tbuckley/cabot-search huggingface dataset:
Abstract 16847: Cardiac Deletion of Liver Kinase B1 Leads to Cardiac Dysfunction, Atrial Arrhythmias and Ultra-Structural Abnormalities That are Not Attributable to AMP-Activated Protein Kinase Inactivation
Authors: Jenna L Ross, Monica Palmeri, Vlad G Zaha, Lawrence H Young
Journal: Circulation (2011)

Liver kinase B1 (LKB1) is an upstream activator of AMP-activated protein kinase (AMPK) as well as 12 other members of the AMPK superfamily. In order to address the potential role of LKB1/AMPK signaling in cardiac development and growth, we generated cardiac specific LKB1 deleted mice (MHC Cre-LKB1flox/flox) in a pure C57/Bl6 background and compared cardiac size, function, electrophysiology and ultra-structure to syngeneic AMPK kinase-dead (AMPK-KD) mice expressing the rat alpha2 K45R mutation. LKB1 mRNA and protein were reduced by &gt;85% in atria and &gt;95% in ventricles in MHC Cre-LKB1flox/flox hearts. MHC Cre-LKB1flox/flox (n = 6) mice were in sinus rhythm at postnatal day 1, but developed atrial fibrillation by two weeks of age (n = 11); in contrast, LKB1flox/flox (n = 5) and AMPK-KD (n = 6) mice did not develop atrial arrhythmias through 10 weeks. Echocardiography revealed significant left atrial (LA) enlargement by 4 weeks of age (1.95 ± 0.11 mm vs. 1.45 ± 0.19 mm, p&lt;0.05), left ventricle (LV) hypertrophy at 6 weeks of age (0.78 ± 0.03 mm vs. 0.67 ± 0.03 mm, p&lt;0.05), and progressive cardiac dysfunction (LV ejection fraction (LVEF): 40.3 ± 2.1% vs. 48.9 ± 2.3%) in MHC Cre-LKB1flox/flox vs. LKB1flox/flox. In contrast, AMPK-KD (n = 6) vs. AMPK-WT (n = 3) hearts had similar LA diameter (1.51 ± 0.15 mm vs. 1.59 ± 0.05 mm), LV wall thickness (0.67 ± 0.03 mm vs. 0.66 ± 0.03 mm), and LVEF (48.9 ± 2.3% vs 47.8 ± 2.4%). Histological analysis revealed marked atrial fibrosis by two weeks of age in MHC Cre-LKB1flox/flox hearts, but normal morphology in AMPK-KD hearts through 10 weeks. Electron microscopy showed disrupted gap junction formation, mitochondrial integrity and the presence of autophagic bodies exclusively in MHC Cre-LKB1flox/flox hearts. In conclusion, this study indicates marked myopathic and arrhythmic abnormalities in LKB1 deleted vs. AMPK-KD mouse hearts. Thus, AMPK-independent signaling, possibly mediated by AMPK-related kinases, appear to be critical for LKB1 regulated cardiac development and growth.
Dexmedetomidine enhances glymphatic brain delivery of intrathecally administered drugs
Authors: Tuomas O. Lilius, Kim Blomqvist, Natalie L. Hauglund, Guojun Liu, Frederik Filip Stæger, Simone Bærentzen, Ting Du, Fredrik Ahlström, Janne T. Backman, Eija A. Kalso, Pekka V. Rauhala, Maiken Nedergaard
Journal: Journal of Controlled Release (2019)

Drug delivery to the central nervous system remains a major problem due to biological barriers. The blood-brain-barrier can be bypassed by administering drugs intrathecally directly to the cerebrospinal fluid (CSF). The glymphatic system, a network of perivascular spaces promoting fluid exchange between CSF and interstitial space, could be utilized to enhance convective drug delivery from the CSF to the parenchyma. Glymphatic flow is highest during sleep and anesthesia regimens that induce a slow-wave sleep-like state. Here, using mass spectrometry and fluorescent imaging techniques, we show that the clinically used α2-adrenergic agonist dexmedetomidine that enhances EEG slow-wave activity, increases brain and spinal cord drug exposure of intrathecally administered drugs in mice and rats. Using oxycodone, naloxone, and an IgG-sized antibody as relevant model drugs we demonstrate that modulation of glymphatic flow has a distinct impact on the distribution of intrathecally administered therapeutics. These findings can be exploited in the clinic to improve the efficacy and safety of intrathecally administered therapeutics.
Exploring Mental Disorders in Patients With Skin Diseases
Authors: April W. Armstrong
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Fas ligand and nitric oxide combination to control smooth muscle growth while sparing endothelium
Authors: Mehmet H. Kural, Juan Wang, Liqiong Gui, Yifan Yuan, Guangxin Li, Katherine L. Leiby, Elias Quijano, George Tellides, W. Mark Saltzman, Laura E. Niklason
Journal: Biomaterials (2019)
Abstract P3-12-20: The use of new delineation tool “MIRADA”, step-by-step development and first results of its use in early and locally advanced breast cancer patients
Authors: H Xu, A Arsene Henry, M Robillard, M Amessis, YM Kirova
Journal: Cancer Research (2019)

Abstract Objectives: To describe the practical procedure of implementation and optimization of delineation using “Mirada” software, as well as evaluation of the automatic segmentation for the daily practice of lymph nodes (LN) and OARs (organs at risk) in early as well as locally advanced stage breast cancer patients. Methods: Forty patients' CT scans in treatment position were selected and re-contoured according to the ESTRO guidelines. The atlas of dataset was then created for automatic delineation. Thirty patients with breast/chest wall and lymph nodes regions irradiated were recruited for evaluation. With the same treatment position, the CT scan images were acquired and then contoured by the MIRADA system automatically as well as by the radiation oncologist manually (as the reference). The Conformity Index (CI) was used to evaluate the concordance between both of them. Results: The mean time for manual contour was 24.1±5.1 mins and 26.4±2.8 mins for the LN and the OARs resp. All the volumes of interest were contoured using the software (including corrections) in 30 minutes, which reduced the time of delineation of target volumes and OAR by about 40%. Of the 30 cases evaluated, the mean CI of 5 principal OARs showed ≥ 0.8. While the automatic contour of LN was less satisfactory with mean CI of 0.43±0.1 (0.23-0.52). Conclusions: For the breast cancer patients, the studied software permitted to save time for delineation with acceptable OAR contours. The improvement of LN regions contour is needed. More cases and further evaluation are needed for the system to realize its routine use. Citation Format: Xu H, Arsene Henry A, Robillard M, Amessis M, Kirova YM. The use of new delineation tool “MIRADA”, step-by-step development and first results of its use in early and locally advanced breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-20.
Plasminogen activator inhibitor-1 promotes immunosuppression in cancer by modulating immune component of tumor microenvironment
Authors: P. Yadav, N. Kumar, A. Kumar, A. Kapoor, S. Beniwal, A. Kalwar
Journal: Annals of Oncology (2018)

Background: Plasminogen activator inhibitor-1 (PAI-1) is corelated with inflammation and tumorigenesis. We investigated the role of PAI-1 in tumor regulating immune component of tumor microenvironment. Methods: Protein expression data proteins and phosphoproteins, tumor infiltrating immune cells with relative fraction of immune cell types and major clinical outcome endpoints were obtained from The Cancer Genome Atlas project. A statistical correlation analysis was performed between the expression and distribution of PAI-1, immune checkpoint expression, tumor infiltrating immune cells fraction and their distribution in each tumor. We used Cox proportional hazards model to evaluate the association of PAI-1 with clinical survival outcomes. Results: The expression and distribution patterns of PAI-1 was measured in 7858 samples from 32 cancer type. PAI-1 had an enrichment in the squamous cancers. Increased expression of PAI-1 was associated with higher tumor stage and grade. Analyses of the tumor microenvironment revealed unanticipated correlation of PAI-1 with immune checkpoint expression and infiltrating immune cells. PAI-1 expression was tightly correlated to TGF-beta response (corr=0.40; p < 0.01), tumor leucocyte fraction (corr=0.33; p < 0.01) and PD-L1 expression (corr=0.29; p < 0.01). PAI-1 was positively corelates with intra-tumor heterogeneity (p < 0.01), proliferation(p < 0.01), stroma fraction (p < 0.01) and macrophages (p < 0.01). PAI-1 was also negatively correlated with lymphocyte fraction, activate CD4 cells, T cells (FH, gamma-delta and CD8). These correlations were also found with individual cancer type. PAI-1 was associated with poor Overall survival (Hazards ratio (HR)= 1.4; p < 0.01), Progression free interval (HR = 1.3; p < 0.01), disease free interval (HR = 1.26; p < 0.01) and disease specific survival (HR = 1.42; p < 0.01). PAI-1 was also associated with poor clinical outcomes in individual cancer type. Legal entity responsible for the study: Narender Kumar. Conclusions: PAI-1 is correlated with PD-L1 and influences the tumor progression by modulating tumor microenvironment. PAI-1 might be valuable target indicating opportunities for personalised combination therapy of cancer. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Enriched gestation activates the IGF pathway to evoke embryo-adult benefits to prevent Alzheimer’s disease
Authors: Enjie Liu, Qiuzhi Zhou, Ao-Ji Xie, Mengzhu Li, Shujuan Zhang, Hezhou Huang, Zhenyu Liuyang, Yali Wang, Bingjin Liu, Xiaoguang Li, Dongsheng Sun, Yuping Wei, Xiaochuan Wang, Qun Wang, Dan Ke, Xifei Yang, Ying Yang, Jian-Zhi Wang
Journal: Translational Neurodegeneration (2019)

Building brain reserves before dementia onset could represent a promising strategy to prevent Alzheimer's disease (AD), while how to initiate early cognitive stimulation is unclear. Given that the immature brain is more sensitive to environmental stimuli and that brain dynamics decrease with ageing, we reasoned that it would be effective to initiate cognitive stimulation against AD as early as the fetal period. After conception, maternal AD transgenic mice (3 × Tg AD) were exposed to gestational environment enrichment (GEE) until the day of delivery. The cognitive capacity of the offspring was assessed by the Morris water maze and contextual fear-conditioning tests when the offspring were raised in a standard environment to 7 months of age. Western blotting, immunohistochemistry, real-time PCR, immunoprecipitation, chromatin immunoprecipitation (ChIP) assay, electrophysiology, Golgi staining, activity assays and sandwich ELISA were employed to gain insight into the mechanisms underlying the beneficial effects of GEE on embryos and 7–10-month-old adult offspring. We found that GEE markedly preserved synaptic plasticity and memory capacity with amelioration of hallmark pathologies in 7–10-m-old AD offspring. The beneficial effects of GEE were accompanied by global histone hyperacetylation, including those at bdnf promoter-binding regions, with robust BDNF mRNA and protein expression in both embryo and progeny hippocampus. GEE increased insulin-like growth factor 1 (IGF1) and activated its receptor (IGF1R), which phosphorylates Ca2+/calmodulin-dependent kinase IV (CaMKIV) at tyrosine sites and triggers its nuclear translocation, subsequently upregulating histone acetyltransferase (HAT) and BDNF transcription. The upregulation of IGF1 mimicked the effects of GEE, while IGF1R or HAT inhibition during pregnancy abolished the GEE-induced CaMKIV-dependent histone hyperacetylation and BDNF upregulation. These findings suggest that activation of IGF1R/CaMKIV/HAT/BDNF signaling by gestational environment enrichment may serve as a promising strategy to delay AD progression.
Abstract 14752: Pressure- and Velocity-Based Physiological Assessment of Stenotic Lesions at Hyperemia in Superficial Femoral Artery Disease; Importance of Hyperemic Stenosis Resistance
Authors: Kuniyasu Ikeoka, Nagahiro Nishikawa, Tetusya Watanabe, Shiro Hoshida
Journal: Circulation (2018)

Introduction: Measurement of the fractional flow reserve (FFR) or vascular flow reserve (VFR) is a feasible approach to diagnose a peripheral arterial physiological condition. However, maximal hype...
Abstract P345: A Diet-Wide Association Study on Blood Pressure- the INTERMAP Study
Authors: Ioanna Tzoulaki, Chirag J Patel, Jeremiah Stamler, Ian J Brown, Queenie Chan, Atul J Butte, John P Ioannidis, Paul Elliott
Journal: Circulation (2012)

Background: Epidemiological studies have examined the relationship between dietary habits and blood pressure. However, studies often test one or only a few factors at a time or examine food patterns (e.g. the Mediterranean diet) not well assessed or defined. Here we use the previously suggested Environmental-wide Association Study (EWAS) paradigm, which evaluates multiple factors concurrently for associations, adjusting for multiplicity of comparisons. Methods: We used data from the INTERMAP cross-sectional epidemiological Study with 4680 persons ages 40 to 59 years from 17 random population samples in China, Japan, the United Kingdom, and the United States. BP was measured 8 times at 4 visits; dietary data (83 nutrients) were obtained from 4 standardized, multipass, 24-hour dietary recalls and 2 timed 24-hour urine collections. We examined association between each nutrient and systolic and diastolic blood pressure in separate linear regression models using a random 50% test sample, stratified across centers, of the INTERMAP population. The most significant results were subsequently validated in the remaining 50%. The false discovery rate (FDR), the expected proportion of false positive results among statistically significant hypotheses, was calculated. We considered an examined nutrient as validated when the FDR was 5% in the training set and P-value for association was &lt;0.05 in the validation set. Results: In models adjusted for multiple confounders, dietary alcohol and urinary sodium-to-potassium ratio had positive associations and non-heme iron intake, dietary phosphorus, vegetable protein, magnesium, total carbohydrate, pantothenic acid, folacin, thiamin, riboflavin and urinary calcium inverse associations with systolic blood pressure (FDR&lt;5% in training and P&lt;0.05 in validation). With the same set of confounders, dietary alcohol had positive and non-heme iron intake, dietary calcium, phosphorus, protein, thiamin and glutamic acid and urinary potassium and magnesium, inverse associations with diastolic blood pressure (FDR&lt;5% in training and P&lt;0.05 in validation). Conclusions: Using the methodology originally proposed for genome-wide association studies studies (GWAS), we replicated previously reported associations between dietary habits and blood pressure, also found some novel associations for B vitamins. As epidemiological studies increasingly collect large amount of data, it is essential to report transparently all analyses, account for multiple tests, and replicate findings.
Lipids. Workshop IV. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health.
Authors: T A Pearson, W V Brown, K Donato, F A Franklin, R B Luepker, P E McBride, R M Mullis, L W Scott, B Shannon, R B Shekelle
Journal: Circulation (1993)

American Heart Association Prevention I Conference dealt exclusively with issues related to blood cholesterol level and disease.'The AHA has endorsed a number of national recommendations and guidelines in this area, including the Adult Treatment Panel Guidelines on the Detection, Evalua- tion, and Treatment of High Blood Cholesterol in Adults,2 the Report of the Expert Panel on Population Strategies for Blood Cholesterol Reduction,3 the Re- port for the Laboratory Standardization Panel of the National Cholesterol Education Program,4 the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents,5 and the joint American Heart Association-National Heart, Lung, and Blood Institute report on cholesterol lowering in patients with established heart disease.6A recent National Institutes of Health consensus conference focused on triglycerides, high-density lipoproteins, and coronary heart dis-
Abstract P6-09-08: High circulating levels of Periostin are associated with a poor survival in primary, non-metastatic breast cancer patients
Authors: O Hoffmann, A Goebel, A-K Bittner, M Rauner, LC Hofbauer, R Kimmig, S Kasimir-Bauer, TD Rachner
Journal: Cancer Research (2019)

Abstract Background: Periostin, also known as osteoblast-specific factor OSF-2, functions as a ligand for integrins to support adhesion and migration of tumor cells which leads to increased cell survival, invasion, angiogenesis and metastasis in different cancer types including breast cancer (BC). Assuming that metastasis requires a dissemination of tumor cells, associated with worse outcome in BC, the aim of this study was to determine the expression of Periostin in blood samples of patients with primary, non-metastatic BC and to correlate the results with clinical parameters including the presence of disseminated tumor cells (DTCs) in the bone marrow (BM), survival and the risk of developing metastatic disease. Patients and Methods: BM and blood sampling were performed before surgery in an adjuvant setting in 509 patients with first diagnosis of BC between Aug 2006 and Dec 2009. Two BM aspirates were analyzed for DTCs using density centrifugation followed by immunocytochemistry applying the pan-cytokeratin antibody A45-B/B3. Blood was collected from each patient and Periostin serum levels were measured by ELISA (Biomedica, Vienna, Austria). Results: Periostin levels were detectable (504.8 ± 178.7 pmol/l) in all BC patients. There were no significant differences between serum Periostin levels when stratifying according to tumor stage, lymph node involvement or grading. Periostin levels were significantly increased in women above the age of 60 (468.6±166.6 pmol/l vs. 540.1±184.2 pmol/l; p&amp;lt;0.0001) and significantly enhanced in postmenopausal compared to peri- or premenopausal women (p&amp;lt;0.05 and p&amp;lt;0.001, respectively). No differences were observed between DTC-positive and DTC-negative patients. When separating patients according to high (top 50%) or low (low 50%) Periostin levels, patients with low Periostin levels had a significantly shorter BC specific survival (HR 0.61; 95%CI 0.39-0.96; p=0.03). Conclusion: In summary, while Periostin levels were unchanged in patients with and without DTCs, high levels of Periostin were associated with a poorer BC specific survival. These results warrant further studies on the role of Periostin in BC. Citation Format: Hoffmann O, Goebel A, Bittner A-K, Rauner M, Hofbauer LC, Kimmig R, Kasimir-Bauer S, Rachner TD. High circulating levels of Periostin are associated with a poor survival in primary, non-metastatic breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-09-08.
Abstract P1-08-30: Triple negative breast cancer: Does ethnicity impact survival?
Authors: M Rushton-Marovac, T Zhang, X Song
Journal: Cancer Research (2019)

Abstract Background: Triple negative breast cancer (TNBC) is a heterogeneous disease with poor outcomes relative to hormone positive breast cancer. Observations in the clinical setting lead to the hypothesis that there may be phenotypic differences among ethnic groups. Previous studies have conflicting results; some suggesting no differences, others showing inferior outcomes for black patients (pts). The purpose of this study was to use a population-based approach to examine survival amongst different ethnicities in triple negative breast cancer (TNBC). Methods Retrospective population-based study using data from the surveillance epidemiology and end results (SEER) database to identify TNBC cases diagnosed 2010 - 2014. We divided pts into 6 ethnic groups: White, Black, American Indian/Alaskan Native (AIAN), Pacific Islander (PI), Asian and Asian Indian (AI). Primary outcome: overall survival (OS); secondary outcome: breast-cancer specific survival (BCSS). Survival analysis was performed using Cox proportional hazards and Kaplan-Meier models. Results 31482 pts were included; 22752 (72.3%) were white, 6319 (20.4%) black, 1720 (5.5%) Asian, 262 (0.8%) AI, 179 (0.6%) AIAN, and 150 (0.5%) PI. Asian pts had the best OS (HR 0.82, 95% CI 0.72-0.94), while Black pts had the worst (HR 1.21 95% CI 1.13-1.29) when compared with White pts. Differences between other ethnicities were not statistically significant for OS. Black pts had significantly worse BCSS (HR 1.20, 95% CI 1.12 -1.29); no other ethnicity had statistically significant differences compared to Whites. Comparing Asian with Black pts in multivariate analysis the HR was 0.68 (95% CI 0.59 – 0.79) for OS and 0.71 (95% 0.61 – 0.84) for BCSS. Older age, advanced stage, male sex, and lack of chemotherapy, radiation or surgery were also found to be statistically significant variables in multivariate analysis. Conclusions In this large population study, we found Asian pts had significantly better OS and Black pts had significantly worse OS and BCSS. These findings confirm the clinical observation and warrant closer molecular analysis of TNBC phenotypes based on patient's ethnicity. Findings may offer insight into the biology of TNBC and lead to development of innovative treatment options. Citation Format: Rushton-Marovac M, Zhang T, Song X. Triple negative breast cancer: Does ethnicity impact survival? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-30.
Paradoxical Early Increase in Prostate-Specific Membrane Antigen Uptake Following Cryoablation for Local Recurrence After Radical Prostatectomy
Authors: Guilherme Cayres Mariotti, Marcelo Livorsi Cunha, Arie Carneiro, Oren Smaletz, Ronaldo Hueb Baroni, Rodrigo Gobbo Garcia
Journal: Clinical Nuclear Medicine (2019)

Abstract We report a case of a 43-year-old man who underwent a radical prostatectomy 3 years before the procedure (June 2015) for a locally advanced Gleason 7(4 + 3) prostate adenocarcinoma (pT3aN0), with negative surgical margins, followed by salvage radiotherapy. He also underwent antiandrogen therapy for biochemical relapse (bicalutamide) from October 2016 through May 2017, but prostate-specific antigen continued to rise (2.5 ng/mL [December 2017] and 3.3 ng/mL [February 2018]). At this point, he underwent a 68 Ga–prostate-specific membrane antigen PET/CT, and after multidisciplinary discussion, the therapeutic option chosen was image-guided salvage cryoablation.