tbuckley/cabot-search huggingface dataset:
Protein kinase A determines platelet life span and survival by regulating apoptosis
Authors: Lili Zhao, Jun Liu, Chunyan He, Rong Yan, Kangxi Zhou, Qingya Cui, Xingjun Meng, Xiaodong Li, Yang Zhang, Yumei Nie, Yang Zhang, Renping Hu, Yancai Liu, Lian Zhao, Mengxing Chen, Weiling Xiao, Jingluan Tian, Yunxiao Zhao, Lijuan Cao, Ling Zhou, Anning Lin, Changgeng Ruan, Kesheng Dai
Journal: Journal of Clinical Investigation (2017)

Apoptosis delimits platelet life span in the circulation and leads to storage lesion, which severely limits the shelf life of stored platelets. Moreover, accumulating evidence indicates that platelet apoptosis provoked by various pathological stimuli results in thrombocytopenia in many common diseases. However, little is known about how platelet apoptosis is initiated or regulated. Here, we show that PKA activity is markedly reduced in platelets aged in vitro, stored platelets, and platelets from patients with immune thrombocytopenia (ITP), diabetes, and bacterial infections. Inhibition or genetic ablation of PKA provoked intrinsic programmed platelet apoptosis in vitro and rapid platelet clearance in vivo. PKA inhibition resulted in dephosphorylation of the proapoptotic protein BAD at Ser155, resulting in sequestration of prosurvival protein BCL-XL in mitochondria and subsequent apoptosis. Notably, PKA activation protected platelets from apoptosis induced by storage or pathological stimuli and elevated peripheral platelet levels in normal mice and in a murine model of ITP. Therefore, these findings identify PKA as a homeostatic regulator of platelet apoptosis that determines platelet life span and survival. Furthermore, these results suggest that regulation of PKA activity represents a promising strategy for extending platelet shelf life and has profound implications for the treatment of platelet number-related diseases and disorders.
AB0165 The efficacy of corticosteroid infiltration and physiotherapy in painful shoulder
Authors: M Bonilla-Hernán, P Aguado, E De Miguel-Mendieta, F Diaz, A Villalba-Yllan, E Martín-Mola
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The efficacy of coticosteroid infiltration and physiotherapy in painful shoulder. <h3>Objectives</h3> To analyse the efficacy of corticosteroid infiltration versus physiotherapy in painful shoulder. <h3>Methods</h3> We studied 36 consecutive patients with painful shoulder (mean age 59 years, range 33–79;29 females, 7 males) without inflammatory arthropaty or traumatic events. All patients were evaluated by a clinical protocol that included: pain scale, range of joint motion, shoulder pain disability index (SPADI), ASES cumulative ADL score (ASES), and ultrasonography exploration at basal visit and at the end of treatment. Patients were treated either with steroidal injection (n = 18) or physiotherapy including electrotherapy and exercises (n = 18). Patients, in both groups, were allow to take analgesics or NSAIDs. Statistical assay was done with paired t-student test and Wilcoxon test. <h3>Results</h3> Infiltration therapy improved pain scale***, abduction**, flexion***, external rotation***, SPADI***, ASES*** and ultrasonographic thickness of biceps tendon*, infraspinous tendon*, subacromio-subdeltoid bursitis* and acromioclavicular joint*. Phisiotherapy improved extension**, external rotation***, ASES* and thickness of supraspinatus tendon*** by ultrasonography. When we studied only patients with ultrasonographic findings of tendinits (n = 25), infiltration (13) improved pain scale**, abbduction**, flexion**, external rotation***, SPADI*** and ASES***, however physiotherapy (n = 12) only improved external rotation***. In patients who had tendinous tears (n = 12), statistical analysis was not significant. <h3>Conclusion</h3> Steroidal infiltration has been shown to be more efficacious than physiotherapy when several parameters like pain, range of motion and functional capacity, were measured. *p &lt; 0.05,**p &lt; 0.01,***p &lt; 0.001.
Detection of Treatment Success after Photodynamic Therapy Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging
Authors: Tom J. L. Schreurs, Igor Jacobs, Klaas Nicolay, Jeanine J. Prompers, Gustav J. Strijkers
Journal: Theranostics (2017)

Early evaluation of response to therapy is crucial for selecting the optimal therapeutic follow-up strategy for cancer patients. PDT is a photochemistry-based treatment modality that induces tumor tissue damage by cytotoxic oxygen radicals, generated by a pre-injected photosensitive drug upon light irradiation of tumor tissue. Vascular shutdown is an important mechanism of tumor destruction for most PDT protocols. In this study, we assessed the suitability of Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to evaluate treatment efficacy within a day after photodynamic therapy (PDT), using the tumor vascular response as a biomarker for treatment success. Methods: DCE-MRI at 7 T was used to measure the micro-vascular status of subcutaneous colon carcinoma tumors before, right after, and 24 h after PDT in mice. Maps of the area under the curve (AUC) of the contrast agent concentration were calculated from the DCE-MRI data. Besides, tracer kinetic parameters including Ktrans were calculated using the standard Tofts-Kermode model. Viability of tumor tissue at 24 h after PDT was assessed by histological analysis. Results: PDT led to drastic decreases in AUC and Ktrans or complete loss of enhancement immediately after treatment, indicating a vascular shutdown in treated tumor regions. Histological analysis demonstrated that the treatment induced extensive necrosis in the tumors. For PDT-treated tumors, the viable tumor fraction showed a strong correlation (ρ ≥ 0.85) with the tumor fraction with Ktrans > 0.05 min-1 right after PDT. The viable tumor fraction also correlated strongly with the enhanced fraction, the average Ktrans , and the fraction with Ktrans > 0.05 min-1 at 24 h after PDT. Images of the viability stained tumor sections were registered to the DCE-MRI data, demonstrating a good spatial agreement between regions with Ktrans > 0.05 min-1 and viable tissue regions. Finally, 3D post-treatment viability detection maps were constructed for the tumors of three mice by applying a threshold (0.05 min-1) to Ktrans at 24 h after PDT. As a proof of principle, these maps were compared to actual tumor progression after one week. Complete tumor response was correctly assessed in one animal, while residual viable tumor tissue was detected in the other two at the locations where residual tumor tissue was observed after one week. Conclusion: This study demonstrates that DCE-MRI is an effective tool for early evaluation of PDT tumor treatment.
Abstract 15798: Yield of Echocardiograms Using Appropriate Use Criteria in an Outpatient Pediatric Cardiology Clinic at an Urban Community Hospital
Authors: Ramya Deepthi Billa, Lida Zeinali, Susan Szpunar, Premchand Anne
Journal: Circulation (2016)

Introduction:  Appropriate Use Criteria (AUC) were published in 2014 to help clinicians determine the need for echocardiograms in an outpatient setting. One hundred thirteen indications were identified based on common clinical scenarios. A separate, independent rating panel evaluated each indication using a scoring scale of 1 to 9, thereby designating each indication as “Appropriate” (A, median score 7 to 9), “May Be Appropriate” (M, median score 4 to 6), or “Rarely Appropriate” (R, median score 1 to 3). Fifty-three indications were identified as Appropriate, 28 as May Be Appropriate, and 32 as Rarely Appropriate.   Objectives:  1. To determine the yield of echo for indications that meet three different sets of criteria, before the publication of AUC; 2. To identify the predictors and reasons of an abnormal echo among the patients falling into 3 different criteria (A, M, R).   Methods:  This was a descriptive chart review of 581 patients who had their first echocardiogram for various indications during the years 2011-2014. Results were analyzed by Pearson’s chi-square test.   Results:  The overall yield was 10%. Female gender (23.1%) had the higher overall yield compared to male (8.8%) (p=0.002). Yield for the A criteria was 15.4%, for M criteria was 8.5%, and for R criteria was 5.4% (p=0.001). Patients ages zero-3 months (67.6%) and 4-11 months (66.7%) had the highest yields in the A criteria group with a yield of 1.5% in the 12-18 years age group (p   Conclusions:  Yield was higher in patients with indications meeting appropriate criteria per AUC, especially among the younger age groups. AUC use in the future, when ordering echocardiograms by pediatric cardiologists, may contribute to a higher yield in the outpatient setting.
TCT-376 Prognostic value of non-ischemic Fractional Flow Reserve in Patients with multi-vessel intermediate grade coronary stenosis
Authors: Hussain Ibrahim, Wasiq Zaidi, Yussr Ibrahim, Muhammad Choudhry, Adnan Khan, Mohamed Almahmoud, Saad Sikanderkhel, Wissam Khalife, Umamahesh Rangasetty, Syed Gilani
Journal: Journal of the American College of Cardiology (2017)
PS01.08: ABOUND.PS2 Interim Safety Results: nab -Paclitaxel/Carboplatin Followed by nab -Paclitaxel in NSCLC Patients with ECOG PS of 2
Authors: Ajeet Gajra, Haythem Ali, Katayoun I. Amiri, Nagla A. Karim, Marc R. Matrana, Deborah Mulford, Teng J. Ong, Alexandra Sanford, Edgardo S. Santos, Mark A. Socinski, David R. Spigel
Journal: Journal of Thoracic Oncology (2016)
Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II
Authors: L. Thorlacius, A. Garg, J.R. Ingram, B. Villumsen, P. Theut Riis, A.B. Gottlieb, J.F. Merola, R. Dellavalle, C. Ardon, R. Baba, F.G. Bechara, A.D. Cohen, N. Daham, M. Davis, L. Emtestam, P. Fernández-Peñas, M. Filippelli, A. Gibbons, T. Grant, S. Guilbault, S. Gulliver, C Harris, C. Harvent, K. Houston, J.S. Kirby, L. Matusiak, A. Mehdizadeh, T. Mojica, M. Okun, D. Orgill, L. Pallack, A. Parks-Miller, E.P. Prens, S. Randell, C. Rogers, C.F. Rosen, S.E. Choon, H.H. van der Zee, R. Christensen, G.B.E. Jemec
Journal: British Journal of Dermatology (2017)

A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items.To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains.The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey.Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments.The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.
TCT-528 Use of guideline directed medical therapy and outcomes in patients with high risk of bleeding undergoing percutaneous coronary intervention in contemporary clinical practice
Authors: Sabato Sorrentino, Usman Baber, Jaya Chandrasekhar, Serdar Farhan, Zhen Ge, Birgit Vogel, Samantha Sartori, Jason Kovacic, Pedro Moreno, Javed Suleman, Pooja Vijay, Clayton Snyder, Madhav Sharma, Hannah Levine, Gennaro Giustino, Annapoorna Kini, Samin Sharma, Roxana Mehran
Journal: Journal of the American College of Cardiology (2017)
TCT-279 Baseline and dobutamine stress hemodynamic physiology of the stenotic aortic valve before and after transcatheter valve implantation
Authors: Nils Johnson, Jo Zelis, Pim Tonino, Patrick Houthuizen, Frederik Zimmermann, Arthur Bouwman, Guus Brueren, Daniel Johnson, Jacques J. Koolen, Erik Korsten, Inge Wijnbergen, Richard L. Kirkeeide, Nico Pijls, K. Lance Gould
Journal: Journal of the American College of Cardiology (2017)
Guías BICHAT para el manejo clínico de la tularemia y de la tularemia relacionada con el bioterrorismo
Authors: P Bossi, A Tegnell, A Baka, F van Loock, A Werner, J Hendriks, H Maidhof, G Gouvras
Journal: Eurosurveillance (2004)

Francisella tularensis es una de las bacterias patogenas mas infecciosas de cuantas se conocen: basta con inocular o inhalar 10 organismos para iniciar la infeccion humana. La tularemia por inhalacion tras un ataque biologico con una cepa virulenta de F.
Pet rodents as possible risk for leptospirosis, Belgium and France, 2009 to 2016
Authors: Marcella Mori, Pascale Bourhy, Marine Le Guyader, Marjan Van Esbroeck, Zorée Djelouadji, Alexandra Septfons, Angeli Kodjo, Mathieu Picardeau
Journal: Eurosurveillance (2017)

Leptospirosis is an under-reported and emerging zoonotic disease which is potentially fatal in humans. Rodents are the main reservoirs for pathogenic Leptospira spp., but diagnosis in these animals is difficult, and their infection, which does not induce symptoms, usually goes unoticed. Although the exposures of most human cases of leptospirosis are poorly documented, we were able to identify six human cases of leptospirosis which were associated with direct contact with pet rodents (mice or rats) in Belgium and France between 2009 and 2016. All cases had severe disease and for all, the presence of Leptospira spp. DNA in the kidneys of their pet animals was confirmed, strongly suggesting that excretion of leptospires in urine was the way of transmission. Half of the cases shared the serogroup Icterohaemorrhagiae, which is usually associated with severe disease, with the pet rats which they were in contact with. With the popularity of rats and mice as pets, this study should contribute to raising awareness on asymptomatic pet rodents as a source of Leptospira infections.
Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea
Authors: Carolina Cubillos-Zapata, Jose Avendaño-Ortiz, Enrique Hernandez-Jimenez, Victor Toledano, Jose Casas-Martin, Anibal Varela-Serrano, Marta Torres, Isaac Almendros, Raquel Casitas, Isabel Fernández-Navarro, Aldara Garcia-Sanchez, Luis A. Aguirre, Ramón Farre, Eduardo López-Collazo, Francisco García-Rio
Journal: European Respiratory Journal (2017)

Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8 + T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human in vitro and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8 + T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8 + T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients.
Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality
Authors: Arjola Bano, Layal Chaker, Francesco U.S. Mattace-Raso, Aad van der Lugt, M. Arfan Ikram, Oscar H. Franco, Robin P. Peeters, Maryam Kavousi
Journal: Circulation Research (2017)

Thyroid hormones have been linked with various proatherogenic and antiatherogenic processes. However, the relationship of thyroid function with manifestations of atherosclerosis remains unclear.To investigate the association of thyroid function with atherosclerosis throughout its spectrum; that is, subclinical atherosclerosis, incident atherosclerotic cardiovascular (ASCV) events, and ASCV mortality.This population-based study was embedded within the Rotterdam Study. The risk of atherosclerosis was evaluated by measuring (1) presence of subclinical atherosclerosis, assessed by coronary artery calcification score >100 AU; (2) ASCV events, defined as fatal and nonfatal myocardial infarction, other coronary heart disease mortality, or stroke; (3) ASCV mortality, defined as death because of coronary heart disease and cerebrovascular or other atherosclerotic diseases. Associations of thyroid-stimulating hormone and free thyroxine with the outcomes were assessed through logistic regression and Cox proportional hazard models, adjusted for potential confounders, including cardiovascular risk factors. A total of 9420 community-dwelling participants (mean age±SD, 64.8±9.7 years) were included. During a median follow-up of 8.8 years (interquartile range, 4.5-11.8 years), 934 incident ASCV events and 612 ASCV deaths occurred. Free thyroxine levels were positively associated with high coronary artery calcification score (odds ratio, 2.28; 95% confidence interval, 1.30-4.02) and incident ASCV events (hazard ratio, 1.87; confidence interval, 1.34-2.59). The risk of ASCV mortality increased in a linear manner with higher free thyroxine levels (hazard ratio, 2.41; confidence interval, 1.68-3.47 per 1 ng/dL) and lower thyroid-stimulating hormone levels (hazard ratio, 0.92; confidence interval, 0.84-1.00 per 1 logTSH). Results remained similar or became stronger among euthyroid participants.Free thyroxine levels in middle-aged and elderly subjects were positively associated with atherosclerosis throughout the whole disease spectrum, independent of cardiovascular risk factors.
PS02.17 A Biomarker-Driven Algorithm for Sequencing of Systemic Therapy for Metastatic Non-Small Cell Lung Cancer (mNSCLC): A Survey of 25 Investigators
Authors: N. Love, G.J. Riely, M. Ladanyi, D. Paley, K. Miller, G. Kelly, J. Moss, K.A. Ziel
Journal: Journal of Thoracic Oncology (2017)
Abstract 18229: HIV-NEF Modulates T-Cell Interaction With Endothelial Cells in a Rac-Dependent Pathway to Enhance Transfer of Nef Protein to Endothelium
Authors: Sarvesh Chelvanambi, Bernhard Meier, Pinar Zorlutuna, Samir Gupta, Matthias Clauss
Journal: Circulation (2016)

Introduction:  Anti-Retroviral therapy (ART) has reduced the incidence of AIDS but HIV+ patients face an increased risk of developing vascular pathologies including pulmonary hypertension and cardiovascular diseases. We found Nef protein in PBMCs of HIV patients on ART and that this protein is transferred to vascular endothelium where it subsequently causes reactive oxygen species production and apoptosis. The mechanism through which Nef protein) transfers to endothelial cells (EC) is poorly understood. In this study, we will study how Nef affects T Cell-EC interaction in a Rac-dependent fashion and confirm these findings in PBMCs from HIV+ patients on ART.   Methods:  SupT1 cells expressing a Nef-ER fusion protein (AIDS reagent repository) serves as a model of inducible Nef activity. For adhesion assays, Nef-ER cells (stained green with calcein AM) were allowed to adhere to endothelial cell monolayer for 1 hr. Non-adhered cells were washed 1x with PBS and adhered cells quantified using flow cytometry & microscopy. For transmigration assays, Nef-ER SupT1 cells were allowed to transmigrate through an EC monolayer. The number of transmigrated cells were quantified using CyQuant Cell quantification kit. To study Nef-Rac interactions, Nef-ER cell lysate was immuneprecipitated using Rabbit anti-Nef serum (AIDS reagent repository) and then analyzed using western blotting.   Results:  Nef expression significantly increased T-Cell adhesion (1.5 fold, p = 0.01) to EC and T-cell migration (1.5 fold, p = 0.0005) through EC monolayer in response to 10% FBS gradient, CXCL12 and CCL21. These effects were neutralized when Nef+ T cells were treated with Rac inhibitor, NSC23766 and Atorvastatin (which pleotropically inhibits Rac activity). Immunoprecipitation of Nef from the cell lysate also pulled down Rac as shown by western blot.   Conclusion:  By upregulating adhesion and transmigration of T cells, Nef increases the time Nef+ T cells spend in contact with ECs allowing Nef to transfer into the vascular endothelium. We are currently confirming these assays in PBMCs of HIV patients on ART to characterize T-Cell - EC interaction in an  ex vivo  model of HIV.
Programa de Formación en Epidemiología de Campo (FETP) en Alemania
Authors: L R Petersen, T Breuer, O Hamouda, A Ammon
Journal: Eurosurveillance (2001)

El Programa de Formacion en Epidemiologia de Campo (FETP) aleman, iniciado en enero de 1996, forma parte de un esfuerzo nacional destinado a mejorar la capacidad de investigacion en la epidemiologia de enfermedades infecciosas en Alemania (1). El objetivo de este programa de dos anos es desarrollar un cuadro de epidemiologos capaz de investigar brotes y de realizar investigaciones epidemiologicas y tareas de vigilancia con arreglo a un estandar internacional medido en articulos publicados en revistas internacionales y evaluados por revisores. Estos epidemiologos tambien recibiran la instruccion necesaria para a su vez formar a epidemiologos y personal sanitario futuros. El programa es similar al del EIS, impartido en los CDC de los EE UU, y al EPIET europeo (2,3). El Ministerio Federal de Educacion e Investigacion de Alemania financio los costes de una plaza de epidemiologo, para ayudar a poner en marcha el programa, en colaboracion con los CDC.
TCT-66 Prognosis of Deferred Non-culprit Lesions According to Fractional Flow Reserve in Patients with Acute Coronary Syndrome
Authors: Ki Hong Choi, Joo Myung Lee, Bon-Kwon Koo, Eun-Seok Shin, Chang-Wook Nam, Joon-Hyung Doh, Doyeon Hwang, Jonghanne Park, Hong-Seok Lim, Myeong-Ho Yoon, Seung-Jea Tahk
Journal: Journal of the American College of Cardiology (2017)
Statin initiation is unrelated to cardiovascular risk score, finds study
Authors: Nigel Hawkes
Journal: BMJ (2017)

General practices in England and Wales start patients on statins seemingly haphazardly, often without documented evidence that their cardiovascular risks have been properly assessed, a study of 248 practices has shown.

GPs are recommended by the UK National Institute for Health and Care Excellence (NICE) to use the QRISK2 score to help decide whether patients should be started on statins. But only around a quarter of patients who began taking the drugs after 2012, when this recommendation was made, have a QRISK2 score documented in their patient record. And of those who do have a score recorded, only 35% of those with a high score were actually started on statins, found Samuel Finnikin and colleagues …
A smoke-free world to protect child health
Authors: Anthony A Laverty, Jasper V Been, Christopher Millett, Filippos T Filippidis
Journal: BMJ (2017)

Britton considers the reasons why smoking has yet to be effectively tackled, with focus on the deceitful behaviour of big tobacco companies.1 We agree that the costs are paid by the rest of society. Moreover, these costs are unevenly distributed across society, having a large effect on the health …