Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting the risk of nephrotoxicity in patients receiving colistimethate sodium: a multicentre, retrospective, cohort study.

OBJECTIVES With increasing rates of infections caused by MDR Gram-negative organisms, clinicians resort to older agents such as colistimethate sodium (CMS) despite a significant risk of nephrotoxicity. Several risk factors for CMS-associated nephrotoxicity have been reported, but they have yet to be validated. We compared the performance of published mathematical models in predicting the risk of CMS-associated nephrotoxicity. METHODS In a multicentre, retrospective, cohort study, adult patients (≥18 years of age) were evaluated from five large academic medical centres in the USA. Patients with normal renal function (baseline serum creatinine ≤1.5 mg/dL) who received intravenous CMS for ≥72 h were followed for up to 30 days. The development of nephrotoxicity was as defined by the RIFLE criteria. Each published model was conditioned using patient-specific variables to predict the risk of nephrotoxicity. The predictive performance of the models was evaluated using the observed-to-expected (O/E) ratio. The most significant cut-off threshold for stratifying patients into high and low risk of nephrotoxicity was identified using classification and regression tree analysis. RESULTS A total of 106 patients were examined (mean age 53.3 ± 14.9 years, 66% male); the overall observed nephrotoxicity rate was 52.8%. We identified a simple model demonstrating reasonable overall nephrotoxicity risk assessment [O/E ratio of 1.07 (95% CI = 0.81-1.39)] and high sensitivity (92.9%) in predicting nephrotoxicity development in patients on CMS therapy. CONCLUSIONS We identified a model that could be incorporated into patient management strategies to reduce the risk of nephrotoxicity in patients requiring CMS therapy.
Doping evolution and polar surface reconstruction of the infinite-layer cuprate Sr 1 − x La x CuO 2

We use angle-resolved photoemission spectroscopy to study the doping evolution of infinite-layer Sr_(1−x)La_xCuO_2 thin films grown by molecular-beam epitaxy. At low doping, the material exhibits a dispersive lower Hubbard band typical of the superconducting cuprate parent compounds. As carriers are added to the system, a continuous evolution from charge-transfer insulator to superconductor is observed, with the initial lower Hubbard band pinned well below the Fermi level and the development of a coherent low-energy band with electron doping. This two-component spectral function emphasizes the important role that strong local correlations play even at relatively high doping levels. Electron diffraction probes reveal a p(2×2) surface reconstruction of the material at low doping levels. Using a number of simple assumptions, we develop a model of this reconstruction based on the polar nature of the infinite-layer structure. Finally, we provide evidence for a thickness-controlled transition in ultrathin films of SrCuO_2 grown on nonpolar SrTiO_3, highlighting the diverse structural changes that can occur in polar complex oxide thin films.
Protection against ethanol injury by prostaglandin in a human intestinal cell line: role of microtubules.

Prostaglandins have been shown to protect the gastrointestinal (GI) epithelium from injury induced by various luminal insults independent of their known acid-inhibitory effects, a process termed "cytoprotection. " The mechanism of this protective action remains unknown. The present investigation determined the role of microtubules (a major cytoskeletal component) in GI injury induced by ethanol (EtOH) and its prevention by 16,16-dimethylprostaglandin E2 (dmPGE2) using cells from a human colonic cell line known as Caco-2 cells. These cells were preincubated in Eagle's minimum essential medium with and without dmPGE2 (2.6 microM) for 15 min and subsequently incubated in media containing 1, 2.5, 5, 7.5, and 10% EtOH. The effects on cell viability and tubulin (the major protein backbone of microtubules) were then determined. EtOH concentrations > or = 2.5% extensively disrupted the microtubules as demonstrated by fragmentation, kinking, and perturbation of the microtubule organizer center. EtOH treatment also led to a significant decrease in the S2 (polymerized) fraction and an increase in the S1 (monomeric) pool of tubulin. Concomitant with these effects were marked decreases in cellular viability. DmPGE2 pretreatment abolished the disruption of microtubules, significantly increased the S2 fraction of tubulin, and increased cellular viability in cultures exposed to EtOH. Furthermore, pretreatment with colchicine, an inhibitor of microtubule assembly, prevented the cytoprotective action of dmPGE2. Taxol, a microtubule stabilizing agent, mimicked the effects of dmPGE2 by also enhancing microtubule integrity and increasing cellular viability in cells exposed to EtOH. Our data indicate that organization and stabilization of microtubules may play an essential role in the mechanism of prostaglandin-induced protection.
Short-Term Memory Capacity in Networks via the Restricted Isometry Property

Cortical networks are hypothesized to rely on transient network activity to support short-term memory (STM). In this letter, we study the capacity of randomly connected recurrent linear networks for performing STM when the input signals are approximately sparse in some basis. We leverage results from compressed sensing to provide rigorous nonasymptotic recovery guarantees, quantifying the impact of the input sparsity level, the input sparsity basis, and the network characteristics on the system capacity. Our analysis demonstrates that network memory capacities can scale superlinearly with the number of nodes and in some situations can achieve STM capacities that are much larger than the network size. We provide perfect recovery guarantees for finite sequences and recovery bounds for infinite sequences. The latter analysis predicts that network STM systems may have an optimal recovery length that balances errors due to omission and recall mistakes. Furthermore, we show that the conditions yielding optimal STM capacity can be embodied in several network topologies, including networks with sparse or dense connectivities.
Individuation and Quantification : Do bare nouns in Mandarin Chinese individuate ?

Some have proposed that speakers of classifier languages such as Mandarin or Japanese, which lack count-mass syntax, have to rely on classifiers for acquiring individuated meanings of nouns (e.g., Borer 2005; Lucy 1992). This paper examines this view by looking at how Mandarin adults interpret bare nouns and use classifier knowledge to guide quantification in three experiments. Experiment 1 found that Mandarin-speaking adults quantify nouns that are equivalent to English count, mass, and mass-count flexible nouns just like English speakers from a previous study. Experiment 2 showed that adults quantified over broken objects using the noun criteria but not classifier knowledge. Our last experiment found that Mandarin adults would attend to classifier syntax when the units of quantification are vague, as in the case of mass-count flexible nouns such as apple or rock. Taken together, we argue that individuation can be specified lexically, and does not come from classifier syntax.
Localization of epileptic foci in children with intractable epilepsy secondary to multiple cortical tubers by using synthetic aperture magnetometry kurtosis.

OBJECT Magnetoencephalography (MEG) has been typically used to localize epileptic activity by modeling interictal activity as equivalent current dipoles (ECDs). Synthetic aperture magnetometry (SAM) is a recently developed adaptive spatial filtering algorithm for MEG that provides some advantages over the ECD approach. The SAM-kurtosis algorithm (also known as SAM[g2]) additionally provides automated temporal detection of spike sources by using excess kurtosis value (steepness of epileptic spike on virtual sensors). To evaluate the efficacy of the SAM(g2) method, the authors applied it to readings obtained in children with intractable epilepsy secondary to tuberous sclerosis complex (TSC), and compared them to localizations obtained with ECDs. METHODS The authors studied 13 children with TSC (7 girls) whose ages ranged from 13 months to 16.3 years (mean 7.3 years). Video electroencephalography, MR imaging, and MEG studies were analyzed. A single ECD model was applied to localize ECD clusters. The SAM(g2) value was calculated at each SAM(g2) virtual voxel in the patient's MR imaging-defined brain volume. The authors defined the epileptic voxels of SAM(g2) (evSAM[g2]) as those with local peak kurtosis values higher than half of the maximum. A clustering of ECDs had to contain > or = 6 ECDs within 1 cm of each other, and a grouping of evSAM(g2)s had to contain > or = 3 evSAM(g2)s within 1 cm of each other. The authors then compared both ECD clusters and evSAM(g2) groups with the resection area and correlated these data with seizure outcome. RESULTS Seizures started when patients were between 6 weeks and 8 years of age (median 6 months), and became intractable secondary to multiple tubers in all cases. Ictal onset on scalp video electroencephalography was lateralized in 8 patients (62%). The MEG studies showed multiple ECD clusters in 7 patients (54%). The SAM(g2) method showed multiple groups of epileptic voxels in 8 patients (62%). Colocalization of grouped evSAM(g2) with ECD clusters ranged from 20 to 100%, with a mean of 82%. Eight patients underwent resection of single (1 patient) and multiple (7 patients) lobes, with 6 patients achieving freedom from seizures. Of 8 patients who underwent surgery, in 7 the resection area covered ECD clusters and grouped evSAM(g2)s. In the remaining patient the resection area partially included the ECD cluster and grouped evSAM(g2)s. Six of the 7 patients became seizure free. CONCLUSIONS The combination of SAM(g2) and ECD analyses succeeded in localizing the complex epileptic zones in children with TSC who had intractable epilepsy secondary to multiple cortical tubers. For the subset of children with TSC who present with early-onset and nonlateralized seizures, MEG studies in which SAM(g2) and ECD are used might identify suitable candidates for resection to control seizures.
Evidence-based oral transmucosal fentanyl citrate (OTFC) dosing guidelines.

OBJECTIVE To review the evidence for dosing and efficacy of oral transmucosal fentanyl citrate in the management of pain and produce dosing guidelines. DESIGN The scientific literature pertaining to oral transmucosal fentanyl citrate was reviewed, focusing upon its pharmacology and clinical experience with use in cancer and noncancer pain. Emphasis was upon published, peer-reviewed English language articles. RESULTS Information was crucially examined and synthesized into guidelines for use and dosing of oral transmucosal fentanyl citrate in cancer and noncancer pain. CONCLUSIONS Oral transmucosal fentanyl citrate is a potent opioid delivery system, which, when used appropriately, is an effective treatment option for pain. Adherence to guidelines should promote its safe and efficacious use in a variety of clinical pain management settings.
A parameter-less genetic algorithm

From the user's point of view, setting the parameters of a genetic algorithm (GA) is far from a trivial task. Moreover, the user is typically not interested in population sizes, crossover probabilities, selection rates, and other GA technicalities. He is just interested in solving a problem, and what he would really like to do, is to hand-in the problem to a blackbox algorithm, and simply press a start button. This paper explores the development of a GA that fulfills this requirement. It has no parameters whatsoever. The development of the algorithm takes into account several aspects of the theory of GAs, including previous research work on population sizing, the schema theorem, building block mixing, and genetic drift.
Learning to Grow Structured Visual Summaries for Document Collections

In this paper we propose a method of summarizing collections of documents with concise topic hierarchies, and show how it can be applied to visualization and browsing of academic search results. The proposed method consists of two steps: building the graph of topics relevant to the documents, and selecting the optimal subgraph thereof. In the ﬁrst step, we map documents to a universal topic hierarchy and extract a graph of relevant topics. In the second step, we learn how to build summaries of the extracted topic graph us-ing a structured output prediction approach. We describe how to build topic graphs based on the network of articles and categories of Wikipedia, cast graph summarization problem into sequential prediction, and apply DAgger (dataset aggregation) to incrementally ‘growing’ graph summaries. Initial experiments suggest that our method is able to learn how to grow good topic summaries from a small number of examples.
Predicting brain structure in population‐based samples with biologically informed genetic scores for schizophrenia

Schizophrenia is associated with brain structural abnormalities including gray and white matter volume reductions. Whether these alterations are caused by genetic risk variants for schizophrenia is unclear. Previous attempts to detect associations between polygenic factors for schizophrenia and structural brain phenotypes in healthy subjects have been negative or remain non‐replicated. In this study, we used genetic risk scores that were based on the accumulated effect of selected risk variants for schizophrenia belonging to specific biological systems like synaptic function, neurodevelopment, calcium signaling, and glutamatergic neurotransmission. We hypothesized that this “biologically informed” approach would provide the missing link between genetic risk for schizophrenia and brain structural phenotypes. We applied whole‐brain voxel‐based morphometry (VBM) analyses in two population‐based target samples and subsequent regions of interest (ROIs) analyses in an independent replication sample (total N = 2725). No consistent association between the genetic scores and brain volumes were observed in the investigated samples. These results suggest that in healthy subjects with a higher genetic risk for schizophrenia additional factors apart from common genetic variants (e.g., infection, trauma, rare genetic variants, or gene–gene interactions) are required to induce structural abnormalities of the brain. Further studies are recommended to test for possible gene–gene or gene–environment effects. © 2017 Wiley Periodicals, Inc.
Bacillus subtilis Pellicle Formation Proceeds through Genetically Defined Morphological Changes

ABSTRACT Biofilms are structured multicellular communities of bacteria that form through a developmental process. In standing culture, undomesticated strains of Bacillus subtilis produce a floating biofilm, called a pellicle, with a distinct macroscopic architecture. Here we report on a comprehensive analysis of B. subtilis pellicle formation, with a focus on transcriptional regulators and morphological changes. To date, 288 known or putative transcriptional regulators encoded by the B. subtilis genome have been identified or assigned based on similarity to other known proteins. The genes encoding these regulators were systematically disrupted, and the effects of the mutations on pellicle formation were examined, resulting in the identification of 19 regulators involved in pellicle formation. In addition, morphological analysis revealed that pellicle formation begins with the formation of cell chains, which is followed by clustering and degradation of cell chains. Genetic and morphological evidence showed that each stage of morphological change can be defined genetically, based on mutants of transcriptional regulators, each of which blocks pellicle formation at a specific morphological stage. Formation and degradation of cell chains are controlled by down- and up-regulation of σD- and σH-dependent autolysins expressed at specific stages during pellicle formation. Transcriptional analysis revealed that the transcriptional activation of sigH depends on the formation of cell clusters, which in turn activates transcription of σH-dependent autolysin in cell clusters. Taken together, our results reveal relationships between transcriptional regulators and morphological development during pellicle formation by B. subtilis.
A Distinctive Pattern of Beauveria bassiana‐biotransformed Ginsenoside Products Triggers Mitochondria/FasL‐mediated Apoptosis in Colon Cancer Cells

Ginseng is one of the most commonly used adaptogens. Transformation into the minor ginsenosides produces compounds with more effective action. Beauveria bassiana, a teleomorph of Cordyceps bassiana, is a highly efficient producer of mammalian steroids and produces large amounts of sugar‐utilizing enzymes. However, the fermentation of steroid glycosides in ginseng with B. bassiana has never been studied. Thus, we evaluated the bioconversion of the major ginsenosides in white ginseng by B. bassiana. Interestingly, B. bassiana increased the total amount of protopanaxadiols and hydrolyzed Rb1 into minor ginsenosides, exhibiting high levels of Rd and Rg3, as well as moderate levels of Rb2 and Rc analyzed by high‐performance liquid chromatography coupled with evaporative light‐scattering detection. The β‐glucosidase activity was highly increased, which led to the selective elimination of sugar moiety at the 20‐C position of Rb1 to Rd, followed by Rg3. Rb2 and Rc accumulated because of the minimal activities of α‐L‐arabinopyranosidase and α‐L‐arabinofuranosidase, respectively. The fermentation product exerted dose‐dependent cytotoxicity in HCT‐15 cells, which are resistant to ginseng. The product, but not white ginseng, exhibited apoptotic effects via the Fas ligand and caspase 8/9. This study demonstrates for the first time that the B. bassiana‐fermented metabolites have potent apoptotic activity in colon cancer cells, linking to a therapeutic use. Copyright © 2015 John Wiley & Sons, Ltd.
Preclinical arterial disease in patients with type 1 diabetes without other major cardiovascular risk factors or micro-/ macrovascular disease

We aimed to investigate preclinical atherosclerosis in T1D and its relationship with glucose profile and endothelial/ inflammatory markers. Thirty-eight T1D patients without additional cardiovascular risk factors or micro-/macrovascular complications and 22 healthy matched subjects were included. FMD and cIMT/fIMT were performed in addition to 72-h continuous glucose monitoring and the measurement of endothelial/inflammatory markers. Lower FMD percentages and greater cIMT/fIMT were observed in patients with T1D in comparison with controls (FMD 7.0±3.1% vs. 9.6±2.2%; p<0.005; cIMT 0.523±0.091 mm vs. 0.471±0.061 mm; p<0.05 and fIMT 0.512±0.172mm vs. 0.394±0.061mm; p<0.01, for patients and controls, respectively). T1D subjects in the highest tertile of cIMT were older than those in the lowest group (39.9±9.5 vs. 29.6±4.7 years; p<0.005) and had a longer duration of the disease (18.7±5.4 years vs. 11.8±6.4 years). The higher the cIMT tertile, the greater the fIMT (0.397±0.114 mm vs. 0.431±0.082 mm vs. 0.583±0.197 mm; p<0.05). MAGE was negatively correlated to FMD (r=-0.328; p<0.05) and positively to cIMT (r=0.322; p<0.05). There were no differences between cIMT tertiles in terms of metabolic parameters or endothelial and inflammatory markers. Signals of preclinical atherosclerosis in T1D even in the absence of cardiovascular risk factors and micro- / macrovascular disease are reported. Our findings suggest that daily glucose instability could negatively impact vascular function and structure.
NET balancing: a problem in inflammatory lung diseases

Neutrophil extracellular traps (NETs) are beneficial antimicrobial defense structures that can help fight against invading pathogens in the host. However, recent studies reveal that NETs exert adverse effects in a number of diseases including those of the lung. Many inflammatory lung diseases are characterized with a massive influx of neutrophils into the airways. Neutrophils contribute to the pathology of these diseases. To date, NETs have been identified in the lungs of cystic fibrosis (CF), acute lung injury (ALI), allergic asthma, and lungs infected with bacteria, virus, or fungi. These microbes and several host factors can stimulate NET formation, or NETosis. Different forms of NETosis have been identified and are dependent on varying types of stimuli. All of these pathways however appear to result in the formation of NETs that contain DNA, modified extracellular histones, proteases, and cytotoxic enzymes. Some of the NET components are immunogenic and damaging to host tissue. Innate immune collectins, such as pulmonary surfactant protein D (SP-D), bind NETs, and enhance the clearance of dying cells and DNA by alveolar macrophages. In many inflammatory lung diseases, bronchoalveolar SP-D levels are altered and its deficiency results in the accumulation of DNA in the lungs. Some of the other therapeutic molecules under consideration for treating NET-related diseases include DNases, antiproteases, myeloperoxidase (MPO) inhibitors, peptidylarginine deiminase-4 inhibitors, and anti-histone antibodies. NETs could provide important biological advantage for the host to fight against certain microbial infections. However, too much of a good thing can be a bad thing. Maintaining the right balance of NET formation and reducing the amount of NETs that accumulate in tissues are essential for harnessing the power of NETs with minimal damage to the hosts.
Hand Mycetoma: The Mycetoma Research Centre Experience and Literature Review

Mycetoma is a devastating, neglected tropical disease characterised by extensive tissue involvement resulting in destruction, deformities and disabilities in the affected patients. The hand is commonly affected by mycetoma thus compromises its functionality and hinder the patient’s daily activities of living. In this communication, we report on 533 patients with hand mycetoma managed over a period of 24 years at the Mycetoma Research Centre, University of Khartoum, Khartoum, Sudan. Eumycetoma was the commonest type of mycetoma (83.3%) encountered. Males were predominately affected (69.2%) with a sex ratio of 2.2:1. The majority of the patients (84%) were young adult below the age of 40 years old at presentation. The generality of patients (86.4%) were from the Sudan mycetoma belt. Children and adolescents (28.1%), farmers (18.2%) and workers (17.4%) were more frequently affected. The majority of patients (67.4%) had disease duration of less than 5 years at presentation. The study, did not document significant history of local trauma, familial tendency, concomitant medical diseases or other predisposing cause for mycetoma in this population. Pain (23.1%) was not a disease feature in this series and 52% of patients had past surgery for mycetoma and recurrence. The right hand was affected most (60.4%), and 64% of them had small lesion at presentation. Conventional x-ray was only helpful in patients with advanced disease and the MRI accurately determined the disease extension. Cytological smears, surgical biopsies histopathological examination and grains culture were the principal diagnostic tools for causative organisms’ identification. In the present series it was difficult to determine the treatment outcome due to high patients follow up dropout.