Miracle-dz/UniFAR-FTUs huggingface dataset:
Adrenal status in children with septic shock using low-dose stimulation test*

Objectives: There is paucity of data on the magnitude of absolute or relative adrenal insufficiency in septic shock, especially in children. We conducted a prospective study to determine the prevalence of adrenal insufficiency in children with septic shock using a low-dose Synacthen (1 &mgr;g) stimulation test. Design: Cross-sectional study. Setting: Pediatric intensive care unit in a tertiary care hospital in northern India. Patients: Children with septic shock. Interventions: None. Measurements and Main Results: We performed cortisol estimation at baseline and after low-dose Synacthen (1 &mgr;g) stimulation at 30 and 60 mins in children with fluid refractory septic shock admitted to our pediatric intensive care unit. Basal cortisol levels <7 &mgr;g/dL and peak cortisol level <18 &mgr;g/dL were used to define adrenal insufficiency. An increment of <9 &mgr;g/dL after stimulation was used to diagnose relative adrenal insufficiency. As there is lack of consensus on the cutoffs for defining relative adrenal insufficiency using the low-dose adrenocorticotropic hormone test, we evaluated different cutoff values (increment at 30 mins, increment at 60 mins, greater of the two increments) and evaluated their association with the incidence of catecholamine refractory shock and outcomes. Children with sepsis but without septic shock were sampled for baseline cortisol levels as a comparison. Thirty children (15 girls) with septic shock were included; median age (95% confidence interval) was 36.5 (9.39– 58.45) months. Median Pediatric Risk of Mortality score was 22.5 (14.13–24.87). Fifteen (50%) children survived. The median (95% confidence interval) cortisol values at baseline and 30 mins and 60 mins after stimulation were 71 (48.74–120.23) &mgr;g/dL, 78.1 (56.9–138.15) &mgr;g/dL, and 91 (56.17–166.44) &mgr;g/dL, respectively. The median baseline cortisol value in age- and gender-matched children with sepsis was 11.5 &mgr;g/dL. None of the children with septic shock fulfilled the criteria for absolute adrenal insufficiency. However, nine (30%) patients had relative adrenal insufficiency (increment in cortisol <9 &mgr;g/dL). Of these nine patients, five (56%) died; of the 21 patients with a greater increment in cortisol after stimulation, ten died (p = .69). Compared with patients in septic shock with normal adrenal reserve, those with relative adrenal insufficiency had a higher incidence of catecholamine refractory shock (p = .019) but no difference in mortality rate (p = .69). On the sensitivity and specificity analysis using various cutoffs of increment, the best discrimination for catecholamine refractory shock was obtained with a peak increment <6 &mgr;g/dL. Conclusions: Relative adrenal insufficiency is common in children with septic shock and is associated with catecholamine refractory shock.
WebLab PROV: computing fine-grained provenance links for XML artifacts

We present a new provenance model for generating fine-grained data and service dependencies within XML data processing workflows. Our approach follows the widely used black box transformation semantics [15] in which service components produce new outputs from their inputs (without transformation). The heart of the model are data dependency rules which are evaluated on XML documents assembling all data produced by some workflow execution (similar to nested collections [5]). Dependency rules are defined in XPath extended with variables and can directly be compiled into XQuery expressions for generating provenance information in RDF-PROV [8]. We also present an implementation of our model, using the WebLab platform [19], showing step-by-step how our model works in a typical media mining use-case.
Effects of GH on body composition and cardiovascular risk markers in young men with abdominal obesity.

CONTEXT Visceral adiposity is associated with increased cardiometabolic risk and decreased GH secretion. OBJECTIVE Our objective was to determine the effects of GH administration in abdominally obese young men on body composition, including liver fat, mitochondrial function, and cardiovascular (CV) risk markers. DESIGN AND PARTICIPANTS This was a 6-month, randomized, double-blind, placebo-controlled study with 62 abdominally obese men (IGF-1 below the mean, no exclusion based on GH level), 21 to 45 years of age. MAIN OUTCOME MEASURES We evaluated abdominal fat depots, thigh muscle and fat (computed tomography), fat and lean mass (dual-energy x-ray absorptiometry), intramyocellular and intrahepatic lipids (proton magnetic resonance spectroscopy), mitochondrial function (dynamic phosphorous magnetic resonance spectroscopy), CV risk markers, carotid intimal-medial thickness, and endothelial function. RESULTS GH administration resulted in a mean IGF-1 SD score increase from -1.9 ± 0.08 to -0.2 ± 0.3 in the GH group and a decrease in visceral adipose tissue (VAT), VAT/sc adipose tissue, trunk/extremity fat, intrahepatic lipids, high-sensitivity C-reactive protein and apolipoprotein B/low-density lipoprotein vs placebo after controlling for the increase in weight observed in both groups. There were inverse associations between change in IGF-1 levels and change in VAT, VAT/sc adipose tissue, trunk fat, trunk/extremity fat, high-sensitivity C-reactive protein, and apolipoprotein B. Mitochondrial function improved in the GH group compared with placebo after controlling for change in glucose. There was no change in thigh fat, muscle mass, intramyocellular lipids, cholesterol, fibrinogen, intimal-medial thickness, or endothelial function. There was no increase in fasting glucose or hemoglobin A1c in the GH vs placebo group, although glucose during the 2-hour oral glucose tolerance test increased slightly. CONCLUSION GH replacement in abdominally obese men improves body composition, including liver fat, mitochondrial function, and markers of CV risk. Although fasting glucose was unchanged, a slight increase in 2-hour glucose during an oral glucose tolerance test was noted.
Information retrieval support systems

Information retrieval support systems (IRSS) are designed with the objective to provide the necessary utilities, tools, and languages that support a user to perform various tasks in finding useful information and knowledge. While existing information retrieval systems (IRS) focus on the search and browsing functionalities, an IRSS focuses on the supporting functionalities. IRSS are more flexible and combine the functionalities of IRS, Web browser and Web search engines. One objective of the paper is to demonstrate the needs for, and the potential benefits of, moving from IRS to IRSS. On the one hand, IRSS is an emerging important research topic, and on the other hand, there is a lack of a systematic study on the topic. Another objective of the paper is to present a framework for IRSS by drawing results from decision support systems (DSS) and intelligent systems. Basic issues of IRSS are discussed, and basic components of an IRSS, as well as its functionalities, are studied.
Vacuum gap model for PSR B0943+10

PSR B0943+10 is known to show remarkably stable drifting subpulses, which can be interpreted in terms of a circumferential motion of 20 sparks, each completing one circulation around the periphery of the polar cap in 37 pulsar periods. We use this observational constraint and argue that the vacuum gap model can adequately describe the observed drift patterns. Further we demonstrate that only the presence of strong non-dipolar surface magnetic field can favor such vacuum gap formation. Subsequently, for the first time we are able to constrain the parameters of the surface magnetic field, and model the expected magnetic structure on the polar cap of PSR B0943+10 considering the inverse Compton scattering photon dominated vacuum gap.
Assessment of Blood Coagulation Under Various Flow Conditions With Ultrasound Backscattering

Several in vitro studies have employed ultrasonic techniques to detect varying properties of coagulating blood under static or stirred conditions. Most of those studies mainly addressed on the development and feasibility of modalities and however were not fully considering the effect of blood flow. To better elucidate this issue, ultrasonic backscattering were measured from the coagulating porcine blood circulated in a mock flow loop with various steady laminar flows at mean shear rates from 10 to 100 s-1. A 3 ml of 0.5 M CaCl2 solution for inducing blood coagulation was added to that of 30 ml blood circulated in the conduit. For each measurement carried out with a 10-MHz transducer, backscattered signals digitized at 100-MHz sampling frequency were acquired for a total of 20 min at temporal resolution of 50 A-lines per s. The integrated backscatter (IB) was calculated for assessing backscattering properties of coagulating blood. The results show that blood coagulation tended to be increased corresponding to the addition of CaCl2 solution: the IB was increased approximately 6.1 plusmn 0.6 (mean plusmn standard deviation), 5.4 plusmn 0.9, and 4.5 plusmn 1.2 dB at 310 plusmn 62, 420 plusmn 88, and 610 plusmn 102 s associated with mean shear rates of 10, 40, and 100 s-1, respectively. The rate of increasing IB for evaluating the growth of clot was estimated to be 0.075 plusmn0.017,0.052 plusmn0.027, and 0.038 plusmn 0.012 DeltadB Deltas-1 corresponding to the increase of mean shear rates. These results consistently demonstrate that higher shear rate tends to prolong the duration for the flowing blood to be coagulated and to decrease the rate of IB. Moreover, the laminar flow was changed to turbulent flow during that the blood was clotting discerned by spatial variations of ultrasound backscattering in the conduit. All these results validate that ultrasound backscattering is feasible to be utilized for detecting and assessing blood coagulation under dynamic conditions.
Discrete Single Vs. Multiple Stream HMMs: A Comparative Evaluation of Their Use in On-Line Handwriting Recognition of Whiteboard Notes

In this paper we study the influence of quantization on the features used in on-line handwriting recognition in order to apply discrete single and multiple stream HMMs. It turns out that the separation of the features in statisticaly independent streams influences the performance of the recognition system: using the discrete “pressure” feature as an example, we show that the statistical dependencies between the features are as important as their proper quantization. In an experimental section we show that a continuous state-of-the-art system for on-line handwritten whiteboard note recognition can be outperformed by r = 2.0 % relative in word level accuracy using a three stream discrete HMM system with well chosen streams. A relative improvement of r = 4.5 % can be achieved when comparing a single stream HMM system with the best performing mutliple stream HMM system.
Mechanisms of Amyloid Deposition in Alzheimer's Disease a

At the cellular level, Alzheimer's disease (AD) must be the result of neuronal dysfunction and degeneration leading to a reduction in synaptic density. Filamentous deposits of amyloid, which define the disease at the molecular level, occur within perikarya, axons, dendrites, and terminals of neurons as neurofibrillary tangles (NFT), in the extracellular neuropil as amyloid plaques (APC), and around blood vessels as amyloid congophilic angiopathy (ACA). These fibrillar amyloid protein aggregates are also found in the brain of all individuals with Down's syndrome after the age of 30 years. The amyloid deposits apparently occur in the terminal zones of neurons that develop NFT. It is suggested that amyloid deposition is of fundamental significance in AD and that a thorough understanding of amyloid formation will eventually lead to successful therapeutic intervention in AD. As elucidation of the reasons behind amyloid deposition must shed some light on the pathogenesis of AD, we review the current state of knowledge on the nature of the AD amyloid protein, its origin, and its formation. Although there is yet no agreement about the chemical nature of the amyloid protein of NFT, the major constituent of both APC and ACA has been shown to be a 4.5-kD amyloid protein originally termed "beta-protein" or "amyloid A4" which we now denote as "beta A4. " Amyloid beta A4 protein is proteolytically derived from a transmembrane protein termed amyloid precursor protein (APP) which is encoded by a widely expressed gene on chromosome 21. Our present results are consistent with the possibility that amyloid formation requires membrane damage or APP molecules that are not or are incorrectly integrated into membranes. To allow the generation of the C-terminus of beta A4, one proteolytic cleavage step has to occur in the sequence that normally forms the transmembrane domain of the APP proteins. This cleavage is crucial for amyloid formation because we could show that the ability of synthetic beta A4 to form amyloid depositions is mainly based on hydrophobic parts of the sequence that have to interact with each other and build up large aggregates under physiologic conditions. Membrane association of APP is expected to interfere with this cleavage and the process of aggregation.
TRAIL, caspases and maturation of normal and leukemic myeloid precursors

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a membrane-bound cytokine molecule that belongs to the family of tumor necrosis factor (TNF). Members of this family share diverse biological effects, including induction of apoptosis and/or promotion of cell survival. Identification of TRAIL has generated considerable enthusiasm for its ability to induce apoptotic cell death in a variety of tumor cells, by engaging the death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5, while sparing most normal cells. Beside its anticancer activity, several studies have suggested a role for endogenously expressed TRAIL in hemopoiesis. In this review, we summarize the knowledge about the different lineage-specific roles of TRAIL and its receptors in hemopoiesis regulation. Moreover, the complex interplay among the signaling pathways triggered by TRAIL/TRAIL-receptors in myeloid cells is discussed in some detail.
Targeted, homology-driven gene insertion in stem cells by ZFN-loaded ‘all-in-one’ lentiviral vectors

Biased integration remains a key challenge for gene therapy based on lentiviral vector technologies. Engineering of next-generation lentiviral vectors targeting safe genomic harbors for insertion is therefore of high relevance. In a previous paper (Cai et al., 2014a), we showed the use of integrase-defective lentiviral vectors (IDLVs) as carriers of complete gene repair kits consisting of zinc-finger nuclease (ZFN) proteins and repair sequences, allowing gene correction by homologous recombination (HR). Here, we follow this strategy to engineer ZFN-loaded IDLVs that insert transgenes by a homology-driven mechanism into safe loci. This insertion mechanism is driven by time-restricted exposure of treated cells to ZFNs. We show targeted gene integration in human stem cells, including CD34+ hematopoietic progenitors and induced pluripotent stem cells (iPSCs). Notably, targeted insertions are identified in 89% of transduced iPSCs. Our findings demonstrate the applicability of nuclease-loaded ‘all-in-one’ IDLVs for site-directed gene insertion in stem cell-based gene therapies. DOI: http://dx.doi. org/10.7554/eLife.12213. 001
Learning in an Uncertain World: Representing Ambiguity Through Multiple Hypotheses

Many prediction tasks contain uncertainty. In some cases, uncertainty is inherent in the task itself. In future prediction, for example, many distinct outcomes are equally valid. In other cases, uncertainty arises from the way data is labeled. For example, in object detection, many objects of interest often go unlabeled, and in human pose estimation, occluded joints are often labeled with ambiguous values. In this work we focus on a principled approach for handling such scenarios. In particular, we propose a frame-work for reformulating existing single-prediction models as multiple hypothesis prediction (MHP) models and an associated meta loss and optimization procedure to train them. To demonstrate our approach, we consider four diverse applications: human pose estimation, future prediction, image classification and segmentation. We find that MHP models outperform their single-hypothesis counterparts in all cases, and that MHP models simultaneously expose valuable insights into the variability of predictions.
Biochemical and Functional Characterization of the Interaction between Liprin-α1 and GIT1: Implications for the Regulation of Cell Motility

We have previously identified the scaffold protein liprin-α1 as an important regulator of integrin-mediated cell motility and tumor cell invasion. Liprin-α1 may interact with different proteins, and the functional significance of these interactions in the regulation of cell motility is poorly known. Here we have addressed the involvement of the liprin-α1 partner GIT1 in liprin-α1-mediated effects on cell spreading and migration. GIT1 depletion inhibited spreading by affecting the lamellipodia, and prevented liprin-α1-enhanced spreading. Conversely inhibition of the formation of the liprin-α1-GIT complex by expression of liprin-ΔCC3 could still enhance spreading, although to a lesser extent compared to full length liprin-α1. No cumulative effects were observed after depletion of both liprin-α1 and GIT1, suggesting that the two proteins belong to the same signaling network in the regulation of cell spreading. Our data suggest that liprin-α1 may compete with paxillin for binding to GIT1, while binding of βPIX to GIT1 was unaffected by the presence of liprin-α1. Interestingly, GIT and liprin-α1 reciprocally regulated their subcellular localization, since liprin-α1 overexpression, but not the GIT binding-defective liprin-ΔCC3 mutant, affected the localization of endogenous GIT at peripheral and mature central focal adhesions, while the expression of a truncated, active form of GIT1 enhanced the localization of endogenous liprin-α1 at the edge of spreading cells. Moreover, GIT1 was required for liprin-α1-enhanced haptotatic migration, although the direct interaction between liprin-α1 and GIT1 was not needed. Our findings show that the functional interaction between liprin-α1 and GIT1 cooperate in the regulation of integrin-dependent cell spreading and motility on extracellular matrix. These findings and the possible competition of liprin-α1 with paxillin for binding to GIT1 suggest that alternative binding of GIT1 to either liprin-α1 or paxillin plays distinct roles in different phases of the protrusive activity in the cell.
A Spatial Framework to Map Heat Health Risks at Multiple Scales

In the last few decades extreme heat events have led to substantial excess mortality, most dramatically in Central Europe in 2003, in Russia in 2010, and even in typically cool locations such as Vancouver, Canada, in 2009. Heat-related morbidity and mortality is expected to increase over the coming centuries as the result of climate-driven global increases in the severity and frequency of extreme heat events. Spatial information on heat exposure and population vulnerability may be combined to map the areas of highest risk and focus mitigation efforts there. However, a mismatch in spatial resolution between heat exposure and vulnerability data can cause spatial scale issues such as the Modifiable Areal Unit Problem (MAUP). We used a raster-based model to integrate heat exposure and vulnerability data in a multi-criteria decision analysis, and compared it to the traditional vector-based model. We then used the Getis-Ord Gi index to generate spatially smoothed heat risk hotspot maps from fine to coarse spatial scales. The raster-based model allowed production of maps at spatial resolution, more description of local-scale heat risk variability, and identification of heat-risk areas not identified with the vector-based approach. Spatial smoothing with the Getis-Ord Gi index produced heat risk hotspots from local to regional spatial scale. The approach is a framework for reducing spatial scale issues in future heat risk mapping, and for identifying heat risk hotspots at spatial scales ranging from the block-level to the municipality level.
The English-Slovene ACQUIS corpus

The paper presents the SVEZ-IJS corpus, a large parallel annotated English-Slovene corpus containing translated legal texts of the European Union, the ACQUIS Communautaire. The corpus contains approx. 2 x 5 million words and was compiled from the translation memory obtained from the Translation Unit of the Slovene Government Office for European Affairs. The corpus is encoded in XML, accordingto the Text Encoding Initiative Guidelines TEI P4, where each translation memory unit contains useful metadata and the two aligned segments (sentences). Both the Slovene and English text islinguistically annotated at the word-level, by context disambiguatedlemmas and morphosyntactic descriptions, which follow the MULTEXTguidelines. The complete corpus is freely available for research, either via an on-line concordancer, or for downloading from the corpushome page at http://nl.ijs. si/svez/.
Immunohistochemical Staining for Ki-67 and p53 Helps Distinguish Endometrial Arias-Stella Reaction from High-Grade Carcinoma, Including Clear Cell Carcinoma

Summary:The distinction of the Arias-Stella reaction from clear cell carcinoma of the endometrium is usually straightforward; however, this differential diagnosis can be difficult when the Arias-Stella reaction occurs outside the setting of pregnancy or in older patients. The differential diagnosis also is problematic when serous or clear cell carcinoma focally arises within an endometrial polyp, as part of “endometrial intra-epithelial carcinoma” (EIC), or in younger patients. The goal of this study was to determine whether immunohistochemical staining can distinguish the Arias-Stella reaction from endometrial high-grade carcinoma, particularly clear cell carcinoma. Cases of endometrial Arias-Stella reaction (n = 27), clear cell carcinoma (n = 11), serous carcinoma (n = 7), and EIC (n = 4) were assessed by immunohistochemical staining with antibodies for Ki-67, p53, estrogen receptor (ER), and progesterone receptor (PR). Composite immunohistochemical scores based on the percentage and intensity of stained cells were calculated, as was the overall positivity (percentage positive cases), using a cutoff value of ≥5% stained cells and at least weak intensity. Appropriate statistical tests were performed. Ki-67 and p53 immunostaining was significantly less in Arias-Stella reaction than in clear cell carcinoma (p < 0.0001 for both) or serous carcinoma/EIC (p < 0.0001 for both), measured by the composite immunohistochemical scores or overall positivity. ER showed a significant difference only between Arias-Stella reaction and clear cell carcinoma; PR showed a significant difference only between Arias-Stella reaction and serous carcinoma/EIC. When clinical or histologic features cannot facilitate the differential diagnosis, immunohistochemical staining for Ki-67 and p53 may help distinguish endometrial Arias-Stella reaction from clear cell carcinoma and other types of high-grade carcinoma.