tbuckley/cabot-search huggingface dataset:
Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning
Authors: Elizabeth Ing-Simmons, Roshan Vaid, Xin Yang Bing, Michael Levine, Mattias Mannervik, Juan M. Vaquerizas
Journal: Nature Genetics (2021)

Abstract The relationship between chromatin organization and gene regulation remains unclear. While disruption of chromatin domains and domain boundaries can lead to misexpression of developmental genes, acute depletion of regulators of genome organization has a relatively small effect on gene expression. It is therefore uncertain whether gene expression and chromatin state drive chromatin organization or whether changes in chromatin organization facilitate cell-type-specific activation of gene expression. Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.
Dissociation between contractile function and oxidative metabolism in postischemic myocardium. Attenuation by ruthenium red administered during reperfusion.
Authors: R HBenzi, RLerch
Journal: Circulation Research (1992)

The oxidative metabolic rate may be disproportionately high compared with contractile function in postischemic reperfused myocardium. To study the potential involvement of intracellular calcium transport in high energy expenditure after reperfusion, we determined in isolated rat hearts the effect of ruthenium red, an inhibitor of mitochondrial calcium transport, on recovery of contractile function and oxidative metabolic rate. Hearts subjected to 60 minutes of no-flow ischemia exhibited, at 15 minutes after the onset of reperfusion, poor recovery of left ventricular pressure development to only 7% of the corresponding value measured in control hearts (p less than 0.01). However, myocardial oxygen consumption was recovered to 84% of control (p = NS). The ratio of isovolumic contractile performance (expressed as the product of heart rate and left ventricular pressure development) to myocardial oxygen consumption was severely depressed to 6% of control (p less than 0.01). Supplementation of the perfusate wit...
Skeletal muscle biochemistry and histology in ambulatory patients with long-term heart failure.
Authors: M JSullivan, H JGreen, F RCobb
Journal: Circulation (1990)

Recent studies in patients with long-term heart failure have suggested that intrinsic abnormalities in skeletal muscle can contribute to the development of early lactic acidosis and fatigue during exercise. The present study provides an analysis of substrate and enzyme content, fiber typing, and capillarization in skeletal muscle biopsy samples obtained at rest from the vastus lateralis in 11 patients with long-term heart failure (left ventricular ejection fraction, 21 +/- 8%) and nine normal subjects. Patients demonstrated a reduced peak exercise oxygen consumption (13.0 +/- 3.3 ml/kg/min) when compared with normals (30.2 +/- 8.6 ml/kg/min, p less than 0.001) and had an accelerated rise in blood lactate levels during exercise. In mixed fiber skeletal muscle, total phosphorylase and glycolytic enzyme activities were not different in the two groups, whereas mitochondrial enzymes involved in terminal oxidation were decreased in patients as compared with normal subjects as indicated by reductions in succinat...
Mechanism of early contractile failure during hypoxia in intact ferret heart: evidence for modulation of maximal Ca2+-activated force by inorganic phosphate.
Authors: HKusuoka, M LWeisfeldt, J LZweier, W EJacobus, EMarban
Journal: Circulation Research (1986)

We tested the hypothesis that accumulation of H+ or inorganic phosphate (Pi) is responsible for the early contractile failure of hypoxia by measuring maximal Ca2+-activated pressure and 31P nuclear magnetic resonance spectra in Langendorff-perfused ferret hearts at 30 degrees C. Maximal Ca2+-activated pressure was identified by the saturation of pressure with respect to [Ca2+]o observed during tetani as [Ca2+]o was increased to 15 mM in HEPES-buffered, 100% O2-bubbled perfusate and during hypoxia induced by bubbling with room air or with 100% N2. Tetani were produced by pacing at 8-12 Hz following exposure to ryanodine (1-5 microM), an inhibitor of Ca2+ release from the sarcoplasmic reticulum, and were elicited once a minute to measure maximal Ca2+-activated pressure during acquisition of nuclear magnetic resonance spectra. An inverse correlation was observed between [Pi] and maximal Ca2+-activated pressure (r = -0.87 mean, n = 12), with an average decline of 8.6% in pressure per 1 mumol/g wet wt. increas...
Comparative accuracy of two-dimensional echocardiography and Doppler pressure half-time methods in assessing severity of mitral stenosis in patients with and without prior commissurotomy.
Authors: M DSmith, RHandshoe, SHandshoe, O LKwan, A NDeMaria
Journal: Circulation (1986)

This study was undertaken to compare the accuracies of the two-dimensional echocardiographic (2DE) and Doppler pressure half-time methods for the noninvasive estimation of cardiac catheterization measurements of mitral valve area in patients with pure mitral stenosis both with and without a previous commissurotomy. Data were retrospectively obtained from 74 consecutive patients who underwent cardiac catheterization within a 30 month period for evaluation of mitral stenosis, and who had two-dimensional echocardiograms performed before catheterization. Six patients (8.1%) had technically inadequate 2DE images and their data were excluded from analysis. Two of these patients had undergone commissurotomy, while the remaining four had not. Continuous-wave Doppler echocardiographic examinations were attempted in 45 patients and adequate measurements of pressure half-times were obtained in all patients studied. Mitral valve area by two-dimensional echocardiography was measured as the planimetered area along the ...
Underwater Versus Conventional Endoscopic Mucosal Resection for Treating Colorectal Polyps: A Systematic Review and Meta-Analysis of Randomized Controlled Studies
Authors: G Tziatzios, P Gkolfakis, K Triantafyllou, L Fuccio, A Facciorusso, IS Papanikolaou, G Antonelli, S Nagl, A Ebigbo, A Probst, C Hassan, M Pellise, H Messmann
Journal: Endoscopy (2021)

Aims Previous meta-analysis including nonrandomized studies showed marginal benefit of underwater endoscopic mucosal resection (U-EMR) compared to conventional EMR (C-EMR) in terms of polypectomy outcomes. We evaluated the effectiveness and safety of U-EMR compared to C-EMR in the treatment of colorectal polyps by including only randomized controlled trials (RCTs).
Metaiodobenzylguanidine [131I] scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure.
Authors: M ARabinovitch, C PRose, J LRouleau, CChartrand, D MWieland, LLepanto, FLegault, SSuissa, LRosenthall, J HBurgess
Journal: Circulation Research (1987)

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [131I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [131I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/h...
Indications, complications, and short-term clinical outcome of percutaneous transvenous mitral commissurotomy.
Authors: MNobuyoshi, NHamasaki, TKimura, HNosaka, HYokoi, HYasumoto, HHoriuchi, HNakashima, TShindo, TMori
Journal: Circulation (1989)

Percutaneous transvenous mitral commissurotomy was performed in 106 consecutive patients. Significant symptomatic improvement was achieved in 97 patients (92%). Mean left atrial pressure decreased (from 18 +/- 8 to 11 +/- 8 mm Hg, p less than 0.00001), mean mitral diastolic pressure gradient decreased (from 12 +/- 7 to 7 +/- 6 mm Hg, p less than 0.00001), and mitral valve area increased (from 1.40 +/- 0.40 to 2.00 +/- 0.50 cm2, p less than 0.00001). Based on echocardiographic characteristics of the mitral apparatus, patients were grouped retrospectively in three categories: pliable (group 1, n = 37), semipliable (group 2, n = 59), and rigid (group 3, n = 10). Clinical success was achieved in 36 patients of group 1 (97%) and in 55 patients of group 2 (93%). Only six patients in group 3 (60%) improved symptomatically (p less than 0.001 vs. group 1, p less than 0.001 vs. group 2). The severity of mitral regurgitation increased in five patients of group 1 (14%), in 12 of group 2 (20%), and in three of group 3...
Re: Bas W.G. van Rhijn, Theo H. van der Kwast, Sultan S. Alkhateeb, et al. A New and Highly Prognostic System to Discern T1 Bladder Cancer Substage. Eur Urol 2012;61:378–84
Authors: Maximilian Burger, Wolfgang Otto, Arndt Hartmann
Journal: European Urology (2012)
Risk of stroke in adults with cyanotic congenital heart disease.
Authors: N D Bridges
Journal: Circulation (1994)

The study of Perloff et all is a welcome addition to the literature on the adult with congenital heart disease in that it presents data regarding the frequency and character of hyperviscosity symptoms in polycythemic, cyanotic adult patients.Furthermore, the authors' recommendation that phlebotomy be reserved for the symptom- atic patient, and not used as a prophylaxis against stroke, is for the most part well reasoned.However, it is important to recognize that the data in this paper do not definitively address the question of whether or not poly- cythemic adult patients without other risk factors for stroke are at increased risk of stroke compared with their acyanotic, nonpolycythemic counterparts in the general population.Based on esti- mates made by the American Heart Association and data from the US Census, the expected incidence of cryptogenic stroke in the age range of the patients in this study would be about 0.001 strokes per patient-year (400 000 strokes per year,2,3 40% of which are cryptogenic,4 in a population of 155 298 000 people).Even if the risk among cyanotic, polycythemic patients were 10 times as great, the amount of patient follow-up in the report of Perloff et al (748 patient years) would be inadequate to detect it at a significance level of .05 and a power of 80% (860 patient-years of follow-up would be needed5).Thus, the authors' statement that "we found no risk of stroke caused by cerebral arterial thrombosis" may be somewhat mislead- ing, and it would be a mistake for readers of this paper to conclude that cyanotic, polycythemic patients are not at increased risk of stroke compared with the general population.Their risk of stroke may well be greater; however, for the reasons discussed by Perloff et al, prophylactic phlebotomy may be as likely to increase as it is to decrease that risk.
Anthracosis Mimicking Mediastinal Lymph Node Metastases With 18F-FCholine in High-Risk Prostate Cancer
Authors: Jean-Baptiste Pinaquy, Philippe Fernandez, Gilles Pasticier, Marie Parrens, Henri De Clermont
Journal: Clinical Nuclear Medicine (2015)

A 62-year-old patient with prostate adenocarcinoma underwent PET with radiolabeled choline (18F-Fcholine) for pretreatment staging of a high-risk prostate cancer. Images showed a significant mediastinal lymph node uptake of 18F-Fcholine. Owing to the rarity of spread to supradiaphragmatic lymph nodes, a surgical removal was performed, revealing anthracosis and no malignant cells. Even if its specificity seems better than 18F-FDG, false positives have been reported and other pathologies could mimic lymph node metastases. Consequently, histology should be performed so that the appropriate treatment can be initiated.
Baroreflex control of the circulation in chronically instrumented fetal lambs.
Authors: JItskovitz, E FLaGamma, A MRudolph
Journal: Circulation Research (1983)

The role of the arterial baroreceptors in regulating the fetal circulation was studied in 18 chronically instrumented fetal lambs, 120-136 days gestation. The results were compared to those obtained in three sinoaortic denervated adult sheep. Nine fetuses underwent sinoaortic denervation and nine fetuses served as sham-operated controls. Two to 3 days after surgery, heart rate and blood pressure were recorded continuously and analyzed over 1-hour periods. In the denervated fetuses, marked fluctuations of the arterial pressure and heart rate were observed. Frequency distribution curves for mean arterial pressure and heart rate showed broader and flatter curves in the denervated fetuses. The average mean arterial pressure and heart rate were not significantly different between the two groups. However, the standard deviation as an index of variability of the mean arterial pressure increased from 2.7 +/- 0.9 (mean +/- standard deviation) in the control group to 6.5 +/- 2.4 in the denervated fetuses, and the s...
Hydrogel Scaffolds: Cell‐Laden Gradient Hydrogel Scaffolds for Neovascularization of Engineered Tissues (Adv. Healthcare Mater. 7/2021)
Authors: Yusheng J. He, Martin F. Santana, Austeja Staneviciute, Marja B. Pimentel, Feipeng Yang, Jacob Goes, Keigo Kawaji, Marcella K. Vaicik, Rayan Abdulhadi, Narutoshi Hibino, Georgia Papavasiliou
Journal: Advanced Healthcare Materials (2021)

In articule number 2001706 by Georgia Papavasiliou and co-workers, vascular cell-laden gradient PEG hydrogels with five types of gradient combinations including immobilized cell adhesion peptide concentration (RGD), stiffness, and protease-sensitivity are designed to investigate their role on spatial variations in vascular sprouting responses in 3D culture.
Electrophysiologic and histologic correlations in chronic complete atrioventricular block.
Authors: SOhkawa, MSugiura, YItoh, KKitano, KHiraoka, KUeda, MMurakami
Journal: Circulation (1981)

Electrophysiologic studies using the His bundle electrogram (HBE) and histologic studies of serial sections of the conduction system were correlated in two groups of deceased patients. Group 1 consisted of five patients with chronic complete atrioventricular block (CAVB) who had narrow QRS complexes and AH block (block proximal to the His bundle deflection). Group 2 consisted of four patients with chronic CAVB who had wide QRS complexes and HV block (block distal to the His bundle deflection). In group 1, the sites of the main lesion were not located in the approaches to the atrioventricular (AV) node or the AV node, but were found in the penetrating portion of the His bundle in one patient and in the branching portion of the His bundle in three patients. In the remaining patient, the main site of block could not be demonstrated histologically in the AV conduction system, but marked fibrosis of the approaches to the sinoatrial node and surrounding atrial muscle was found. In all patients of group 2, the s...
EULAR Points to Consider (PtC) for designing, analysing and reporting of studies with work participation as an outcome domain in patients with inflammatory arthritis
Authors: Annelies Boonen, Polina Putrik, Mary Lucy Marques, Alessia Alunno, Lydia Abasolo, Dorcas Beaton, Neil Betteridge, Mathilda Bjørk, Maarten Boers, Boryana Boteva, Bruno Fautrel, Francis Guillemin, Elsa F Mateus, Elena Nikiphorou, Márta Péntek, Fernando Pimentel Santos, Johannes L Severens, Suzanne M M Verstappen, Karen Walker-Bone, Johan Karlsson Wallman, Marieke M ter Wee, René Westhovens, Sofia Ramiro
Journal: Annals of the Rheumatic Diseases (2021)

Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses.To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain.The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously.Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9).Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP.
ZFN-mediated in vivo gene editing in hepatocytes leads to supraphysiologic α-Gal A activity and effective substrate reduction in Fabry mice
Authors: Silvere Pagant, Marshall W. Huston, Luciana Moreira, Lin Gan, Susan St Martin, Scott Sproul, Michael C. Holmes, Kathleen Meyer, Thomas Wechsler, Robert J. Desnick, Makiko Yasuda
Journal: Molecular Therapy (2021)

Fabry disease, a lysosomal storage disorder resulting from the deficient activity of α-galactosidase A (α-Gal A), is characterized by cardiac, renal, and/or cerebrovascular disease due to progressive accumulation of the enzyme's substrates, globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3). We report here the preclinical evaluation of liver-targeted in vivo genome editing using zinc-finger nuclease (ZFN) technology to insert the human α-galactosidase A (hGLA) cDNA into the albumin "safe harbor" locus of Fabry mice, thereby generating an albumin-α-Gal A fusion protein. The mature α-Gal A protein is secreted into the circulation for subsequent mannose-6-phosphate receptor-mediated tissue uptake. Donor vector optimization studies showed that replacing the hGLA cDNA signal peptide sequence with that of human iduronate 2-sulfatase (IDS) achieved higher transgene expression. Intravenous adeno-associated virus (AAV) 2/8-mediated co-delivery of the IDS-hGLA donor and ZFNs targeting the albumin locus resulted in continuous, supraphysiological plasma and tissue α-Gal A activities, which essentially normalized Gb3 and Lyso-Gb3 levels in key tissues of pathology. Notably, this was achieved with <10% of hepatocytes being edited to express hGLA, occurring mostly via non-homologous end joining (NHEJ) rather than homology-directed repair (HDR). These studies indicate that ZFN-mediated in vivo genome editing has the potential to be an effective one-time therapy for Fabry disease.
DNA Testing to Identify Rapists in the Former Yugoslavia-Reply
Authors: Shana Swiss
Journal: JAMA (1994)

<h3>In Reply.</h3> —Informed consent for victims of war crimes and protection of confidentiality of all evidence in a case, including DNA evidence, is, of course, essential. It is also important that standardized procedures for DNA testing be applied. Two concerns over forensic DNA testing should be distinguished. First, as alluded to by Drs Geller and Rauch, the quality of the evidentiary samples and performance of the DNA test procedure must meet minimum technical standards. The National Research Council has called for accreditation of DNA laboratories that are stringent but are well within the capabilities of most modern molecular biology laboratories.<sup>1</sup>In the United States, compliance with TWGDAM (The Technical Working Group on DNA Analysis Methods) standards has been recognized by the National Research Council as meeting generally accepted standards of practice. Their report endorsed these procedures as fundamentally sound for use in investigations and court cases. Similar standards for
Infarct size-limiting effect of ischemic preconditioning is blunted by inhibition of 5'-nucleotidase activity and attenuation of adenosine release.
Authors: MKitakaze, MHori, TMorioka, TMinamino, STakashima, HSato, YShinozaki, MChujo, HMori, MInoue
Journal: Circulation (1994)

BACKGROUNDWe have previously reported that ischemic preconditioning increases 5'-nucleotidase activity and adenosine release during ischemia and reperfusion. However, its direct cause-and-effect relation has not been proven. To test the idea that the infarct size-limiting effect of ischemic preconditioning is blunted by inhibition of ectosolic 5'-nucleotidase activity, we assessed 5'-nucleotidase activity, adenosine release, and infarct size caused by sustained ischemia with and without an exposure to alpha,beta,-methylene adenosine 5'-diphosphate (AOPCP) in the ischemia-preconditioned myocardium.METHODS AND RESULTSIn 67 open-chest dogs, the left anterior descending coronary artery was cannulated and perfused with an extracorporeal bypass tube from the carotid artery. After hemodynamic stabilization, the coronary artery was occluded four times for 5 minutes separated by 5 minutes of reperfusion (ischemic preconditioning, n = 10). After this procedure, the coronary artery was occluded for 90 minutes follow...
Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion.
Authors: EFalk
Journal: Circulation (1985)

Extensive microscopic examination of epicardial arteries and myocardium was performed in 25 cases of sudden death due to acute coronary thrombosis. Eighty-one percent of the thrombi had a layered structure with thrombus material of differing age, indicating that they were formed successively by repeated mural deposits that caused progressive luminal narrowing over an extended period of time. This episodic growth of the thrombus was accompanied by intermittent fragmentation of thrombus in 73% of the cases, with peripheral embolization causing microembolic occlusion of small intramyocardial arteries associated with microinfarcts. The period of unstable angina before the final heart attack was, in all but one of 15 patients, characterized by such an ongoing thrombotic process in a major coronary artery where recurrent mural thrombus formation seemed to have alternated with intermittent thrombus fragmentation. The culmination of this dynamic thrombotic process in total vascular occlusion caused the final in...