Miracle-dz/UniFAR-FTUs huggingface dataset:
Adult Acute Myeloid Leukemia – A Possible Relation to Disease Invasion and the Impact of Independent Prognostic Markers Associated with Survival Outcome

Over the past decade, leukemia exists and frequently occurs in adults. Radiation ex‐ posure, hereditary syndromes, smoking, age, and many other unknown factors are generally the major risk factors for leukemia. Acute myeloid leukemia (AML) is a hematological malignancy that is dispersed from its beginning and may be perceived as a prototype of metastatic cancer, yet leukemia is considered a highly malignant ne‐ oplasms responsible for a large number of cancer-related deaths. In addition, to unin‐ hibited proliferation, leukemic cells dispense early from the bone marrow into the peripheral blood, followed by an infiltration of various organs such as lymph nodes, liver, spleen, lungs, intestinal tract, skin, or mucous membranes. Several studies are concerned with the critical role of angiogenesis in the development and growth of sol‐ id tumors and hematological malignancies. Moreover, angiogenic mediators created by AML cells act through external or internal autocrine loops, thereby directly indors‐ ing cell survival, spread, and disease development. In recent years, many researchers focus on angiopioetins (Ang), an innovative family of angiogenic mediators, which have shown to be vital regulators of angiogenesis and vascular stability. Ang-1 and its antagonist Ang-2 act via the receptor tyrosine kinase sTie 2, which is expressed in en‐ dothelial cells (ECs) of the vasculature and in subset of hematopoietic stem cells. Binding of Ang-1 causes phosphorylation of sTie2 and ensures the integrity of the vasculature by stimulating interactions between ECs and endothelial support cells. This chapter reviews the incidence, mortality, pathogenesis, and diagnostic proce‐ dures of AML. As well as aims at evaluating serum levels of endostatin, MMP9, and uPAR in acute myeloid leukemia patients before chemotherapy and after achieving complete remission. At the same time, the chapter also assesses the pretreatment lev‐ els of plasma Ang-1, Ang-2, and sTie2, and the calculated ratio of Ang2/sTie2 receptor in a cohort of AML patients also studies their impact on the AML patients' overall sur‐ vival.
Blue light and near-infrared fundus autofluorescence in acute Vogt–Koyanagi–Harada disease

Background/aims To investigate the characteristics of fundus autofluorescence (FAF) in acute Vogt–Koyanagi–Harada (VKH) disease. Methods FAF photography with blue light (BL-FAF) and near-infrared light (NIR-FAF) was performed on 10 eyes of five patients using a confocal scanning laser ophthalmoscope before and after treatment. The FAF images were followed for 6 months and retrospectively reviewed with comparisons of the other imaging modalities. Results At presentation, four eyes of two patients who presented soon after the initial ocular symptoms showed mild and uniform hyperautofluorescence in the macula mixed with hypoautofluorescence in the areas of serous retinal detachment. After immediate treatment with an intravenous high-dose steroid, the abnormal FAF returned to normal at 6 months. The other six eyes of three patients, who presented weeks after the symptoms, initially demonstrated diffuse and mottled hyperautofluorescence over the posterior pole, mixed with hypoautofluorescence induced by serous retinal detachment in four eyes. After treatment with an intravenous high-dose steroid, all six eyes showed scattered and widespread hyperautofluorescence, which gradually became evident and concentrated in the macula, partially resulting in some hypoautofluorescent dots at 6 months. The BL-FAF and the NIR-FAF demonstrated similar FAF patterns, but more evidently in NIR-FAF. Conclusion FAF photography non-invasively visualised sequential metabolic and functional changes in the retinal pigment epithelium (RPE) in acute VKH disease. The results suggest that early and sufficient treatment with a high-dose steroid might prevent persistent RPE damage. In addition, NIR-FAF can be an alternative method for the early detection of RPE abnormality.
Evidence for a gender and age inequality in the prescribing of preventative cardiovascular therapies to the elderly in primary care.

SIR—The decline in ischaemic heart disease (IHD) in Ireland has been slower in women compared with men [1] and previous evidence suggests that differential patterns exist for men and women in the prescribing of secondary preventative therapies in primary care [2]. Little information is available regarding drug treatment in the elderly population (over 65 years) in Ireland, who constitute one-third of the General Medical Services scheme (GMS) population nationally, and consume almost double the national average cost of medicine [3]. Also there is a poor evidence base for such prescribing. The aim of this study was to examine the extent to which preventative cardiovascular therapies (i.e. statins, beta-blockers) are prescribed to the elderly compared with other cardiovascular treatments, and to determine whether a gender or age bias exists in such prescribing, in particular in those at high risk with (i) IHD and (ii) diabetes.
Classification criteria for rheumatoid arthritis--time to abandon rheumatoid factor?

Criteria for rheumatoid polyarthritis diagnosis (PR) have been proposed and used for more than 10 years, and have been elaborated based on a large group of patients in which the illness evolved on average in 7 years. Therefore, these criteria do not satisfy the present requests of the early PR. At least two individual criteria are in debate under this particular aspect: the presence of erosions and of rheumatoid factor (FR). Articular erosions can be nowadays discovered in the pre-radiographic phase, through methods such as sonography and magnetic resonance, and our recommendation is to introduce the remissive therapy before their appearance. On the other hand, though FR is a marker for the persistence of the disease, it isn’t present in all cases, and its specificity is low. Since the year 2000 there have been introduced in practice the methods for discovering the anti-cyclic citrullinated peptide antibodies (PCC), which have the advantage of precocity, specificity, and predictability of the evolution of the disease under the aspect of the appearance of articular erosions. The right attitude should be the concomitant determination of FR and anti-PCC antibodies, for an early recognition of PR, and the evaluation of its evolutional potential.
Effects of the Immunoglobulin A1 Protease on Neisseria gonorrhoeae Trafficking across Polarized T84 Epithelial Monolayers

ABSTRACT We previously demonstrated that the Neisseria IgA1 protease cleaves LAMP1 (lysosome-associated membrane protein 1), a major integral membrane glycoprotein of lysosomes, thereby accelerating its degradation rate in infected A431 human epidermoid carcinoma cells and resulting in the alteration of lysosomes in these cells. In this study, we determined whether the IgA1 protease also affects the trafficking of Neisseria gonorrhoeae across polarized T84 epithelial monolayers. We report that N. gonorrhoeaeinfection of T84 monolayers, grown on a solid substrate or polarized on semiporous membranes, also results in IgA1 protease-mediated reduction of LAMP1. We demonstrate that iga mutants in two genetic backgrounds exited polarized T84 monolayers in fewer numbers than the corresponding wild-type strains. Finally, we present evidence that these mutants have a statistically significant and reproducible defect in their ability to traverse T84 monolayers. These results add to our previous data by showing that the IgA1 protease alters lysosomal content in polarized as well as unpolarized cells and by demonstrating a role for the protease in the traversal of epithelial barriers by N. gonorrhoeae.
Scholarly Contributions of Required Senior Research Projects in a Doctor of Pharmacy Curriculum

Objective. To determine dissemination outcomes and faculty perceptions of senior research projects conducted from 2008 to 2011 by PharmD students in a curricular pathway focused on direct patient care. Methods. Preceptors’ reported dissemination outcomes of research projects were surveyed and their perceptions of the precepting experience were rated using a web-based survey. Results were compared to those from an earlier pharmaceutical care cohort (2002-2007) and a combined cohort of 2, more research-intensive curricular pathways at the school. Results. The overall response rate was 90.2%. Project dissemination included 61.3% at an institutional forum, 42.3% as a submitted publication, 37.8% as a poster, and 4.5% as an oral presentation. Projects completed from 2008-2011 were significantly more likely than those from 2002-2007 to be submitted for publication (42.3% vs 10.7%, p<0.001) and published (28.8% vs 5.3%, p<0.001). Most preceptors found their research projects valuable to them professionally (88.3%) and to their own or another institution (83.5% and 78.5%, respectively). Ninety-five percent of preceptors would precept again. Conclusion. Dissemination rates for pharmaceutical care projects increased over time. Despite modest dissemination levels, the majority of preceptors agreed that required student research projects provide a valuable learning experience for students.
Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study

Abstract Objective: To investigate the relation between decreased maternal food intake and risk factors for coronary heart disease in adult Design: Cross sectional study. Subjects: 169 subjects exposed to malnutrition in utero (intrauterine group) during the siege of Leningrad (now St Petersburg) in 1941-4; 192 subjects born in Leningrad just before rationing began, before the siege (infant group); and 188 subjects born concurrently with the first two groups but outside the area of the siege (unexposed group). Setting: Ott Institute of Obstetrics and Gynaecology, St Petersburg. Main outcome measures: Development of risk factors for coronary heart disease and diabetes mellitus—obesity, blood pressure, glucose tolerance, insulin concentrations, lipids, albumin excretion rate, and clotting factors. Results: There was no difference between the subjects exposed to starvation in utero and those starved during infant life in: (a) glucose tolerance (mean fasting glucose: intrauterine group 5.2(95% confidence interval 5.1 to 5.3), infant group 5.3 (5.1 to 5.5), P=0.94; mean 2 hour glucose: intrauterine group 6.1 (5.8 to 6.4), infant group 6.0 (5.7 to 6.3), P=0.99);(b) insulin concentration; (c) blood pressure; (d)lipid concentration; or (e) coagulation factors. Concentrations of von Willebrand factor were raised in the intrauterine group (156.5 (79.1 to 309.5)) compared with the infant group (127.6 (63.9 to 254.8); P<0.001), and female subjects in the intrauterine group had a stronger interaction between obesity and both systolic (P=0.01) and diastolic (P=0.04) blood pressure than in the infant group. Short adult stature was associated with raised concentrations of glucose and insulin 2 hours after a glucose load—independently of siege exposure. Subjects in the unexposed group had non-systematic differences in subscapular to triceps skinfold ratio, diastolic blood pressure, and clotting factors compared with the exposed groups. Conclusions:Intrauterine malnutrition was not associated with glucose intolerance, dyslipidaemia, hypertension, or cardiovascular disease in adulthood. Subjects exposed to malnutrition showed evidence of endothelial dysfunction and a stronger influence of obesity on blood pressure. Key messages Relations between intrauterine growth and adult disease such as diabetes and cardiovascular disease have been linked to poor nutrition during pregnancy In this study, however, intrauterine exposure to malnutrition was not associated with glucose intolerance Intrauterine malnutrition did not affect insulin concentration, blood pressure, or concentration of lipids or coagulation factors Concentration of von Willebrand factor, a marker of endothelial damage, was raised in the subjects exposed to intrauterine malnutrition Obesity and blood pressure were more strongly related in subjects exposed to intrauterine malnutrition than in subjects either unexposed to malnutrition or exposed to malnutrition only as infants
In vitro and In vivo Evidence of Metallopanstimulin-1 in Gastric Cancer Progression and Tumorigenicity

Purpose: The metallopanstimulin-1 (MPS-1) gene is a growth factor–inducible gene, which is highly expressed in many human cancers and may be involved in the progression towards tumor malignancy. However, it is unclear whether MPS-1 plays any role in gastric cancer development or progression. Our studies were designed to clarify the MPS-1 expression pattern and to explore its potential role in gastric cancer. Experimental Design: The expression pattern of MPS-1 was determined in primary gastric cancer specimens and gastric cancer cell lines via immunohistochemistry and Western blotting. To investigate the functional significance of MPS-1 expression, three small interfering RNA (siRNA) expression plasmids were constructed and transfected into gastric cancer cell line SGC7901. The stable cell lines transfected with the siRNA targeting MPS-1 mRNA plasmids were selected and the biological features of these cells were examined. Results: MPS-1 was overexpressed in 86% of the gastric cancer tissues and all gastric cancer cells. In addition, MPS-1 expression was significantly increased and corresponded with the tumor-node-metastasis clinical stage, and was significantly higher in the late stage (P < 0.01). The MPS-1 expression level was significantly decreased in the transfected cells with MPS-1-specific siRNA expression plasmid pRNAT-133. Furthermore, the stable transfected cancer cells exhibited an increase in the incidence of spontaneous apoptosis and a decrease in growth ability and tumorigenicity in nude mice. Conclusions: These results provide strong evidence that MPS-1 plays an important role in gastric cancer cell proliferation and development, and suggests that MPS-1 is a promising target for gastric cancer treatment.
Adaptive learning control for non-minimum phase linear systems

The aim of this paper is to show the existence of a local solution to the output tracking problem for uncertain linear systems in which the output reference signal is periodic with known period. An output-feedback adaptive learning control is designed which relies on the Fourier approximation theory and on two adaptive observers. It guarantees, under suitable conditions, exponential output tracking and exponential estimation (with sufficiently high precision) of the: i) constant system parameters; ii) periodic input reference signal. No minimum phase assumption is required. Simulation results illustrate the effectiveness of the proposed approach.
MIT Open Access

—We consider ﬁnite-dimensional Markovian open quantum systems, and characterize the extent to which time-independent Hamiltonian control may allow to stabilize a target quantum state or subspace and optimize the resulting convergence speed. For a generic Lindblad master equation, we introduce a dissipation-induced decomposition of the associated Hilbert space, and show how it serves both as a tool to analyze global stability properties for given control resources and as the starting point to synthesize controls that ensure rapid convergence. The resulting design principles are illustrated in realistic Markovian control settings motivated by quantum information processing, including quantum-optical systems and nitrogen-vacancy centers in diamond.
Assessment of Glacier Volume Change Using ASTER-Based Surface Matching of Historical Photography

Glaciated regions are known to be particularly sensitive to climate change. Historical archives of glacier volume change are important, as they provide context for present-day changes. Although photogrammetric archives exist for many regions, their usefulness is often limited by a lack of contemporary ground control. High quality digital elevation models (DEMs) underpin a range of change analysis activities. This paper presents a cost-effective solution which utilizes Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) DEMs as control for the scaling and orientation of archival data sets. Instead of relying upon ground-control points, a robust surface matching algorithm is employed to automatically determine the transformation required to register two overlapping DEMs. Through application to the Slakbreen glacier system in Svalbard, Norway, the strategy is assessed by first matching an ASTER DEM to a fixed lidar reference surface. This demonstrates that ASTER DEMs are effectively correct in scale, supporting their use as a control surface. The second stage of the research implements this by matching an aerial photogrammetric DEM to an ASTER reference surface. Resultant volumetric and annual elevation change rates are compared to those derived from lidar data, which are considered in this paper as a truth data set. ASTER-based matching produced a mean annual elevation change rate of -4.12 ma-1, compared to a value of -4.11 ma-1 derived from the lidar data. In volumetric terms, this equates to a difference of 0.6%. A major advantage of this approach is the near-global coverage offered by ASTER data and the opportunity that this presents for remote glacial change analysis over regional extents.
Inhibition of tobramycin diffusion by binding to alginate

[3H]tobramycin bound to sodium alginate and to exopolysaccharide prepared from two mucoid strains of Pseudomonas aeruginosa. Binding to sodium alginate was similar to binding to exopolysaccharide, both in the dependence on tobramycin concentration and in the maximum binding observed at saturation. Incorporation of sodium alginate into agar plates reduced the zone sizes of growth inhibition caused by tobramycin. The reductions in zone sizes were quantitatively accounted for by the binding of tobramycin to sodium alginate during diffusion of the antibiotic away from the well in which it had been placed at the start of the experiment. However, the binding of tobramycin to the exopolysaccharide of P. aeruginosa, and the resulting inhibition of diffusion of the antibiotic, did not significantly increase the penetration time of a spherical microcolony with a radius of 125 micron, such as might be found in the respiratory tract of a patient with cystic fibrosis (from a 90% penetration time of 12 s in the absence of exopolysaccharide to one of 35 s with an exopolysaccharide concentration of 1.0% [wt/vol]).
Enhanced anti-HIV-1 activity of G-quadruplexes comprising locked nucleic acids and intercalating nucleic acids

Two G-quadruplex forming sequences, 5′-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol (twisted intercalating nucleic acid, TINA). Incorporation of LNA or INA/TINA monomers provide as much as 8-fold improvement of anti-HIV-1 activity. We demonstrate for the first time a detailed analysis of the effect the incorporation of INA/TINA monomers in quadruplex forming oligonucleotides (QFOs) and the effect of LNA monomers in the context of biologically active QFOs. In addition, recent literature reports and our own studies on the gel retardation of the phosphodiester analogue of T30177 led to the conclusion that this sequence forms a parallel, dimeric G-quadruplex. Introduction of the 5′-phosphate inhibits dimerisation of this G-quadruplex as a result of negative charge–charge repulsion. Contrary to that, we found that attachment of the 5′-O-DMT-group produced a more active 17-mer sequence that showed signs of aggregation—forming multimeric G-quadruplex species in solution. Many of the antiviral QFOs in the present study formed more thermally stable G-quadruplexes and also high-order G-quadruplex structures which might be responsible for the increased antiviral activity observed.
Examining SNOMED from the perspective of formal ontological principles: Some preliminary analysis and observations

The Systematized Nomenclature of Medicine -Clinical Terms (SNOMED CT) is a terminological resource designed to support electronic applications in health and medicine. Its design has evolved over a period of more than thirty years, and continues to evolve. Recently several authors working on formal ontological theory have observed that applying certain principles and constraints to terminology construction may result in a more consistent and useful terminology. In this paper we report on a preliminary analysis of SNOMED CT by two of its developers, from the perspective of a few such formal ontological principles, giving examples of prior design decisions that appear to be supported by these principles as well as examples of prior design decisions that may be at variance with them. We believe that design changes suggested by formal ontological principles have great potential for improving consistency. Empirical evidence of usefulness should accompany theoretically-inspired moves towards more fine-tuned representations of reality.
The Turn of the Century North American Drought: Global Context, Dynamics, and Past Analogs*

Abstract The causes and global context of the North American drought between 1998 and 2004 are examined using atmospheric reanalyses and ensembles of atmosphere model simulations variously forced by global SSTs or tropical Pacific SSTs alone. The drought divides into two distinct time intervals. Between 1998 and 2002 it coincided with a persistent La Nina–like state in the tropical Pacific, a cool tropical troposphere, poleward-shifted jet streams, and, in the zonal mean, eddy-driven descent in midlatitudes. During the winters reduced precipitation over North America in the climate models was sustained by anomalous subsidence and reductions of moisture convergence by the stationary flow and transient eddies. During the summers reductions of evaporation and mean flow moisture convergence drove the precipitation reduction, while transient eddies acted diffusively to oppose this. During these years the North American drought fitted into a global pattern of circulation and hydroclimate anomalies with noticeab.
SWI/SNF tumor suppressor gene PBRM1/BAF180 in human clear cell kidney cancer

ABSTRACT Mutations within chromatin modulating protein complexes have dominated the novel cancer gene landscape. However, little is known about how individual aberrations contribute to cancer formation. A novel Pbrm1 kidney cancer mouse model examining the role of Pbrm1 provides much needed clue concerning how SWI/SNF complexes might function as tumor suppressors.
High Resolution Finite Volume Scheme Based on Minimized Dispersion and Controllable Dissipation Reconstruction

The minimized dispersion and controllable dissipation (MDCD) reconstruction tech- nique optimizes dispersion and dissipation separately and shows desirable properties of both dis- persion and dissipation. A low dispersion finite volume scheme based on MDCD reconstruction is proposed which is capable of handling flow discontinuities and resolving a broad range of length scales. Although the proposed scheme is formally second order of accuracy, the optimized disper- sion and dissipation make it very accurate and robust so that the rich flow features and complex geometry encountered in many practical engineering applications can be handled properly. A number of test cases are computed to verify the performances of the proposed scheme.