Miracle-dz/UniFAR-FTUs huggingface dataset:
IgA anti-transglutaminase antibodies as a tool for screening atypical forms of coeliac disease in a French at-risk paediatric population

Objective The diagnosis of coeliac disease (CD) is often delayed because many children are free from the major symptoms characteristic of this enteropathy. The aim of the present study was to determine the efficacy of antibodies directed against tissue transglutaminase (tTG Abs) for early detection of CD in a population with few symptoms of the disease, as well as in children with an autoimmune disorder. Methods This was a prospective study in a paediatric population including 638 patients with clinical symptoms frequently associated with CD, autoimmune diseases such as type 1 diabetes mellitus (DM1), autoimmune thyroiditis or hepatitis, and Turner's syndrome. Anti-endomysium, tTG Abs and antigliadin antibodies were analysed in these patients using an indirect immunofluorescence technique and enzyme-linked immunosorbent assay techniques. Intestinal biopsies were performed for some patients with positive or negative antibodies. Results tTG Abs were detected in 2.6% of children with symptoms associated with CD, such as digestive signs and growth failure, and in 5.4% of children with DM1. No other autoimmune disease was positive for tTG Abs. Biopsies performed in the patients with positive tTG Abs showed mucosal atrophy confirming the diagnosis of CD in all cases. Conclusion Children displaying minimal symptoms frequently associated with CD and children with DM1 should be systematically screened for tTG Abs.
Spinal projections of the A5, A6 (locus coeruleus), and A7 noradrenergic cell groups in rats

The pontine noradrenergic cell groups, A5, A6 (locus coeruleus), and A7, provide the only noradrenergic innervation of the spinal cord, but the individual contribution of each of these populations to the regional innervation of the spinal cord remains controversial. We used an adeno‐associated viral (AAV) vector encoding green fluorescent protein under an artificial dopamine beta‐hydroxylase (PRSx8) promoter to trace the spinal projections from the A5, A6, and A7 groups. Projections from all three groups travel through the spinal cord in both the lateral and ventral funiculi and in the dorsal surface of the dorsal horn, but A6 axons take predominantly the dorsal and ventral routes, whereas A5 axons take mainly a lateral and A7 axons a ventral route. The A6 group provides the densest innervation at all levels, and includes all parts of the spinal gray matter, but it is particularly dense in the dorsal horn. The A7 group provides the next most dense innervation, again including all parts of the spinal cord, but is it denser in the ventral horn. The A5 group supplies only sparse innervation to the dorsal and ventral horns and to the cervical and lumbosacral levels, but provides the densest innervation to the thoracic intermediolateral cell column, and in particular to the sympathetic preganglionic neurons. Thus, the pontine noradrenergic cell groups project in a roughly topographic and complementary fashion onto the spinal cord. The pattern of spinal projections observed suggests that the locus coeruleus might have the greatest effect on somatosensory transmission, the A7 group on motor function, and the A5 group on sympathetic function. J. Comp. Neurol. 520:1985–2001, 2012. © 2011 Wiley Periodicals, Inc.
Effect of aprotinin on neutrophil function after major vascular surgery

High‐dose aprotinin reduces blood loss and blood transfusion requirements during liver transplantation and cardiac and vascular surgery. The mechanism of the haemostatic efect of aprotinin is unclear. A general effect on the anti‐inflammatory response may be involved. Because leucocyte activation is part of this process, white cell function was measured in patients undergoing aortic surgery who received high‐dose aprotinin therapy (n = 10) and was compared with the results from controls who did not (n = 10). The test group received an intravenous bolus (2 × 106 kallikrein inhibitor units) of aprotinin after induction of anaesthesia followed by continuous infusion (0.5 × 106 kallikrein inhibitor units/h) until the end of the operation. Blood samples were obtained before operation, immediately after surgery, and 1 and 7 days after operation. Aprotinin maintained significantly better postoperative white cell function as measured by bipolar shape formation (P < 0.001), unstimulated nitroblue tetrazolium (NBT) reduction (P < 0.001) and chemotaxis (P < 0.001). Endotoxin‐stimulated NBT reduction was similar in both groups, indicating that neutrophils from treated individuals retained the capacity to respond to oxidative stimuli. Aortic surgery activates neutrophils in vivo, as reflected by impaired chemotaxis and increased superoxide production. Aprotinin protects the cells against this potentially deleterious efect without afecting their ability to respond when provoked. Whether this afects leucocyte interaction with coagulation pathways and contributes to the reduction in blood loss remains to be determined.
Logics of pre-merger decision-making processes: the case of Karolinska University Hospital.

PURPOSE The purpose of this paper is to examine how and why a decision to merge two university hospitals in a public context might occur by using an in-depth case study of the pre-merger process of Karolinska University Hospital. DESIGN/METHODOLOGY/APPROACH Based on extensive document analysis and 35 key informant interviews the paper reconstructed the pre-merger process, searched for empirical patterns, and interpreted those by applying neo-institutional theory. FINDINGS Spanning nearly a decade, the pre-merger process goes from idea generation through transition to decision, and took place on two arenas, political, and scientific. Both research excellence and economic efficiency are stated merger motives. By applying a neo-institutional perspective, the paper finds that the two initial phases are driven by decision rationality, which is typical for political organizations and that the final phase demonstrated action rationality, which is typical for private firms. Critical factors behind this radical change of decision logic are means convergence, uniting key stakeholder groups, and an economic and political crisis, triggering critical incidents, which ultimately legitimized the formal decision. It is evident from the paper that merger decisions in the public sector might not necessarily result from stated and/or economic drivers only. PRACTICAL IMPLICATIONS This paper suggests that a change of decision logic from decision to action rationality might promote effective decision making on large and complex issues in a public context. ORIGINALITY/VALUE This is the first systematic in-depth study of a university hospital merger employing a decision-making perspective.
Attachment of Nontypable Haemophilus influenzae to Human Pharyngeal Epithelial Cells Mediated by a Ganglioside Receptor

Nontypable Haemophilus influenzae (NTHI) is one of the major pathogens of human respiratory infections and has the ability to attach to pharyngeal epithelial cells. We characterized the epithelial cell receptor to which NTHI bind. Neuraminidase pretreatment of pharyngeal epithelial cells resulted in a significant decrease in NTHI attachment, suggesting sialic acid as an important component of the receptor. The attachment was not decreased in NTHI pretreated with 1,000 μg/ml of fucose, N‐acetyl‐neuraminic acid, N‐acetyl‐glucosamine, N‐acetyl‐galactosamine, acetyl‐salicylic acid and colominic acid. Only treatment with gangliosides D1a, D1b and D2 at a concentration of 12.5 μg/ml significantly decreased the attachment. On the other hand, treatment with gangliosides M1, M2, M3, D3, T1b and asialoganglioside M1 did not decrease the attachment of NTHI. Only ganglioside D2 inhibited the attachment significantly at a concentration of 12.5 ng/ml. Other isolates of NTHI showed a decrease in attachment after treatment with ganglioside D2. Treatment of cells with anti‐human GD2 monoclonal antibody also decreased the attachment of NTHI in a dose‐dependent manner. This study indicates that sialic acid glycoconjugate, GD2, is one of the receptors of NTHI on human pharyngeal epithelial cells.
UV-B and temperature enhancement affect spring and autumn phenology in Populus tremula.

Perennial plants growing at high latitudes synchronize growth and dormancy to appropriate seasons by sensing environmental cues. Autumnal growth cessation, bud set and dormancy induction are commonly driven by the length of photoperiod and light quality, and the responses are modified by temperature. However, although ultraviolet (UV)-B radiation is well known to affect plant growth and development, information on the effects on bud phenology is scarce. We examined the separate and combined effects of enhanced temperature and UV-B on autumnal bud set and spring bud break in female and male clones of Populus tremula in an outdoor experiment in Joensuu, Eastern Finland. Enhancements of UV-B and temperature were modulated to +30% and +2 °C, respectively, from June to October 2012. Enhanced UV-B accelerated bud set, while increased temperature delayed it. For both UV-B and temperature, we found sex-related differences in responsiveness. Temperature increase had a stronger delaying effect on bud maturation in male compared with female clones. Also, male clones were more responsive to UV-B increase than female clones. Increasing autumnal temperature enhanced bud break in spring for both sexes, while UV-B enhanced bud break in male clones. In conclusion, we found that UV-B affected phenological shifts in P. tremula, and that temperature and UV-B affected genders differently.
Binary architecture of the Nav1.2-β2 signaling complex

To investigate the mechanisms by which β-subunits influence Nav channel function, we solved the crystal structure of the β2 extracellular domain at 1. 35Å. We combined these data with known bacterial Nav channel structural insights and novel functional studies to determine the interactions of specific residues in β2 with Nav1.2. We identified a flexible loop formed by 72Cys and 75Cys, a unique feature among the four β-subunit isoforms. Moreover, we found that 55Cys helps to determine the influence of β2 on Nav1.2 toxin susceptibility. Further mutagenesis combined with the use of spider toxins reveals that 55Cys forms a disulfide bond with 910Cys in the Nav1.2 domain II pore loop, thereby suggesting a 1:1 stoichiometry. Our results also provide clues as to which disulfide bonds are formed between adjacent Nav1.2 912/918Cys residues. The concepts emerging from this work will help to form a model reflecting the β-subunit location in a Nav channel complex. DOI: http://dx.doi. org/10.7554/eLife.10960. 001
Are Insulin Resistance Index, IGF-1 and Metabolic Syndrome Components Correlates with Severe Preeclampsia?

Objective. Analyse the relation between insulin resistance and severe preeclampsia (SPE). Methods. Case control study paired by body mass index and gestational age; including 16 patients with severe SPE and 16 normotensive controls. Insulin resistance was assessed through the HOMA-IR and QUICKI-IS indexes. Results. There was no significant difference between the groups regarding the HOMA-IR and QUICKI-IS indexes and HDL cholesterol. Triglyceride levels were higher and the IGF-1 was lower in the SPE group than in the control group. Conclusions. There were no differences in the insulin resitance indexes between the group with SPE and normal controls.
An Anatomic Study of the Sacral Hiatus: A Basis for Successful Caudal Epidural Block

Study DesignAn anatomic study of the sacral hiatus using isolated sacra. ObjectivesTo clarify the anatomic variations of the sacral hiatus using the bony landmarks of the sacrum for improving the reliability of caudal epidural block (CEB). Background DataThe CEB has been widely used for the diagnosis and treatment of lumbar spinal disorders. The reliability of CEB is 70%–80% in the literatures. The cause of failure of CEB may depend on anatomic basis. MethodsA total of 92 isolated sacra were used in this study. The bony landmarks were sacral hiatus and sacral cornua. Morphologic types of the sacral hiatus were classified using these landmarks. Also, location of the apex of sacral hiatus, diameter of the sacral canal at the apex of sacral hiatus, and the distance between bilateral cornua were measured. Two orthopedic surgeons performed measurements independently. ResultsFourty-two percent of the cases have both hiatus and cornu. Four percent of the cases showed the absent hiatus. The apex of sacral hiatus existed at the level of S4 vertebrae in 64% of the cases. The average diameter of the sacral canal was 6.0 ± 1.9 mm. The average distance of bilateral sacral cornua was 10.2 ± 0.35 mm. There were closed hiatus in 3% of cases. ConclusionsThe sacral hiatus has anatomic variations. Understanding of these variations may improve the reliability of CEB.
Drowsiness and Poor Feeding in a Breast-Fed Infant: Association with Nefazodone and its Metabolites

OBJECTIVE: To investigate whether adverse effects in a premature neonate could be attributed to nefazodone exposure via breast milk. CASE SUMMARY: The breast-fed white infant (female, 2.1 kg, 36 weeks corrected gestational age) of a 35-year-old woman (60 kg) taking nefazodone 300 mg/d was admitted to the hospital because she was drowsy, lethargic, unable to maintain normal body temperature, and was feeding poorly. A diagnosis of exposure to nefazodone via breast milk was considered only after other more likely diagnoses had been excluded. After breast feeding was discontinued, the infant's symptoms resolved slowly over a period of 72 hours. The maternal plasma and milk concentration—time profiles for nefazodone and its metabolites, triazoledione, HO-nefazodone, and m-chlorphenylpiperazine, were quantified by HPLC. The calculated infant dose for nefazodone and its active metabolites (as nefazodone equivalents) via the milk was only 0.45% of the weight-adjusted maternal nefazodone daily dose. DISCUSSION: Our data suggest a putative association between maternal nefazodone ingestion and adverse effects in a premature breast-fed neonate. The measured amount of drug exposure would normally be considered safe in a full-term infant. However, there was a temporal relationship between resolution of adverse effects in the infant and cessation of breastfeeding. CONCLUSIONS: This case highlights the importance of individualizing the risk—benefit analysis for exposure to antidepressants in breast milk, especially when dealing with premature neonates.
Single-stage soft-switching PFC converter based on DCVM buck and flyback converters

Single stage PFC converters have interesting characteristics of simple topology and control circuit, low number of active and passive elements and low cost. These kinds of PFC converters have disadvantages such as high voltage stress, especially in the light load and heavier loss comparing with a typical DC-DC converter. These characteristics seriously limit their practical applications. In this paper a new single-stage soft switching PFC converter is presented. The most important advantage of the proposed topology is that the voltage across the bulk capacitor is low even at the light loads and the input current is continuous. The proposed topology is derived from a DCVM buck converter integrated with a flyback converter. Also an active clamp is added to the proposed converter to achieve soft switching, reducing losses and recycling energy trapped in the leakage inductance of flyback transformer. This structure significantly improves the justification of topology for practical applications. The presented simulation results of the proposed converter justify the theoretical analysis.
Dynamical delocalization in one-dimensional disordered systems with oscillatory perturbation.

The effect of dynamical perturbation on the quantum localization phenomenon in a one-dimensional disordered quantum system (1DDS) is investigated systematically by a numerical method. The dynamical perturbation is modeled by an oscillatory driving force containing M independent (mutually incommensurate) frequency components. For M>or=2 a diffusive behavior emerges and in the presence of the finite localization length of the asymptotic wave packet can no longer be detected numerically. The diffusive motion obeys a subdiffusion law characterized by the exponent alpha as xi(t)(2) proportional t(alpha), where xi(t)(2) is the mean square displacement of the wave packet at time t. With an increase in M and/or the perturbation strength, the exponent alpha rapidly approaches 1, which corresponds to normal diffusion. Moreover, the space-time (x-t) dependence of the distribution function P(x,t) is reduced to a scaled form decided by alpha and another exponent beta such that P(x,t) approximately exp(-constx(x/t(alpha/2))(beta)), which contains the two extreme limits, i.e., the localization limit (alpha=0, beta=1) and the normal-diffusion limit (alpha=1, beta=2) in a unified manner. Some 1DDSs driven by the oscillatory perturbation in different ways are examined and compared.
Hepatitis C Virus NS2 Protein Serves as a Scaffold for Virus Assembly by Interacting with both Structural and Nonstructural Proteins

ABSTRACT Many aspects of the assembly of hepatitis C virus (HCV) remain incompletely understood. To characterize the role of NS2 in the production of infectious virus, we determined NS2 interaction partners among other HCV proteins during productive infection. Pulldown assays showed that NS2 forms complexes with both structural and nonstructural proteins, including E1, E2, p7, NS3, and NS5A. Confocal microscopy also demonstrated that NS2 colocalizes with E1, E2, and NS5A in dot-like structures near lipid droplets. However, NS5A did not coprecipitate with E2 and interacted only weakly with NS3 in pulldown assays. Also, there was no demonstrable interaction between p7 and E2 or NS3 in such assays. Therefore, NS2 is uniquely capable of interacting with both structural and nonstructural proteins. Among mutations in p7, NS2, and NS3 that prevent production of infectious virus, only p7 mutations significantly reduced NS2-mediated protein interactions. These p7 mutations altered the intracellular distribution of NS2 and E2 and appeared to modulate the membrane topology of the C-terminal domain of NS2. These results suggest that NS2 acts to coordinate virus assembly by mediating interactions between envelope proteins and NS3 and NS5A within replication complexes adjacent to lipid droplets, where virus particle assembly is thought to occur. p7 may play an accessory role by regulating NS2 membrane topology, which is important for NS2-mediated protein interactions and therefore NS2 function.
A genetically encoded, high-signal-to-noise maltose sensor

We describe the generation of a family of high‐signal‐to‐noise single‐wavelength genetically encoded indicators for maltose. This was achieved by insertion of circularly permuted fluorescent proteins into a bacterial periplasmic binding protein (PBP), Escherichia coli maltodextrin‐binding protein, resulting in a four‐color family of maltose indicators. The sensors were iteratively optimized to have sufficient brightness and maltose‐dependent fluorescence increases for imaging, under both one‐ and two‐photon illumination. We demonstrate that maltose affinity of the sensors can be tuned in a fashion largely independent of the fluorescent readout mechanism. Using literature mutations, the binding specificity could be altered to moderate sucrose preference, but with a significant loss of affinity. We use the soluble sensors in individual E. coli bacteria to observe rapid maltose transport across the plasma membrane, and membrane fusion versions of the sensors on mammalian cells to visualize the addition of maltose to extracellular media. The PBP superfamily includes scaffolds specific for a number of analytes whose visualization would be critical to the reverse engineering of complex systems such as neural networks, biosynthetic pathways, and signal transduction cascades. We expect the methodology outlined here to be useful in the development of indicators for many such analytes. Proteins 2011; 79:3025–3036. © 2011 Wiley‐Liss, Inc.
Fast and fuel efficient? Optimal use of wind by flying albatrosses

The influence of wind patterns on behaviour and effort of free–ranging male wandering albatrosses (Diomedea exulans) was studied with miniaturized external heart–rate recorders in conjunction with satellite transmitters and activity recorders. Heart rate was used as an instantaneous index of energy expenditure. When cruising with favourable tail or side winds, wandering albatrosses can achieve high flight speeds while expending little more energy than birds resting on land. In contrast, heart rate increases concomitantly with increasing head winds, and flight speeds decrease. Our results show that effort is greatest when albatrosses take off from or land on the water. On a larger scale, we show that in order for birds to have the highest probability of experiencing favourable winds, wandering albatrosses use predictable weather systems to engage in a stereotypical flight pattern of large looping tracks. When heading north, albatrosses fly in anticlockwise loops, and to the south, movements are in a clockwise direction. Thus, the capacity to integrate instantaneous eco–physiological measures with records of largescale flight and wind patterns allows us to understand better the complex interplay between the evolution of morphological, physiological and behavioural adaptations of albatrosses in the windiest place on earth.
Transmission of hepatitis C virus between spouses: the important role of exposure duration.

OBJECTIVES Although interspousal transmission of hepatitis C virus (HCV) has been studied, the factors responsible for it remain unclear. METHODS To investigate the transmission of HCV between spouses and the related risk factors, 100 anti-HCV-positive index patients and their spouses were studied. RESULTS Overall, anti-HCV was detected in 17 (17%) spouses, 15 of whom were also positive for HCV RNA, and 11 couples were infected with the same genotype. The anti-HCV-positive rate was higher in spouses married longer than 20 yr compared with those married less than 20 yr (22 vs 6%, p < 0.05), and the infection was correlated with the duration of their actual exposure to the index patients but not with serum HCV titers. The infected couples had more frequent sexual contacts and more commonly shared tooth-brushes than those with uninfected spouses. CONCLUSION Spouses of patients with chronic hepatitis C have a higher risk of acquiring HCV that increases with longer marriage and duration of exposure, and they should be educated about how to avoid contracting HCV infection from their spouses.