tbuckley/cabot-search huggingface dataset:
Abstract 11787: Traumatic Acute Myocardial Infarction Following Blunt Chest Trauma
Authors: nazila naderi, Timothy Dao, Marvin Eng
Journal: Circulation (2014)

Coronary artery dissection is a rare complication following blunt chest trauma, accounting for &lt;2% of blunt cardiac injuries. The diagnosis is frequently missed likely due to intervening concomitant injuries or sudden death. We report a case of motorcycle collision causing multiple injuries including blunt chest trauma associated with new inferior injury pattern on ECG in 43-year-old previously healthy man. Initially the patient was hypertensive and tachycardic. Electrocardiogram showed inferior ST elevation, bedside echocardiogram revealed distal apical and inferoapical hypokinesis with normal ejection fraction without pericardial effusion. Given the mechanism of injury, CT angiography and TEE first excluded the initial working diagnosis of aortic dissection. Urgent angiography showed a distal dissection of a wrap around LAD. Attempted revascularization was unsuccessful due to the inability to find the true lumen. Concomitant multiple fractures, lung contusion and a small mediastinal hematoma prevented anticoagulation therapy and conservative management ensued. Follow-up echocardiogram confirmed a sustained infarction with distal anterior and apical akinesis but preserved ejection fraction. No arrhythmia or recurrent ischemia noted during hospital admission, however he was chosen to manage conservatively for his wrist fracture due to recent infarction. This case report underscores need for a high index of suspicion for cardiac injury and the need to maintain a broad differential following chest trauma. Additionally, presence of an injury pattern should prompt confirmatory angiography to differentiate coronary injury from cardiac contusion as they have different long-term outcome.
Allergic airway sensitization impairs antibacterial IgG antibody responses during bacterial respiratory tract infections
Authors: Arthur H. Totten, Li Xiao, Danlin Luo, David Briles, Joanetha Y. Hale, Donna M. Crabb, Trenton R. Schoeb, Ammar Saadoon Alishlash, Ken B. Waites, T. Prescott Atkinson
Journal: Journal of Allergy and Clinical Immunology (2018)
Collagen XV Is Necessary for Modeling of the Extracellular Matrix and Its Deficiency Predisposes to Cardiomyopathy
Authors: KarolinaRasi, JarkkoPiuhola, MarcusCzabanka, RaijaSormunen, MikaIlves, HannaLeskinen, JaanaRysä, RistoKerkelä, PaulJanmey, RitvaHeljasvaara, KeijoPeuhkurinen, OlliVuolteenaho, HeikkiRuskoaho, PeterVajkoczy, TainaPihlajaniemi, LauriEklund
Journal: Circulation Research (2010)

Rationale:The extracellular matrix (ECM) is a major determinant of the structural integrity and functional properties of the myocardium in common pathological conditions, and changes in vasculature contribute to cardiac dysfunction. Collagen (Col) XV is preferentially expressed in the ECM of cardiac muscle and microvessels. Objective:We aimed to characterize the ECM, cardiovascular function and responses to elevated cardiovascular load in mice lacking Col XV (Col15a1−/−) to define its functional role in the vasculature and in age- and hypertension-associated myocardial remodeling. Methods and Results:Cardiac structure and vasculature were analyzed by light and electron microscopy. Cardiac function, intraarterial blood pressure, microhemodynamics, and gene expression profiles were studied using echocardiography, telemetry, intravital microscopy, and PCR, respectively. Experimental hypertension was induced with angiotensin II or with a nitric oxide synthesis inhibitor. Under basal conditions, lack of Col XV...
Steps Toward Percutaneous Aortic Valve Replacement
Authors: YounesBoudjemline, PhilippBonhoeffer
Journal: Circulation (2002)

Background— To date, the surgical approach is the only option to replace the aortic valve. Percutaneous pulmonary valve replacement has recently opened new perspectives on transcatheter replacement of cardiac valves. We report our experience of aortic valve replacement through a percutaneous technique in lambs. Methods and Results— A bovine jugular vein containing a valve was dissected and sutured into a stent. Twelve lambs were divided into 3 groups. In the first, a valved stent was implanted in the descending aorta after creation of an aortic insufficiency. In the second, the valve was implanted in the native position. In the third, we inserted a valved stent in the native position using an orientation mechanism. All valves were successfully delivered and functioned perfectly in short-term evaluation. All experiments in group 2 failed: 1 valve obstructed the coronary artery orifices, 1 stent was responsible for a major mitral valve insufficiency, and the third implant migrated prematurely. A paraprosthe...
Common Carotid Artery Intima-Media Thickness and Brain Infarction
Authors: Pierre-JeanTouboul, AlexisElbaz, CorneliaKoller, ChristianLucas, ValérieAdraï, FrançoisChédru, PierreAmarenco
Journal: Circulation (2000)

Background—The use of intima-media thickness (IMT) as an outcome measure in observational studies and intervention trials relies on the view that it reflects early stages of atherosclerosis and cardiovascular risk. There is little knowledge concerning the relation between IMT and brain infarction (BI). Methods and Results—We investigated the relation of IMT with BI and its subtypes in 470 cases and 463 controls. Cases with BI proven by MRI were consecutively recruited and classified into subtypes by cause of BI. Controls were recruited among individuals hospitalized at the same institutions and matched for age, sex, and center. IMT was measured at the far wall of both common carotid arteries (CCA) using an automatic detection system. Adventitia-to-adventitia diameters and CCA-IMT were measured on transverse views; lumen diameter was computed using these measures. Mean (±SEM) CCA-IMT was higher in cases (0.797±0.006 mm) than in controls (0.735±0.006 mm; P<0.0001). This difference remained after adjustment ...
Seeding With Omental Cells Prevents Late Neointimal Hyperplasia in Small-Diameter Dacron Grafts
Authors: MiralemPasic, WernerMüller-Glauser, BernhardOdermatt, MarioLachat, BurkhardtSeifert, MarkoTurina
Journal: Circulation (1995)

Background The influence of complete endothelialization of a prosthetic graft on development of late neointimal hyperplasia is unknown. This study was designed to investigate the effect of complete coverage with endothelial-like cells on late neointimal hyperplasia in small-diameter Dacron grafts seeded with omental cells in a canine model. Methods and Results Four-mm-ID Dacron grafts were seeded with cells from omentum and implanted in the carotid arteries in 24 mongrel dogs. Each dog received one seeded and one nonseeded graft. The graft patencies were assessed by angiography at 1, 5, 12, 26, and 52 weeks after surgery. The prostheses were explanted at 5, 12, 26, and 52 weeks after surgery and underwent microscopic studies. The actuarial patency rates at 1, 5, 12, 26, and 52 weeks were 100%, 95%, 95%, 95%, and 95% for seeded grafts and 100%, 86%, 49%, 40%, and 13% for nonseeded grafts, respectively. The seeded grafts exhibited a uniform endothelial-like luminal monolayer without the development of late ...
Abstract 688: Triphenylstannyl 2-(benzylcarbamoyl)benzoate (Ch-319) modulates AKT/FOXO3a signaling and inhibits progression of prostate cancer
Authors: Durdana Waseem, Deeba N. Syed, Gul Majid Khan, Ihsan-ul Haq, Hasan Mukhtar
Journal: Cancer Research (2018)

Abstract Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous malignancy in men in the United States. Moreover, its incidence is predicted to surge in many parts of the world due to increase in aging population and change in dietary habits. The PTEN/AKT axis plays a critical role in regulating PCa growth and survival. Synthetic and natural compounds have been explored in preclinical models as potential inhibitors of AKT pathway that can suppress proliferation or induce apoptosis in PCa cells. Triphenyltin compounds are complexes of tin with three phenyl groups attached to hydrocarbon ligands. Structural modifications have been attempted to yield organotins with enhanced cytotoxicity against cancer cells. Here, we synthesized a series of triphenyltin (IV) carboxylate derivatives and evaluated their efficacy against PCa. From this library, triphenylstannyl 2-(benzylcarbamoyl)benzoate (Ch-319) was selected for further studies on the basis of its selective cytotoxicity towards cancer cells. Treatment of PTEN-null PC3M and DU145 PCa cells with Ch-319 (250-500 nM) resulted in reduced viability and induction of cell cycle arrest associated with downregulation of PI3K and dephosphorylation of AKT and PRAS40. In parallel, elevation of FOXO3a expression, activation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl2 protein was observed. Flowcytometry revealed increased population of apoptotic cells in Ch-319 treated cells. Presensitization of PCa cells with Ch-319 augmented the effect of cabazitaxel, a commonly used taxane in patients with castration-resistant PCa. We next evaluated the effect of Ch-319 in a prostate-specific Pten-/- model where AKT activation is the major driving force for development of prostate adenocarcinoma. Mice treated with Ch-319 (5 µg/animal:intraperitoneally) for 6 weeks showed decreased tumor weights as compared to DMSO treated controls. Histological studies indicated a decrease in the number and size of foci in Ch-319 treated tumors. Consistently, reduced expression of androgen receptor, decreased phosphorylation of AKT and PRAS40 and increase in FOXO3a was observed in Ch-319 treated animals with no signs of organ toxicity. Our studies identify AKT/FOXO3a signaling as a target of triphenyltin (IV) carboxylate derivative Ch-319 and provide a molecular basis of its growth inhibitory effect in PCa cells. We propose that Ch-319 has potential to be developed as an anticancer agent against PCa. Citation Format: Durdana Waseem, Deeba N. Syed, Gul Majid Khan, Ihsan-ul Haq, Hasan Mukhtar. Triphenylstannyl 2-(benzylcarbamoyl)benzoate (Ch-319) modulates AKT/FOXO3a signaling and inhibits progression of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 688.
Nonsense-Mediated mRNA Decay and Ubiquitin–Proteasome System Regulate Cardiac Myosin-Binding Protein C Mutant Levels in Cardiomyopathic Mice
Authors: NicolasVignier, SaskiaSchlossarek, BodvaelFraysse, GiuliaMearini, ElisabethKrämer, HervéPointu, NathalieMougenot, JosianeGuiard, RudolphReimer, HeinrichHohenberg, KettySchwartz, MurielVernet, ThomasEschenhagen, LucieCarrier
Journal: Circulation Research (2009)

Rationale: Mutations in the MYBPC3 gene encoding cardiac myosin-binding protein (cMyBP)-C are frequent causes of hypertrophic cardiomyopathy, but the mechanisms leading from mutations to disease remain elusive. Objective: The goal of the present study was therefore to gain insights into the mechanisms controlling the expression of MYBPC3 mutations. Methods and Results: We developed a cMyBP-C knock-in mouse carrying a point mutation. The level of total cMyBP-C mRNAs was 50% and 80% lower in heterozygotes and homozygotes, respectively. Surprisingly, the single G>A transition on the last nucleotide of exon 6 resulted in 3 different mutant mRNAs: missense (exchange of G for A), nonsense (exon skipping, frameshift, and premature stop codon) and deletion/insertion (as nonsense but with additional partial retention of downstream intron, restoring of the reading frame, and almost full-length protein). Inhibition of nonsense-mediated mRNA decay in cultured cardiac myocytes or in vivo with emetine or cycloheximide ...
Abstract 2788: VB6-845d tumor cell killing elicits biologic features of immunogenic cell death
Authors: Rachelle L. Dillon, Shilpa Chooniedass, Arjune Premsukh, Glen C. MacDonald, Jeannick Cizeau, Gregory P. Adams
Journal: Cancer Research (2018)

Abstract VB6-845d is a Targeted Protein Therapeutic, TPT, that comprises a Fab fragment specific for the Epithelial Cell Adhesion Molecule (EpCAM) genetically fused to deBouganin via a furin protease sensitive linker. DeBouganin (deB) is a de-immunized variant of bouganin, a ribosome inactivating protein (RIP), that when internalized blocks protein synthesis thereby leading to cell death. While all cytotoxic molecules induce tumor cell killing, only some are capable of inducing biological manifestations indicative of immunogenic cell death (ICD). ICD is characterized by the collective appearance of distinct cellular changes termed damage associated molecular patterns, or DAMPs, which play a role in immune cell activation by triggering pro-inflammatory processes. Key DAMPs necessary for defining ICD are cell surface translocation of calreticulin, an endoplasmic reticulum chaperone protein, ATP secretion and release of HMGB1 (high mobility group box 1). To evaluate whether VB6-845d cell killing elicits the hallmark features of ICD, VB6-845d treated tumor cell lines were assessed for the presence of these distinct signaling molecules. In vitro studies showed that VB6-845d cytotoxicity induces the translocation of calreticulin to the cell surface as well as the release of ATP and HMGB1. The expression of other potential immune regulators following VB6-845d treatment was also examined. In summary, the data presented suggests that VB6-845d mediates tumor cell killing by an ICD pathway. The potential cross-priming effect initiated by VB6-845d-induced ICD suggests the use of VB6-845d in combination with immune checkpoint inhibitors may enhance their effectiveness in EpCAM-positive epithelial cancers. Citation Format: Rachelle L. Dillon, Shilpa Chooniedass, Arjune Premsukh, Glen C. MacDonald, Jeannick Cizeau, Gregory P. Adams. VB6-845d tumor cell killing elicits biologic features of immunogenic cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2788.
Mutations in Sarcomere Protein Genes in Left Ventricular Noncompaction
Authors: SabineKlaassen, SusanneProbst, ErwinOechslin, BrendaGerull, GregorKrings, PiaSchuler, MatthiasGreutmann, DavidHürlimann, MustafaYegitbasi, LuciaPons, MichaelGramlich, Jörg-DetlefDrenckhahn, ArndHeuser, FelixBerger, RolfJenni, LudwigThierfelder
Journal: Circulation (2008)

Background— Left ventricular noncompaction constitutes a primary cardiomyopathy characterized by a severely thickened, 2-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses. The genetic basis of this cardiomyopathy is still largely unresolved. We speculated that mutations in sarcomere protein genes known to cause hypertrophic cardiomyopathy and dilated cardiomyopathy may be associated with left ventricular noncompaction. Methods and Results— Mutational analysis in a cohort of 63 unrelated adult probands with left ventricular noncompaction and no other congenital heart anomalies was performed by denaturing high-performance liquid chromatography analysis and direct DNA sequencing of 6 genes encoding sarcomere proteins. Heterozygous mutations were identified in 11 of 63 samples in genes encoding β-myosin heavy chain (MYH7), α-cardiac actin (ACTC), and cardiac troponin T (TNNT2). Nine distinct mutations, 7 of them in MYH7, 1 in ACTC, and 1 in TNNT2, were found. Clinical ev...
Abstract 200: Computer-Assisted Monitoring of Hemodynamic Condition During a Simulated Experiment of Hypovolemia Using Lower Body Negative Pressure
Authors: AshwinBelle, MaxwellSpadafore, HarmDerksen, KevinWard, KayvanNajarian
Journal: Circulation (2014)

Background: Real-time physiologic status monitoring of hemorrhaging war-fighter or civilian from the point of injury and along ensuing echelons of care in austere environments pose significant challenges. These challenges range for those arising from the environment to the physical profiles of monitors and the types of measures they make. Objective: To develop an automated clinical support system capable of using low level physiologic signals such as the electrocardiogram (ECG) to monitor hemodynamic compensation in response to injury or illness. Methods: An adapted low profile portable and wearable armband monitor was used to collect prolonged measurement of a single lead ECG from volunteer human subjects undergoing lower body negative pressure (LBNP) as a model of human hemorrhage. Fifty-five subjects underwent 5-minute intervals of progressive LBNP until hemodynamic decompensation at which time LBNP was halted. Using several advanced signal processing techniques including novel applications of the Stoc...
Abstract LB-158: Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number
Authors: Dong Hang, Hongmei Nan, Ane Sørlie Kværner, Immaculata De Vivo, Andrew T. Chan, Zhibin Hu, Hongbing Shen, Edward Giovannucci, Mingyang Song
Journal: Cancer Research (2018)

Abstract Adiposity may cause adverse health outcomes by increasing oxidative stress and systemic inflammation, which can be reflected by altered telomere length (TL) and mitochondrial DNA copy number (mtCN) in peripheral blood leukocytes. However, little is known about the influence of lifetime adiposity on TL and mtCN in later life. This study was performed to investigate the associations of lifetime adiposity with leukocyte TL and mtCN in 9613 participants from the Nurses' Health Study. A group-based trajectory modelling approach was used to create trajectories of body shape from age 5 through 60 years, and a genetic risk score (GRS) was created based on 97 known adiposity susceptibility loci. Associations of body shape trajectories and GRS with dichotomized TL and mtCN were assessed by logistic regression models. After adjustment for lifestyle and dietary factors, compared with the lean-stable group, the lean-marked increase group had higher odds of having below-median TL (OR = 1.18, 95% CI: 1.04, 1.35; P = 0.01), and the medium-marked increase group had higher odds of having below-median mtCN (OR = 1.28, 95% CI:1.00,1.64; P = 0.047). There was a suggestive trend toward lower mtCN across the GRS quartiles (P for trend = 0.07). In conclusion, telomere attrition may be accelerated by marked weight gain in middle life, whereas mtCN is likely to be reduced persistently by adiposity over the life course. The findings indicate the importance of lifetime weight management to preserve functional telomeres and mitochondria. Citation Format: Dong Hang, Hongmei Nan, Ane Sørlie Kværner, Immaculata De Vivo, Andrew T. Chan, Zhibin Hu, Hongbing Shen, Edward Giovannucci, Mingyang Song. Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-158.
Assessment of Environmental Sustainability and Corporate Social Responsibility Reporting by Large Health Care Organizations
Authors: Emily Senay, Philip J. Landrigan
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Sustainability practices by large corporations are increasingly important to reduce the environmental and social impacts of the business enterprise. The health care industry represents 18% of the US economy, employs more people than any other economic sector, and is responsible for 10% of US carbon emissions. The engagement of large health care delivery organizations in reporting sustainability efforts has not been previously assessed. <h3>Objective</h3> To evaluate sustainability reporting by large US health care delivery organizations compared with reporting trends in all other economic sectors. <h3>Design, Setting, and Participants</h3> Cohort study of 49 large health care organizations (HCOs) by inclusion on one of the following lists in 2015 or 2016: Fortune 500, S&amp;P (Standard &amp; Poor) 500, Forbes 100 Largest Charities, Becker’s Hospital Review of largest HCOs, and 24/7 Wall St’s largest state employers. Each HCO was analyzed for sustainability reporting by reviewing the main corporate website, Google search, and search of publicly available databases. The percentage of sustainability reporting by HCOs on each list was compared with the percentage of sustainability reporting by all corporations on each list as obtained from public reports and publicly available databases. Data analysis was conducted in January 2018. <h3>Main Outcomes and Measures</h3> The percentages of large health care corporations and other corporations publicly reporting sustainability information. <h3>Results</h3> Forty-nine large for-profit and nonprofit US HCOs were analyzed (10 appeared on &gt;1 list but were analyzed only once) appearing on the Fortune 500 (8 [16%]), S&amp;P 500 (3 [6%]), Forbes 100 Largest Charities (8 [16%]), largest state employers (14 [29%]), largest for-profit HCOs (11 [22%]), and largest nonprofit HCOs (17 [35%]) by facilities owned for sustainability reporting. Among them, 4 of 8 (50%) on the Fortune 500, 1 of 3 (33%) on the S&amp;P 500, and 6 of all 49 health care corporations (12%) published a sustainability report compared with 389 of 500 (78%) on the Fortune 500 and 410 of 500 (82%) on the S&amp;P 500 reporting by all economic sectors. <h3>Conclusions and Relevance</h3> The health care delivery sector lags behind other US economic sectors in sustainability reporting. Publicly reporting sustainability activities would provide HCOs with an incentive to quantify and reduce their environmental impacts, lower costs, and protect human health.
Abstract 17692: The Development of a Risk Score for Incident Atrial Fibrillation in Japanese General Population Cohorts: a Collaborative Meta-analysis
Authors: Yoshihiro Kokubo, Hironori Imano, Jun Hata, Nobuyuki Murakoshi, Yoshifusa Aizawa, Hiroyasu Iso, Toshiharu Ninomiya, Fumiaki Nakamura, Yoshihiro Miyamoto, Tomonori Okamura, Hirofumi Tomita, Ken Okumura
Journal: Circulation (2016)

Purpose: Atrial fibrillation (AF) is a strong risk factor for mortality and morbidity. Nevertheless, few risk scores exist for incident AF that reflect nationwide. We conducted a meta-analysis to d...