Miracle-dz/UniFAR-FTUs huggingface dataset:
A touch of TRALI

Transfusion‐related acute lung injury (TRALI) is a leading cause of transfusion‐associated morbidity and mortality. The National Heart, Lung, and Blood Institute (NHLBI) and Canadian Consensus Conference definitions of TRALI exclude cases of mild TRALI. As a result, many cases of mild TRALI are likely to be missed. Three cases are reported in which patients experienced the acute onset of breathlessness in association with transfusion of blood components containing human leukocyte antigen (HLA) antibodies reactive with recipient HLA antigens. Despite the sudden onset of a pulmonary syndrome in association with transfusion, clinicians caring for these patients did not consider TRALI, and no case would meet recent consensus definitions. Nevertheless, supporting clinical and serologic evidence for TRALI was found in each case. Benefits in recognizing mild cases of TRALI include quantifying the true incidence of TRALI, understanding the physiology of mild versus severe TRALI, and preventing subsequent cases of TRALI due to donors found to have HLA antibodies.
Interleukin‐4 inhibits cyclo‐oxygenase‐2 expression and prostaglandin E2 production by human mature dendritic cells

Interleukin‐4 (IL‐4) is considered the key cytokine for inducing T helper type 2 (Th2) cell differentiation, while interferon‐γ and IL‐12 are pivotal cytokines for Th1 immune responses. Paradoxically, IL‐4 has also been demonstrated to enhance IL‐12 production by dendritic cells, suggesting an IL‐4‐dependent regulatory feedback of the Th1/Th2 system. In addition, prostaglandin E2 (PGE2), a lipid mediator of inflammation, has been implicated in the enhancement of Th2‐type responses acting directly on T and B lymphocytes. PGE2 synthesis is dependent on the serial engagement of various enzymes, among which the inducible cyclo‐oxygenase‐2 (COX‐2) exerts a critical role in monocytes and dendritic cells. In this study we demonstrate that IL‐4 inhibits COX‐2 gene expression and consequently prevents secretion of PGE2 by mature human dendritic cells. We also show that PGE2 does not regulate IL‐12 and IL‐10 production by dendritic cells in an autocrine fashion. Hence, we suggest that IL‐4 may exploit an IL‐12‐independent regulatory feedback of the Th1/Th2 system through PGE2 inhibition.
Phylogeography of maritime pine inferred with organelle markers having contrasted inheritance

Range‐wide variation of maritime pine was studied at maternally inherited and paternally inherited markers (mitochondrial DNA and chloroplast DNA). While chloroplast DNA exhibits the highest diversity, phylogeographic inferences from this marker are blurred by homoplasy and extensive pollen flow. In contrast, the only three mitochondrial haplotypes found provide a clear picture of nonoverlapping areas colonized from different refugia, with no single population having a mixed composition (GST = 1). Comparison of the genetic structure inferred from both organelle genomes allows the investigation of differential seed and pollen dispersal, pointing to pollen, but not seed, dispersal across the Strait of Gibraltar (from Morocco into Iberia). A comparison with already available genetic information, especially that of one of the maritime pine's most threatening insect pests, the bast scale Matsucoccus feytaudi, further completes the picture.
Use of automated microscopy for the detection of disseminated tumor cells in bone marrow samples.

The use of automated microscopy has reached the maturity necessary for its routine use in the clinical pathology laboratory. In the following study we compared the performance of an automated microscope system (MDS) with manual method for the detection and analysis of disseminated tumor cells present in bone marrow preparations from breast carcinoma patients. The MDS System detected rare disseminated tumor cells among bone marrow mononuclear cells with higher sensitivity than standard manual microscopy. Automated microscopy also proved to be a method of high reproducibility and precision, the advantage of which was clearly illustrated by problems of variability in manual screening. Accumulated results from two pathologists who had screened 120 clinical slides from breast cancer patients both by manual microscopy and by use of the MDS System revealed only two (3.8%) missed by the automatic procedure, whereas as many as 20 out of 52 positive samples (38%) were missed by manual screening.
Geodesic grassfire for computing mixed-dimensional skeletons

Skeleton descriptors are commonly used to represent, understand and process shapes. While existing methods produce skeletons at a fixed dimension, such as surface or curve skeletons for a 3D object, often times objects are better described using skeleton geometry at a mixture of dimensions. In this paper we present a novel algorithm for computing mixed-dimensional skeletons. Our method is guided by a continuous analogue that extends the classical grassfire erosion. This analogue allows us to identify medial geometry at multiple dimensions, and to formulate a measure that captures how well an object part is described by medial geometry at a particular dimension. Guided by this analogue, we devise a discrete algorithm that computes a topology-preserving skeleton by iterative thinning. The algorithm is simple to implement, and produces robust skeletons that naturally capture shape components.
The Inflammatory Mediator Leukotriene D4 Induces β-Catenin Signaling and Its Association with Antiapoptotic Bcl-2 in Intestinal Epithelial Cells*

Increased levels of the inflammatory mediator leukotriene D4 (LTD4) are present at sites of inflammatory bowel disease, and such areas also exhibit an increased risk for subsequent cancer development. It is known that LTD4 affects the expression of many proteins that influence survival and proliferation of intestinal epithelial cells. We demonstrate here that after LTD4 exposure, β-catenin translocates to the nucleus where it signals activation of the TCF/LEF family of transcription factors. These events are mediated via a phosphatidylinositol 3-kinase-dependent phosphorylation of the inhibitory Ser-9 residue of glycogen synthase kinase 3β. We also show that in the presence of LTD4, free β-catenin translocates to the mitochondria where it associates with the cell survival protein Bcl-2. We hypothesize that LTD4 may enhance cell survival via activation of β-catenin signaling, in particular, by promoting the association of β-catenin with Bcl-2 in the mitochondria. Similar to Wnt-1 signaling, LTD4 signals an increased level of free β-catenin and elevated TCF/LEF promotor activity. This work in intestinal epithelial cells further lends credence to the idea that inflammatory signaling pathways are intrinsically linked with potential oncogenic signals involved in cell survival and apoptosis.
Genetic evidence for the neuronal nitric oxide synthase gene (NOS1) as a susceptibility locus for infantile pyloric stenosis.

The etiological role of the gene for neuronal nitric oxide synthase (NOS1) in infantile pyloric stenosis (PS) was investigated by analysis of two intragenic polymorphisms (NOS1a and NOS1b) in 27 families. There was significant overall transmission disequilibrium between PS and NOS1a (P = .006). Consideration of each allele independently revealed a highly significant tendency for allele 7 (210 bp) to be preferentially transmitted to the affected offspring (P = .0006). These observations suggest that NOS1 is a susceptibility locus for PS.
WH2 and proline‐rich domains of WASP‐family proteins collaborate to accelerate actin filament elongation

WASP‐family proteins are known to promote assembly of branched actin networks by stimulating the filament‐nucleating activity of the Arp2/3 complex. Here, we show that WASP‐family proteins also function as polymerases that accelerate elongation of uncapped actin filaments. When clustered on a surface, WASP‐family proteins can drive branched actin networks to grow much faster than they could by direct incorporation of soluble monomers. This polymerase activity arises from the coordinated action of two regulatory sequences: (i) a WASP homology 2 (WH2) domain that binds actin, and (ii) a proline‐rich sequence that binds profilin–actin complexes. In the absence of profilin, WH2 domains are sufficient to accelerate filament elongation, but in the presence of profilin, proline‐rich sequences are required to support polymerase activity by (i) bringing polymerization‐competent actin monomers in proximity to growing filament ends, and (ii) promoting shuttling of actin monomers from profilin–actin complexes onto nearby WH2 domains. Unoccupied WH2 domains transiently associate with free filament ends, preventing their growth and dynamically tethering the branched actin network to the WASP‐family proteins that create it. Collaboration between WH2 and proline‐rich sequences thus strikes a balance between filament growth and tethering. Our work expands the number of critical roles that WASP‐family proteins play in the assembly of branched actin networks to at least three: (i) promoting dendritic nucleation; (ii) linking actin networks to membranes; and (iii) accelerating filament elongation.
System for Observing Staff Promotion of Activity and Nutrition (SOSPAN).

BACKGROUND Frontline-staff are critical to achieving policies related to child physical activity and nutrition (PAaN) in out-of-school-time programs (OSTP). Recent policies call upon staff to demonstrate behaviors related to PAaN. Currently, no instrument exists to measure these behaviors. This study fills the gap between policy mandates and staff behaviors by describing the development of the System for Observing Staff Promotion of Activity and Nutrition (SOSPAN) in OSTP. METHODS SOSPAN items were aligned with existing OSTP policies. Reliability and validity data of SOSPAN were collected across 8 OSTP: 4 summer day camps and 4 afterschool programs. Validity of SOSPAN staff behaviors/management of PA was established using the percent of children active measured concurrently via direct observation. RESULTS A total of 6437 scans were performed. Interrater percent agreement ranged from 74%-99% across PAaN behaviors. Children's activity was associated with staff facilitative behaviors/management, such as playing with the children and providing 2 or more activities for children to choose, while prohibitive behaviors/management, such as waiting in line were related to increased sedentary behavior. Staff nutrition behaviors were observed in less than 0.6% of scans. CONCLUSION SOSPAN is a reliable and valid tool to assess staff behaviors/management of PAaN in OSTPs.
Diagnostic Techniques in Neurovascular Disorders

When evaluating a patient with an intracranial vascular disorder, it may be unclear, which neuroimaging modality is optimal; magnetic resonance angiography (MRA), computed tomography angiography (CTA), intra-arterial digital subtraction angiography (DSA), or routine magnetic resonance imaging (MRI) or computed tomography (CT). We will discuss each angiographic technique, then outline the advantage of each imaging modality in the context of specific cases.
Optogenetic study of networks in epilepsy

Currently, approximately 30% of patients with epilepsy do not have adequate seizure control. A greater understanding of the underlying mechanisms by which seizures start or propagate could lead to new therapeutic strategies. The recent development of optogenetics, because of its unprecedented precision for controlling activity within distinct neuronal populations, has revolutionized neuroscience, including epilepsy research. This Review discusses recent breakthroughs made with optogenetics in epilepsy research. These breakthroughs include new insights into the key roles that different cell types play in mediating seizures as well as in the development of epilepsy. Subsequently, we discuss how targeting different brain regions and cell populations has opened up the possibility of highly specific therapies that can stop seizures on demand. Finally, we illustrate how combining newly available neuroscience tools with whole‐brain imaging techniques will allow researchers to understand better the spread of seizures on a network level. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
POSTER: Improving Anonymity of Services Deployed Over Tor by Changing Guard Selection

Many P2P applications are emerging that use Tor to ensure anonymity of their users. Each user in such an application creates an onion service so that the user can receive requests from other users. Such large-scale use of onion services leak a lot of sensitive information to guards in Tor. The cause of these leaks is diversity in guards' resources and the guard selection algorithm in Tor that is designed to use guards' resources efficiently. We describe a preliminary approach for selecting guards which reduces the amount of sensitive information leaked to guards while using guards' resources with same efficiency. Experiments in the context of a P2P publish/subscribe application shows that the approach reduces information leaked to guards by 25%.
Risk factors for tumors of the brain and meninges: Results from the Adelaide adult brain tumor study

A population‐based case‐control study of incident primary brain tumors in adults was carried out in Adelaide, Australia in the period 1987 through 1990. It included 110 subjects with newly diagnosed primary glioma, 60 subjects with meningioma and 417 controls selected from the Australian Electoral Roll and frequency‐matched to cases for age (within 2 years), sex and postal code. Some interesting new associations were found: (I) an increased risk of glioma in women who reported working with cathode‐ray tubes (relative risk = 4.1, 95% confidence interval: 1.3–13.2); (2) a decreased risk of glioma in those with a history of allergic diseases (relative risk = 0.5, 95% confidence interval: 0.3–0.9); and (3) an increased risk of meningioma in those exposed to passive smoking from a spouse, especially amongst females (relative risk = 2.7, 95% confidence interval: 1.2–6.1). A pooled analysis of the multi‐center group of studies to which the present study belongs should allow more confident claims concerning risk factors for brain tumors.
Electrode Independence in Intraneural Cochlear Nerve Stimulation

Objectives/Hypothesis: We have previously reported feline electrophysiological and anatomical studies focused on the development of an intraneural auditory neuroprosthesis. Because only the tips of the electrodes implanted in the cochlear nerve are the stimulating elements that abut the nerve axons, we hypothesize that intraneural stimulation will be highly focal in nature. In this article, we report the electrophysiological characterization of the selective activation of subpopulations of cochlear nerve fibers via electrodes implanted in feline cochlear nerve. Study Design: We have used a forward-masking paradigm to estimate the extent of stimulation overlap produced by pairs of electrodes implanted into the cochlear nerve. Methods: The technique uses sequential stimulation via masking and probe electrodes and monitoring of the electrically evoked auditory brain stem response as an index of cochlear nerve fiber recruitment. We investigated overlap in all possible electrode pair combinations. Results and Conclusion: Many electrode pairs manifest virtually no overlap in the subpopulations of fibers excited by perithreshold stimuli, whereas most had considerable overlap at higher stimulation levels. However, we also noted that our measured overlap was similar across electrodes possibly because of lack of specificity of the whole nerve electrically evoked auditory brain stem response as an assay for this parameter. These findings indicate that direct cochlear nerve stimulation via intraneural electrodes provides selective excitation of small subpopulations of cochlear nerve fibers, and suggest that cochlear nerve stimulation may selectively evoke narrow-band frequency percepts.
Vector Competence of Ixodes muris (Acari: Ixodidae) for Borrelia burgdorferi

Abstract The vector competence of Ixodes muris (Bishopp & Smith) was determined for Borrelia burgdorferi, the etiologic agent of Lyme disease. Larval I. muris were fed on ICR outbred mice infected with the B-31 laboratory strain of B. burgdorferi. Replete larvae, at 5 d after feeding, were assayed for infection by culture in Barbour-Stoner-Kelly (BSK-H) media. Infection frequency in I. muris replete larvae was 66%. Resultant nymphs were fed on naive ICR outbred mice to determine the ability of I. muris to transmit infection. Infection frequency in fed nymphs declined to 38% and only 1/5 mice was positive for B. burgdorferi on ear biopsy culture. We demonstrated that I. muris is capable of acquiring and transmitting B. burgdorferi but is a relatively poor vector compared with I. scapularis (Say).
HIV-1 Viral Escape in Infancy Followed by Emergence of a Variant-Specific CTL Response1

Mutational escape from the CTL response represents a major driving force for viral diversification in HIV-1-infected adults, but escape during infancy has not been described previously. We studied the immune response of perinatally infected children to an epitope (B57-TW10) that is targeted early during acute HIV-1 infection in adults expressing HLA-B57 and rapidly mutates under this selection pressure. Viral sequencing revealed the universal presence of escape mutations within TW10 among B57- and B5801-positive children. Mutations in TW10 and other B57-restricted epitopes arose early following perinatal infection of B57-positive children born to B57-negative mothers. Surprisingly, the majority of B57/5801-positive children exhibited a robust response to the TW10 escape variant while recognizing the wild-type epitope weakly or not at all. These data demonstrate that children, even during the first years of life, are able to mount functional immune responses of sufficient potency to drive immune escape. Moreover, our data suggest that the consequences of immune escape may differ during infancy because most children mount a strong variant-specific immune response following escape, which is rarely seen in adults. Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection.
Reliability and Validity of the Group Embedded Figures Test across the Life Span

Data from a previous investigation were reanalyzed to determine the split-half reliability and two forms of validity, i.e., internal consistency and construct, of the Group Embedded Figures Test across the life span. Subjects were 175 females, ranging in age from 17 to 72 yr. , who fell into one of seven age groups. The Group Embedded Figures had adequate split-half reliability for the entire sample and for each age group. Significant, consistent differences between performance on Parts II and III of the GEFT were found. Estimates of internal consistency were adequate. Though satisfactory construct validity for the total correct on Parts II and III was obtained as correlations with the Portable-Rod-and-Frame Test for the entire sample, the construct validity of the Group Embedded Figures and separate parts was not adequately demonstrated within all age groups.
Evaluation of two PET motion correction techniques for simultaneous real-time PET-MR acquisitions using an MR-derived motion model

Respiratory motion during PET imaging causes the resulting images to become corrupted by artifacts. Respiratory motion models have found application in estimating and correcting for the effects of motion in a wide range of applications. In this work we evaluate the performance of an MR-derived motion model for motion-correction of PET data that is suitable for use in a simultaneous PET-MR imaging system. The technique is based on the formation of a subject-specific respiratory motion model from near real-time dynamic MR images and is capable of making real-time motion estimates based on an MR navigator signal. This approach has an advantage over gating based approaches in that individual motion corrections can be applied at each time point, avoiding the need to combine large amounts of PET data for correction by a single transformation for each gate. In our investigation, we evaluate the effects of the MR-derived motion model and PET motion compensation using dynamic PET simulations based on dynamic MR data (105 real-time frames, 0.7s each) of the thorax acquired from a healthy volunteer. This large amount of data, acquired during different breathing patterns, allows us to more accurately simulate the complex respiratory motion variation that is observed in real PET acquisitions. PET images are corrected for motion using two approaches: reconstruct-transform-average (RTA) and motion compensated image reconstruction (MCIR). We compare the methods in terms of quantification and visualization of three tumors that were artificially added to the emission and attenuation maps of the volunteer close to the diaphragm. It is demonstrated that our motion model can be used to correct successfully for motion in real-time dynamic PET-MR acquisitions. The correction is feasible using either RTA or MCIR, although the latter provides
Single-Domain Antibody-SH3 Fusions for Efficient Neutralization of HIV-1 Nef Functions

ABSTRACT HIV-1 Nef is essential for AIDS pathogenesis, but this viral protein is not targeted by antiviral strategies. The functions of Nef are largely related to perturbations of intracellular trafficking and signaling pathways through leucine-based and polyproline motifs that are required for interactions with clathrin-associated adaptor protein complexes and SH3 domain-containing proteins, such as the phagocyte-specific kinase Hck. We previously described a single-domain antibody (sdAb) targeting Nef and inhibiting many, but not all, of its biological activities. We now report a further development of this anti-Nef strategy through the demonstration of the remarkable inhibitory activity of artificial Nef ligands, called Neffins, comprised of the anti-Nef sdAb fused to modified SH3 domains. The Neffins inhibited all key activities of Nef, including Nef-mediated CD4 and major histocompatibility complex class I (MHC-I) cell surface downregulation and enhancement of virus infectivity. When expressed in T lymphocytes, Neffins specifically inhibited the Nef-induced mislocalization of the Lck kinase, which contributes to the alteration of the formation of the immunological synapse. In macrophages, Neffins inhibited the Nef-induced formation of multinucleated giant cells and podosome rosettes, and it counteracted the inhibitory activity of Nef on phagocytosis. Since we show here that these effects of Nef on macrophage and T cell functions were both dependent on the leucine-based and polyproline motifs, we confirmed that Neffins disrupted interactions of Nef with both AP complexes and Hck. These results demonstrate that it is possible to inhibit all functions of Nef, both in T lymphocytes and macrophages, with a single ligand that represents an efficient tool to develop new antiviral strategies targeting Nef.