tbuckley/cabot-search huggingface dataset:
Abstract 082: Deletion of Mitochondrial Aldehyde Dehydrogenase 2 Restrains Cardiac Fatty Acid Oxidation during Pressure-Overload Induced Heart Failure
Authors: Fan Fan, Aijun Sun, Guang Xia, Yunzeng Zou, Kai Hu, Junbo Ge
Journal: Circulation Research (2013)

Rationale: Mitochondrial Aldehyde dehydrogenase 2 (ALDH2) is regarded as an inner protector of cardiac diseases, which downregulation has been reported to induce cardiac metabolic remodeling and augmented glucose uptake. However, it has not been investigated whether myocardial fatty acid oxidation (FAO) could be regulated by ALDH2. Objective: We hypothesized that global deletion of ALDH2 would deteriorate heart function and energy generation, inhibit cardiac FAO and promote the development of pressure-overload induced heart failure. Methods and Results: ALDH2 knockout (ALDH2-/-) did not led to considerable birth defects and cardiac dysfunction in base line. Pressure overload were induced by transverse aortic constriction (TAC) for 4weeks. In echocardiographic and hemodynamic test, left ventricular systolic functions were decreased in ALDH2-/- TAC mice compared with wild type (WT) TAC mice. Myocardial morphology and subcellular structure examinations shown ALDH2-/- TAC mice exhibited cardiac hypertrophy with a significant mitochondrial destroy relative to WT-TAC. Meanwhile, a decreased FAO and ATP production were detected (54±3.6% and 77±1.5%, p&lt;0.05,respectively) in ALDH2-/- sham myocardium, which were aggravated by pressure overload. Therefore, ALDH2 deletion accelerated cardiac energy remolding. Furthermore, ALDH2-/- repressed AMP-activated protein kinase (AMPK) phosphorylation(49±4.6%, p&lt;0.05) and subsequently inhibited the activation of peroxisome proliferator-activated receptor a (PPARa) (31±2.9%, p&lt;0.05) - carnitine palmitoyl transferase 1 (CPT1) (81.5±5.2%, p&lt;0.05) - fatty acid transportation pathway, which induced inefficient of FAO. Conclusions: These data of present study suggest that ALDH2 deficiency promotes heart failure and cardiac metabolic remodeling by inhibiting myocardial FAO through AMPK-PPARa-CPT1 pathway.
Recovery in Patients With Dilated Cardiomyopathy With Loss-of-Function Mutations in the Titin Gene
Authors: Kevin Luk, Abeer Bakhsh, Nadia Giannetti, Eleanor Elstein, Mark Lathrop, George Thanassoulis, James C. Engert
Journal: JAMA Cardiology (2017)

This study compares the prevalence of titin gene mutations in patients with dilated cardiomyopathy receiving standard pharmacological therapy with and without recovery of systolic function.
Neurocognitive Trajectory of Boys Who Received a Hematopoietic Stem Cell Transplant at an Early Stage of Childhood Cerebral Adrenoleukodystrophy
Authors: Elizabeth I. Pierpont, Julie B. Eisengart, Ryan Shanley, David Nascene, Gerald V. Raymond, Elsa G. Shapiro, Rich S. Ziegler, Paul J. Orchard, Weston P. Miller
Journal: JAMA Neurology (2017)

Untreated childhood cerebral adrenoleukodystrophy (cALD) is a fatal disease associated with progressive cerebral demyelination and rapid, devastating neurologic decline. The standard of care to enhance long-term survival and stabilize cerebral disease is a hematopoietic stem cell transplant (HSCT). Neurologic outcomes are better when HSCT occurs at an earlier stage of cALD, yet there is limited understanding of the neurocognitive trajectory of patients who undergo HSCT.To characterize neurocognitive outcomes of boys with cALD and early-stage cerebral disease who were treated with an allogeneic HSCT and to identify disease- and treatment-related factors associated with long-term functioning.Baseline and follow-up neurocognitive test performance was analyzed for all boys with cALD who received an HSCT at the University of Minnesota between January 1, 1991, and October 20, 2014, and who had a pretransplant magnetic resonance imaging (MRI) severity score of less than 10 (scale range, 0-34; higher scores indicate greater severity).Longitudinal neurocognitive test performance in 4 domains (verbal comprehension, perceptual [visual] reasoning, working memory, and processing speed) were the primary outcome measures. Secondary analysis at the most recent evaluation also included measures of sustained attention, verbal memory, visual-motor integration, and fine motor function.Among the 62 boys in this study (mean [SD] age at transplant, 8.37 [2.80] years; range, 4-16 years), there was a significant association of pretransplant MRI severity and baseline verbal comprehension (r = -0.340; P = .008), perceptual reasoning (r = -0.419; P = .001), and processing speed (r = -0.285; P = .03) scores. Higher pretransplant MRI severity scores were also associated with a steeper decline in neurocognitive functioning during the 5-year follow-up period. Twenty-two of 33 patients (67%) with available long-term follow-up neurocognitive testing had severe impairment in at least 1 neurocognitive domain at the most recent evaluation.Boys with cALD who have greater than minimal cerebral disease detected on MRI scans at the time of an HSCT are at risk for severe, persistent neurocognitive deficits. These findings motivate further exploration of methods of detecting cerebral disease prior to development of lesions observable on MRI scans, an endeavor that may be facilitated by newborn screening for adrenoleukodystrophy. These findings may serve a benchmark role in evaluating the efficacy of novel interventions for cALD.
Aortic Root Abscess Clearly Shown on 111In-Leukocyte Scan But Less Obvious on Transesophageal Echocardiogram
Authors: Harleen Kaur, John Seitz, Mitchel Muhleman, David Cragg, Feng Qing
Journal: Clinical Nuclear Medicine (2017)

A 79-year-old man with history of aortic stenosis, status post bioprosthetic aortic valve replacement, episodes of bacteremia, and endocarditis presented to hospital with fever. Clinical assessment led to suspicion of possible endocarditis. Initial interpretation of transesophageal echocardiogram was inconclusive without vegetation in mitral/aortic valve. An 111In-leukocyte scan demonstrated increased uptake in the area of aortic valve, suggestive of infection. Further review of the transesophageal echocardiogram showed signs of annular abscess. This case highlights that combination of echocardiography with white blood cell imaging increases the sensitivity to detect endocarditis/perivalvular abscess.
Influenza Vaccination in Patients With Rheumatic Diseases
Authors: Anne Herron
Journal: JAMA (1979)

The safety and efficacy of influenza vaccination were studied in 32 healthy volunteers and in 62 patients with systemic lupus erythematosus (SLE), rheumatoid arthritis, degenerative joint disease, and other rheumatic diseases. These individuals, none of whom was acutely ill, were examined at the time of immunization and one week, three weeks, and four months later. Flare-ups of rheumatic disease following immunization were infrequent and usually minor. Seroconversion to A/New Jersey/76 developed in 62% to 87% of all individuals and to A/Victoria /75 in 62% to 69%. Antibody responses to A/New Jersey/76 were significantly lower in young patients taking glucocorticoids compared to those not taking glucocorticoids. The antibody responses to A/New Jersey/76 and A/Victoria/75 in patients with SLE were not different from normal responses. Administration of these vaccines was safe in these patients with stable disease and induced antibody responses in most individuals. (<i>JAMA</i>242:53-56, 1979)
Mother Donors Improve Outcomes after HLA Haploidentical Hematopoietic Transplantation: A Retrospective Study By the Cell Therapy and Immunobiology Working Party of the EBMT
Authors: Andrea Velardi, Loredana Ruggeri, Dimitris Ziagkos, Anja van Biezen, Mara Merluzzi, Attilio Bondanza, Nathasja Bootsman, Maria Speranza Massei, Lucia Amico, Sara Piccinelli, Maddalena Noviello, Fabio Ciceri, Thomas Klingebiel, Yener Koc, Hendrik Veelken, Franco Locatelli, William Arcese, Bernd Gruhn, Flavia Salvi, Chiara Bonini, Jon J. van Rood
Journal: Blood (2016)
Abstract 199: Whole-Transcript Genomics Reveals Atrial KCNE1 Downregulation in a Model of Postoperative Atrial Fibrillation Susceptibility
Authors: Ritu Kant, Zhaoyang Hu, Vikram Kanda, David J Christini, Paul Heerdt, Geoffrey W Abbott
Journal: Circulation Research (2012)

Lone atrial fibrillation (AF) is associated with various ion channel gene sequence variants, notably the common S38G loss-of-function polymorphism in the KCNE1 K + channel ancillary subunit gene. New-onset postoperative AF (PAF) generally occurs 48-72 hours after major surgery, particularly following procedures within the chest, but its molecular bases remain poorly understood. Here, to begin to address this gap in knowledge, we analyzed molecular changes in the left atrium (LA) three days following left upper lung lobectomy in Sinclair swine in relation to simultaneous changes in hemodynamics, LA effective refractory period (ERP), and the capacity to sustain electrically-induced AF. Relative to control pigs (no previous surgery), lobectomy increased mean pulmonary artery pressure (16 ± 3 vs 22 ± 5 mm Hg; P = 0.045) and pulmonary vascular resistance (273 ± 93 vs 481 ± 142 dyn¶s/cm 5 ; P = 0.025), whereas other hemodynamic parameters were unchanged. Left atrial ERP measured from a 300 ms cycle length trended toward reduction in lobectomy animals (187 ± 37 vs 170 ± 44 ms, P &gt;0.05). None of the lobectomy pigs developed spontaneous postoperative AF as assessed by telemetric ECG. However, all lobectomy pigs, but none of the controls, were able to sustain AF induced by a 10 s burst of rapid pacing for ≥30 s ( P =0.0079), independent of atrial ERP; AF was sustained ≥60 s in 3/5 postoperative pigs versus 0/5 controls and correlated with a shorter ERP overall ( P =0.023). Whole-transcript genomics of left atrial tissue using 25 probes per transcript revealed 13 genes with expression changes ≥2-fold in postoperative pigs. Strikingly, of these, atrial KCNE1 showed the statistically strongest link to surgery, and was the most downregulated gene in the postoperative group compared to controls (2.2-fold reduced, P =0.0027), recapitulated at the protein level with western blotting ( P =0.039). The data suggest KCNE1 remodeling as a potential marker or influencing factor in the early progression of, or susceptibility to, PAF [[Unable to Display Character: –]] uncovering a possible common predisposing genetic factor in PAF and lone AF.
Reply to Philipp Dahm, Vikram Narayan, and Jae Hung Jung's Letter to the Editor re: Richard J. Sylvester, Steven E. Canfield, Thomas B.L. Lam, et al. Conflict of Evidence: Resolving Discrepancies When Findings from Randomized Controlled Trials and Meta-analyses Disagree. Eur Urol 2017;71:811–9
Authors: Thomas B.L. Lam, Richard J. Sylvester, Steven E. Canfield, Lorenzo Marconi, Steven MacLennan, Yuhong Yuan, Muhammad Imran Omar, James N’Dow
Journal: European Urology (2017)
TCTAP A-069 Survival Analysis of Patients with ST Elevation Myocardial Infarction (STEMI) Underwent Transradial Primary Percutaneous Coronary Intervention (PPCI) with Intra-hospital Bleeding Events: A Single-centered Study
Authors: Nanda Iryuza, Sunarya Soerianata, Dafsah Arifa Juzar, Wishnu Aditya Widodo, Doni Firman, Nur Haryono, Amir Aziz Alkatiri
Journal: Journal of the American College of Cardiology (2017)
Contents, Vol. 29, 1978
Authors: H.F. Ellenberger, Elisabeth Croufer-North, Hannelore Bobon-Schrod, Jacques Fraipont, M. Laxenaire, M. Mitscherlich, J. Cosnier, Helmut Enke, Claude Bloch, Andre Haynal, Irena Braun, Stanislaw Grochmal, P. Jonckheere, P. van Meerbeeck, Miguel A. Leibovich, F.E. Mairlot, Jacques Launay, M. Laxenaire, P. Bour, J.A.C. Bleeker, Mélinée Agathon, Ellen Corin, H. Schaffer, M. Nicolle, J.C. Archambault, P. Fouquet, L. Lasselin, Jerome D. Frank, Jacques Cain, R. Misés, M.J. Bailly-Salin, P. Sivadon, Cavin P. Leeman, Sharon Autio, Jean-Marie Delacroix, Milan Popović, N.N. Dracoulidès, Gilbert Pinard, Jacques Darquey, Michel de Boucaud, Alfredo Tridenti, Malkah T. Notman, Carol C. Nadelson, Mona B. Bennett, Marie-Aimée Guilhot, P. Caillé, L. Kaufmann, O. Masson, D. Masson, E. Fivaz, G. Basecqz, Clarice J. Kestenbaum, Harley C. Shands, J. Bastiaans, H.M. van der Ploeg, Mario Berta, Joseph Wolpe, D.R. Henny, Jerzy W. Aleksandrowicz, Edgar Heim, Einar Johnsen, Claudine Lilienfeld, Helga Stauffacher, Patrik Wirz, C. Bardet-Giraudon, Jorge E. Garcia Badaracco, Daniel Schurmans, H.O. Badura, E.M. Steinmeyer, Anne Cain, H. Davanloo, C. Benoit, H. Davanloo, Astrid Heiberg, E. Gillieron, Robert Dauteuil, Louis Faurobert, J. Rainaut, Jean M. Sutter, Jacqueline Falguière, Claude Ouzilou, P. Dubor, Owen S. Robbins, Peter E. Sifneos, A.A. Dahl, C.-I. Dahl, Astrid Heiberg, Ragnhild Husby, O.M. Olafsen, Tom Sørensen, L. Weisaeth, Jacqueline Verdeau-Pailles, H. Iwai, A. Homma, H. Amamoto, M. Asakura, Francesco Parenti, P.-B. Schneider, Finn Magnussen
Journal: Psychotherapy and Psychosomatics (1978)
Genetic Sost Deletion and Pharmacological Inhibition of Sclerostin Prevent Multiple Myeloma-Induced Bone Loss without Affecting Tumor Growth
Authors: Jesus Delgado-Calle, Judith Anderson, Meloney D. Cregor, Dan Zhou, Lilian I. Plotkin, Teresita M. Bellido, G. David Roodman
Journal: Blood (2016)
Abstract 376: Amino Terminal C0-C1f Region of Cardiac Myosin Binding Protein-C is Essential for Normal Cardiac Function
Authors: Thomas L Lynch, Diederik W Kuster, David Barefield, Mayandi Sivaguru, Michael J Previs, Kyounghwan Lee, Suresh Govindan, Roger Craig, David M Warshaw, Sakthivel Sadayappan
Journal: Circulation Research (2015)

Rationale: Cardiac myosin binding protein-C (cMyBP-C) is a trans-filament protein that has been shown to regulate cardiac function via its amino terminal (N’) regions. However, it is unknown whether the first 271 residues (C0-C1f region) are necessary to regulate contractile function in vivo. Hypothesis: The N’-region of cMyBP-C is critical for proper cardiac function in vivo. Methods and Results: Transgenic mice with approximately 80% expression of mutant truncated cMyBP-C missing C0-C1f (cMyBP-C 110kDa ), compared to endogenous cMyBP-C, were generated and characterized at 3-months of age. cMyBP-C 110kDa hearts had significantly elevated heart weight/body weight ratio, fibrosis, nuclear area and collagen content compared to hearts from non-transgenic (NTG) littermates. Electron microscopic analysis revealed normal sarcomere structure in cMyBP-C 110kDa hearts but with apparently weaker cMyBP-C stripes. Furthermore, the ability of cMyBP-C to slow actin-filament sliding within the C-zone of native thick filaments isolated from NTG hearts was lost on thick filaments from cMyBP-C 110kDa hearts. Short axis M-mode echocardiography revealed a significant increase in left ventricular (LV) internal diameter during diastole in cMyBP-C 110kDa hearts. Importantly, cMyBP-C 110kDa hearts displayed a significant reduction in fractional shortening compared to hearts from NTG littermates. We further observed a decrease in the thickness of the LV interventricular septum and free wall during systole in cMyBP-C 110kDa hearts. Strain analysis using images acquired from ECG-Gated Kilohertz Visualization identified a significant deficit in global longitudinal strain in cMyBP-C 110kDa hearts compared to NTG hearts. Conclusion: The N’-region of cMyBP-C is indispensable for maintaining normal cardiac morphology and function and loss of this region promotes contractile dysfunction both at the molecular and tissue levels.
Targeted antigen delivery to dendritic cell via functionalized alginate nanoparticles for cancer immunotherapy
Authors: Chuangnian Zhang, Gaona Shi, Ju Zhang, Huijuan Song, Jinfeng Niu, Shengbin Shi, Pingsheng Huang, Yanming Wang, Weiwei Wang, Chen Li, Deling Kong
Journal: Journal of Controlled Release (2017)
NHS must assess the evidence before closing emergency departments, report warns
Authors: Gareth Iacobucci
Journal: BMJ (2017)

NHS bosses must properly assess the evidence before shutting or downgrading emergency departments given the damaging impact of previous closures, a new analysis has warned.

A report1 published by the think tank the Centre for Health and the Public Interest examined how the closure of two emergency departments in north west London in 2014 affected performance against the target of seeing 95% of patients within four hours.

In the winter that followed the closures of departments at Central Middlesex and Hammersmith hospitals, performance against the target dropped …
Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial
Authors: Anthony B El-Khoueiry, Bruno Sangro, Thomas Yau, Todd S Crocenzi, Masatoshi Kudo, Chiun Hsu, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore H Welling, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine dela Cruz, Lixin Lang, Jaclyn Neely, Hao Tang, Homa B Dastani, Ignacio Melero
Journal: The Lancet (2017)
DOES INJURY DEFINITION MATTER? THE INFLUENCE OF INJURY DEFINITION ON INTERPRETATIONS OF INJURY RISK IN PRE-PROFESSIONAL BALLET AND CONTEMPORARY DANCERS
Authors: Sarah Kenny, Luz Palacios-Derflingher, Jackie Whittaker, Carolyn Emery
Journal: British Journal of Sports Medicine (2017)

Background The influence of injury definition on the interpretation of epidemiological outcomes of injury risk has not been previously evaluated in a dance population. Objective To determine the influence of injury definition (i.e., time loss, medical attention, all complaints) on the prevalence and rate of musculoskeletal injuries in pre-professional ballet and contemporary dancers. Design Prospective cohort. Setting Pre-professional ballet school; university dance program. Participants Dancers registered in full-time pre-professional ballet [n=85, 77 females, median (range) age 15 yrs (11–19 yrs)] and contemporary [n=60, 58 females, 19 yrs (17–30 yrs)] training. Main Outcome Measurements Dancers completed a weekly online questionnaire (modified Oslo Sports Trauma Research Centre's Questionnaire on Health Problems) using three definitions for dance-related injuries: (1) time loss (an inability to complete one or more classes, rehearsals or performances one or more days beyond onset); (2) medical attention; and (3) any complaint. Physiotherapists completed injury report forms, capturing dance-related medical attention and time loss injuries. Percent agreement was estimated between injury registration methods. Descriptive statistics [proportions, 95% confidence intervals (95% CI)] summarized injury prevalence (IP; seasonal proportion of dancers injured). Injury incidence rates (IIR; number of new injuries/1000 dance exposure hours) were examined for each definition, registration method, and dance style. Results Dancer questionnaire response rate was 98.99%. Agreement between injury registration methods ranged between 58.82% (time loss) and 72.94% (medical attention). Depending on definition, registration, and dance style, IP varied from 9.41% (95% CI: 4.15, 17.71; time loss) to 82.35% (95% CI: 72.56, 89.77; all complaint), and IIRs spanned 0.09 (95% CI: 0.01, 0.17; time loss) to 4.89 (95% CI: 4.04, 5.74; all complaint) injuries/1000 dance hours. Conclusions Injuries resulting in time loss and medical attention underestimate the burden of injury in a pre-professional dance population. To understand the full impact of injury on a dance population, it is imperative that registration methodologies consider definitions that capture all injuries.
Medical devices face tougher premarket testing under new EU laws
Authors: Deborah Cohen
Journal: BMJ (2017)

The European Parliament has passed new legislation to tighten regulation of medical devices that will require high risk devices, such as hip implants, to undergo more premarket testing and assessment.

European device regulation has come in for criticism after a series of high profile failures—including hip replacements, breast implants, and pelvic meshes—that have resulted in harm to patients.

MEPs voted in a raft of changes detailed in a 600 page dossier that has taken over five years to agree. At the heart of the updated legislation is the need for more clinical evaluation before and after a device is put on the market. Manufacturers of high risk devices will have to perform clinical investigations, and the results of these will have to be published on an accessible database.

If a company is to …
Abstract #LB-205: PG11047, A Polyamine Analog, Induces Potent Antitumor Activity in a Preclinical Model of Non-Small Cell Lung Cancer in Combination with Cisplatin.
Authors: Keith Dredge, John Kink, Randolph Johnson, Ian Bytheway, Paul Handley, Laurence Marton
Journal: Cancer Research (2009)

PG11047 is a conformationally restricted analog of the polyamine N1, N12-bisethylspermine, and is currently in Phase I trials for advanced cancer both as a monotherapy and in combination with a number of approved anti-cancer agents. The use of polyamines as a target for antiproliferative therapy is based on many studies indicating that cells synthesize more polyamines when induced to grow and that polyamine metabolism is frequently dysregulated in cancers. A selective polyamine transport system provides access for PG11047 into cells. PG11047 decreases the activities of the polyamine biosynthetic enzymes and induces the polyamine catabolic enzymes spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMO). The induction of these two enzymes could subsequently induce reactive oxygen species that contribute to tumor cell responses to PG11047. Additionally, PG11047 likely replaces the naturally occurring polyamines at intracellular binding sites, but with altered function. We will present data showing the antitumor efficacy of PG11047 as a single agent in lung (A549) and prostate (DU-145) models of cancer, as well as its efficacy when used in combination with a variety of approved agents. When used in combination with bevacizumab or docetaxel (DU-145), the significant potency of the PG11047 alone and of each of the other agents alone, at the dose tested, precluded the evaluation of potential additive or synergistic effects. However, when combined with a standard dose of cisplatin, the combination therapy of PG11047 and cisplatin led to a potent antitumor effect far superior to either agent alone. In all experiments, PG11047 was well tolerated with no adverse effects on bodyweight gain. Particularly in the case of the cisplatin study, the preclinical data supports the rationale for the current Phase I clinical trial which is assessing PG11047 as a monotherapy and in combinations that include one of a number of approved anti-cancer agents per treatment arm, including cisplatin, bevacizumab and docetaxel.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-205.
Surface functionalization of acrylic based photocrosslinkable resin for 3D printing applications
Authors: A. Ronca, F. Maiullari, M. Milan, V. Pace, A. Gloria, R. Rizzi, R. De Santis, L. Ambrosio
Journal: Bioactive Materials (2017)

The limited number of resins, available for stereolithography applications, is one of the key drivers in research applied to rapid prototyping. In this work an acrylic photocrosslinkable resin based on methyl methacrylate (MMA), butyl methacrylate (BMA) and poly(ethylene glycol) dimethacrylate (PEGDA) was developed with different composition and characterized in terms of mechanical, thermal and biological behaviour. Two different systems have been developed using different amount of reagent. The influence of every components have been evaluated on the final characteristic of the resin in order to optimize the final composition for applications in bone tissue engineering. The crosslinked materials showed good mechanical properties and thermal stabilities and moreover cytotoxicity test confirms good biocompatibility with no cytotoxic effect on cells metabolism. Moreover two different treatments have been proposed, using fetal bovine serum (FBS) and methanol (MeOH), in order to improve cell recognition of the surfaces. Samples threatened with MeOH allow cell adhesion and survival, promoting spreading, elongation and fusion of C2C12 muscle myoblast cells.