman, Sonali M. Smith, Jeremy P. Segal, Pin Lu, Y. Lynn Wang
Journal: Blood (2016)