tbuckley/cabot-search huggingface dataset:
Abstract P300: Major Risk Factors For Coronary And Aorto-iliac Calcium In Middle-aged Black And White Adults: Results From CARDIA
Authors: David C Goff, David Jacobs, J G Terry, Stephen Sidney, J J Carr
Journal: Circulation (2012)

Background: Abdominal aorto-iliac atherosclerosis occurs earlier in the course of disease than coronary artery atherosclerosis and is often present in persons free of coronary atherosclerosis. Accounting for this early stage of disease might improve the ability to evaluate risk factors for atherosclerosis. Objective: We examined the associations of major risk factors with the presence of coronary artery calcium (CAC) and abdominal aorto-iliac calcium (AoIC) in the absence of CAC in 1994 black and white men and women participating in the CARDIA study at the year 25 exam in 2010–11. Methods: Multinomial logistic regression was used to examine the associations of risk factors measured at year 15 with the presence of CAC and AoIC (Agatston scores ≥1) at year 25. Ordinary logistic regression was used to examine the associations of risk factors with presence of CAC (ignoring AoIC) at year 25. Results: 457 (22.9%) had both CAC and AoIC, 139 (7.0%) had CAC only, 632 (31.7%) had AoIC only, and 766 (38.4%) had neither. The 596 with CAC (+/−AoIC) were analyzed as one group vs. AoIC only, both in comparison with no calcification. Most risk factors had similar association with CAC (+/−AoIC) and AoIC only, including total and HDL cholesterol, triglycerides, systolic and diastolic blood pressure, smoking status, waist circumference and education. When comparing odds ratios (OR) for CAC (+/−AoIC) and AoIC only, both vs. no calcification, substantial differences were seen for comparisons of blacks vs whites (0.52 for CAC, p&lt;0.0001 and 0.88 for AoIC, p=0.34), women vs men (0.34 for CAC, p&lt;0.0001 and 0.96 for AoIC, p=0.77), and use vs. nonuse of drugs for blood pressure lowering (2.24, p=0.0023 and 1.27, p=0.36) and lipid lowering drugs (2.39, p=0.07 and 0.98, p=0.97). Accounting for the presence of AoIC without CAC resulted in uniform strengthening of the associations of risk factors with CAC. The most impressive change was for current smoking. The OR for CAC was 2.01 (95% CI: 1.53, 2.65) when ignoring AoIC and 4.47 (3.15, 6.32) when accounting for AoIC. AoIC alone was also strongly associated with smoking with an OR of 3.84 (2.80, 5.28). Conclusions: AoIC, an early manifestation of subclinical atherosclerosis, is associated with the major risk factors for CAC. The race and sex differences shown here, including little race or sex difference in AoIC only, are consistent with previous autopsy studies and deserve further etiologic research. Accounting for the presence of AoIC without CAC results in stronger estimates of risk factor associations with CAC. Studies that have not accounted for the presence of atherosclerosis in other vascular beds may have under-estimated the associations of established and novel risk factors with CAC.
Role of Neutrophils in Myocardial Ischemia and Reperfusion
Authors: Peter RiisHansen
Journal: Circulation (1995)

Abstract In the intact organism, ischemic myocardial injury initiates an acute inflammatory response in which polymorphonuclear leukocytes (PMNs) are major participants. Evidence indicates that the interplaying inflammatory reactions are augmented by reperfusion and that accumulating PMNs can contribute to myocardial damage, eg, by release of oxygen-derived free radicals, proteases, and leukotrienes. In experimental models, interventions aimed at PMN inhibition can exert cardioprotective effects, and some of these strategies raise hope for future clinical applications. A greater understanding of the mechanisms involved in PMN-mediated myocardial damage is necessary for designing a rational approach to reduce the putative detrimental effects of PMNs without antagonizing their favorable consequences in tissue healing.
Abstract 4602: PTEN and ERG expression in MRI-ultrasound guided fusion biopsy correlated with radical prostatectomy findings in men with prostate cancer
Authors: Andrew Erickson, Utku Lokman, Kanerva Lahdensuo, Sara Tornberg, Harri Visapää, Robin Bergroth, Henrikki Santti, Anssi Petas, Tuomas Mirtti, Antti Rannikko
Journal: Cancer Research (2018)

Abstract Introduction &amp; Objectives We previously compared ERG and PTEN protein expression in systematic biopsies with radical prostatectomy (RP) findings. MRI-Ultrasound (MRI-US) guided biopsies are expected to more accurately reflect the biological changes in the RP specimens. Here, we studied the correlation of PTEN and ERG status in MRI-US fusion biopsies (FBx) and RP specimens, and assessed the predictive value of FBx on disease stage and grade at RP. Material &amp; Methods The study included patients who had undergone RP in Helsinki University Hospital between June 2015 and May 2017, and had preoperative FBx tissue available (n=110). Matched FBx specimens and tissue microarrays constructed from RP were immunostained with ERG and PTEN antibodies, and scored as either negative or positive. The RP TMA contained one to three clinically relevant cancer foci per patient. Results A high correlation of both PTEN and ERG status was observed between FBx and RP materials (Table 1). The correlation of PTEN status was particularly better compared with our previous findings in systematic 12-core biopsies (Lokman et al. 2017), where there was no significant concordance. High grade RP (grade group 4&amp;5) correlated with ERG negativity in FBx (p=0.021), whereas PTEN was lost in high stage RP (pT≥3) to a higher extent than in low stage RP (pT2, p= n.s). Higher FBx grade group was associated with stage increase in RP (p=0.014). Conclusions FBx is feasible method to assess ERG and PTEN status correctly in RP specimens. More validation studies, accompanied with MRI features, are warranted. Table 1A. Concordance of ERG IHC status in fusion biopsies (FBx) and radical prostatectomy (RP) specimens.RP ERG NegativeRP ERG PositiveP-valueFBx ERG Negative54 (90.0)6 (10.0)&amp;lt;0.001aFBx ERG Positive3 (7.1)39 (92.9)Table 1B. Concordance of PTEN IHC (Any PTEN Loss) status in FBx and RP specimens.RP Any PTEN LossRP PTEN IntactP-valueFBx Any PTEN Loss14 (73.7)5 (26.3)0.002aFBx PTEN Intact22 (32.4)46 (67.6)Table 1C. Concordance of PTEN IHC (Complete PTEN Loss) status in FBx and RP specimens.RP Complete PTEN LossRP PTEN IntactP-valueFBx Complete PTEN Loss6 (50.0)3 (50.0)&amp;lt;0.001aFBx PTEN Intact3 (4.0)72 (96.0)aFisher''s exact test. All p-values two-tailed. Citation Format: Andrew Erickson, Utku Lokman, Kanerva Lahdensuo, Sara Tornberg, Harri Visapää, Robin Bergroth, Henrikki Santti, Anssi Petas, Tuomas Mirtti, Antti Rannikko. PTEN and ERG expression in MRI-ultrasound guided fusion biopsy correlated with radical prostatectomy findings in men with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4602.
Abstract 19939: Efficacy of Thrombo-suction in Primary Percutaneous Coronary Intervention of Acute Myocardial Infarction (ETAMI): Korean Prospective Randomized Multicenter Trial
Authors: Hong-Seok Lim, Sang Sik Chung, Jang Ho Bae, Seung Woon Rha, Duk Kyu Cho, Byung Eun Park, Dong-Ju Choi, Young Guk Ko, Bum Kee Hong, Jung Han Yoon, Jei Keon Chae, Yong Seok Jung, Nam Ho Lee, Kyoo Rok Han, Yong Jin Choi, Myung Ho Jeong, Seung Ho Hur, Sang Wook Lim, Seung Jin Lee, Sung Ho Hur, Jang Hyun Jo, Eun Suk Shin, Jung-Dong Lee, Seung-Jea Tahk
Journal: Circulation (2017)

Introduction and objective: Despite the theoretical reasoning of the usefulness of intracoronary thrombus aspiration during P-PCI in STEMI patients, its efficacy and safety are debated and have not...
Response to the Letter by Opolski et al Regarding Article, “Computed Tomography Coronary Angiography in Patients With Acute Myocardial Infarction Without Significant Coronary Stenosis”
Authors: AnnachiaraAldrovandi, FilippoCademartiri, DanieleArduini, DanielaLina, FabrizioUgo, EricaMaffei, AlbertoMenozzi, ChiaraMartini, AlessandroPalumbo, FedericoBontardelli, TizianoGherli, LiviaRuffini, DiegoArdissino
Journal: Circulation (2013)
Lewis A. Conner
Authors: JeffreyFisher
Journal: Circulation (2000)

Abstract—Lewis A. Conner, MD (1867 to 1950), was a pioneer in public health cardiology, cardiac rehabilitation, and cardiac psychology. He helped establish the Burke Rehabilitation Hospital and was the founding president of the New York and American Heart Associations (AHA). Dr Conner was the founder of the American Heart Journal, America’s first medical subspecialty journal, and the official publication of the American Heart Association until 1950, when Circulation was created. Conner spent more than a half-century on the staff of the New York Hospital and Cornell University Medical College and was Chairman of Medicine from 1916 to 1932. During this time, he created the innovative Cornell Pay Clinic and united the “old” New York Hospital with the new and scientifically-oriented Cornell University Medical College on a modern and inspiring urban campus. An extraordinary clinician and a humanist with great equanimity, Conner devoted his career to the Oslerian tradition of scholarship, leadership, and organi...
Margaret McCartney: If you don’t pay for it you are the product
Authors: Margaret McCartney
Journal: BMJ (2018)

GlasgowWhen I search for "cow's milk protein allergy" the first website to come up is Allergy UK.The first page has an offer for "a new masterclass for GPs in 2018!" 1 It's free, but it's sponsored by Nutricia, which makes formula milk.Elsewhere on the Allergy UK website parents are offered information relating to "delayed Cow's Milk Allergy," in the form of "What symptoms should I look out for?"-andI wonder how many babies have not had any of the eczema/diarrhoea/colic/constipation/not feeding/reflux/vomiting symptoms listed.As there are "no tests for delayed Cow's Milk Allergy," the website continues, if you're formula feeding "your GP will need to switch your infant over to a prescribed formula," 2 such as one of the ones Nutricia makes.It's 2018, and we're surely all getting tired of the charade that people are immune to advertising.Surely, it should be clear: don't take education from people who tell you that you're not using enough of the stuff they sell.
Abstract 4321: Up-regulation of METTL3 promoted m6A modification and epigenetic silencing of SOCS2 in human liver cancer
Authors: Mengnuo Chen, Lai Wei, Cheuk-Ting Law, Felice H. Tsang, Jialing Shen, Carol L. Cheng, Long-Hin Tsang, Daniel W. Ho, David K. Chiu, Joyce M. Lee, Carmen C. Wong, Irene O. Ng, Chun-Ming Wong
Journal: Cancer Research (2018)

Abstract Epigenetic alteration is a common trait of human cancers. Chemical modifications on DNA and core histone proteins are the major mechanisms for epigenetic regulation. Recently, emerging evidence suggested that reversible chemical modifications on RNA also play a critical role in epigenetic control of gene expression. N6-methyladenosine (m6A) is the most abundant modification found in mammalian mRNA. m6A is involved in regulating mRNA stability, splicing, and translation. However, the implications of m6A modification in human carcinogenesis remain poorly understood. In this study, we investigated the expression of m6A methyltransferases and demethylases in human hepatocellular carcinoma (HCC). We found the major m6A methyltransferase METTL3 was remarkably up-regulated in HCC. High METTL3 expression was associated with poor overall and disease-free survival in HCC patients. Consistent with the METTL3 overexpression, we found that mRNA m6A level was significantly elevated in human HCC. To investigate the roles of METTL3 in human HCC, we employed lentiviral-based shRNA and CRISPR/Cas9 systems to inactivation METTL3 in HCC cell lines. We showed that knockdown and knockout of METTL3 drastically suppressed HCC proliferation and migration in vitro and abolished HCC tumorigenicity and lung metastasis in vivo. In contrast, overexpression of METTL3 by CRISPR/dCas9 SAM system promoted HCC growth. Using RNA-seq and m6A-Seq, we identified tumor suppressor gene SOCS2 as a novel target of METTL3. We detected m6A modification in SOCS2 mRNA and the m6A modification was diminished upon METTL3 knockdown. m6A modification promoted SOCS2 mRNA degradation. We demonstrated that knockdown of METTL3, mutation of m6A modification sites, and treatment of demethylating agent augmented SOCS2 mRNA expression in HCC cells. In addition, knockdown of YTHDF2, an m6A reader protein, also rescued SOCS2 mRNA expression in HCC cells. The above findings together demonstrated that up-regulation of METTL3 lead to m6A modification of SOCS2, which in turn promotes SOCS2 mRNA degradation through YTHDF2 dependent mechanism. Our findings provided a proof-of-concept model to demonstrate the importance of aberrant m6A modification in epigenetic silencing of tumor suppressor genes. Citation Format: Mengnuo Chen, Lai Wei, Cheuk-Ting Law, Felice H. Tsang, Jialing Shen, Carol L. Cheng, Long-Hin Tsang, Daniel W. Ho, David K. Chiu, Joyce M. Lee, Carmen C. Wong, Irene O. Ng, Chun-Ming Wong. Up-regulation of METTL3 promoted m6A modification and epigenetic silencing of SOCS2 in human liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4321.
Effects of Hypertension, Diabetes Mellitus, and Hypercholesterolemia on Endothelin Type B Receptor–Mediated Nitric Oxide Release From Rat Kidney
Authors: MasaoKakoki, YasunobuHirata, HiroshiHayakawa, AkihiroTojo, DaisukeNagata, EtsuSuzuki, KenjiroKimura, AtsuoGoto, KazuyaKikuchi, TetsuoNagano, MasaoOmata
Journal: Circulation (1999)

Background—Although endothelin-1 is a potent vasoconstrictor peptide, stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in pathological conditions are largely unknown. Methods and Results—We studied the effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance and nitric oxide (NO) release in the isolated, perfused kidney of rats with hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at concentrations of ≤10−10 mol/L reduced renal perfusion pressure in Dahl salt-resistant (R) rats but increased renal perfusion pressure in Dahl salt-sensitive (S) rats (10−10 mol/L: −10.3±0.6% versus 11.2±1.5%, R versus S; P<0.01). BQ-3020 caused a dose-dependent release of NO in both R and S rats, although the level of NO release in S rats was lower, as detected by chemiluminescence (10−10 mol/L: 10....
Enhanced Progression of Early Carotid Atherosclerosis Is Related to Chlamydia pneumoniae (Taiwan Acute Respiratory) Seropositivity
Authors: DirkSander, KerstinWinbeck, JürgenKlingelhöfer, ThorleifEtgen, BastianConrad
Journal: Circulation (2001)

Background—Chlamydia pneumoniae (Cp) infection has been associated with atherosclerosis and has been proposed as a possible additional cardiovascular risk factor. However, the relationship between Cp seropositivity and the progression of early carotid atherosclerosis is not unequivocally clarified. Methods and Results—We evaluated the association between serological detection of Cp IgG and/or IgA antibodies and the progression of the intima-media thickness (IMT) of the common carotid artery using duplex ultrasonography in a prospective study with a follow-up of 3 years in 272 consecutive patients with cerebrovascular disease. Cp-seropositive patients showed a significantly enhanced progression of the IMT even after adjustment for other cardiovascular risk factors (0.12 mm/y [95% CI 0.11 to 0.14] versus 0.07 mm/y [0.05 to 0.09]; P<0.005). Patients with increased C-reactive protein (≥0.5 mg/dL) and Cp seropositivity showed the most pronounced IMT progression. Multivariate regression analysis revealed Cp ser...
Comorbidity Patterns In Alpha-1-Antitrypsin Deficiency Depend On Natural History And Substitution Therapy
Authors: S. W. Fahndrich, F. Biertz, A. Karch, B. Kleibrink, A. Koch, H. Teschler, T. Welte, T. Greulich, H.-U. Kauczor, S. Janciauskiene, R. Jörres, C. Vogelmeier, R. Bals
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Generation of Cardiomyocytes From Vascular Adventitia-Resident Stem Cells
Authors: Subba Rao Mekala, Philipp Wörsdörfer, Jochen Bauer, Olga Stoll, Nicole Wagner, Laurens Reeh, Kornelia Loew, Georg Eckner, Chee Keong Kwok, Erhard Wischmeyer, Mary Eleanor Dickinson, Harald Schulze, David Stegner, Ralf A. Benndorf, Frank Edenhofer, Verena Pfeiffer, Stefanie Kuerten, Stefan Frantz, Süleyman Ergün
Journal: Circulation Research (2018)

Regeneration of lost cardiomyocytes is a fundamental unresolved problem leading to heart failure. Despite several strategies developed from intensive studies performed in the past decades, endogenous regeneration of heart tissue is still limited and presents a big challenge that needs to be overcome to serve as a successful therapeutic option for myocardial infarction.One of the essential prerequisites for cardiac regeneration is the identification of endogenous cardiomyocyte progenitors and their niche that can be targeted by new therapeutic approaches. In this context, we hypothesized that the vascular wall, which was shown to harbor different types of stem and progenitor cells, might serve as a source for cardiac progenitors.We describe generation of spontaneously beating mouse aortic wall-derived cardiomyocytes without any genetic manipulation. Using aortic wall-derived cells (AoCs) of WT (wild type), αMHC (α-myosin heavy chain), and Flk1 (fetal liver kinase 1)-reporter mice and magnetic bead-associated cell sorting sorting of Flk1+ AoCs from GFP (green fluorescent protein) mice, we identified Flk1+CD (cluster of differentiation) 34+Sca-1 (stem cell antigen-1)-CD44- AoCs as the population that gives rise to aortic wall-derived cardiomyocytes. This AoC subpopulation delivered also endothelial cells and macrophages with a particular accumulation within the aortic wall-derived cardiomyocyte containing colonies. In vivo, cardiomyocyte differentiation capacity was studied by implantation of fluorescently labeled AoCs into chick embryonic heart. These cells acquired cardiomyocyte-like phenotype as shown by αSRA (α-sarcomeric actinin) expression. Furthermore, coronary adventitial Flk1+ and CD34+ cells proliferated, migrated into the myocardium after mouse myocardial infarction, and expressed Isl-1+ (insulin gene enhancer protein-1) indicative of cardiovascular progenitor potential.Our data suggest Flk1+CD34+ vascular adventitia-resident stem cells, including those of coronary adventitia, as a novel endogenous source for generating cardiomyocytes. This process is essentially supported by endothelial cells and macrophages. In summary, the therapeutic manipulation of coronary adventitia-resident cardiac stem and their supportive cells may open new avenues for promoting cardiac regeneration and repair after myocardial infarction and for preventing heart failure.
The maiming fields of Gaza
Authors: Derek Summerfield, David Halpin, Swee Ang, Andrea Balduzzi, Franco Camandona, Gianni Tognoni, Ireo Bono, Marina Rui, Vittorio Agnoletto
Journal: BMJ (2018)

The BMJ reports on Gaza’s post-conflict health infrastructure.1 Since 30 March 2018, Palestinians civilians who have been living as refugees in Gaza since 1948 have been gathering in mass, unarmed demonstrations about their political predicament and the ongoing effects of the 12 year long Israeli siege. Since 2014 Israel has further tightened the passage of essential medicines and equipment into Gaza, where hospitals are depleted of …
Abstract LB-040: New conditional Kras-alleles generated by CRISPR-based genome editing to model tumor initiation
Authors: Maria Paz Zafra, Emma M. Schatoff, Teng Han, Lukas E. Dow
Journal: Cancer Research (2018)

Abstract KRAS is the most frequently mutated oncogene in human cancers, and specific cancer types show a clear bias in the types and frequency of Kras alterations. However, we do not have a clear understanding of how distinct Kras mutations dictate tumor biology and response to therapy. The generation of conditional animal models, such as Lox-Stop-Lox (LSL) KrasG12D and LSL-KrasG12Vgeo mice, have provided important tools to dissect the impact of Kras mutation in tumor development, but these models alone do not recapitulate the spectrum of Kras alterations in human cancer. To better reflect the Kras mutational landscape in human cancers, we have developed a series of critical LSL-Kras mouse models that recapitulate common Kras alterations observed in colorectal (G13D), pancreatic (G12R), and lung cancer (G12C), allowing the direct interrogation of the effects of these Kras mutations on disease phenotype and treatment response. To do this, we targeted embryonic stem cells (ESCs) carrying the LSL-KrasG12D allele, by co-transfection of a modified high-fidelity Cas9 (Cas9-HFz), a LSL-Kras-targeted sgRNA, and an HDR template carrying the new mutation. While Cas9-HFz displayed a slight decrease in homology-directed repair (HDR) efficiency in comparison with wildtype Cas9, it enabled high specificity editing of only the LSL allele. Targeted deep sequencing revealed a significant reduction in ‘off-target' events in wildtype Kras locus in Cas9-HFz transfected samples compared to unmodified Cas9. We next generated transgenic mice by blastocyst injection and produced mice carrying each LSL-Kras variant, a pancreas specific Cre (p48-Cre) and a far-red fluorescent Cre-reporter (mKate2). We are now analyzing the impact of specific Kras alterations in tumor initiation in distinct tissues such as the pancreas, colon and lung. Together with available LSL-KrasG12D and LSL-KrasG12V already available, our new alleles will serve as critical tools for better dissect the genetic factors that dictate disease initiation, progression, and response to therapy. Citation Format: Maria Paz Zafra, Emma M. Schatoff, Teng Han, Lukas E. Dow. New conditional Kras-alleles generated by CRISPR-based genome editing to model tumor initiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-040.