tbuckley/cabot-search huggingface dataset:
Abstract 13428: The Long-term Therapy With Low-dose Aspirin Did Not Reduce Cardiovascular Events in Patients With Type 2 Diabetes in Primary Prevention Setting: 10-year Follow-up of a Randomized Controlled Trial
Authors: Yoshihiko Saito, Sadanori Okada, Hisao Ogawa, Hirofumi Soejima, Mio Sakuma, Masafumi Nakayama, Naofumi Dohi, Hideaki Jinnouchi, Masako Waki, Takeshi Morimoto
Journal: Circulation (2016)

Introduction: It takes long time to conclude efficacy and safety of an intervention on primary prevention of cardiovascular events. Up to date, there is no study to investigate the effect of the low-dose aspirin therapy on primary prevention of cardiovascular events in patients with diabetes with a follow-up period longer than 10 years. Hypothesis: The long-term therapy with low-dose aspirin prevents cardiovascular events in patients with diabetes and no pre-existing cardiovascular diseases. Methods: The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized controlled trial to examine whether the low-dose aspirin therapy reduces cardiovascular events in 2,539 Japanese patients with type 2 diabetes. The original JPAD trial reported that the low-dose aspirin therapy did not reduce cardiovascular events for a median of 4.4 years. After the JPAD trial was completed in 2008, we followed the patients until July 2015. In this period, the low-dose aspirin therapy was decided by each physician. We analyzed the effect of low-dose aspirin on incidence of cardiovascular events, according to the per-protocol principle. Results: The median follow-up period was 10.3 years, and 2,160 (85 %) patients remained the original allocation. The low-dose aspirin therapy did not reduce cardiovascular events based on the per-protocol cohort (HR, 1.14; 95% CI, 0.91 - 1.42; Figure). Cox proportional hazard models showed similar results (HR, 1.04; 95% CI, 0.83 - 1.30), adjusting age, sex, HbA1c, eGFR, history of smoking, and presence of hypertension and dyslipidemia. There were 54 (5%) hemorrhagic events in the aspirin group, and 72 (6%) in the no aspirin group ( P = 0.5). Sensitivity analyses on the intention-to-treat cohort showed the similar results (HR, 1.01; 95% CI: 0.82 - 1.25). Conclusions: The low-dose aspirin therapy did not reduce cardiovascular events in patients with type 2 diabetes in primary prevention setting for 10-year follow-up.
Targeted iron nanoparticles with platinum-(IV) prodrugs and anti-EZH2 siRNA show great synergy in combating drug resistance in vitro and in vivo
Authors: Chang Yu, Binbin Ding, Xinyang Zhang, Xiaoran Deng, Kerong Deng, Ziyong Cheng, Bengang Xing, Dayong Jin, Ping'an Ma, Jun Lin
Journal: Biomaterials (2017)
Cas groupés de coqueluche détecté via la surveillance active à Chypre en 2003
Authors: M Theodoridou, A Hadjipanagis, N Persianis, S Makri, C Hadjichristodoulou
Journal: Eurosurveillance (2007)

La coqueluche est une maladie d’importance considerable sur le plan de la sante publique mais elle ne beneficie toujours pas d’un systeme de surveillance efficace. Depuis 1930, c’est une maladie a declaration obligatoire a Chypre dont l’incidence s’etablit a 1 pour 100 000 personnes au cours des 10 dernieres annees.
Abstract 20870: Impact of Lead-Related Tricuspid Regurgitation in Patients With Heart Failure and Implantable Cardioverter-Defibrillator or Cardiac Resynchronization Therapy
Authors: Yeonjeong Park, Jae-Sun Uhm, Hee-Tae Yu, Pil-Sung Yang, Jaewon oh, Tae-Hoon Kim, Boyoung Joung, Hui-Nam Pak, Seok-Min Kang, Moon-Hyoung Lee
Journal: Circulation (2017)

Introduction: Implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) have a survival benefit for a certain group of patients with heart failure. However, implantab...
TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and leukemic clearance
Authors: Yinmeng Yang, M. Eric Kohler, Christopher D. Chien, Christopher T. Sauter, Elad Jacoby, Chunhua Yan, Ying Hu, Kelsey Wanhainen, Haiying Qin, Terry J. Fry
Journal: Science Translational Medicine (2017)

TCR engagement induces CD8 CAR T cell exhaustion and poor in vivo functionality in mice.
Pembrolizumab in patients with advanced/metastatic acral lentiginous melanoma
Authors: H. Loong, C. Yuen, F. Mo, T-C Chan, K.W.C. Lee, A.C.Y. Chan, A.C.Y. Wong, K.C.W. Wong, C-M Lam, J. Tong, C.K.H. Wong, W. Yeo
Journal: Annals of Oncology (2017)
Complete cure of advanced hepatocellular carcinoma with right adrenal gland metastasis and portal vein thrombosis by multiple applications of an interdisciplinary therapy: case report with 8-year follow up
Authors: Hojung Jung, Byung Ik Kim, Yong Kyun Cho, Woo Kyu Jeon, Hong Joo Kim, Hyun Pyo Hong
Journal: Clinical and Molecular Hepatology (2017)

Hepatocellular carcinoma (HCC) is the sixth most common cause of death worldwide and the main cause of primary liver cancer. The principle problem of HCC is the poor prognosis, since advanced HCC reportedly has a median survival of only 9 months. The standard therapies are sorafenib and regorafenib, but the outcomes remain unclear. We report a 60-year-old man with advanced HCC with right adrenal gland metastasis and portal vein tumor thrombosis, who showed a complete response to multiple applications of an interdisciplinary therapy.
Patients’ preferences for adjuvant sorafenib after resection of renal cell carcinoma in the SORCE trial: what makes it worthwhile?
Authors: P.L. Blinman, I.D. Davis, A. Martin, S. Troon, S. Sengupta, E. Hovey, X. Coskinas, R. Kaplan, A. Ritchie, A. Meade, T. Eisen, M.R. Stockler
Journal: Annals of Oncology (2017)
Correlation of Opioid Mortality with Prescriptions and Social Determinants: A Cross-sectional Study of Medicare Enrollees
Authors: Christos A. Grigoras, Styliani Karanika, Elpida Velmahos, Michail Alevizakos, Myrto-Eleni Flokas, Christos Kaspiris-Rousellis, Ioannis-Nektarios Evaggelidis, Panagiotis Artelaris, Constantinos I. Siettos, Eleftherios Mylonakis
Journal: Drugs (2017)
Outcome of patients with relapsed/refractory acute lymphoblastic leukemia after blinatumomab failure: No change in the level of CD19 expression
Authors: Elias Jabbour, Johannes Düll, Musa Yilmaz, Joseph D. Khoury, Farhad Ravandi, Nitin Jain, Hermann Einsele, Guillermo Garcia‐Manero, Marina Konopleva, Nicholas J. Short, Philip A. Thompson, William Wierda, Naval Daver, Jorge Cortes, Susan O'brien, Hagop Kantarjian, Max S. Topp
Journal: American Journal of Hematology (2017)

Blinatumomab, a bi-specific T-cell engaging CD3-CD19 antibody construct, has shown significant activity in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). Despite this improvement, most patients relapse. Here, we describe the outcome of 68 patients with R/R ALL after failure of blinatumomab therapy: 38 (56%) blinatumomab refractory; 30 (44%) relapsing after initial response. After a median follow-up of 49 months, 9 (13%) patients remained alive. The median overall survival after blinatumomab failure was 5.2 months. At the time of failure, among 61 patients evaluated for immunophenotype, 56 (92%) had CD19-positive blasts; only five (8%) had ALL recurrence with CD19-negative disease. Two patients progressed with lower CD19 expression. In summary, the outcome of patients with R/R ALL after blinatumomab failure is poor and treatment of these patients remains an unmet medical need. Our findings indicate that blinatumomab therapy would not exclude a significant number of patients from the potential benefit of subsequent CD19-directed therapies such as chimeric antigen receptor T-cell therapy.
Clonal evolution of a lethal prostate cancer: Integrated whole genome analysis case study
Authors: Kallio Hml., M Annala, K Kivinummi, G Hognas, G Gundem, D C Wedge, P Van Loo, H Heyn, M R Emmert-Buck, W B Isaacs, M Esteller, U McDermott, M Nykter, T Visakorpi, G S Bova
Journal: Cancer Research (2015)
Para uma profilaxia padrão pós-exposição ao VIH para trabalhadores de cuidados de saúde na Europa
Authors: V Puro, S Cicalini, G De Carli, F Soldani, G Ippolito
Journal: Eurosurveillance (2004)

Em toda a Europa se utiliza profilaxia anti-retroviral apos exposicao profissional (PEP) ao VIH em trabalhadores de cuidados de saude (HCWs), mas tal nao e feito de forma consistente. Um painel de peritos, financiado pela Comissao Europeia, formulou um conjunto de recomendacoes. 
Quando seja decidido que as caracteristicas da exposicao indicam a instituicao de PEP, esta deve ser iniciada o mais rapidamente possivel; a instituicao esta desaconselhada depois das 72 horas. PEP deve ser instituida por rotina com qualquer combinacao tripla de anti-retrovirais aprovada para o tratamento de doentes infectados pelo VIH; deve preferir-se um regime de duas classes de farmacos. Deve procurar-se obter a historia terapeutica do doente fonte. Deve efectuar-se aconselhamento, apoio psicologico, teste do VIH e avaliacao clinica na linha de base, as 6-8 semanas e pelo menos 6 meses apos a exposicao. Deve considerar-se monitorizacao clinica e laboratorial adicional decorridas uma e duas semanas, dado que a adesao ao tratamento e sua tolerância podem provocar reaccoes adversas e potencial toxicidade. Nao se recomenda a realizacao por rotina de testes de resistencia ao VIH no doente fonte e ensaios virais directos no HCW exposto.
Reduction of body iron in HFE -related haemochromatosis and moderate iron overload (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial
Authors: Sim Y Ong, Lyle C Gurrin, Lara Dolling, Jeanette Dixon, Amanda J Nicoll, Michelle Wolthuizen, Erica M Wood, Gregory J Anderson, Grant A Ramm, Katrina J Allen, John K Olynyk, Darrell Crawford, Louise E Ramm, Paul Gow, Simon Durrant, Lawrie W Powell, Martin B Delatycki
Journal: The Lancet Haematology (2017)
Abstract 9304: Chain Length and Saturation of Primary Dietary Fats Mediate Impaired or Preserved Triglyceride Dynamics and Contractility in Decompensated Hearts
Authors: Ryan Lahey, E. Douglas Lewandowski
Journal: Circulation (2012)

Oxidation of long chain fatty acids (LCFA) provides approximately 70% of ATP in the heart. Alternatively, LCFAs incorporate into the endogenous lipid pool as triacylglyceride (TAG). The dynamic process of TAG turnover, a source of LCFA for beta-oxidation and nuclear receptor activation, is reduced in cardiac hypertrophy. The current study tested the hypothesis that LCFA storage kinetics are influenced by acyl chain composition by comparing incorporation of two major plasma LCFAs, palmitate (16-carbon, saturated) and oleate (18-carbon, monounsaturated), into the TAG pool of sham operated control (SHAM) and hypertrophied (HYP) rat hearts. Isolated hearts were perfused with buffer containing 5 mM glucose, 1 mM lactate and 0.4 mM of either 13C-palmitate or 13C-oleate. Sequential 13C NMR of intact hearts and endpoint LC/MS enabled quantitation of TAG dynamics. With palmitate, HYP hearts contained 48% less TAG vs SHAM (P&lt;0.01), while oleate maintained similar TAG in HYP and SHAM. LCFA incorporation into TAG displayed two distinct kinetic components: a saturable exponential, reflecting LCFA uptake, and a linear component, reflecting TAG turnover. Time contants of the exponential uptake phase reflected similar rates of uptake of either LCFA in SHAM and HYP. However, HYP displayed reduced TAG turnover with palmitate (HYP: 46.7 +/- 12.2 nmol/gdw/min, SHAM: 84.3 +/- 4.9; P&lt;0.01), while oleate supported similarly elevated turnover in both groups (HYP: 140.4 +/- 11.2 nmol/gdw/min, SHAM: 143.9 +/- 15.6). Work output (rate-pressure-product) was reduced simlarly in HYP with either LCFA. In contrast, oleate supported greater contractility than palmitate in HYP for both +dP/dt (25%) and -dP/dt (23%) (P&lt;0.05), despite no differences in the contribution of either LCFA to beta-oxidation. These data demsontrate the influence of FA composition on TAG turnover in both normal and hypertrophied myocardium, with oleate being more readily incorporated into TAG than palmitate. The findings link reduced TAG turnover rates to impaired dP/dt which can be mediated by LCFA species. Furthermore, oleate confers improved lipid content and storage dynamics in comparison to palmitate in the setting of pressure-overload hypertrophy, which are linked to cardiac contractility.
Desacetylvinblastine Monohydrazide Disrupts Tumor Vessels by Promoting VE-cadherin Internalization
Authors: Xueping Lei, Minfeng Chen, Maohua Huang, Xiaobo Li, Changzheng Shi, Dong Zhang, Liangping Luo, Youwei Zhang, Nan Ma, Heru Chen, Huafeng Liang, Wencai Ye, Dongmei Zhang
Journal: Theranostics (2017)

Vinca alkaloids, the well-known tubulin-binding agents, are widely used for the clinical treatment of malignant tumors. However, little attention has been paid to their vascular disrupting effects, and the underlying mechanisms remain largely unknown. This study aims to investigate the vascular disrupting effect and the underlying mechanisms of vinca alkaloids. Methods: The capillary disruption assay and aortic ring assay were performed to evaluate the in vitro vascular disrupting effect of desacetylvinblastine monohydrazide (DAVLBH), a derivate of vinblastine, and the in vivo vascular disrupting effect was assessed on HepG2 xenograft model using magnetic resonance imaging, hematoxylin and eosin staining and immunohistochemistry. Tubulin polymerization, endothelial cell monolayer permeability, western blotting and immunofluorescence assays were performed to explore the underlying mechanisms of DAVLBH-mediated tumor vascular disruption. Results: DAVLBH has potent vascular disrupting activity both in vitro and in vivo. DAVLBH disrupts tumor vessels in a different manner than classical tubulin-targeting VDAs; it inhibits microtubule polymerization, promotes the internalization of vascular endothelial cadherin (VE-cadherin) and inhibits the recycling of internalized VE-cadherin to the cell membrane, thus increasing endothelial cell permeability and ultimately resulting in vascular disruption. DAVLBH-mediated promotion of VE-cadherin internalization and inhibition of internalized VE-cadherin recycling back to the cell membrane are partly dependent on inhibition of microtubule polymerization, and Src activation is involved in DAVLBH-induced VE-cadherin internalization. Conclusions: This study sheds light on the tumor vascular disrupting effect and underlying mechanisms of vinca alkaloids and provides new insight into the molecular mechanism of tubulin-targeting VDAs.
Magnetic Nanowire Networks for Dual-Isolation and Detection of Tumor-Associated Circulating Biomarkers
Authors: HyungJae Lee, Mihye Choi, Jiyun Lim, Minkyung Jo, Ji-Youn Han, Tae Min Kim, Youngnam Cho
Journal: Theranostics (2017)

Purpose: Recent developments in genomic and molecular methods have revolutionized the range of utilities of tumor-associated circulating biomarkers in both basic and clinical research. Herein, we present a novel approach for ultrasensitive extraction of cfDNA and CTCs, at high yield and purity, via the formation of magnetic nanowire networks. Materials and Methods: We fabricated and characterized biotinylated cationic polyethylenimine and biotinylated antibody cocktail-conjugated magnetic polypyrrole NWs (PEI/mPpy NW and Ab cocktail/mPpy NW, respectively). We applied these NWs to the extraction of cfDNA and CTC from the blood of 14 patients with lung cancer. We demonstrated reliable detection of EGFR mutations based on digital droplet PCR analysis of cfDNA and CTC DNA from patients with lung cancer. Results: The NW networks confined with a high density of magnetic nanoparticles exhibited superior saturation magnetization, which enabled rapid and high-yield capture whilst avoiding or minimizing damage and loss. The NW networks enabled the co-isolation of CTCs and cfDNA of high quality and sufficient quantities, thus allowing the amplification of rare and low-prevalence cancer-related mutations. Conclusion: The simple, versatile, and highly efficient nanowire network tool allows sensitive and robust assessment of clinical samples.
The malleability of linguistic representations poses a challenge to the priming-based experimental approach
Authors: Rachel Ryskin, Sarah Brown-Schmidt
Journal: Behavioral and Brain Sciences (2017)

Abstract Recent findings show that experience with a syntactic structure has long-term consequences for how that structure will be processed in the future, which suggests that linguistic representations are not static entities that can be probed reliably without alteration. Thus, leveraging the effect of previous exposure to a syntactic structure appears to be an inappropriate method for studying invariant properties of language.
Achilles tendon rupture: the evaluation and outcome of percutaneous and minimally invasive repair
Authors: Michael R Carmont
Journal: British Journal of Sports Medicine (2018)

My thesis looked at optimising the outcome of patients following percutaneous and minimally invasive repair following Achilles tendon rupture.

Early studies on the management of Achilles tendon ruptures used complications as a primary outcome measure. Recent randomised controlled trials have shown no difference in patient-reported outcome measure (PROM) but patients are weaker after non-operative treatment compared with operative repair.

Following Achilles tendon rupture treated with percutaneous repair, the majority of patients have excellent/good outcome scores but many of these patients had alteration to the resting posture of the ankle joint, which may represent elongation of the Achilles tendon, causing the plantar flexion weakness (figure 1). I wanted to investigate this.



Figure 1 
This police officer returned to active duty and competitive recreational netball reporting an Achilles tendon Total Rupture Score of 97 points at 12 months following operative …
P2.04-010 Afatinib in Combination with Pembrolizumab in Patients with Stage IIIB/IV Squamous Cell Carcinoma (SCC) of the Lung
Authors: J. Riess, J. Bennouna, L. Paz-Ares, M. Chisamore, C. Lybeck Lind, B. Sadrolhefazi, B. Levy
Journal: Journal of Thoracic Oncology (2017)
Presenza endemica del sierotipo Cerro di Salmonella enterica in Italia meridionale
Authors: C Mammina, L Cannova, S CarfiPavia, A Nastasi
Journal: Eurosurveillance (2000)

La tipizzazione molecolare dei ceppi di salmonella isolati in Italia meridionale tra il 1997 e il 1999, condotta dal Centro per gli Enterobatteri Patogeni dell'Italia Meridionale, ha mostrato un'elevata frequenza di Salmonella enterica col sierotipo Cerro. Questo sierotipo e estremamente raro tra gli esseri umani poiche predomina ampiamente il ribotipo rt2. Gli autori esaminano l'ipotesi che questo sierotipo si stia diffondendo nella Sicilia orientale e sollecitano un'attenta sorveglianza sul fenomeno.
Abstract 16086: Impact of Statin Prescription and Intensity at Discharge After an Atherosclerotic Cardiovascular Event (ASCVD)—Real-World Experience in a Large Integrated Healthcare System: The IMPRES Study
Authors: Jeffrey L Anderson, Kirk U Knowlton, Heidi T May, Tami L Bair, Donald L Lappé, Joseph B Muhlestein
Journal: Circulation (2017)

Introduction: Statins are indicated for ASCVD, with high versus moderate intensity dosing determined by age and tolerance. However, multiple surveys have found large treatment gaps in clinical appl...
Abstract 11442: Prevalence and Prognostic Significance of Early Repolarisation in Patients With Idiopathic VF
Authors: Peter Larsen, Bijia Shi, Scott Harding
Journal: Circulation (2012)

Background:  While some studies have argued that an early repolarisation ECG pattern in idiopathic VF patients is associated with increased risk of tachyarrhythmia, others have failed to observe this relationship. This study compared the frequency of early repolarisation patterns between idiopathic VF patients and patients receiving ICDs with an ischaemic etiology, and examined the prognostic significance of early replorisation ECG patterns.   Methods:  All patients receiving a new ICD during 2008-2011 were reviewed. All idiopathic VF patients were included, and matched to randomly selected patients with ischaemic etiologies. Pre-implant ECGs were examined for the presence of J waves and elevated J points.   Results:  During the study period 258 patients were implanted with new ICD systems. Of these, 26 (10%) were classified as having idiopathic VT/VF. In the idiopathic VF group 10 (39%) had J waves and a further 7 (27%) had an elevated J point, so in total 17 (65%) had evidence of an early repolarisation abnormality. In 26 patients with an ischaemic etiology, 6 (23%) had J waves and a further 10 (39%) had an elevated J point, and in total 16 (62%) had evidence of an early repolarisation abnormality. Median follow-up was 22 months, and in this time 14 (27%) patients had received appropriate therapy from their device, 5 (19%) from the idiopathic VF group and 9 (35%) from the ischaemic group. The rate of therapy was not significantly different between the two groups (hazard ratio (HR) 0.52, 95% confidence intervals (CI) 0.2-1.5), and the presence of J waves (HR 1.4, CI 0.4-4.7), or any early repolarisation (HR 1.04, CI 0.30-3.5) was not associated with an increased risk of appropriate therapy.   Conclusions:  While early repolarisation abnormalities may be common in patients with idiopathic VT/VF, they are as common in ICD patients with an underlying ischaemic etiology. We did not observe early repolarisation abnormalities to be associated with an increased risk of device therapy.
Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis
Authors: Arthur Kavanaugh, Ronald F van Vollenhoven, Roy Fleischmann, Paul Emery, Iain Sainsbury, Stefan Florentinus, Su Chen, Benoît Guérette, Hartmut Kupper, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To compare responses in patients with early rheumatoid arthritis (RA) initially treated with the tumour necrosis factor inhibitor (TNFi) adalimumab+methotrexate (MTX) versus MTX monotherapy who may have continued receiving MTX or switched to adalimumab rescue therapy after inadequate response to MTX. Methods OPTIMA enrolled MTX-naive patients with active RA for &lt;1 year. This post hoc analysis determined the proportion of patients, stratified by initial treatment, who achieved 28-joint modified Disease Activity Score based on C reactive protein &lt;3.2, normal function and/or no radiographic progression at weeks 26, 52 and 78. Results Significantly greater proportions of patients initially treated with adalimumab+MTX (n=466) compared with MTX monotherapy (n=460) achieved good clinical (53% vs 30%), functional (45% vs 33%) and radiographic (87% vs 72%) outcomes at week 26. From weeks 26 to 78, adalimumab rescue patients achieved similar clinical and functional outcomes versus patients initially treated with adalimumab+MTX. However, significantly more patients initially treated with adalimumab+MTX had no radiographic progression at weeks 52 and 78 versus patients initially treated with MTX (both timepoints: 86% vs 72%). Conclusions In early RA, starting with MTX monotherapy and adding TNFi after 26 weeks yields similar longer term clinical results as starting with TNFi+MTX combination therapy but allows a small but significant accrual of radiographic damage.