Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron Chelation Therapy with Deferasirox in the Management of Iron Overload in Primary Myelofibrosis

Deferasirox (DSX) is the principal option currently available for iron-chelation-therapy (ICT), principally in the management of myelodysplastic syndromes (MDS), while in primary myelofibrosis (PMF) the expertise is limited. We analyzed our experience in 10 PMF with transfusion-dependent anemia, treated with DSX from September 2010 to December 2013. The median dose tolerated of DSX was 750 mg/day (10 mg/kg/day), with 3 transient interruption of treatment for drug-related adverse events (AEs) and 3 definitive discontinuation for grade 3/4 AEs. According to IWG 2006 criteria, erythroid responses with DSX were observed in 4/10 patients (40%), 2 of them (20%) obtaining transfusion independence. Absolute changes in median serum ferritin levels (Delta ferritin) were greater in hematologic responder (HR) compared with non-responder (NR) patients, already at 6 months of ICT respect to baseline. Our preliminary data open new insights regarding the benefit of ICT not only in MDS, but also in PMF with the possibility to obtain an erythroid response, overall in 40 % of patients. HR patients receiving DSX seem to have a better survival and a lower incidence of leukemic transformation (PMF-BP). Delta ferritin evaluation at 6 months could represent a significant predictor for a different survival and PMF-BP. However, the tolerability of the drug seems to be lower compared to MDS, both in terms of lower median tolerated dose and for higher frequency of discontinuation for AEs. The biological mechanism of action of DSX in chronic myeloproliferative setting through an independent NF-κB inhibition could be involved, but further investigations are required.
The Evolutionary Analysis of Emerging Low Frequency HIV-1 CXCR4 Using Variants through Time—An Ultra-Deep Approach

Large-scale parallel pyrosequencing produces unprecedented quantities of sequence data. However, when generated from viral populations current mapping software is inadequate for dealing with the high levels of variation present, resulting in the potential for biased data loss. In order to apply the 454 Life Sciences' pyrosequencing system to the study of viral populations, we have developed software for the processing of highly variable sequence data. Here we demonstrate our software by analyzing two temporally sampled HIV-1 intra-patient datasets from a clinical study of maraviroc. This drug binds the CCR5 coreceptor, thus preventing HIV-1 infection of the cell. The objective is to determine viral tropism (CCR5 versus CXCR4 usage) and track the evolution of minority CXCR4-using variants that may limit the response to a maraviroc-containing treatment regimen. Five time points (two prior to treatment) were available from each patient. We first quantify the effects of divergence on initial read k-mer mapping and demonstrate the importance of utilizing population-specific template sequences in relation to the analysis of next-generation sequence data. Then, in conjunction with coreceptor prediction algorithms that infer HIV tropism, our software was used to quantify the viral population structure pre- and post-treatment. In both cases, low frequency CXCR4-using variants (2.5–15%) were detected prior to treatment. Following phylogenetic inference, these variants were observed to exist as distinct lineages that were maintained through time. Our analysis, thus confirms the role of pre-existing CXCR4-using virus in the emergence of maraviroc-insensitive HIV. The software will have utility for the study of intra-host viral diversity and evolution of other fast evolving viruses, and is available from http://www.bioinf. manchester.ac. uk/segminator/.
Factors Affecting Corporate Social Responsibility: An Empirical Study

Corporate social responsibility (CSR) has captured significant attention of managers and executives especially at multinational and multi-divisional firms. However, links between CSR's drivers (strategic planning, firm culture) and CSR have seen little or no empirical verification, particularly in South Asia. The present study aims to test two antecedents if they contribute in shaping firms' CSR. This study considers formal strategic planning and humanistic culture as drivers of CSR. Data were collected from CEOs of 800 randomly selected organizations in Pakistan, with 21.5% response rate. Results from hierarchical regression indicate that formal strategic planning and firm's humanistic culture, over and above the impact of formal strategic planning, are linked positively with CSR. Copyright © 2012 John Wiley & Sons, Ltd.
Informal Communication and Awareness in Virtual Teams Why We Need Smart Technologies to Support Distributed Teamwork

This paper illustrates the importance of awareness and informal communication in work environments, and outlines the resulting implications for the design of future information and communication technologies. The paper starts by providing an introduction into intellectual teamwork, showing its benefits and explaining, why informal communication and awareness are decisive factors for successful teamwork. After a brief characterization of virtual teams, it is shown, how the lack of physical proximity effects distributed teamwork. The paper closes with an assessment of state-of-the-art communication media and illustration of why existing communication technologies are not adequate for supporting awareness and informal communication in future work environments.
Honneth on work and recognition

This paper explores the development of Honneth’s thought on work. It considers how his initial concerns with the embodied experience of labour and the absence of a contemporary and compelling class-specific lexicon with which to explore suffering at work have been surpassed and subordinated by his analysis of the social relations of recognition in civil society, which is distributed according to a contested and contestable achievement principle. I argue that despite the purchase of the criticisms offered by recent rejoinders, they fail to engage with the strength of his analysis: that modern economics contains a normative (recognition) order which works to justify the extant division of labour and income, even if its current formulation supports inequity, exclusion and exploitation. Feminist political economy is an ally in this analysis. The paper explores the points of intersection between these projects, but argues that incorporating feminist insights will require a fundamental revision to Honneth’s account of social rationalization in modernity.
Neural Collaborative Filtering

In recent years, deep neural networks have yielded immense success on speech recognition, computer vision and natural language processing. However, the exploration of deep neural networks on recommender systems has received relatively less scrutiny. In this work, we strive to develop techniques based on neural networks to tackle the key problem in recommendation --- collaborative filtering --- on the basis of implicit feedback. Although some recent work has employed deep learning for recommendation, they primarily used it to model auxiliary information, such as textual descriptions of items and acoustic features of musics. When it comes to model the key factor in collaborative filtering --- the interaction between user and item features, they still resorted to matrix factorization and applied an inner product on the latent features of users and items. By replacing the inner product with a neural architecture that can learn an arbitrary function from data, we present a general framework named NCF, short for Neural network-based Collaborative Filtering. NCF is generic and can express and generalize matrix factorization under its framework. To supercharge NCF modelling with non-linearities, we propose to leverage a multi-layer perceptron to learn the user-item interaction function. Extensive experiments on two real-world datasets show significant improvements of our proposed NCF framework over the state-of-the-art methods. Empirical evidence shows that using deeper layers of neural networks offers better recommendation performance.
Convolutional Spike Timing Dependent Plasticity based Feature Learning in Spiking Neural Networks

Brain-inspired learning models attempt to mimic the cortical architecture and computations performed in the neurons and synapses constituting the human brain to achieve its efficiency in cognitive tasks. In this work, we present convolutional spike timing dependent plasticity based feature learning with biologically plausible leaky-integrate-and-fire neurons in Spiking Neural Networks (SNNs). We use shared weight kernels that are trained to encode representative features underlying the input patterns thereby improving the sparsity as well as the robustness of the learning model. We demonstrate that the proposed unsupervised learning methodology learns several visual categories for object recognition with fewer number of examples and outperforms traditional fully-connected SNN architectures while yielding competitive accuracy. Additionally, we observe that the learning model performs out-of-set generalization further making the proposed biologically plausible framework a viable and efficient architecture for future neuromorphic applications.
Activation of AP-1-Dependent Transcription by a Truncated Translation Initiation Factor

ABSTRACT Int6/eIF3e is a highly conserved subunit of eukaryotic translation initiation factor 3 (eIF3) that has also been reported to interact with subunits of the proteasome and the COP9 signalosome. Overexpression of full-length Int6 or a 13-kDa C-terminal fragment, Int6CT, in the fission yeast Schizosaccharomyces pombe causes multidrug resistance that requires the otherwise inessential AP-1 transcription factor Pap1. Here we show for the first time that Int6CT acts to increase the transcriptional activity of Pap1. Microarray hybridization data indicate that Int6CT overexpression resulted in the up-regulation of 67 genes; this expression profile closely matched that of cells overexpressing Pap1. Analysis of the upstream regulatory sequences of these genes showed that the majority contained AP-1 consensus binding sites. Partial defects in ubiquitin-dependent proteolysis have been suggested to confer Pap1-dependent multidrug resistance, but no such defect was seen on Int6CT overexpression. Indeed, none of the previously identified interactions of endogenous Int6 was required for the activation of Pap1 transcription described here. Moreover, Int6CT-induced activation of Pap1-responsive gene expression was independent of the ability of Pap1 to undergo a redox-regulated conformational change which mediates its relocalization to the nucleus and expression of oxidative stress response genes. Int6CT therefore activates Pap1-dependent transcription by a novel mechanism.
Intra‐ and interindividual variability of fatty acid unsaturation in six different human adipose tissue compartments assessed by 1H‐MRS in vivo at 3 T

It is generally accepted that the amount and distribution of adipose tissue (AT) in the human body play an important role in the pathogenesis of metabolic diseases. In addition, metabolic effects of released saturated fatty acids (FAs) in blood are known to be more critical than those of unsaturated FAs. However, little is known about the variability in unsaturation of FAs in various AT compartments. The aim of this prospective study was the assessment of mono‐ and polyunsaturated FAs in various AT compartments by localized 1H‐MRS in order to obtain insight into the intra‐ and interindividual variability. Associations of FA unsaturation with intrahepatic lipids (IHLs), insulin sensitivity and related AT volumes were analyzed.
The Role of a Skeptic Agent in Testing and Benchmarking of SAT Algorithms

This paper introduces a persistent agent called skeptic who supplies instances from well-deflned equivalence classes to test and benchmark SAT solvers. On such classes, met- rics such as max/min ratio of time-to-solve should approach the value of 1.0. Experiments suggested by the skeptic on the instances of the same class show (1) the time-to-solve max/min ratios for a given solver can exhibit a range from 2 to 1000 and beyond, and (2) max/min ratios for another solver may be several orders of magnitude better, including a signiflcantly lower time-to-solve average value. Both of these factors point out that (1) SAT solvers can not only be much improved but also more reliably tested for any such improvement, and (2) the intrinsic complexity or 'hardness' of SAT instances cannot be gauged reliably with the current generation of SAT solvers.
Advantages and Limitations of Different p62-Based Assays for Estimating Autophagic Activity in Drosophila

Levels of the selective autophagy substrate p62 have been established in recent years as a specific readout for basal autophagic activity. Here we compared different experimental approaches for using this assay in Drosophila larvae. Similar to the more commonly used western blots, quantifying p62 dots in immunostained fat body cells of L3 stage larvae detected a strong accumulation of endogenous p62 aggregates in null mutants for Atg genes and S6K. Importantly, genes whose mutation or silencing results in early stage lethality can only be analyzed by microscopy using clonal analysis. The loss of numerous general housekeeping genes show a phenotype in large-scale screens including autophagy, and the p62 assay was potentially suitable for distinguishing bona fide autophagy regulators from silencing of a DNA polymerase subunit or a ribosomal gene that likely has a non-specific effect on autophagy. p62 accumulation upon RNAi silencing of known autophagy regulators was dependent on the duration of the knockdown effect, unlike in the case of starvation-induced autophagy. The endogenous p62 assay was more sensitive than a constitutively overexpressed p62-GFP reporter, which showed self-aggregation and large-scale accumulation even in control cells. We recommend western blots for following the conversion of overexpressed p62-GFP reporters to estimate autophagic activity if sample collection from mutant larvae or adults is possible. In addition, we also showed that overexpressed p62 or Atg8 reporters can strongly influence the phenotypes of each other, potentially giving rise to false or contradicting results. Overexpressed p62 aggregates also incorporated Atg8 reporter molecules that might lead to a wrong conclusion of strongly enhanced autophagy, whereas expression of an Atg8 reporter transgene rescued the inhibitory effect of a dominant-negative Atg4 mutant on basal and starvation-induced autophagy.
Anti-TNF Treatment for Extraintestinal Manifestations of Inflammatory Bowel Disease in the Swiss IBD Cohort Study

Background: Extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) are frequently observed. Little is known about the efficacy of anti–tumor necrosis factor (TNF) in EIM management. We assessed the effect of 3 anti-TNF agents (infliximab, adalimumab, and certolizumab pegol) on EIM evolution. Methods: Data on 1249 patients from the Swiss IBD Cohort Study (SIBDCS) were analyzed. All EIMs were diagnosed by relevant specialists. Response was classified into improvement, stable disease, and clinical worsening based on the physician's interpretation. Results: Of the 366 patients with at least 1 EIM, 213 (58.2%) were ever treated with an anti-TNF. A total of 299 treatments were started for 355 EIMs. Patients with EIM were significantly more often treated with anti-TNF compared with those without EIM (58.2% versus 21.0%, P < 0.001). Infliximab was the most frequently used drug (63.2%). In more than 71.8%, a clinical response of the underlying EIM to anti-TNF therapy was observed. In 92 patients (43.2%), anti-TNF treatments were started for the purpose of treating EIM rather than IBD. Response rates to anti-TNF were generally good and best for psoriasis, aphthous stomatitis, uveitis, and peripheral arthritis. In 11 patients, 14 EIM occurred under anti-TNF treatment. Conclusions: Anti-TNF was frequently used among patients with EIM. In more than 40%, anti-TNF treatments are started to treat EIM rather than IBD. Given the good response rates, anti-TNF seems to be a valuable option in the treatment of EIM, whereas appearance of EIM under anti-TNF does not seem to be a source of considerable concern.
Factors associated with thrombocytopenia in severe leptospirosis (Weil's disease)

OBJECTIVE: This study was conducted to investigate factors associated with thrombocytopenia in a large cohort of patients with leptospirosis in an endemic area. METHODS: This retrospective study included 374 consecutive patients with leptospirosis who were admitted to tertiary hospitals in Fortaleza, Brazil. All patients had a diagnosis of severe leptospirosis (Weil's disease). Acute kidney injury was defined according to the RIFLE criteria. Thrombocytopenia was defined as a platelet count <100,000/mm3. RESULTS: A total of 374 patients were included, with a mean age of 36.1±15.5 years, and 83.4% were male. Thrombocytopenia was present at the time of hospital admission in 200 cases (53.5%), and it developed during the hospital stay in 150 cases (40.3%). The patients with thrombocytopenia had higher frequencies of dehydration (53% vs. 35.3%, p = 0.001), epistaxis (5.7% vs. 0.8%, p = 0.033), hematemesis (13% vs. 4.6%, p = 0.006), myalgia (91.5% vs. 84.5%, p = 0.038), hematuria (54.8% vs. 37.6%, p = 0.011), metabolic acidosis (18% vs. 9.2%, p = 0.016) and hypoalbuminemia (17.8% vs. 7.5%, p = 0.005). The independent risk factors associated with thrombocytopenia during the hospital stay were lengthy disease (OR: 1.2, p = 0.001) and acute kidney injury (OR: 6.6, p = 0.004). Mortality was not associated with thrombocytopenia at admission (12.5% vs. 12.6%, p = 1.000) or during the hospital stay (12.6% vs. 11.3%, p = 0.748). CONCLUSIONS: Thrombocytopenia is a frequent complication in leptospirosis, and this condition was present in more than half of patients at the time of hospital admission. Lengthy disease and acute kidney injury are risk factors for thrombocytopenia. There was no significant association between thrombocytopenia and mortality.
Higher fasting plasma free fatty acid levels are associated with lower insulin secretion in children and adults and a higher incidence of type 2 diabetes.

CONTEXT There are limited data in humans on the association between fasting free fatty acid (FFA) levels and pancreatic β-cell function. OBJECTIVE Our objective was to examine this association in children and adults with normal glucose tolerance and to explore fasting FFA levels in relation to subsequent risk of impaired glucose tolerance (IGT) and type 2 diabetes (T2D). DESIGN We measured FFA, glucose, and insulin levels after an overnight fast and 30 min after an oral glucose load in 797 children aged 8 yr in the Avon Longitudinal Study of Parents and Children and 770 adults aged 44-71 yr in the Medical Research Council Ely Study. We calculated the homeostasis model assessment to estimate fasting insulin sensitivity, the insulinogenic index to estimate insulin secretion, and the disposition index to assess insulin secretion corrected for insulin sensitivity. RESULTS Higher fasting FFA levels were associated with lower insulin secretion in children (boys, P = 0.03; girls, P = 0.001) and adults (men, P = 0.03, women, P = 0.04). Associations with insulin sensitivity were more variable, but after adjustment for insulin sensitivity, higher fasting FFA levels remained associated with lower insulin secretion (disposition index). Compared with adults in the lowest tertile of fasting FFA levels, those in the middle and highest tertiles had a 3-fold higher incidence of IGT or T2D over the following 5-8 yr. CONCLUSIONS Higher fasting FFA levels were consistently associated with lower insulin secretion in children and adults with normal glucose tolerance. Furthermore, higher fasting FFA levels were prospectively associated with a greater risk of subsequent IGT and T2D.
Culture, Corporate Governance and Disclosure in Malaysian Corporations

Evidence from research conducted on corporate accounting indicates that the interaction of environmental factors in fluences disclosure practices. The purpose of this study is to examine the importance of various corporate governance and cultural (race and education) characteristics, in addition to firm–specific factors, as possible determinants of voluntary (non–mandatory accounting and non–accounting information) disclosures in the annual reports of Malaysian listed corporations. The results of the regression analysis indicate significant associations (at the 5 per cent level) between two corporate governance variables (viz. chair who is a non–executive director and domination of family members on boards) and the extent of voluntary disclosure. This finding has implications for corporate governance policy formulation by the Malaysian Institute of Corporate Governance (MISG). One cultural factor (proportion of Malay directors on the board) is significantly associated (at the 5 per cent level) with the extent of voluntary disclosure suggesting that governmental focus on culture may solicit a response to secrecy from those who feel threatened.
Diffusion-Weighted Imaging Tractography-Based Parcellation of the Human Parietal Cortex and Comparison with Human and Macaque Resting-State Functional Connectivity

Despite the prominence of parietal activity in human neuroimaging investigations of sensorimotor and cognitive processes, there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species, but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI)-based tractography, and functional interactions were assessed by correlations in activity measured with functional MRI at rest. Resting-state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment, and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into 10 component clusters. The resting-state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex.