julilili42/papers huggingface dataset:
Blood-brain barrier permeability imaging using perfusion computed tomography
2014-09-03

Abstract Background. The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases. Conclusions. Blood-brain barrier permeability can be evaluated in vivo by perfusion computed tomography - an efficient diagnostic method that involves the sequential acquisition of tomographic images during the intravenous administration of iodinated contrast material. The major clinical applications of perfusion computed tomography are in acute stroke and in brain tumor imaging.
A Risk Prediction Model for Screening Bacteremic Patients: A Cross Sectional Study
2014-09-03

Applying the proposed models, more than ten percent of patients with suspected blood stream infection were identified having minimal risk for bacteraemia. Based on these data the application of this model as an automated decision support tool for physicians is conceivable leading to a potential increase in the cost-effectiveness of blood culture sampling. External prospective validation of the model's generalizability is needed for further appreciation of the usefulness of this tool.
Diffusion-weighted imaging during MR-guided radiofrequency ablation of hepatic malignancies: analysis of immediate pre- and post-ablative diffusion characteristics
2014-09-03

Background Previous studies have shown a benefit of magnetic resonance (MR)-diffusion-weighted imaging (DWI) for follow-up after liver radiofrequency (RF) ablation. However, no data are available concerning acute changes of DWI characteristics immediately after RF ablation. Purpose To analyze and compare the MR-diffusion characteristics of pre-interventional hepatic malignancies and the ablation zone during successful MR-guided RF ablation. Material and Methods This retrospective study was conducted in accordance with the guidelines of the local institutional review board. Forty-seven patients with 29 HCC (24 patients) and 30 hepatic metastases (23 patients) underwent MR-guided radiofrequency ablation including DWI before and immediately after ablation (b = 50, 400, 800 s/mm 2 ). Two reviewers (A and B) analyzed DWI with focus on detectability of the tumor before ablation and characteristics of the coagulative area after treatment. Mean apparent diffusion coefficient (ADC) was compared between liver, untreated tumor, and hyperintense areas in post-ablative DWI (b = 800 s/mm 2 ) with the paired Student’s t-test. Results Pre-ablative: the reviewers classified 19/29 (A) and 23/29 (B) HCC and 25/30 (A and B) metastases as detectable in DWI. Post-ablative: a hyperintense rim surrounding the ablation zone was observed in 28/29 treated HCC and 30/30 treated metastases (A and B). A homogenous hypointense central ablation zone was found in 18/29 (A) and 20/29 (B) treated HCC and 17/30 (A &amp; B) treated metastases in DWI. ADC of the rim was significantly lower than ADC of the liver ( P &lt; 0.001). Conclusion DWI enables visualization of the target tumor in MR-guided liver radiofrequency ablation in most cases. A common post-ablative DWI finding is a hyperintense rim with decreased ADC surrounding the ablation zone.
Design and Analysis of Infectious Disease Studies
2014-09-03

The epidemiology of airborne infectious diseases, such as influenza, is\\ncharacterised by multiple modes of transmission. In the case of influenza\\nthree modes of transmission have been identified;\\nairborne transmission mediated by respirable droplet nuclei, \\ndroplet transmission mediated by inspirable large\\ndroplets, and contact transmission mediated by droplets settled in the environment. \\nTheir relative importance and the efficiency of control measures depend, among other factors, \\non the inactivation of viruses in different environmental media. \\nUnderstanding the dynamics of transmission of influenza and the relative importance of the\\nassociated modes of transmission is of major interest since it would uncover\\nthe underlying biological and physical processes, and it can be of use for the\\ndesign of effective and efficient intervention strategies.\\nA series of mathematical models that describe the transmission dynamics\\nof influenza in humans explicitly incorporating the modes of transmission,\\nsuch as transmission via respiratory droplets and contact in space and time,\\nwere developed. Droplets dynamics is determined by their physical properties,\\nwhereas population dynamics is determined by, among other properties,\\nthe pathogen infectivity and the host contact rates. A fundamental time\\ndependent model suggests that airborne infections, mediated by respirable\\ndroplets, provides the dominant mode of transmission in middle and long range\\nepidemics whereas larger, so called inspirable droplets, be they airborne\\nor settled, characterise short-term epidemics with high attack rates.
A meta‐analysis of the strength and nature of cytoplasmic genetic effects
2014-09-04

Abstract Genetic variation in cytoplasmic genomes (i.e. the mitochondrial genome in animals, and the combined mitochondrial and chloroplast genomes in plants) was traditionally assumed to accumulate under a neutral equilibrium model. This view has, however, come under increasing challenge from studies that have experimentally linked cytoplasmic genetic effects to the expression of life history phenotypes. Such results suggest that genetic variance located within the cytoplasm might be of evolutionary importance and potentially involved in shaping population evolutionary trajectories. As a step towards assessing this assertion, here we conduct a formal meta‐analytic review to quantitatively assess the extent to which cytoplasmic genetic effects contribute to phenotypic expression across animal and plant kingdoms. We report that cytoplasmic effect sizes are generally moderate in size and associated with variation across a range of factors. Specifically, cytoplasmic effects on morphological traits are generally larger than those on life history or metabolic traits. Cytoplasmic effect sizes estimated at the between‐species scale (via interspecies mix‐and‐matching of cytoplasmic and nuclear genomes) are larger than those at the within‐species scale. Furthermore, cytoplasmic effects tied to epistatic interactions with the nuclear genome tend to be stronger than additive cytoplasmic effects, at least when restricting the data set to gonochorous animal species. Our results thus confirm that cytoplasmic genetic variation is commonly tied to phenotypic expression across plants and animals, implicate the cytoplasmic–nuclear interaction as a key unit on which natural selection acts and generally suggest that the genetic variation that lies within the cytoplasm is likely to be entwined in adaptive evolutionary processes.
Latent Infection with Cytomegalovirus Is Associated with Poor Memory CD4 Responses to Influenza A Core Proteins in the Elderly
2014-09-04

Abstract Influenza remains a major pathogen in older people. Infection with CMV and the accumulation of late-differentiated T cells associated with it have been implicated in poor Ab responsiveness to influenza vaccination in the elderly, most of whom are CMV positive. However, whether CMV infection also affects memory T cell responses to influenza remains unknown. To investigate this, we assessed T cell responses to influenza A matrix protein and nucleoprotein ex vivo in 166 Dutch individuals (mean age 62.2 y, range 42–82) and validated the results in a second cohort from North America (mean age 73.1 y, range 65–81, n = 28). We found that less than half of the CMV-infected older subjects mounted a CD4 T cell response to influenza Ags, whereas ∼80% of uninfected elderly did so. A similar proportion of younger subjects possessed influenza A virus–responsive CD4 T cells, and, interestingly, this was the case whether they were CMV-infected. Thus, the effect of CMV was only seen in the older donors, who may have been exposed to the virus for decades. The percentage of donors with CD8 responses to influenza A virus was lower than those with CD4; this was not influenced by whether the subjects were CMV seropositive or seronegative. CMV-seropositive responders had significantly higher frequencies of late-differentiated CD4 T-cells (CD45RA+/−CCR7−CD27−CD28−) compared with CMV-infected nonresponders. These data add to the accumulating evidence that infection with CMV has profound but heterogeneous effects on responses to the products of other viruses and have implications for the design of influenza vaccines, especially in the elderly.
Synthesis and Properties of the Weakly Coordinating Anion [Me3NB12Cl11]−
2014-09-04

Abstract The weakly coordinating anion [Me 3 NB 12 Cl 11 ] − has been prepared by a simple two‐step procedure. The anion [Me 3 NB 12 Cl 11 ] − is easily obtained in batches of up to 20 g by chlorination of the known [H 3 NB 12 H 11 ] − anion with SbCl 5 at about 190 °C and subsequent N ‐methylation with methyl iodide. Starting from Na[Me 3 NB 12 Cl 11 ], several synthetically useful salts with reactive cations ([NO] + , [Ph 3 C] + , and [(Et 3 Si) 2 H] + ) were prepared. Full spectroscopic (NMR, IR, Raman, TGA, MS) characterization and single‐crystal X‐ray diffraction studies confirmed the identity and purity of the products. The thermal, chemical, and electrochemical stability as well as the basicity of the [Me 3 NB 12 Cl 11 ] − anion is similar to that of the structurally related weakly coordinating 1‐carba‐ closo ‐dodecaborate and closo ‐dodecaborate anions. The facile preparation of the [Me 3 NB 12 Cl 11 ] − anion and its ideal chemical and physical properties make it a cheap alternative to other classes of weakly coordinating anions.
Monocyte-Induced Development of Th17 Cells and the Release of S100 Proteins Are Involved in the Pathogenesis of Graft-versus-Host Disease
2014-09-04

Abstract Graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. However, the pathophysiology of GvHD remains poorly understood. In this study, we analyzed the induction of Th17 cells by monocytes of patients with GvHD in vitro, demonstrating that monocytes isolated from patients with acute skin and intestinal GvHD stage I–IV and chronic GvHD induce significantly increased levels of Th17 cells compared with patients without GvHD. S100 proteins are known to act as innate amplifier of inflammation. We therefore investigated the presence of S100 proteins in the stool, serum, and bowel tissue of patients with GvHD and the influence of S100 proteins on the induction of Th17 cells. Elevated levels of S100 proteins could be detected in patients with acute GvHD, demonstrating the release of these phagocyte-specific proteins during GvHD. Furthermore, stimulation of monocytes with S100 proteins was found to promote Th17 development, emphasizing the role of S100 proteins in Th17-triggered inflammation. Altogether, our results indicate that induction of Th17 cells by activated monocytes and the stimulatory effects of proinflammatory S100 proteins might play a relevant role in the pathogenesis of acute GvHD. Regarding our data, S100 proteins might be novel markers for the diagnosis and follow-up of GvHD.
Higher order Arabidopsis 14-3-3 mutants show 14-3-3 involvement in primary root growth both under control and abiotic stress conditions
2014-09-04

Arabidopsis 14-3-3 proteins are a family of conserved proteins that interact with numerous partner proteins in a phospho-specific manner, and can affect the target proteins in a number of ways; e.g. modification of enzymatic activity. We isolated T-DNA insertion lines in six 14-3-3 genes within the non-epsilon group that phylogenetically group in three closely related gene pairs. In total, 6 single, 3 double, 12 triple, and 3 quadruple mutants were generated. The mutants were phenotyped for primary root growth on control plates: single and double mutants were indistinguishable from WT, whereas six triples and all quadruples showed a shorter primary root. In addition, length of the first epidermal cell with a visible root hair bulge (LEH) was used to determine primary root elongation on medium containing mannitol and 1-aminocyclopropane-1-carboxylic acid (ACC). This analysis showed clear differences depending on the stress and 14-3-3 gene combinations. Next to the phenotypic growth analyses, a 14-3-3 pull-down assay on roots treated with and without mannitol showed that mannitol stress strongly affects the 14-3-3 interactome. In conclusion, we show gene specificity and functional redundancy among 14-3-3 proteins in primary root elongation under control and under abiotic stress conditions and changes in the 14-3-3 interactome during the onset of stress adaptation.
Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers
2014-09-05

Abstract Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.
Synaptic remodeling generates synchronous oscillations in the degenerated outer mouse retina
2014-09-05

During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs) establish contacts with remnant cone photoreceptors (cones) as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca(2+) imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs), we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from interneurons such as HCs and/or possibly interplexiform cells. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type) cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates) the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells.
Evolutionary Conservation in Biogenesis of β-Barrel Proteins Allows Mitochondria to Assemble a Functional Bacterial Trimeric Autotransporter Protein
2014-09-05

Yersinia adhesin A (YadA) belongs to a class of bacterial adhesins that form trimeric structures. Their mature form contains a passenger domain and a C-terminal β-domain that anchors the protein in the outer membrane (OM). Little is known about how precursors of such proteins cross the periplasm and assemble into the OM. In the present study we took advantage of the evolutionary conservation in the biogenesis of β-barrel proteins between bacteria and mitochondria. We previously observed that upon expression in yeast cells, bacterial β-barrel proteins including the transmembrane domain of YadA assemble into the mitochondrial OM. In the current study we found that when expressed in yeast cells both the monomeric and trimeric forms of full-length YadA were detected in mitochondria but only the trimeric species was fully integrated into the OM. The oligomeric form was exposed on the surface of the organelle in its native conformation and maintained its capacity to adhere to host cells. The co-expression of YadA with a mitochondria-targeted form of the bacterial periplasmic chaperone Skp, but not with SurA or SecB, resulted in enhanced levels of both forms of YadA. Taken together, these results indicate that the proper assembly of trimeric autotransporter can occur also in a system lacking the lipoproteins of the BAM machinery and is specifically enhanced by the chaperone Skp.
Increased cerebrospinal fluid calpain activity and microparticle levels in Alzheimer's disease
2014-09-05

Abstract Background Calpain has been associated with the pathophysiology of Alzheimer's disease (AD) and with apoptotic neuronal cell death leading to microparticles (MPs) formation. Methods A total of 64 patients with AD and 52 age‐ and gender‐matched cognitively healthy elderly controls were included in the study. We measured calpain activity and levels of MPs, amyloid beta (Aβ1–42), h‐tau, and p‐tau181. Results AD patients showed significantly increased calpain activity and higher levels of MPs in cerebrospinal fluid (CSF) and significantly decreased calpain activity and lower levels of MPs in serum and plasma compared with healthy controls. Combined assessment of calpain activity and Aβ1–42 levels in CSF improved diagnostic accuracy as compared with singular or combined traditional CSF biomarkers of AD. Conclusions This is the first study showing increased calpain activity and microparticle levels in CSF of AD patients. Calpain activity could represent a novel diagnostic and prognostic biomarker and promising treatment target for AD.
Probing the gamma-ray emission from HESS J1834–087 using H.E.S.S. andFermiLAT observations
2014-09-05

Previous observations with HESS have revealed the existence of an extended very-high-energy (VHE; E&gt;100 GeV) gamma-ray source, HESS J1834-087, coincident with the SNR W41. The origin of the gamma-ray emission has been further investigated with HESS and the Fermi-LAT. The gamma-ray data provided by 61h (HESS) and 4 yrs (Fermi LAT) of observations cover over 5 decades in energy (1.8GeV - 30TeV). The morphology and spectrum of the TeV and GeV sources have been studied and multi-wavelength data have been used to investigate the origin of the observed emission. The TeV source can be modeled with a sum of two components: one point-like and one significantly extended (sig_TeV = 0.17{\\\\deg}), both centered on SNR W41 and exhibiting spectra described by a power law of index 2.6. The GeV source detected with Fermi is extended (sig_GeV =0.15{\\\\deg}) and morphologically matches the VHE emission. Its spectrum can be described by a power-law with index 2.15 and joins smoothly the one of the whole TeV source. A break appears in the spectra around 100 GeV. Two main scenarios are proposed to explain the emission: a pulsar wind nebula (PWN) or the interaction of SNR W41 with a molecular cloud. X-ray observations suggest the presence of a point-like source (pulsar candidate) near the center of the SNR and non-thermal X-ray diffuse emission which could arise from a potential PWN. The PWN scenario is supported by the match of of the TeV and GeV positions with the putative pulsar. However, the overall spectrum is reproduced by a 1-zone leptonic model only if an excess of low-energy electrons is injected by a high spin-down power pulsar. This low-energy component is not needed if the point-like TeV source is unrelated to the extended GeV and TeV sources. The interacting SNR scenario is supported by the spatial coincidence between the gamma-ray sources, the detection of OH maser lines and the hadronic modeling.
Soil micromorphogenesis and Early Holocene paleoclimate at the desert margin of Southern Arabia .
2014-09-05

The Ramlat as-Sab’atayn desert margin near Ma’rib, Yemen, displays well-preserved Early Holocene paleosols that are documented by micromorphological and pedological data. The buried soils, which are represented by Ahb horizons, indicate soil formation mostly before 8.3 cal ka BP. In contrast, sandy cover sediments without signs of pedogenesis appeared between 8.3 and 6.6 cal ka BP due to increasing aridity. Characteristic micromorphological features of the cover sediments are a single grain microstructure, crystallitic b-fabric, predominant occurrence of fresh sideromelane, and remnants of microlayers. Micromorphological pedogenic features in the buried Ah horizons include a subangular blocky microstructure, undifferentiated b-fabric as a result of enrichment of organic matter and decalcification, and the predominant occurrence of completely altered sideromelane. Most of these horizons appeared to be nearly completely decalcified so that in parts a stipple speckled b-fabric and neoformed clay coatings could be detected as a result of stronger weathering and soil formation. Pedogenic data provide important information about Holocene climate fluctuations, including the amount of precipitation, which was calculated on the basis of geochemical data from buried A, AB and B horizons. The buried paleosols represent moist climate conditions with precipitation ranging from 400 to 600 mm a&lt;sup&gt;-1&lt;/sup&gt;.
Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD
2014-09-08

In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.).