tbuckley/cabot-search huggingface dataset:
Abstract P353: Cardiometabolic Risk is Related to Body Size Misperception and Knowledge of Cardiovascular Disease in Young Hispanic Women
Authors: Dena E Hayes, Juviza K Rodriguez, Robert R Sciacca, Elsa-Grace V Giardina
Journal: Circulation (2015)

Introduction: Body size perception as well as knowledge and awareness of cardiovascular disease (CVD) are considerations that may contribute to cardiometabolic risk. Compared to non-Hispanic white women, Hispanic women are more likely to misperceive body size and have lower CVD knowledge.

Hypothesis: To explore how body size misperception and CVD knowledge relate to cardiometabolic risk in Hispanic women, we assessed the relationship between body size perception and presence of cardiometabolic risk factors (CMRF), as well as the relationship between CVD knowledge and presence of CMRF.

Methods: Women ≥18 years of age (n= 253) completed a 7-page standardized questionnaire adapted from the validated Centers for Disease Control and Prevention BRFSS. Perception of size was assessed using validated Stunkard figural stimuli. CMRF included obesity, hypertension, hyperlipidemia, smoking history, and type-2 diabetes. Obesity was defined by body mass index (BMI) calculated from measured height and weight. Remaining CMRF were self-reported.

Results: Participants were Hispanic (82.2%, 208/253), African American (11.1%, 28/253), non-Hispanic white (4.0%, 10/253), Asian/Pacific Islander (1.2%, 3/253), and other (1.6%, 4/253). Mean age was 38.8 ± 7.5 years (24-64 years); mean education was 11.8 ± 3.3 years (1-20 years). Nearly half (47.4%, 120/253) had > 1 CMRF including obesity (30.4%, 77/253), hypertension (15.0%, 38/253), hyperlipidemia (10.3%, 26/253), smoking history (7.9%, 20/253), and type-2 diabetes (4.7%, 12/253). More than half were overweight (37.2%, 94/253) or obese (30.4%, 77/253) and 32% (81/253) were normal weight.

While 53.8% (136/253) accurately perceived their size, over one-third (37.5%, 95/253) underestimated size. Among overweight and obese women, 35.1% (33/94) and 71.4% (55/77) respectively, underestimated size versus 8.6% (7/81) of normal weight women (both p<0.001). Women with CMRF were more likely to underestimate size than those without CMRF (64.2% [61/95] vs. 35.8% [34/95], p<0.001).

Of the women, 27.8% (70/252) correctly chose heart disease as the leading cause of death among U.S. women. Additionally, 66.3% (167/252) identified the signs and symptoms of a heart attack. Women with CMRF were more likely to know the leading cause of death than those with no CMRF (60% [42/70] vs. 40% [28/70], p<0.05) which is possibly related to health-provider interactions prompted by existing CMRF.

Conclusions: Though usually assumed that younger women are at low risk for CVD, nearly half had ≥1 CMRF. Underestimation of true size was common, especially among those with CMRF. Furthermore, less than one-third recognized heart disease as the leading cause of death. Innovative strategies to enable recognition of abnormal weight and to improve CVD knowledge, particularly among young obese Hispanic women, are necessary to combat obesity and subsequent CMRF leading to CVD.
Retrospective molecular and phenotypic analysis of poliovirus vaccine strains isolated in Greece
Authors: V. Pliaka, M.E. Filliponi, Z. Kyriakopoulou, I.G.A. Ruether, D. Tsakogiannis, C. Gartzonika, S. Levidiotou-Stefanou, P. Markoulatos
Journal: Clinical Microbiology and Infection (2011)
CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by SIRT1
Authors: Ben Zhou, Yi Zhang, Fang Zhang, Yulei Xia, Jun Liu, Rui Huang, Yuangao Wang, Yanan Hu, Jingxia Wu, Changgui Dai, Hui Wang, Yanyang Tu, Xiaozhong Peng, Yiqian Wang, Qiwei Zhai
Journal: Hepatology (2014)

The protein deacetylase, sirtuin 1 (SIRT1), involved in regulating hepatic insulin sensitivity, shows circadian oscillation and regulates the circadian clock. Recent studies show that circadian misalignment leads to insulin resistance (IR); however, the underlying mechanisms are largely unknown. Here, we show that CLOCK and brain and muscle ARNT-like protein 1 (BMAL1), two core circadian transcription factors, are correlated with hepatic insulin sensitivity. Knockdown of CLOCK or BMAL1 induces hepatic IR, whereas their ectopic expression attenuates hepatic IR. Moreover, circadian change of insulin sensitivity is impaired in Clock mutant, liver-specific Bmal1 knockout (KO) or Sirt1 KO mice, and CLOCK and BMAL1 are required for hepatic circadian expression of SIRT1. Further studies show that CLOCK/BMAL1 binds to the SIRT1 promoter to enhance its expression and regulates hepatic insulin sensitivity by SIRT1. In addition, constant darkness-induced circadian misalignment in mice decreases hepatic BMAL1 and SIRT1 levels and induces IR, which can be dramatically reversed by resveratrol. These findings offer new insights for coordination of the circadian clock and metabolism in hepatocytes by circadian regulation of hepatic insulin sensitivity via CLOCK/BMAL1-dependent SIRT1 expression and provide a potential application of resveratrol for combating circadian misalignment-induced metabolic disorders.
Abstract 3694: Relationship between <i>in vivo</i> antitumor activity of ADC and payload release in preclinical models
Authors: Fu Li, Xinqun Zhang, Kim Emmerton, Mechthild Jonas, Jocelyn Setter, Bill Arthur, Nicole Okeley, Robert Lyon, Dennis Benjamin, Che-Leung Law
Journal: Cancer Research (2014)

Abstract Antibody-drug conjugates (ADC) deliver cytotoxic payloads to target cells via receptor-mediated internalization. We have demonstrated that SGN-35 (cAC10-vcMMAE) binds to CD30 on target cells and releases intracellular monomethyl auristatin E (MMAE) in vitro, contributing to potent killing of CD30+ cells. Using a set of auristatin-based ADCs, we evaluated whether the intratumoral concentration of the released payload is a predictive indicator of antitumor activity in preclinical models. We first treated CD30+, anaplastic large cell lymphoma (ALCL) Karpas 299 tumors with SGN-35 or a non-binding control ADC (IgG-vcMMAE). The plasma ADC and MMAE PK measurements were similar in SGN-35 and IgG-vcMMAE treated tumor-bearing animals. In contrast, SGN-35 generated 5-fold greater intratumoral MMAE exposure than IgG-vcMMAE, which correlated with tumor regression observed in the SGN-35- treated group. We then examined the relationship between released MMAE and in vitro cytotoxicity by targeting different receptors expressed on the same cells. The lymphoma cell line L82 expresses CD30, CD70, and CD71 receptors. Although auristatin-based ADCs targeting each of these targets has a different IC50, the intracellular MMAE was similar when 50% growth inhibition was achieved (approximately 200 nM). In vivo, CD30, CD70, or CD71-directed ADCs demonstrated similar antitumor activity for a given dose level (0.5, 1, or 3 mg/kg). Concordantly, equal intratumoral MMAE concentrations were observed for a given dose level, regardless of the antigen target. The cell permeable MMAE has been shown to mediate bystander killing in vitro. To evaluate whether intratumoral MMAE mediates bystander killing in vivo, an admixed tumor model consisting CD30+ and CD30- Karpas 299 cells was treated with SGN-35. As predicted, both CD30+ and CD30- tumor cells were killed, presumably due to intratumoral diffusion of MMAE across cell membranes. In contrast, a conjugate with a highly polar form of auristatin (MMAF) was unable to kill the CD30-negative cell population of the admixed tumors. These preclinical results provide evidence that the concentration of released MMAE within the tumor correlates with the ADC antitumor activity in vitro and in vivo. Moreover, the in vivo bystander activity of MMAE may improve utility of this chemotype in tumors with heterogeneous antigen expression. Citation Format: Fu Li, Xinqun Zhang, Kim Emmerton, Mechthild Jonas, Jocelyn Setter, Bill Arthur, Nicole Okeley, Robert Lyon, Dennis Benjamin, Che-Leung Law. Relationship between in vivo antitumor activity of ADC and payload release in preclinical models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3694. doi:10.1158/1538-7445.AM2014-3694
LONG-TERM SURVIVAL FOLLOWING AORTIC VALVE REPLACEMENT AMONG HIGH-RISK ELDERLY PATIENTS IN THE UNITED STATES: INSIGHTS FROM THE STS ADULT CARDIAC SURGERY DATABASE, 1991-2007
Authors: J. Matthew Brennan, Fred Edwards, Yue Zhao, Sean O&apos;Brien, Pamela Douglas, eric D. peterson
Journal: Journal of the American College of Cardiology (2012)
Contralateral distribution of nonmelanoma skin cancer between older Hispanic/Latino and non-Hispanic/non-Latino individuals
Authors: M.P. McLeod, K.M. Ferris, S. Choudhary, Y. Alqubaisy, M. Shiman, J. Loring-Warsch, S. Mlacker, S. Jawitz, A. Perez, K. Nouri
Journal: British Journal of Dermatology (2012)

A recent review of the SEER database revealed that melanoma and Merkel cell carcinoma occur more commonly on the left side of the body. Similarly, a trend was reported in which nonmelanoma skin cancers (NMSCs) were found to be distributed more frequently on the left side of the body. To compare the sidedness of NMSC in a large patient population. There were five primary objectives of the present study: (i) to confirm or refute the left-sided trend of NMSC in the largest patient population studied for asymmetry to date; (ii) to determine whether the left-sided trend existed in Hispanic/Latino individuals; (iii) to examine skin cancer in older individuals across ethnicities; (iv) to compare distribution across anatomical location and ethnicity; and (v) to measure gender differences in the distribution of NMSC. The last 3026 cases referred to the Mohs surgical unit at the University of Miami Miller School of Medicine during 2008-2011 were reviewed. The patient's age, gender, tumour side, tumour type, anatomical location and ethnicity were recorded. There were 1505 (50·2%) right-sided tumours and 1495 (49·8%) left-sided tumours (P=0·52). The Hispanic/Latino group had a nonsignificant right-sided trend with 607 (52·7%) right-sided cases and 545 (47·3%) left-sided cases (P=0·06). The non-Hispanic/non-Latino group between the ages of 60 and 85 years had 605 (46·9%) right-sided tumours and 686 (53·1%) left-sided tumours (P=0·024). The Hispanic/Latino group between the ages of 60 and 85 years demonstrated 404 (54·0%) right-sided tumours and 344 (46·0%) left-sided tumours (P=0·028). One hundred and fifty-four skin cancers were located on the upper extremities of non-Hispanic/non-Latino individuals with 64 (41·6%) being right sided and 90 (58·4%) left sided (P=0·036). Seventy-eight skin cancers were located on the upper extremities of Hispanic/Latino individuals with 49 (62·8%) being right sided and 29 (37·2%) left sided (P=0·024). Males had most of the skin cancers at 2125 (70·8%) cases and females had 875 (29·2%) cases (P<0·001). NMSC appears to be more common on the left side of older non-Hispanic/non-Latino individuals, while it is more common on the right side of older Hispanic/Latino individuals. This is likely to be secondary to an environmental factor, such as ultraviolet radiation. NMSC is significantly more common in males relative to females, which may be attributed to differences in gender roles or referral practices.
Abstract 3925: The <i>PIK3CA</i> <i>H1047R</i> mutation can initiate tumorigenesis in the colon
Authors: Cheri Pasch, Molly Maher, Dustin Deming
Journal: Cancer Research (2014)

Abstract Background: Our understanding of how mutations within the intestinal epithelium result in tumor development and progression is continuously evolving. We have previously described the FC PIK3ca* murine colon cancer model which expresses a constitutively activated phosphoinositide-3 kinase (PI3K) in the intestinal epithelium. The expression of this dominantly active form of PI3K resulted in invasive mucinous adenocarcinomas in the proximal colon through a non-canonical mechanism. We sought to determine if the hotspot PIK3CA H1047R mutation, commonly found in human colorectal cancers, can also induce intestinal tumorigenesis. Methods: Female FVB mice carrying a conditional PIK3CA H1047R mutation (PIK3CAH1047R) were crossed to B6 males carrying atransgene in which the fatty acid binding protein promoter is fused to Cre recombinase (FC). (FVB x B6)F1 FC PIK3CAH1047R progeny express this constitutively active form of PI3K in epithelial cells of the distal small bowel and colon. 22 F1 FC PIK3CAH1047R mice were examined. Necropsy was performed at approximately 200 days of age or once moribund. Results: 50% of FC PIK3CAH1047R mice develop invasive adenocarcinomas within the colon. These cancers are highly mucinous and often penetrate through the serosal layer of the colon. These lesions can be found throughout the colon, but are more common proximally. No tumors were identified within the small intestine. These cancers can have associated invasion into the regional lymphatics and metastases to the mesentery. Interestingly these cancers have a minimal luminal component compared to the amount of submucosal extension. Precursor lesions are able to be identified and are not polypoid. These cancers demonstrate activation of the AKT signaling pathway, but do not demonstrate nuclear localization of β-catenin. Conclusion: This is the first report of the hotspot PIK3CA H1047R mutation leading to intestinal tumorigenesis through a non-canonical mechanism, resulting in flat mucinous invasive adenocarcinomas. Citation Format: Cheri Pasch, Molly Maher, Dustin Deming. The PIK3CAH1047R mutation can initiate tumorigenesis in the colon. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3925. doi:10.1158/1538-7445.AM2014-3925
Abstract 16515: Differential Functions of HCN1 and HCN4 Pacemaker Channels Within the Sinoatrial Node for the Stable and Precise Beating of the Heart
Authors: Stefanie Fenske, Vanessa Marks, Stefanie Koenigsbauer, Sami I Hassan, Tilman Ziegler, Christian Kupatt, Biel Martin, Christian A Wahl-Schott
Journal: Circulation (2014)

The heart beat is initiated by the generation of spontaneous action potentials in pacemaker cells of the sinoatrial node (SAN) region. The maintenance of a stable heart beat requires mechanisms which protect the SAN pacemaker cells from potential perturbing influences which arise from inside and outside the sinoatrial network. Our previous work suggests that the hyperpolarization-activated cyclic nucleotide gated channel subtype 1 (HCN1) protects against such perturbations and thereby increases the stability, the precision and the safety of the sinoatrial network. Here, we investigate the role of HCN4 channels within this context. Using genetic mouse models deficient for HCN channels as well as mouse models expressing engineered HCN channels, we performed a detailed functional characterization of pacemaker mechanisms in single isolated sinoatrial node cells, explanted beating sinoatrial node preparations, with telemetric in vivo electrocardiography, echocardiography, and in vivo electrophysiology. We provide evidence that HCN4 has a critical role in counteracting and balancing potentially destabilizing effects of the autonomic nervous system on the regulation of the heart rate. Specifically, HCN4 channels smooth the transition of the heart rate to a new equilibrium. Furthermore, we provide evidence that the cAMP- dependent fine tuning of HCN4 channel activity could provide the exact dosage of current to balance and counteract overshooting responses of the heart rate to autonomic regulation. In the absence of such a protecting effect, mice display a brady- tachy syndrome.
Abstract 978: microRNA-211 modulates energy metabolism in human melanoma cells by destabilizing HIF1-α and downregulating PDK4
Authors: Joseph Mazar, Adam Richardson, Feng Qi, Bongyong Lee, Angeles Duran, Subramaniam Govindarajan, John Shelley, Laurence M. Brill, Jian-Liang Li, Xianlin Han, Jorge Moscat, Ranjan Joseph Perera
Journal: Cancer Research (2014)

Abstract MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in cellular physiology and tumorigenesis. We have previously reported that the expression of the melanocyte-specific miRNA miR-211 is significantly reduced or absent in non-pigmented melanoma cells and clinical melanoma samples. Here we report that ectopic expression of miR-211 in non-pigmented melanoma cells increases mitochondrial number, NADP to NADPH ratio, oxygen consumption, and fatty acid synthesis. Ectopic expression of miR-211 destabilizes hypoxia inducible factor 1α (HIF-1α) and downregulates pyruvate dehydrogenase kinase 4 (PDK4), which is known to convert cellular pyruvate to acetyl co-enzyme A. miR-211-expressing cells were characterized by uptake of glutamine, rather than glucose, as a source of cellular energy. Global proteomic, transcriptomic, lipidomic, and metabolomic profiling with integrated analysis revealed that miR-211 modulates several “-omics” signatures associated with oxidative phosphorylation. Here we show for the first time that a microRNA and its target genes play a key role in regulating mitochondrial energy metabolism in melanomas. Citation Format: Joseph Mazar, Adam Richardson, Feng Qi, Bongyong Lee, Angeles Duran, Subramaniam Govindarajan, John Shelley, Laurence M. Brill, Jian-Liang Li, Xianlin Han, Jorge Moscat, Ranjan Joseph Perera. microRNA-211 modulates energy metabolism in human melanoma cells by destabilizing HIF1-α and downregulating PDK4. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 978. doi:10.1158/1538-7445.AM2014-978
NICKEL ALLERGY AND ATOPY.
Authors: JAN E. WAHLBERG, ERIK SKOG
Journal: British Journal of Dermatology (1971)

Journal Article NICKEL ALLERGY AND ATOPY: THRESHOLD OF NICKEL SENSITIVITY AND IMMUNOGLOBULIN E DETERMINATIONS Get access JAN E. WAHLBERG, JAN E. WAHLBERG Department of Occupational Dermatology, National Institute of Occupational Health, and Karolinska Sjukhuset, 104 01 Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar ERIK SKOG ERIK SKOG Department of Occupational Dermatology, National Institute of Occupational Health, and Karolinska Sjukhuset, 104 01 Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 85, Issue 2, 1 August 1971, Pages 97–104, https://doi.org/10.1111/j.1365-2133.1971.tb07192.x Published: 01 August 1971 Article history Accepted: 22 April 1971 Published: 01 August 1971
Efficacy of Intralesional Botulinum Toxin A for Treatment of Painful Cutaneous Leiomyomas
Authors: Haley B. Naik, Seth M. Steinberg, Lindsay A. Middelton, Stephen M. Hewitt, Rena C. Zuo, W. Marston Linehan, Heidi H. Kong, Edward W. Cowen
Journal: JAMA Dermatology (2015)

Cutaneous leiomyomas can be associated with severe paroxysmal pain in which nerve conduction may have a key role. Medical management of painful cutaneous leiomyomas is generally unsatisfactory.To assess the efficacy of intralesional botulinum toxin A in the management of pain associated with cutaneous leiomyomas.Randomized, double-blind, placebo-controlled pilot study conducted from January 5, 2009, to March 27, 2014. The setting was a single-center study at the National Institutes of Health among participants 18 years or older with cutaneous leiomyomas characterized by pain at least once weekly and pain of at least 4 on a pain scale ranging from 0 to 10.Eighteen participants were randomized to receive intralesional botulinum toxin A (5 U per 1 cm2) or equivalent volumes of intralesional saline placebo.The primary outcomes were the differences in average lesional pain assessed by the Brief Pain Inventory and visual analog scale before and after ice provocation over a 4-week period.No significant difference in average lesional pain was observed between the study arms. Decreased pain was reported in the botulinum toxin vs placebo arms by visual analog scale scores before ice provocation (median, 0.00; range, -3.30 to 0.70 for botulinum toxin and median, 0.40; range, -1.30 to 1.50 for placebo; P = .06); however, this finding was nonsignificant. No significant difference was observed in change in pain after ice provocation. A significant difference was seen between the arms in skin-related quality of life by total Dermatology Life Quality Index (median, -4.00; range, -8.00 to 2.00 for botulinum toxin and median, 0.00; range, -1.00 to 4.00 for placebo; P = .007) and with the specific skin pain-related question on the Dermatology Life Quality Index (median, -1.00; range, -2.00 to 1.00 for botulinum toxin and median, 0.00; range, -1.00 to 0.00 for placebo; P = .048). No significant difference was found in pain as ascertained by Patient Global Impression of Change at week 4. No serious adverse events related to botulinum toxin use were observed.The use of botulinum toxin to treat painful cutaneous leiomyomas was associated with improved quality of life and with a trend toward improved pain at rest.clinicaltrials.gov Identifier: NCT00971620.
C-reactive protein in psoriasis
Authors: A. Sergeant, A. Makrygeorgou, W.C. Chan, A. Thorrat, D. Burden
Journal: British Journal of Dermatology (2007)

Journal Article C‐reactive protein in psoriasis Get access A. Sergeant, A. Sergeant Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. E‐mail: annsergeant@doctors.org.uk; annsergeant@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar A. Makrygeorgou, A. Makrygeorgou Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. E‐mail: annsergeant@doctors.org.uk; annsergeant@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar W.C. Chan, W.C. Chan Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. E‐mail: annsergeant@doctors.org.uk; annsergeant@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar A. Thorrat, A. Thorrat Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. E‐mail: annsergeant@doctors.org.uk; annsergeant@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar D. Burden D. Burden Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. E‐mail: annsergeant@doctors.org.uk; annsergeant@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 2, 1 February 2008, Pages 417–419, https://doi.org/10.1111/j.1365-2133.2007.08334.x Published: 01 February 2008