tbuckley/cabot-search huggingface dataset:
Detection of DNA methylation in inflammatory breast tumours by a multiplex nested methylation-specific PCR
Authors: I. Van der Auwera, S. Van den Bosch, S. Van Laere, G. Van den Eynden, P. van Dam, C. Colpaert, M. van Engeland, E. Van Marck, P. Vermeulen, L. Dirix
Journal: Journal of Clinical Oncology (2007)

21027 Background: Hypermethylation of gene promoters is a common mechanism of loss of gene function in cancer cells. Few data on epigenetic alterations in inflammatory breast cancer (IBC) cells are available. Microarray studies have shown that IBC is characterised by a distinct gene expression profile when compared to non-IBC. We sought to determine whether the profiles of gene hypermethylation differ between IBC and non-IBC by using a multiplex nested methylation-specific PCR (MSP). We selected genes for which evidence exists for their involvement in breast carcinogenesis by means of methylation. Methods: The SLμCut system (MMI) was used for laser capture microdissection of paraffin-embedded tissues. 10-μm-thick sections from 10 patients with IBC and 12 patients with non-IBC were used. Genomic DNA from the microdissected tissue was extracted and treated with sodium bisulfite. The methylation status of the promoter regions of APC, E- cadherin, THBSP-1, DAPK, GSTP1, RASSF1A and BRCA1 were investigated using a multiplex nested MSP method. DNA isolated from normal peripheral lymphocytes from healthy individuals served as a negative methylation control. In vitro methylated DNA served as the positive methylation control. MSP products were analyzed on agarose gel electrophoresis, and were determined to have methylation if a visible band was observed in the methylation reaction. Results: Methylation of the APC gene promoter was observed in 33.3% (4/12) of non-IBC samples and 70% (7/10) of IBC samples. Methylation of the BRCA1 gene promoter was observed in 16.7% (2/12) of non-IBC samples and 30% (3/10) of IBC samples. Methylation of the DAPK gene promoter was observed in 16.7% (2/12) of non-IBC samples and 10% (1/10) of IBC samples. Methylation of the GSTP1 gene promoter was observed in 33.3% (4/12) of non-IBC samples and 30% (3/10) of IBC samples. No methylation of the E-cadherin and THBSP-1 gene promoters was observed in non-IBC samples or IBC samples. Conclusions: Also in this study, the multiplex nested MSP approach was proven to be very suitable for the detection of methylation in samples harbouring small amounts of poor quality DNA. In the near future, the methylation status of other genes will be determined and the study population will be enlarged. No significant financial relationships to disclose.
Factor VIII exhibits chaperone-dependent and glucose-regulated reversible amyloid formation in the endoplasmic reticulum
Authors: Juthakorn Poothong, Anita Pottekat, Marina Siirin, Alexandre Rosa Campos, Adrienne W. Paton, James C. Paton, Jacqueline Lagunas-Acosta, Zhouji Chen, Mark Swift, Niels Volkmann, Dorit Hanein, Jing Yong, Randal J. Kaufman
Journal: Blood (2020)
Phase 1 study of ARQ 197, a selective inhibitor of the c-Met RTK in patients with metastatic solid tumors reaches recommended phase 2 dose
Authors: A. Garcia, L. Rosen, C. C. Cunningham, J. Nemunaitis, C. Li, N. Rulewski, A. Dovholuk, R. Savage, T. Chan, R. Bukowksi, T. Mekhail
Journal: Journal of Clinical Oncology (2007)

3525 Background: ARQ 197 is a selective inhibitor of the c-Met receptor tyrosine kinase, an oncogene implicated in tumor invasiveness, metastasis, cancer cell proliferation, resistance to apoptosis, chemoresistance and angiogenesis. The c-Met RTK is a high-affinity receptor for hepatocyte growth factor (HGF). c-Met and HGF are dysregulated in a broad spectrum of cancers, thus inhibitors of c-Met could be promising targeted agents deserving clinical investigation. Methods: A phase 1 dose escalation study in metastatic pts who failed standard therapy was initiated to determine safety, tolerability, RP2D, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ARQ 197. Cycles consisted of twice-daily oral dosing of ARQ197 for two out of 3 weeks. Results: Thirty-eight pts were enrolled with data available for 36 pts (21M/15F; median age 61). Ten cohorts were assessed ranging from 10 to 360 mg/day. ARQ 197 was well tolerated and no DLT was observed. All treated pts achieved plasma drug concentrations significantly above the in vitro IC 50 . Doses through 70 mg b.i.d. revealed C max and AUC (0–12hr) increased linearly. There was no further increase in systemic exposure in pts treated with 90 through 180 mg b.i.d. There was notable inter-patient variability in C max and AUC (0–12hr), typical of oral dosing. The effects of cytochrome P450 polymorphism will be discussed. Adverse events (N=29) were generally mild with the most common being: fatigue (24 %), diarrhea (21%), and constipation (21%). Grade 3 or greater events possibly or probably related to ARQ 197 include: elevated ALP (3%), ALT (3%) and AST (3%). Of the 38 pts enrolled, 36 received at least one complete cycle of ARQ 197 with 33 evaluable for efficacy. Two pts achieved a PR (1 confirmed) and 19 had stable disease (SD) 21 10+ to 34+ weeks. Conclusions: Based on pharmacokinetic data, a RP2D for ARQ 197 was determined to be 120 mg b.i.d. Higher oral doses did not result in increased systemic systemic exposure to the drug. Eleven pts remain on study and continue to receive ARQ 197 treatment. A favorable adverse event profile and encouraging signs of anti-tumor activity was observed and continuous daily dosing of ARQ 197 is now being explored to better define clinical toxicity and efficacy. [Table: see text]
Abstract P380: Steps Per Day and Step Intensity are Associated With a Lower Risk of Diabetes. The Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
Authors: Carmen Cuthbertson, Christopher Moore, Daniela Sotres-Alvarez, Gerardo M HEISS, Olga Garcia-Bedoya, Yasmin Mossavar-Rahmani, Carmen R Isasi, Jordan A Carlson, Linda Gallo, David Goldsztajn Farelo, Maria Llabre, Kelly R Evenson
Journal: Circulation (2020)

Introduction: Physical activity has been associated with a lower risk of diabetes but less is known about the association of steps per day (steps/d) and step intensity with incident diabetes. Hypothesis: We hypothesized an inverse association between both number of steps/d and time spent at a stepping rate corresponding to purposeful steps ( &gt; 40 steps/min) with the risk of incident diabetes. Methods: We included 7247 participants free of diabetes at baseline in the prospective HCHS/SOL cohort of Latinos sampled from four communities in the United States. Steps/d and minutes per day (min/d) at a stepping rate &gt; 40 steps/min were assessed at baseline with the Actical accelerometer (2008-2011), and incident diabetes was ascertained at a follow-up visit (2014-2017). The association of steps with incidence rates (per 1,000 person-years) of diabetes and incidence rate ratios (IRR) was estimated using Poisson regression, accounting for the sampling design and adjusted for age, ethnicity, gender, education, smoking status, alcohol intake, and accelerometer wear time. Results: The average age at baseline was 38 years (range 18 - 74 years) and 52% were female. Over a median of 5.9 years, 850 participants (9%) developed diabetes. The median step count was 7360 steps/d and the median minutes per day at a stepping rate of &gt; 40 steps/min was 55 minutes. For each 1,000 step/d increment, the risk of diabetes was 5% lower (Table, IRR= 0.95(95% confidence interval (CI) 0.88, 1.02)). Compared to adults who engaged in 2,000 steps/d, those who engaged in 5,000 and 10,000 steps/d had a 13% and 26% lower risk of diabetes. The risk of diabetes was 5% lower (IRR=0.95 (95% CI 0.89, 1.00)) per 10 minute increase in time spent at a stepping rate &gt; 40 steps/min. Compared to adults who spent 10 min/d at &gt; 40 step/min, those who spent 30, 60, and 120 min/d had a 10%, 20%, and 32% lower risk of diabetes. Conclusion: The number of steps per day and time spent at a stepping rate that corresponds to purposeful steps are inversely associated with the risk of developing diabetes among adults.
Abstract 11003: Hypothalamic Activated Microglia With Morphological Changes Accelerate Blood Pressure Elevation During the Hypertension Development Phase in Stroke-prone Spontaneously Hypertensive Rats
Authors: Ko Takesue, Takuya Kishi, Yoshitaka Hirooka
Journal: Circulation (2015)

Introduction: A recent paradigm shift in cardiovascular pathophysiology is the impact of inflammation on hypertension. Inflammation within the paraventricular nucleus of the hypothalamus (PVN) is an important pathology of sympathetic hyperactivity, and is mainly mediated by innate immune cells, microglia. Activated microglia with alteration of their morphology produce inflammatory cytokines. Previous reports demonstrated that microglia within the PVN have activated morphology in angiotensin II-induced hypertensive rats and spontaneously hypertensive rats compared with normotensive control Sprague-Dawley rats or Wistar-Kyoto (WKY) rats. However, the role of activated microglia in the PVN in blood pressure elevation associated with sympathetic hyperactivity remains unknown. In the present study, we determined whether inhibition of microglial activation within the PVN attenuates the blood pressure elevation in genetically hypertensive rats. Methods and Results: We evaluated the activation of PVN microglia, identified by microglia specific ionized calcium-binding adaptor molecule 1 immunoreactivity, by measuring the roundness and the perimeter of microglia at 6 weeks of age, early hypertension development phase in stroke-prone spontaneously hypertensive rats (SHRSP) and compared with them in age-matched normotensive WKY rats. At 6 weeks of age, increased roundness and shortening of perimeter of microglia, indicating activated microglia, were observed in SHRSP compared with those in WKY rats. Then, we performed intracerebroventricular (ICV) administration of minocycline (5 μg/h) to deactivate microglia at 6 weeks of age for 4 weeks. ICV administration of minocycline significantly attenuated systolic blood pressure elevation in SHRSP over 4 weeks (at the end of experiments; 203.2±2.2 mm Hg vs. 215.9±2.7 mm Hg, n=8-9, P&lt;0.05), but not in WKY rats. At 10 weeks of age, morphological analysis revealed that ICV minocycline significantly decreased the roundness and increased the perimeter of microglia, indicating deactivation of microglia, within the PVN in SHRSP. Conclusions: Hypothalamic activated microglia with morphologic changes accelerate blood pressure elevation during the hypertension development phase in SHRSP.
Short-term and Long-term Returns for States Implementing Pediatric Alternative Payment Models
Authors: Nathaniel Z. Counts, Alexander Billioux, James M. Perrin
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 Pediatrics journal
Abstract 06: Social Networks are Associated With Ideal Cardiovascular Health in Young Black Females: A Latent Class Analysis
Authors: Jewel Scott, Susan Silva, Leigh Ann Simmons
Journal: Circulation (2020)

Black females experience diminished cardiovascular health (CVH) earlier than other females in the U.S. Young adulthood is a pivotal period for developing and maintaining positive health behaviors and social relationships. Social isolation is a risk factor for cardiovascular disease morbidity and mortality, and that risk may begin early in life. Research with middle-aged adults suggests race and sex moderate the association between social isolation and CVH, underscoring the need to further elucidate this relationship in young Black females. Hypothesis: We assessed the hypothesis that (a) there are distinct latent classes of social networks for young Black females; (b) latent social network classes are associated with CVH; and (c) perceived stress and depression mediate this relationship. Methods: Data are from 517 Black females, age 24-32, who participated in the National Longitudinal Adolescent to Adult Health Study, a population cohort study. Social network included three components of the Berkman Syme Index (number of close friends, religious participation, volunteer/community service activities) and perceived isolation. The primary outcome was the AHA Ideal CVH score, a composite measure that includes diet, physical activity, BMI, smoking, cholesterol, blood pressure, and glucose. Proposed mediators were perceived stress and depression. A latent class analysis was conducted to identify distinct social network subgroups. General and generalized linear models were used to test for subgroup differences in ideal CVH and mediator effects. Results: The best fit latent class analysis identified a three-class model: (1) strong, diverse, social network, 31.5%; (2) moderate social network with no perceived social isolation, 42.6%; and limited social network with perceived social isolation, 25.9%. All subsequent analyses covaried for income because these subgroups differed on income (p=0.0003) and low income was associated with lower ideal CVH scores (p&lt;0.001). Social network was associated with ideal CVH (p=0.004), with the strong, diverse network subgroup having better CVH scores compared to the other subgroups (p&lt;0.005), which did not differ. Black women with a strong, diverse or a moderate network with no perceived isolation had lower probability of perceived stress and depression compared to those with a limited network and perceived isolation (p&lt;0.018). Perceived stress and depression, however, were not associated with CVH scores and did not mediate the social network-CVH relationship. Conclusion: In young Black women, social networks may influence health behaviors and overall cardiovascular health, independent of mental health status. Future research should explore mediators of this relationship to effectively tailor lifestyle interventions to establish and maintain CVH and reduce health disparities.
Loss of iRhom2 accelerates fat gain and insulin resistance in diet-induced obesity despite reduced adipose tissue inflammation
Authors: Joseph Skurski, Christie M. Penniman, Ramasatyaveni Geesala, Garima Dixit, Priyanjali Pulipati, Gourav Bhardwaj, David K. Meyerholz, Priya D. Issuree, Brian T. O'Neill, Thorsten Maretzky
Journal: Metabolism (2020)
Abstract P546: Social Jetlag is Associated With Cardiorespiratory Fitness in Male But Not Female Adolescents
Authors: Simon Higgins, Lee Stoner, Alex Lubransky, Anna Howe, Jyh Eiin Wong, Katherine Black, Paula Skidmore
Journal: Circulation (2020)

Introduction: Cardiorespiratory fitness (CRF) has been highlighted by the AHA as a vital sign that can significantly improve risk classification for adverse health outcomes across the lifespan. While many lifestyle-related factors are known to influence CRF, including physical activity and sedentary behaviors, few have examined the relationship between sleep characteristics and CRF. Social jetlag (SJL), a characteristic of sleep habits that is particularly prevalent in adolescents, is a mismatch between an individual’s circadian clock and sleep schedule. SJL has been associated with adiposity and increased cardiometabolic risk, independent of sleep duration and quality, but has not been associated with CRF. Objective: To quantify the relationship between SJL and CRF, independent of other sleep characteristics. Methods: CRF, anthropometric, and lifestyle-related data were collected from 276 adolescents in Otago, New Zealand (14-18 years, n=145 [52.5%] female). CRF was expressed as VO 2max (ml/kg/min) relative to body weight, estimated from a 20-meter multi-stage shuttle run. Lifestyle-related factors such as physical activity and the number of screens in the bedroom were quantified via an online lifestyle survey. Sleep variables including average sleep duration, sleep disturbances (trouble falling and staying asleep), and SJL were collected using the validated Sleep Habits Survey for Adolescents. SJL was measured as the difference in hours between the midpoint of sleep during week (school) days and on weekend (free) days. Linear regression assessed the association between each sleep outcome and CRF, controlling for (1) age, sex, school decile, fat mass, and the number of screens in the bedroom, and (2) moderate-to-vigorous intensity physical activity. Stratified analyses examined sex-specific relationships. Results: Mean (SD) VO 2max was greater in males than females (48.47 [7.12] vs. 43.34 [5.62] ml/kg/min, p&lt;.001). Sleep characteristics included a longer average sleep duration (9.48 [.92] vs. 9.19 [1.12] hours, p=.017), a greater occurrence of sleep disturbances (p=.001), and a lower SJL (1.67 [.08] vs. 2.09 [1.12] hours, p=.003) in females relative to their male peers. Multivariate analyses indicated that a one-hour increase in SJL was associated with a .71 ml/kg/min decrease in VO 2max (95% CI: -1.30, -.11), independent of other sleep variables, which were not associated with CRF. Sex-specific models further indicated an association in males (b=-.93, 95% CI: -1.78, -.08), but an inconclusive association for females (b=-.29, 95% CI: -1.15, .57). Conclusions: SJL is negatively associated with CRF, with a more conclusive association in adolescent males, and may be a simple, measurable target for future public health interventions.
Revascularization and limb salvage following critical limb ischemia by nanoceria-induced Ref-1/APE1-dependent angiogenesis
Authors: In-Su Park, Chinmaya Mahapatra, Ji Sun Park, Khandmaa Dashnyam, Jong-Wan Kim, Jin Chul Ahn, Phil-Sang Chung, Dong Suk Yoon, Nandin Mandakhbayar, Rajendra K. Singh, Jung-Hwan Lee, Kam W. Leong, Hae-Won Kim
Journal: Biomaterials (2020)

In critical limb ischemia (CLI), overproduction of reactive oxygen species (ROS) and impairment of neovascularization contribute to muscle damage and limb loss. Cerium oxide nanoparticles (CNP, or 'nanoceria') possess oxygen-modulating properties which have shown therapeutic utility in various disease models. Here we show that CNP exhibit pro-angiogenic activity in a mouse hindlimb ischemia model, and investigate the molecular mechanism underlying the pro-angiogenic effect. CNP were injected into a ligated region of a femoral artery, and tissue reperfusion and hindlimb salvage were monitored for 3 weeks. Tissue analysis revealed stimulation of pro-angiogenic markers, maturation of blood vessels, and remodeling of muscle tissue following CNP administration. At a dose of 0.6 mg CNP, mice showed reperfusion of blood vessels in the hindlimb and a high rate of limb salvage (71%, n = 7), while all untreated mice (n = 7) suffered foot necrosis or limb loss. In vitro, CNP promoted endothelial cell tubule formation via the Ref-1/APE1 signaling pathway, and the involvement of this pathway in the CNP response was confirmed in vivo using immunocompetent and immunodeficient mice and by siRNA knockdown of APE1. These results demonstrate that CNP provide an effective treatment of CLI with excessive ROS by scavenging ROS to improve endothelial survival and by inducing Ref-1/APE1-dependent angiogenesis to revascularize an ischemic limb.
Abstract P558: Association Between Stroke Prevalence and Depression, Functional Ability, and Cognitive Function in Six Low and Middle Income Countries: The WHO Study on Global AGEing and Adult Health
Authors: Carin Northuis, Lama Ghazi
Journal: Circulation (2020)

Background: There are substantial gaps in stroke morbidity in low and middle income countries (LMIC) compared to high income countries (HIC). Stroke incidence and mortality are higher in LMIC compared to HIC. While education has been associated with stroke incidence and common stroke outcomes in HIC, the pattern of this social determinant of health may be reversed in LMIC. We examined the association between stroke prevalence and depression, cognitive function and functional ability utilizing the WHO Study on Global AGEing and Adult Health (SAGE). We also assessed if education modified this association. Methods: We used data from the WHO SAGE, wave 1 (2007-10), which is a nationally representative cohort from six LMIC: China, Ghana, India, Mexico, Russia, and South Africa. Stroke prevalence was classified by self-reported stroke or stroke symptoms. Outcomes included 1) depression [ICD-10 diagnostic criteria]; 2) cognitive function [z-score of performance on executive function, verbal fluency, and memory]; and 3) functional ability [WHO Disability Assessment Schedule]. Generalized linear models were fit for the association between stroke prevalence and outcomes. For our secondary analysis, educational attainment was included as a modifier. All models were adjusted for demographics, socioeconomic status, and health variables. Results: We included 39,896 individuals who had data on their stroke status. Stroke prevalence was 5.1% (n=2,034). Stroke survivors had lower mean cognitive function (-0.1±.8 vs 0.1±0.7, p&lt;0.001), lower functional ability (71.3±21.8 vs 84.6±17.0, p&lt;0.001), and higher percentage of depression (13.0% vs 5.3%, p&lt;0.001) compared to those who did not have a stroke. Prevalence of stroke was associated with significantly higher adjusted odds of depression (Odds Ratio (OR): 1.7; 95% Confidence Interval (CI): 1.3, 2.0), lower cognitive function (Risk Difference (RD): 0.07; 95% CI: -0.1, -0.03), and lower functional ability (RD: -7.4; 95% CI: -8.3, -6.5). Education modified the association of stroke with functional ability but not with depression or cognitive impairment. Stroke survivors with primary or less education had significantly lower physical function than those with tertiary or more (p for interaction=0.04). Conclusion: Stroke was associated with a higher odds of depression and higher risk of reduced cognitive function and functional ability. Unlike in HIC, these six LMIC did not display a significant inverse association between education and depression and cognitive function. Future studies should assess predictors of poorer post-stroke outcomes and if other socioeconomic measures modify consequences of stroke in LMIC.