Miracle-dz/UniFAR-FTUs huggingface dataset:
A targetable androgen receptor-positive breast cancer subtype hidden among the triple-negative cancers.

CONTEXT Triple-negative breast cancer (TNBC) is a subgroup of breast cancers that by definition lack expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). A diverse group of tumors, TNBC shares some morphologic and molecular features with basal-like breast cancer, a category of breast cancer defined by gene expression profiling. More likely to occur in young women and African Americans, TNBCs may exhibit aggressive behavior and are associated with poor prognosis despite their initial response to conventional chemotherapy. Because hormonal or HER2-targeted therapies are ineffective for these tumors, the main therapeutic option is systemic chemotherapy. Therefore, identification of new targets for therapy is urgently needed for this group. OBJECTIVE To review and present recent literature along with our own experience regarding the clinical and morphologic characteristics and the prevalence of androgen receptor (AR) expression in TNBC, and to discuss the potential use of AR as a therapeutic target for AR(+) TNBC. DATA SOURCES Data sources are published articles from peer-reviewed journals in PubMed (US National Library of Medicine). CONCLUSIONS AR is the most commonly expressed hormone receptor among all breast carcinomas, with a prevalence of 25% to 75% among TNBCs. Therefore, we strongly support the routine assessment of AR in TNBC, and preferably in all breast carcinomas.
Elasticity and wrinkled morphology of Bacillus subtilis pellicles

Wrinkled morphology is a distinctive phenotype observed in mature biofilms produced by a great number of bacteria. Here we study the formation of macroscopic structures (wrinkles and folds) observed during the maturation of Bacillus subtilis pellicles in relation to their mechanical response. We show how the mechanical buckling instability can explain their formation. By performing simple tests, we highlight the role of confining geometry and growth in determining the symmetry of wrinkles. We also experimentally demonstrate that the pellicles are soft elastic materials for small deformations induced by a tensile device. The wrinkled structures are then described by using the equations of elastic plates, which include the growth process as a simple parameter representing biomass production. This growth controls buckling instability, which triggers the formation of wrinkles. We also describe how the structure of ripples is modified when capillary effects are dominant. Finally, the experiments performed on a mutant strain indicate that the presence of an extracellular matrix is required to maintain a connective and elastic pellicle.
Business Analytics Applications for the Vehicle Routing Problem

This paper reviews optimization methods and software products for efficiently solving Vehicle Routing Problem variants. First a brief introduction of all the VRP variants will be given. Next different optimization methods will be explained. These methods have an important role in this paper. Then the Traveling Salesman Problem (TSP) will be discussed. Two software products, the Concorde solver and the TSP solver in R, are being reviewed. The Concorde solver uses a Branch and Bound algorithm. The TSP solver uses an arbitrary insertion algorithm with two opt refinement. The Concorde solver is on average 3% better than the TSP solver in R. After this the Vehicle Routing Problem (VRP) will be handled, where two software products will be reviewed and compared with each other. The software products are open source and each have a different solution method. The first software product is a VBA algorithm that uses an insertion heuristic with the improvement heuristics 2-opt, 3-opt and swap operations. The second, a genetic algorithm in Mathlab, uses a 2-opt improvement heuristic. The VBA algorithm has on average 7% better results. The last part of this paper will discuss the Dynamic Vehicle Routing Problem with Time Windows. This problem is based on the VRP, but now all the customers have a certain time interval in which they would like to be served. There are two types of customers, known customers and new customers. The known customers are already scheduled into routes. New customers can call in, and the company must immediately specify a time window in which the start of the service will be provided. The BARTOC method is a successful method for solving this problem, but it is outdated for today’s optimization problems. The BARTOC method has only a time and distance constraint but today’s problems have more constrains. Therefore it has to be extended so it can handle more constrains.
Mechanical determinants of myocardial oxygen consumption with special reference to external work and efficiency.

OBJECTIVE The aim of the study was to investigate the ambiguous effect of left ventricular afterload on myocardial work, oxygen consumption, and efficiency. METHODS Myocardial oxygen consumption and mechanical parameters of the left and right ventricle were measured in situ in a modified heart-lung preparation in the rat. Left ventricular afterload was adjusted arbitrarily by means of a Starling resistor mounted in a shunt circuit between the left ventricle and the caudal caval vein. Left and right ventricular pressure and aortic pressure as well as pulmonary flow and the flow in the shunt circuit were measured. The left ventricular pressure and volume values were converted into wall stress and length data assuming a thick walled sphere, and external work was calculated from left ventricular force and shortening. RESULTS Left ventricular external work ran through a maximum with decreasing aortic pressure. Left ventricular oxygen consumption per gram and beat correlated linearly with left ventricular peak wall stress, tension-time integral, and maximum rate of stress development. Left ventricular force and shortening, the two components of external work, acted differently: force determined left ventricular oxygen consumption, whereas shortening had no direct effect on myocardial oxygen consumption, but was important in determining left ventricular efficiency. CONCLUSIONS The interplay between left ventricular afterload and coronary perfusion pressure is of special significance for the heart in situ. The decrease in shortening and external work as well as the diminution in efficiency, observed at low aortic pressure values, can be attributed to impaired coronary perfusion. The coronary perfusion pressure must therefore be taken into consideration for the critical examination of the efficiency of the heart in situ.
Dietary sodium and potassium intake in relation to non-alcoholic fatty liver disease

Abstract A few epidemiological data are available assessing the associations of intakes of sodium (Na) and potassium (K) with non-alcoholic fatty liver disease (NAFLD). We aimed to examine the associations of dietary intake of Na and K with the prevalence of ultrasound-diagnosed NAFLD. We performed a cross-sectional study of 100 177 participants (46 596 men and 53 581 women) who underwent a health screening examination and completed a FFQ at the Kangbuk Samsung Hospital Total Healthcare Centers, South Korea, between 2011 and 2013. NAFLD was defined by ultrasonographic detection of fatty liver in the absence of excessive alcohol intake or other known causes of liver disease. The proportion of NAFLD was 35·6 % for men and 9·8 % for women. Increasing prevalence of NAFLD was observed with increasing Na intake. The multivariable-adjusted prevalence ratios (PR) of NAFLD comparing the highest with the lowest quintile of energy-adjusted Na intake were 1·25 (95 % CI 1·18, 1·32; P trend<0·001) in men and 1·32 (95 % CI 1·18, 1·47; P trend <0·001) in women. However, when we additionally adjusted for body fat percentage, the association became attenuated; the corresponding PR of NAFLD were 1·15 (95 % CI 1·09, 1·21) in men and 1·06 (95 % CI 0·95, 1·17) in women. No inverse association was observed for energy-adjusted K intake. Our findings suggest that higher Na intake is associated with a greater prevalence of NAFLD in young and middle-aged asymptomatic adults, which might be partly mediated by adiposity.
Author ' s personal copy Mixing at the interface between fresh and salt waters in 3 D steady flow with application to a pumping well in a coastal aquifer

We consider 3D steady flow of fresh water over a salt water body in a confined aquifer of constant thickness D, with application to a pumping well in a coastal aquifer. With neglect of mixing, a sharp interface separates the two fluid bodies and an existing analytical solution, based on the Dupuit assumption, is adopted. The aim is to solve for the mixing between the fresh and salt waters for aT/D 1 (aT transverse dispersivity), as field studies indicate that aT = O(10 3 10 2 m). The mixing zone around the interface is narrow and solutions by existing codes experience numerical difficulties. The problem is solved by the boundary layer (BL) approximation, extending a method, applied previously to two-dimensional flows. The BL equations of variable-density flow are solved by using the Von Karman integral method, to determine the BL thickness and the rate of entrainment of salt water along the interface. Application to the pumping well problem yields the salinity of the pumped water, as function of the parameters of the problem (well discharge, seaward discharge, well distance from the coast and density difference). 2008 Elsevier Ltd. All rights reserved.
Patterns of antihypertensive medication use in hemodialysis patients.

PURPOSE Patterns of antihypertensive drug use in patients undergoing long-term hemodialysis therapy were studied. METHODS Patients attending seven outpatient hemodialysis units in Ohio were eligible for the study if they had been receiving the treatment for at least three months. Demographic and clinical data were obtained from patient interviews and computerized databases, and blood pressure (BP) measurements were obtained before dialysis. Labeled names and dosages of antihypertensive drugs were recorded from containers the patients brought with them. Patients were asked to describe their adherence to the medications, their ability to afford the drugs, and their knowledge and beliefs about hypertension. Physical impairments in taking medication were also evaluated. RESULTS The frequency of hypertension was 89% in the 270 participants. Antihypertensive drugs were prescribed for 76% of the patients; 25% required three or more drugs. Hypertensive patients who were not receiving antihypertensive drugs (14%) had significantly higher BP than patients who were. Calcium-channel blockers were prescribed for 60% of patients, angiotensin-converting-enzyme inhibitors for 33%, and beta-blockers for 34%. Eighty-three percent said the cost of drugs was never a problem, and 23% said they sometimes forgot to take their medication. Almost all patients said they would not stop taking antihypertensive drugs if they were feeling better and agreed that monitoring BP was important. Twenty-two percent could not read the warning on a standard tablet container, and 12% could not remove one tablet from the container. CONCLUSION Multidrug antihypertensive therapy was common among hemodialysis patients and was associated with significantly lower BP; calcium-channel blockers were the most frequently prescribed agents. Most patients said they could afford drugs and reported good adherence to antihypertensive drug therapy.
Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study.

PURPOSE To compare the efficacy of a standard anthracycline-based regimen to a dose-intensified anthracycline regimen in locally advanced breast cancer. PATIENTS AND METHODS Locally advanced breast cancer patients were randomly assigned onto a study comparing cyclophosphamide (C; 75 mg/m(2) orally days 1 to 14), epirubicin (E; 60 mg/m(2) intravenously [IV] days 1, 8), and fluorouracil (F; 500 mg/m(2) IV days 1, 8) six cycles every 28 days versus E (120 mg/m(2) IV day 1), C (830 mg/m(2) IV day 1), and granulocyte colony-stimulating factor (filgrastim; 5 micro g/kg/d subcutaneously days 2 to 13) six cycles every 14 days. The study was designed to detect a 15% improvement; that is, from 50% to 65% in median progression-free survival (PFS) in favor of the dose-intensified regimen. RESULTS A total of 448 patients were enrolled over a period of 3 years. The median dose intensity delivered for C and E reached, respectively, 85% and 87% of that planned in the CEF arm and 96% and 95% of that planned in the EC arm. The dose-intensified arm was slightly more emetogenic and generated more grade 3 to 4 anemia but less febrile neutropenia episodes. After a median follow-up of 5.5 years, 277 events have been reported. The median PFS was 34 and 33.7 months for CEF and EC, respectively (P =.68), and the 5-year survival rate was 53% and 51% for CEF and EC, respectively (P =.94). CONCLUSION Dose-intensified EC does not provide a measurable therapeutic benefit over CEF as neoadjuvant chemotherapy for unselected locally advanced breast cancer patients.
TIPSTER Panel - DR-LINK's Linguistic-Conceptual Approach to Document Detection

There is a continuum of levels of linguistic-conceptual processing which can produce enrichments of the original text in order to explicitly represent documents at more conceptual levels for more accurate matching to queries. To produce richer representations of documents and topic statements we have developed a system whose architecture is modular in design and which uses lexical, syntactic, semantic and discourse processing techniques
Controlled multiple imputation methods for sensitivity analyses in longitudinal clinical trials with dropout and protocol deviation

Sensitivity analyses are commonly requested as part of the analysis of longitudinal clinical trials when data are missing. There are many ways in which such sensitivity analyses can be constructed. This article focuses on one particular approach, so-called controlled imputation. This combines two statistical ingredients, pattern-mixture models and multiple imputation. The aim is to assess sensitivity of the original conclusions to alternative assumptions about the statistical behavior of the patients’ outcomes following dropout and withdrawal. Such assumptions must reflect postulated treatment compliance when intention-to-treat-like inferences are required. Many such scenarios could be considered, depending on the clinical setting. The advantage of this approach is that it makes such assumptions explicit in the sensitivity analysis and hence readily accessible to the user.
Proteomic alterations of the variants of human aldehyde dehydrogenase isozymes correlate with hepatocellular carcinoma

To develop novel markers for hepatocellular carcinomas (HCC), 10 cases were analyzed by 2‐dimensional electrophoresis (2DE) and matrix‐assisted laser desorption ionization mass spectrometry. Results were compared to those of paired adjacent nontumorous liver tissues. Comparative analysis of the respective spot patterns in 2DE revealed that 3 variants of class 3 aldehyde dehydrogenase (ALDH‐3) newly appeared while 2 variants of ALDH‐2 diminished to undetectable levels in HCC. However, 4 ALDH‐1 variants with different pIs remained unaffected. This pattern of concomitant appearance and disappearance of ALDH‐3 and ALDH‐2 variants was consistently observed in all HCC tissues. Our results suggest that alterations of ALDH isozyme variants may be closely correlated to HCC and that proteomic analysis of these proteins might be a novel approach to identify the molecular events in detail during hepatocarcinogenesis. © 2002 Wiley‐Liss, Inc.
Hydroxylation of tanshinone IIa in human liver microsomes is specifically catalysed by cytochrome P4502A6

Tanshinone IIa, the primary active component of a traditional Chinese medicine Salvia miltiorrhiza (Danshen), has a wide range of pharmacological activities. In the present study, the metabolism of tanshinone IIa (5 μM) by cytochrome P450s (CYPs) was investigated in human liver microsomes. One mono-hydroxylated metabolite was detected in a reaction catalysed by human liver microsomes, and was identified as tanshinone IIb by comparing the tandem mass spectra and the chromatographic retention time with that of the standard compound. The study with a chemical selective inhibitor, cDNA-expressed human cytochrome P450s, correlation assay, and kinetics study demonstrated that CYP2A6 was the specific isozyme responsible for the hydroxyl metabolism of tanshinone IIa (5 μM) in human liver microsomes.
Acromegaly

Histochemical and electron microscopic findings were studied in biopsied deltoid and external intercostal muscle from a patient with acromegaly. The patient had proximal muscle weakness and motor unit potentials of reduced amplitude and duration on electromyography. In both biopsies, the most striking finding was a preferential hypertrophy of histochemical subtype llB fibers. On electron microscopy, a reduction in the size and apparent number of myofibrils was observed. In some fibers, entire myofibrils were degenerated and the spaces occupied by glycogen granules. In the deltoid, there were a large number of satellite cells and, in several of these, centrioles were observed.
Towards a Guideline for Design of a Corporate Entrepreneurship Function for Business Development in Medium‐Sized Technology‐Based Companies

The speed with which global high-technology markets evolve makes companies recognize that an effective innovation process is the best way to guarantee competitiveness. However, when (medium-sized) companies then wish to set up a corporate entrepreneurship function to enhance business development processes, they can find little material available in literature to assist in such processes. In this article we have described a guideline and some backgrounds for creating a corporate entrepreneurship function to realize business development in a high-tech context.
Genes outside The Hla Region affecting Susceptibility to Type 1 Diabetes - The Role of Iddm2 and Iddm9 in the Finnish Population

Antti-Pekka Laine Genes outside the HLA region affecting susceptibility to type 1 diabetes – the role of IDDM2 and IDDM9 in the Finnish population Immunogenetics laboratory, University of Turku, Turku, Finland Annales Universitatis Turkuensis Turku, Finland 2007 HLA region defines half of the genetic susceptibility to type 1 diabetes. Several susceptibility loci residing outside the HLA region have been reported and three loci have been confirmed to convey type 1 diabetes susceptibility. In the present study twelve of these loci were tested for linkage in 107 Finnish type 1 diabetes multiplex families. In the follow-up study, 121 Finnish type 1 diabetes multiplex families were analyzed for linkage across the IDDM9 region at 3q21, and 384 Finnish type 1 diabetes simplex families were analyzed for association with two markers in the same region. Additionally, the IDDM2 region was analyzed for interaction with HLA haplotypes of varying disease risk in order to assess its potential regarding refinement of disease risk prediction. In an additional attempt to refine the IDDM2 region disease risk prediction, subtyping of the protective VNTR class III haplotypes and an association study was performed in the Finnish and Swedish populations. No significant or suggestive linkage was found in the complete dataset outside the HLA region. The highest non-HLA LOD score was seen with the IDDM9 region marker D3S3576 (MLS=1.05). The follow-up study at the IDDM9 region revealed a stronger LOD score at the marker D3S1589 (MLS=3.4). Association with the disease was found close to D3S1589 with marker AFM203wd10 (TDT p=0.0002). Our linkage results did not confirm previous findings in other studies. The follow-up study revealed a LOD score close to genome-wide significance and a significant association at the 3q21 region which warrant a more comprehensive association study at this region. The predisposing MspI-2221 genotype CC was more common in diabetics with moderate or low HLA risk compared with the high risk group, and the genotype distribution between said groups also showed significant difference (p=0.05 and p=0.01 respectively). The VNTR analysis revealed a significantly stronger protective effect for the VNTR IIIA/IIIA genotype when compared to other class III genotypes. These findings suggest that etiological heterogeneity between protective lineages of the IDDM2 region possibly exist and that the HLA region could modify the IDDM2 risk and further that deconstructing the IDDM2 heterogeneity has potential in enhancing the sensitivity and specificity of type 1 diabetes risk estimation.
Image Structure Retrieval via L0 Minimization

Retrieving salient structure from textured images is an important but difficult problem in computer vision because texture, which can be irregular, anisotropic, non-uniform and complex, shares many of the same properties as structure. Observing that salient structure in a textured image should be piece-wise smooth, we present a method to retrieve such structures using an minimization of a modified form of the relative total variation metric. Thanks to the characteristics shared by texture and small structures, our method is effective at retrieving structure based on scale as well. Our method outperforms state-of-art methods in texture removal as well as scale-space filtering. We also demonstrate our method's ability in other applications such as edge detection, clip art compression artifact removal, and inverse half-toning.
Reflectarray Design With Similarity-Shaped Fragmented Sub-Wavelength Elements

A new technique for synthesizing reflectarray antennas is presented. It utilizes fragmented elements in a manner that allows the elements of the reflectarray to be shaped-optimized so that a high degree of geometrical similarity is maintained between adjacent elements. The implication is that in a reflectarray of such elements each element will see an electromagnetic environment that more closely emulates the infinite periodic one used to compute the element properties. We show experimentally that this indeed results in aperture efficiencies closely approaching the upper bounds achievable for some selected feed system, and offers a significant improvement over that obtained with conventional reflectarrays (that is, those not using similarity-synthesized fragmented elements). It is also shown that a reflectarray surface that uses fragmented elements can be simultaneously patterned with a visual image while still closely maintaining the desired reflection phase from its surface to yield a high-gain antenna.
Continual Learning for Unsupervised Anomaly Detection in Continuous Auditing of Financial Accounting Data

International audit standards require the direct assessment of a financial statement's underlying accounting journal entries. Driven by advances in artificial intelligence, deep-learning inspired audit techniques emerged to examine vast quantities of journal entry data. However, in regular audits, most of the proposed methods are applied to learn from a comparably stationary journal entry population, e.g., of a financial quarter or year. Ignoring situations where audit relevant distribution changes are not evident in the training data or become incrementally available over time. In contrast, in continuous auditing, deep-learning models are continually trained on a stream of recorded journal entries, e.g., of the last hour. Resulting in situations where previous knowledge interferes with new information and will be entirely overwritten. This work proposes a continual anomaly detection framework to overcome both challenges and designed to learn from a stream of journal entry data experiences. The framework is evaluated based on deliberately designed audit scenarios and two real-world datasets. Our experimental results provide initial evidence that such a learning scheme offers the ability to reduce false-positive alerts and false-negative decisions.