tbuckley/cabot-search huggingface dataset:
Lipoprotein Particle Profiles, Standard Lipids, and Peripheral Artery Disease Incidence
Authors: Aaron W. Aday, Patrick R. Lawler, Nancy R. Cook, Paul M Ridker, Samia Mora, Aruna D. Pradhan
Journal: Circulation (2018)

Background: Despite strong and consistent prospective associations of elevated low-density lipoprotein (LDL) cholesterol concentration with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. Atherogenic dyslipidemia characterized by increased small LDL particle (LDL-P) concentration, rather than total LDL cholesterol content, along with elevated triglyceride-rich lipoproteins and low high-density lipoprotein (HDL) cholesterol (HDL-C), may be the primary lipid driver of PAD risk. Methods: The study population was a prospective cohort study of 27 888 women ≥45 years old free of cardiovascular disease at baseline and followed for a median of 15.1 years. We tested whether standard lipid concentrations, as well as nuclear magnetic resonance spectroscopy–derived lipoprotein measures, were associated with incident symptomatic PAD (n=110) defined as claudication and/or revascularization. Results: In age-adjusted analyses, while LDL cholesterol was not associated with incident PAD, we found significant associations for increased total and small LDL-P concentrations, triglycerides, and concentrations of very LDL (VLDL) particle (VLDL-P) subclasses, increased total cholesterol (TC):HDL-C, low HDL-C, and low HDL particle (HDL-P) concentration (all P for extreme tertile comparisons &lt;0.05). Findings persisted in multivariable-adjusted models comparing extreme tertiles for elevated total LDL-P (adjusted hazard ratio [HR adj ] 2.03; 95% CI, 1.14–3.59), small LDL-P (HR adj 2.17; 95% CI, 1.10–4.27), very large VLDL-P (HR adj 1.68; 95% CI, 1.06–2.66), medium VLDL-P (HR adj 1.98; 95% CI, 1.15–3.41), and TC:HDL-C (HR adj , 3.11; 95% CI, 1.67–5.81). HDL was inversely associated with risk; HR adj for extreme tertiles of HDL-C and HDL-P concentration were 0.30 ( P trend &lt; 0.0001) and 0.29 ( P trend &lt; 0.0001), respectively. These components of atherogenic dyslipidemia, including small LDL-P, medium and very large VLDL-P, TC:HDL-C, HDL-C, and HDL-P, were more strongly associated with incident PAD than incident coronary and cerebrovascular disease. Finally, the addition of LDL-P and HDL-P concentration to TC:HDL-C measures identified women at heightened PAD risk. Conclusions: In this prospective study, nuclear magnetic resonance–derived measures of LDL-P, but not LDL cholesterol, were associated with incident PAD. Other features of atherogenic dyslipidemia, including elevations in TC:HDL-C, elevations in triglyceride-rich lipoproteins, and low standard and nuclear magnetic resonance–derived measures of HDL, were significant risk determinants. These data help clarify prior inconsistencies and may elucidate a unique lipoprotein signature for PAD compared to coronary and cerebrovascular disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique Identifier: NCT00000479.
Abstract 20319: Increased Inducibility of Atrial Fibrillation in Pitx2c Mice Exposed to Ibrutinib and Potential Mechanistic Insights
Authors: William Gomes de Oliveira, Brandon Chalazan, Liang Hong, Arvind Sridhar, Felipe Mendez, Meihong Zhang, Srikanth Perike, Mark McCauley, Dawood Darbar
Journal: Circulation (2017)

Introduction: Ibrutinib is rapidly becoming the treatment of choice for many B-cell malignancies, but its proarrhythmic effects may limit its widespread use. Ibrutinib recipients are at 4-fold incr...
The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial
Authors: Valeria Saglimbene, Suetonia C. Palmer, Marinella Ruospo, Patrizia Natale, Ausilia Maione, Antonio Nicolucci, Mariacristina Vecchio, Gianni Tognoni, Jonathan C. Craig, Fabio Pellegrini, Giuseppe Lucisano, Jörgen Hegbrant, Rosario Ariano, Olga Lamacchia, Antonio Sasso, Susanna Morano, Tiziana Filardi, Salvatore De Cosmo, Giuseppe Pugliese, Deni A. Procaccini, Loreto Gesualdo, Giuseppe Palasciano, David W. Johnson, Marcello Tonelli, Giovanni F.M. Strippoli
Journal: Journal of the American Society of Nephrology (2018)

Background The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear. Methods In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP&lt;130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events. Results Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%). Conclusions Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors.
DICER1 Syndrome
Authors: Laryssa A. Huryn, Amy Turriff, Laura A. Harney, Ann Garrity Carr, Patricia Chevez-Barrios, Dan S. Gombos, Radha Ram, Robert B. Hufnagel, D. Ashley Hill, Wadih M. Zein, Kris Ann P. Schultz, Rachel Bishop, Douglas R. Stewart
Journal: Ophthalmology (2018)
Review: In VTE, reduced- and full-dose extended DOAC therapies do not differ and are better than no extended therapy
Authors: Thomas DeLoughery
Journal: Annals of Internal Medicine (2018)

Source Citation Vasanthamohan L, Boonyawat K, Chai-Adisaksopha C, Crowther M. Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost. 2018;16:1288-95. 29772108
Neutrophil Extracellular Traps Induced by IL8 Promote Diffuse Large B-cell Lymphoma Progression via the TLR9 Signaling
Authors: Man Nie, Linbin Yang, Xiwen Bi, Yu Wang, Peng Sun, Hang Yang, Panpan Liu, Zhiming Li, Yi Xia, Wenqi Jiang
Journal: Clinical Cancer Research (2018)

More than 30% of patients with diffuse large B-cell lymphoma (DLBCL) experience treatment failure after first-line therapy. Neutrophil extracellular traps (NETs), a pathogen-trapping structure in tumor microenvironment, can promote the transition of autoimmunity to lymphomagenesis. Here, we investigate whether NETs play a novel role in DLBCL progression and its underlying mechanism.Experimental Design: NETs in DLBCL tumor samples and plasma were detected by immunofluorescence and ELISA, respectively. The correlation between NETs and clinical features were analyzed. The effects of NETs on cellular proliferation and migration and mechanisms were explored, and the mechanism of NET formation was also studied by a series of in vitro and in vivo assays.Higher levels of NETs in plasma and tumor tissues were associated with dismal outcome in patients with DLBCL. Furthermore, we identified NETs increased cell proliferation and migration in vitro and tumor growth and lymph node dissemination in vivo. Mechanistically, DLBCL-derived IL8 interacted with its receptor (CXCR2) on neutrophils, resulting in the formation of NETs via Src, p38, and ERK signaling. Newly formed NETs directly upregulated the Toll-like receptor 9 (TLR9) pathways in DLBCL and subsequently activated NFκB, STAT3, and p38 pathways to promote tumor progression. More importantly, disruption of NETs, blocking IL8-CXCR2 axis or inhibiting TLR9 could retard tumor progression in preclinical models.Our data reveal a tumor-NETs aggressive interaction in DLBCL and indicate that NETs is a useful prognostic biomarker and targeting this novel cross-talk represents a new therapeutic opportunity in this challenging disease.
Abstract 12902: The Influences of Obesity on Cardiac Remodeling, Geometric Alteration and Diastolic Patterns in a Large Asian Population With Preserved Ejection Fraction
Authors: Yau-Huei Lai, Kuo-Tzu Sung, Jen-Yuan Kuo, Jia-Yin Hou, Hung-I Yeh, Chung-Lieh Hung
Journal: Circulation (2014)

Introduction: Metabolic syndrome associated with excessive body weight and size is a key feature of preserved ejection fraction heart failure. The aim of this study is to evaluate the potential imp...
Benserazide As a Novel Fetal Hemoglobin Inducer: An Observational Study in Non-Carriers of Hemoglobin Disorders
Authors: Marina Erê A. H. P. Santos, Felipe Vendrame, Alvaro Henrique Junqueira Tavares, Leticia Marani, Paula C. de Azevedo, Luiza G Piovesana, Fernando F. Costa, Kleber Yotsumoto Fertrin
Journal: Blood (2018)
FRI0124 Prevention of extensive bone marrow oedema and consequent rapid radiographic progression by short term usage of biologics in drards resistant patients with early destructive rheumatoid arthritis
Authors: K. Katayama, T. Okubo, T. Sato, R. Fukai, Y. Kon, Y. Makino, S. Kodama, H. Ito
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To investigate possible preventive effect of radiographic joint damage, especially RRP by short term treatment with biologics in non-biological disease-modifying ant-rheumatic drugs(non-bio DMARDs) resistant early RA (Clinical registration number; UMIN-CTR 000013614). <h3>Methods</h3> Fifty early RA patients with extensive BE by hand MRI test despite treatment with non-bio DMARDs were recruited. Among these, 44 patients were diagnosed as RRP. Twenty three patients (male 5, female 18) were treated with combination of non-bio DMARD and biologic DMARDs (Bio group) and 26 patients were treated with enhanced DMARDs therapy using MTX with or without other DMARDs (enhanced DMARDs group). Baseline demographics of both groups were not significantly different (Data not shown). In the Bio group, the following biologics were added: Adalimumab (13 cases), Tocilizumab (3 cases), Abatacept (3 cases), Infliximab (2 cases), Certolizumab (1 case), Golimumab (1 case). In enhanced DMARDs group, mean MTX dose was increased from 7.3 mg/w to 11.3 mg/w or other DMARDs were added. Bone destruction was determined before and 3 or 6 months after treatment by modified total Sharp scoring (mTSS) using by conventional radiography, and expressed as yearly progression of mTSS (ΔmTSS/y). BE score was measured by RAMRIS method using T1 or STIR image of hand MRI (HITACHI, Elis, 0.5T). <h3>Results</h3> Significant reduction in DAS28-ESR values after 3 or 6 months treatment were observed: from 4.2 to 3.3(p=0.0004) in the enhanced DMARDs group, and 4.37 to 3.0(p&lt;0.0001) in the Bio groups. Similarly, improvement of BE: 7 out of 26 (26.9%) and 14 out of 23 patients (60.9%), mean ΔmTSS/y: 5.8 and 2.4, incidence of RRP: 9 (34.6%) and 9 (34.6%), and structural remission: 5 (21.7%) and 16 patients (69.6%), in the enhanced DRAERDs and the Bio group, respectively. Accordingly, improvement of BE and incidence of structural remission was higher, whereas mean ΔmTSS/y value was significantly lower (p&lt;0.05) in the Bio group compared to in the enhanced DMARDs group (table 1, figure 1). <h3>Conclusions</h3> Results of this study indicated that short term (3 or 6 months) treatment with biologics is effective in the reducing BE, and consequently prevent further progression of the disease into RRP status in 80% of early destructive RA despite extensive DMARDs therapy. The effect of withdrawal of biologics in RA improving BE are currently under investigation (figure 1). We consider that a short-term treatment with biologics for early RA patients, who are resistant to DMARDs and at high risk to transit to RRP, will be an effective and economical treatment strategy. <h3>Disclosure of Interest</h3> None declared
Clinical courses of patients with small cell lung cancer after complete resection followed by adjuvant chemotherapy
Authors: Y. Shinno, S. Kanda, J. Sato, R. Morita, Y. Matsumoto, S. Murakami, Y. Goto, H. Horinouchi, Y. Fujiwara, N. Yamamoto, Y. Ohe
Journal: Annals of Oncology (2018)
Individual response variations in scaffold-guided bone regeneration are determined by independent strain- and injury-induced mechanisms
Authors: Natalie Reznikov, Oliver R. Boughton, Shaaz Ghouse, Anne E. Weston, Lucy Collinson, Gordon W. Blunn, Jonathan R.T. Jeffers, Justin P. Cobb, Molly M. Stevens
Journal: Biomaterials (2018)

This study explored the regenerative osteogenic response in the distal femur of sheep using scaffolds having stiffness values within, and above and below, the range of trabecular bone apparent modulus. Scaffolds 3D-printed from stiff titanium and compliant polyamide were implanted into a cylindrical metaphyseal defect 15 × 15 mm. After six weeks, bone ingrowth varied between 7 and 21% of the scaffold pore volume and this was generally inversely proportional to scaffold stiffness. The individual reparative response considerably varied among the animals, which could be divided into weak and strong responders. Notably, bone regeneration specifically within the interior of the scaffold was inversely proportional to scaffold stiffness and was strain-driven in strongly-responding animals. Conversely, bone regeneration at the periphery of the defect was injury-driven and equal in all scaffolds and in all strongly- and weakly-responding animals. The observation of the strain-driven response in some, but not all, animals highlights that scaffold compliance is desirable for triggering host bone regeneration, but scaffold permanence is important for the load-bearing, structural role of the bone-replacing device. Indeed, scaffolds may benefit from being nonresorbable and mechanically reliable for those unforeseeable cases of weakly responding recipients.
IGF-1 receptor cooperates with integrin to promote cervical cancer proliferation and invasion
Authors: Cheng-Yang Chou, Meng-Ru Shen
Journal: Cancer Research (2004)

4347  The pathogenesis of cervical cancer shows multiple stages of progression, from HPV-related cellular growth dysregulation to cervical cancer. However, only a small fraction of those infected by HPV develop cancer, indicating that other factors contribute to the progression to cervical cancer. This study is aimed to identify the specific growth factors which are critically involved in cervical cancer cell invasion and proliferation, and test the hypothesis that adhesion receptors of integrin family and growth factor receptor signalings may cooperate functionally to promote cancer proliferation and invasion. The results demonstrate that cervical cancer SiHa and CaSki cells migrated in response to the stimulation of insulin-like growth factor 1 (IGF-1), epidermal growth factor, and transforming growth factor beta. Dose-response assays done with both cell types established that 50 ng/ml IGF-1 was an optimal concentration for maximal stimulation of tumor invasion. SiHa and CaSki cells presented the better capability of invasion than that of normal epithelial cells in the absence of any stimulation of growth factors. Although IGF-1 modestly stimulated the invasion of normal epithelial cells, the invasive capability of SiHa and CaSki cells was markedly enhanced by IGF-1 stimulation. Furthermore, IGF-1-stimulated invasion was completely inhibited by functional-blocking monoclonal antibody against α-subunit of IGF-1 receptor (IGF-1R), whereas the invasion was unaffected by either IgG or monoclonal antibody to insulin receptor (IR). This indicates that IGF-1-stimulating invasion was specifically mediated through IGF-1R signaling. Functional-blocking monoclonal antibody against integrins αvβ3, but not α2, α3, α4, α6,β1, β4 or α2β1, abolished the IGF-1-stimulating invasion of SiHa and CaSki cells, indicating that αvβ3 integrins might play a critical role in the IGF-1-stimulating invasion of cervical cancer cells. We also studied cell proliferation under various culture conditions, to test whether the growth of cervical cancer cells is regulated by IGF-1. The growth of SiHa and CaSki cells was stimulated dose-dependently by IGF-1, whereas that of normal cervical epithelial cells was not. In addition, the antagonistic monoclonal antibody of IGF-1R, but not IR and IgG, abolished IGF-1-stimulated cancer growth. Blocking αvβ3 integrin occupancy also resulted in attenuation of the cellular proliferation in response to IGF-1 stimulation. In addition, growth retardation induced by monoclonal antibody of IGF-1R or αvβ3 integrin was in parallel by increased ratio of apoptosis, suggesting IGF-1R and αvβ3 integrin mediate the survival factors that inhibit apoptosis. In conclusion, the signalings of IGF-1R and αvβ3 integrin cooperate functionally to promote cervical cancer proliferation and invasion.
SP0150 Functional rehabilitation for the relief of complex persistent pain
Authors: C. Mccabe
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Persistent pain, by definition, is a long-term condition that cannot be resolved by available medical or other treatments. Historically, the focus for pain and rehabilitation specialities has been on management, to improve quality of life and function in the presence of pain. However, most patients seek pain relief. Research by the Bath Pain group, and other published literature indicates that people make hypotheses about bodily feelings based on prior performance and the current environment. This is an active process. Pain related adaptations to the sensory and motor systems ensure we act to minimise potential threats. These adaptations impact on bodily feelings and modify autonomic and limbic systems. The degree of adaptation can be minor and brief, or significant and persistent. Where adaptive mechanisms continue to engage beyond what is deemed as useful, this can be considered hyper-adaptive. I will present clinical evidence of pain related hyper-adaptations that people with persistent pain describe in clinic. For example, perceived changes in the painful limb, ownership, temperature, and size, as well as feelings of peculiarity, discomfort, pain, and altered movement trajectory when motor output does not match expected sensory feedback. People with Rheumatoid Arthritis, Fibromyalgia, Complex Regional Pain Syndrome, or after limb fracture all describe altered body perceptions. Individuals may, for example, perceive a painful hand (and an object held within it), as excessively heavy and enlarged (when in reality it is not), report clumsiness, and difficulty moving the hand due to a perceived inability to 'engage' with it. We have described visual neglect and emotional changes about the painful limb, and consequent impacts on motor and autonomic function. The sensory system encodes the characteristics and location of stimuli and determines if these are harmful or innocuous. This process is impaired in a painful body part. The ability to determine the texture or temperature of materials applied to the painful skin is commonly lost; or non-painful stimuli, such as light touch, are perceived as painful (allodynia). This session will describe work that has focused on aiming to increase our understanding of the pain-related adaptations in sensorimotor processing and associated behaviours, in order to design interventions that help to redefine this hyper-adaptive response, essentially broadening sensorimotor function, and relieving persistent pain. <h3>Disclosure of Interest</h3> None declared
Protein expression of MMP2, TIMP2 in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, and patient survival.
Authors: T. Christopher Windham, Gina Z. D’Amato, Elizabeth A. Keschman, Subhra Mohapatra, Audrey C. Burns, Daniel Sullivan, G. Douglas Letson, Rich Jove, W. Jack Pledger
Journal: Cancer Research (2006)

5009   Background/Aims: Matrix metalloproteinase-2 (MMP-2) is involved in the processes of tumor invasion and metastasis. However, studies on MMP-2 and tissue inhibitor of MMP-2 (TIMP-2) in hepatocellular carcinoma (HCC) are rare, and there are no studies on the correlations with these expressions and HCC patient’s suvival. Methods : We immunohistochemically examined the expression of these proteins and the relationships between these expressions and histological grade, clinicopathological parameters and patient’s survival in 106 patients with HCC. We also examined gelatin zymography and western blotting, using 12 fresh samples of HCC. Results : MMP-2 and TIMP-2 immunoreactivities were presented in HCC cells as well as in non-HCC cells. MMP-2 expression significantly correlated with TIMP-2 expression, and these expressions were stronger in non-tumorous lesions than in tumor lesions. These immunohistochemical results were nearly consistent with the results of western blotting. MMP-2 expression significantly correlated with HCC grade. Though there were no relations between the MMP-2 or TIMP-2 expression and several clinicopathological parameters, overexpressions of MMP-2 and TIMP-2 were associated with poor prognosis of HCC’s patients. Moreovre, TIMP-2 expression was identified as the best predictive factor for determining the prognosis in patients with HCC. Conclusion : MMP-2 and TIMP-2 are involved in HCC progression, and their overexpression is associated with poor prognosis.
Social Media and Gender Equity in Oncology
Authors: Miriam A. Knoll, Reshma Jagsi
Journal: JAMA Oncology (2018)

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Abstract 15995: Survival and Reintervention After Pulmonary Valve Replacement in Tetralogy of Fallot
Authors: Anna Sabate Rotes, Harold M Burkhart, Benjamin W Eidem, Jordan K Rosedahl, Crystal R Bonnichsen, Hartzell V Schaff, Joseph A Dearani
Journal: Circulation (2013)

Background: Surgical pulmonary valve replacement (PVR) in previously repaired tetralogy of Fallot (TOF) is frequently required. There are few data on large numbers of patients with long follow-up. ...