tbuckley/cabot-search huggingface dataset:
Bacterial modulators of bone remodeling in the periodontal pocket
Authors: Brian Henderson, Frank Kaiser
Journal: Periodontology 2000 (2017)

Abstract The signaling network involved in the pathogenesis of periodontal disease is not yet fully understood. This review aims to describe possible mechanisms through which the bacterial modulators may be linked directly or indirectly to the process of alveolar bone loss in periodontitis. From the late 1970s to present, new paradigm shifts have been developed regarding our understanding of pathological bone remodeling in periodontal disease. Upcoming evidence suggests that in periodontal disease the local immune response is exacerbated and involves the existence of signaling pathways that have been shown to modulate bone‐cell function leading to alveolar bone loss. Those complex signaling pathways have been observed not only between bacteria but also between bacteria and the gingival surface of the host. More specifically, it has been shown that bacteria, through their secretion molecules, may interact indirectly and directly with immune‐type cells of the host, resulting in the production of osteolytic agents that enhance bone resorption. Further research is required to provide a clear understanding of the role of these molecules in the pathogenesis of periodontal disease, and the availability of new technologies, such as next‐generation sequencing and metagenomic analysis, may be useful tools in achieving this.
2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants
Authors: Gordon F. Tomaselli, Kenneth W. Mahaffey, Adam Cuker, Paul P. Dobesh, John U. Doherty, John W. Eikelboom, Roberta Florido, William Hucker, Roxana Mehran, Steven R. Messé, Charles V. Pollack, Fatima Rodriguez, Ravindra Sarode, Deborah Siegal, Barbara S. Wiggins
Journal: Journal of the American College of Cardiology (2017)
PEGylated human IL-10 (AM0010) in combination with an anti-PD-1 in advanced NSCLC
Authors: D. Wong, J.G. Schneider, R. Aljumaily, W.M. Korn, J. Infante, M. Patel, K. Autio, K. Papadopoulos, A. Naing, N.Y. Gabrail, P. Munster, J. Goldman, N. Ratti, P. Van Vlasselaer, A. Hung, M. Oft, E. Garon
Journal: Annals of Oncology (2017)
Gene expression induced by the platelet-derived growth factor receptors (PDGFR) alpha and beta in childhood medulloblastomas
Authors: Thamara Abouantoun
Journal: Cancer Research (2007)

432   Objective: Medulloblastoma is the most common malignant brain tumor in children. Survival rates are below 50% in patients with metastatic tumors, and close to 0% in those who relapse with metastatic tumors compared to greater than 80% in patients without tumor metastasis. We previously showed that overexpression of the platelet-derived growth factor receptor (PDGFR) correlates with metastatic medulloblastoma. Upon binding to the ligand PDGF, PDGFR, a receptor tyrosine kinase (RTK), undergoes autophosphorylation which in turn initiates signal transduction through the RAS/MAPK and PI3K-AKT pathways leading to cell proliferation, migration, survival and gene transcription.  Methods: To determine whether PDGFR signaling is critical to these processes in medulloblastoma cells, we inhibited the PDGFR expression and activity in Daoy human medulloblastoma cells using three separate methods: 1) small interfering RNA (siRNA) to PDGFR; 2) RTK inhibition of PDGFR with Gleevec; and 3) anti-PDGF neutralizing antibodies, and measured the resultant changes in gene expression and survival following PDGF stimulation. These changes were compared to baseline serum-depleted cells, with and without PDGFR inhibition, stimulated with PDGF.  Results: PDGFR-active cells stimulated with PDGF showed enhanced survival and proliferation and exhibited gene expression changes at 24h, as measured by Affymetrix microarray profiling, that were specific to the subtype of ligand (PDGFAA or PDGFBB) used for stimulation. PDGFBB, which activates both the alpha and the beta receptor subtypes, was more potent than the PDGFAA, which only activates the alpha receptor subtype of PDGFR. PDGFBB induced gene expression encoding effectors that primarily regulate signal transduction and cell-cycle control, while PDGFAA enduced gene expression encoding effectors that predominantly affect chemotaxis. Following Gleevec treatment, both PDGFAA and BB up-regulated expression of PI3K and induced Akt phosphorylation in a portion of surviving cells, suggesting a bypass pathway to overcome the effect of PDGFR tyrosine kinase inhibition. PDGF neutralizing antibodies and transient siRNA transfection abrogated the gene expression changes and subsequent survival, indicating that this effect is dependent on the presence of PDGFR and its interaction with PDGF.  Conclusion: These results suggest that PDGFR is critical for medulloblastoma survival through a signal transduction mechanism that promotes pro-survival gene transcription. In addition, physical interaction of the receptor in the membrane seems to exert a significant effect on PDGFR-induced gene expression because only siRNA silencing was able to abrogate this PDGFR-induced gene expression. Thus, a fully intact PDGFR appears to be important for maintaining signal transduction, gene expression, survival and migration in medulloblastoma cells.
Humane Language for People in the Criminal Justice System—Reply
Authors: Jason Chertoff
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 12033: PCI De Lucs: A Prehospital Pathway Direct to the Cath Lab for Patients Suffering From Out-of Hospital Cardiac Arrest
Authors: Christer Axelsson, Maria Jimenez-Herrera, Johan Herlitz, Johan Holmen
Journal: Circulation (2016)

Purpose: In Sweden, the ambulance response time from call to arrival is 11 minutes in patients with an out-of-hospital cardiac arrest (OHCA). However, there is a small group of OHCA patients (20%) in whom this delay is minimized, namely those that occur minutes before or after the arrival of the ambulance. Despite CPR and/or defibrillation within one minute, only 20% survive to hospital discharge. The objective was therefore to determine whether a pathway with direct transportation to the cath lab, using mechanical chest compression (LUCAS), could improve survival in this selected group. Aim: To describe characteristics, feasibility and outcome among a selected group of OHCA patients transported directly to the cath lab by the ambulance in a new pathway Method: A prospective observational study from November 2013 to November 2015 Inclusion criteria: 1. Crew-witnessed cardiac arrest (CA) of cardiac origin or CA immediately defibrillated to return of spontaneous circulation (ROSC) by public access. 2. CA occurring two to three minutes before ambulance arrival where the patient had immediate bystander CPR of high quality. 4. CA occurring two to three minutes before ambulance arrival where the patient was still breathing at ambulance arrival. Exclusion criteria: Non-cardiac origin CA or high physiologic age (hospice patients) Result: Sixty-four patients fulfilled the inclusion criteria and 14 were excluded. Of the remaining 50 patients, 25 were transported with mechanical CPR to the cath lab. The time from CA to hospital was a median of 38 minutes. Survival to 30 days was 38% among all patients, 47% among VF (N=34) and 12% (N=25) among those who were transported with mechanical CPR. Conclusion: The pathway appears safe and feasible, but the inclusion criteria need to be less complex. The vast majority of survivors were found in the VF population. There were survivors (12%) among patients transported with ongoing CPR (N=25) directly to the cath lab by the ambulance.
Factors Impacting Quality of Life in Thalassemia Patients; Results from the Intercontinenthal Collaborative Study
Authors: Ali Amid, Rebecca Leroux, Manuela Merelles-Pulcini, Saeed Yassobi, Antoine N Saliba, Richard Ward, Mehran Karimi, Ali T. Taher, Robert J Klaassen, Melanie Kirby-Allen
Journal: Blood (2016)
Nanomaterials for treating cardiovascular diseases: A review
Authors: Wensen Jiang, Dana Rutherford, Tiffany Vuong, Huinan Liu
Journal: Bioactive Materials (2017)

Nanomaterials such as nanostructured surfaces, nanoparticles, and nanocomposites represent new viable sources for future therapeutics for cardiovascular diseases. The special properties of nanomaterials such as their intrinsic physiochemical properties, surface energy and surface topographies could actively enhance desirable cellular responses within the cardiovascular system, projecting a growing potential for clinical translation. Recent progress on nanomaterials opened up new opportunities for treating cardiovascular diseases. Successful translation of nanomaterials into cardiovascular applications requires a comprehensive understanding of both nanomaterials and biomedicine, and, thus, it is critical to stress current advancements on both sides. In this review, the authors introduced crucial fabrication techniques for promising nanomaterials for cardiovascular applications. This review highlighted the key elements to consider for their fabrication, properties and applications. The important concerns relevant to cardiovascular nanomaterials, such as cellular responses to nanomaterials and the toxicity of nanomaterials, are also discussed. This review provided an overview of necessary knowledge and key concerns on nanomaterials specific for treating cardiovascular diseases, from the perspectives of both material science and biomedicine.
Respiratory Responses to Ozone Exposure. MOSES (The Multicenter Ozone Study in Older Subjects)
Authors: Mehrdad Arjomandi, John R. Balmes, Mark W. Frampton, Philip Bromberg, David Q. Rich, Paul Stark, Neil E. Alexis, Maria Costantini, Danielle Hollenbeck-Pringle, Nicholas Dagincourt, Milan J. Hazucha
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Acute respiratory effects of low-level ozone exposure are not well defined in older adults.MOSES (The Multicenter Ozone Study in Older Subjects), although primarily focused on acute cardiovascular effects, provided an opportunity to assess respiratory responses to low concentrations of ozone in older healthy adults.We performed a randomized crossover, controlled exposure study of 87 healthy adults (59.9 ± 4.5 yr old; 60% female) to 0, 70, and 120 ppb ozone for 3 hours with intermittent exercise. Outcome measures included spirometry, sputum markers of airway inflammation, and plasma club cell protein-16 (CC16), a marker of airway epithelial injury. The effects of ozone exposure on these outcomes were evaluated with mixed-effect linear models. A P value less than 0.01 was chosen a priori to define statistical significance.The mean (95% confidence interval) FEV1 and FVC increased from preexposure values by 2.7% (2.0-3.4) and 2.1% (1.3-2.9), respectively, 15 minutes after exposure to filtered air (0 ppb). Exposure to ozone reduced these increases in a concentration-dependent manner. After 120-ppb exposure, FEV1 and FVC decreased by 1.7% (1.1-2.3) and 0.8% (0.3-1.3), respectively. A similar concentration-dependent pattern was still discernible 22 hours after exposure. At 4 hours after exposure, plasma CC16 increased from preexposure levels in an ozone concentration-dependent manner. Sputum neutrophils obtained 22 hours after exposure showed a marginally significant increase in a concentration-dependent manner (P = 0.012), but proinflammatory cytokines (IL-6, IL-8, and tumor necrosis factor-α) were not significantly affected.Exposure to ozone at near ambient levels induced lung function effects, airway injury, and airway inflammation in older healthy adults. Clinical trial registered with www.clinicaltrials.gov (NCT01487005).
Integrated Molecular Characterization of the Lethal Pediatric Cancer Pancreatoblastoma
Authors: Tomoya Isobe, Masafumi Seki, Kenichi Yoshida, Masahiro Sekiguchi, Yusuke Shiozawa, Yuichi Shiraishi, Shunsuke Kimura, Misa Yoshida, Yoshikage Inoue, Akira Yokoyama, Nobuyuki Kakiuchi, Hiromichi Suzuki, Keisuke Kataoka, Yusuke Sato, Tomoko Kawai, Kenichi Chiba, Hiroko Tanaka, Teppei Shimamura, Motohiro Kato, Akihiro Iguchi, Asahito Hama, Tomoaki Taguchi, Masaharu Akiyama, Junya Fujimura, Akiko Inoue, Tsuyoshi Ito, Takao Deguchi, Chikako Kiyotani, Tomoko Iehara, Hajime Hosoi, Akira Oka, Masashi Sanada, Yukichi Tanaka, Kenichiro Hata, Satoru Miyano, Seishi Ogawa, Junko Takita
Journal: Cancer Research (2017)

Pancreatoblastoma is a rare pediatric pancreatic malignancy for which the molecular pathogenesis is not understood. In this study, we report the findings of an integrated multiomics study of whole-exome and RNA sequencing as well as genome-wide copy number and methylation analyses of ten pancreatoblastoma cases. The pancreatoblastoma genome was characterized by a high frequency of aberrant activation of the Wnt signaling pathway, either via somatic mutations of CTNNB1 (90%) and copy-neutral loss of heterozygosity (CN-LOH) of APC (10%). In addition, imprinting dysregulation of IGF2 as a consequence of CN-LOH (80%), gain of paternal allele (10%), and gain of methylation (10%) was universally detected. At the transcriptome level, pancreatoblastoma exhibited an expression profile characteristic of early pancreas progenitor-like cells along with upregulation of the R-spondin/LGR5/RNF43 module. Our results offer a comprehensive description of the molecular basis for pancreatoblastoma and highlight rational therapeutic targets for its treatment.Significance: Molecular genetic analysis of a rare untreatable pediatric tumor reveals Wnt/IGF2 aberrations and features of early pancreas progenitor-like cells, suggesting cellular origins and rational strategies for therapeutic targeting. Cancer Res; 78(4); 865-76. ©2017 AACR.
Successful guidewire placement across hilar malignant biliary stricture after deceased donor liver transplantation using new digital cholangioscopy
Authors: Ryunosuke Hakuta, Hirofumi Kogure, Yousuke Nakai, Naminatsu Takahara, Suguru Mizuno, Minoru Tada, Kazuhiko Koike
Journal: Endoscopy (2017)

A 70-year-old man with metastatic rectal cancer was referred to our department for endoscopic management of obstructive jaundice due to metastatic lymph nodes. He previously received deceased donor liver transplantation with duct-to-duct biliary reconstruction. Computed tomography and magnetic resonance cholangiopancreatography showed hilar biliary stricture due to metastatic lymph nodes at the duct-to-duct anastomosis ([Fig. 1], [Fig. 2]). Endoscopic retrograde cholangiopancreatography revealed a markedly dilated recipient bile duct and a stricture of the donor hepatic duct ([Fig. 3]). Multiple attempts to pass the hilar stricture using a 0.035-inch hydrophilic guidewire and a cannula or a rotatable sphincterotome failed because a guidewire easily advanced to the remnant cystic duct just below the stricture. Hence, after endoscopic sphincterotomy, guidewire passage using SpyGlass DS Direct Visualization System (SpyDS; Boston Scientific Japan, Tokyo, Japan) was attempted. Cholangioscopy allowed direct visualization of both torturous biliary stricture with non-tumorous mucosa and the wide-opening remnant cystic duct ([Fig. 4]). A guidewire was readily passed through the stricture into the left intrahepatic duct under SpyDS and fluoroscopy guidance ([Fig. 5]). Given the presence of high-grade hilar biliary stricture, bilateral metal stent placement in a partially stent-in-stent method was successfully performed with rapid resolution of jaundice ([Fig. 6]).
Patient characteristics influence the choice of biological drug in RA, and will make non-TNFi biologics appear more harmful than TNFi biologics
Authors: Thomas Frisell, Eva Baecklund, Karin Bengtsson, Daniela Di Giuseppe, Helena Forsblad-d’Elia, Johan Askling
Journal: Annals of the Rheumatic Diseases (2017)

With the wide range of biological disease-modifying anti-rheumatic drugs (bDMARDs) available for treating rheumatoid arthritis (RA), and limited evidence to guide the choice for individual patients, we wished to evaluate whether patient characteristics influence the choice of bDMARD in clinical practice, and to quantify the extent to which this would bias direct comparisons of treatment outcome.Register-based study of all Swedish patients with RA initiating necrosis factor inhibitor (TNFi), rituximab, abatacept or tocilizumab in 2011-2015 as their first bDMARD (n=6481), or after switch from TNFi as first bDMARD (n=2829). Group differences in demographics, clinical characteristics and medical history were assessed in multivariable regression models. Predicted differences in safety and treatment outcomes were calculated as a function of patient characteristics, through regression modelling based on observed outcomes among patients with RA starting bDMARDs 2006-2010.Patients starting non-TNFi were older than those starting TNFi, had lower socioeconomic status, higher disease activity and higher burden of diseases including malignancy, serious infections and diabetes. Differences were most pronounced at first bDMARD initiation. These factors were linked to treatment outcome independent of therapy, yielding worse apparent safety and effectiveness for non-TNFi biologics, most extreme for rituximab. Standardising to the age/sex distribution of the TNFi group reduced differences considerably.There was significant channelling of older and less healthy patients with RA to non-TNFi bDMARDs, in particular as first bDMARD. Whether this channelling represents a maximised benefit/risk ratio is unclear. Unless differences in age, medical history and disease activity are accounted for, they will substantially confound non-randomised comparative studies of available bDMARDs' safety and effectiveness.
Concerns About Conclusions of Self-monitoring of Blood Glucose—Reply
Authors: Laura A Young, John B Buse, Katrina E Donahue
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine
Authors: Kiterie M E Faller, Dorothee Atzler, Debra J McAndrew, Sevasti Zervou, Hannah J Whittington, Jillian N Simon, Dunja Aksentijevic, Michiel ten Hove, Chi-un Choe, Dirk Isbrandt, Barbara Casadei, Jurgen E Schneider, Stefan Neubauer, Craig A Lygate
Journal: Cardiovascular Research (2017)

Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality.Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function.Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases.
Know-do-itis and no-do encephalopathy
Authors: Linda S Franck
Journal: BMJ (2017)

Countries around the world invest millions annually to ensure that healthcare is evidence based and that health systems deliver patient care that reflects the most current and rigorous research evidence.

Despite these efforts, there is a surprising and silent epidemic of clinician and health system resistance to the practice of evidence based healthcare. No amount of training, retraining, professional incentives, or governmental regulation seems to overcome this resistance. Moreover, the condition is often contagious, causing intermittent outbreaks of I’m-going-to-do-this-my-way. Recent advances have enabled characterisation of this condition and provided new insights into the mechanisms and possible treatments.

Resistance …