105 research outputs found

    Liver secretin receptor predicts portoenterostomy outcomes and liver injury in biliary atresia

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    Biliary atresia (BA) is a chronic neonatal cholangiopathy characterized by fibroinflammatory bile duct damage. Reliable biomarkers for predicting native liver survival (NLS) following portoenterostomy (PE) surgery are lacking. Herein we explore the utility of 22 preidentified profibrotic molecules closely connected to ductular reaction (DR) and prevailing after successful PE (SPE), in predicting PE outcomes and liver injury. We used qPCR and immunohistochemistry in a BA cohort including liver samples obtained at PE (n = 53) and during postoperative follow-up after SPE (n = 25). Of the 13 genes over-expressed in relation to cholestatic age-matched controls at PE, only secretin receptor (SCTR) expression predicted cumulative 5-year NLS and clearance of jaundice. Patients in the highest SCTR expression tertile showed 34–55% lower NLS than other groups at 1–5 years after PE (P = 0.006–0.04 for each year). SCTR expression was also significantly lower [42 (24–63) vs 75 (39–107) fold, P = 0.015] among those who normalized their serum bilirubin after PE. Liver SCTR expression localized in cholangiocytes and correlated positively with liver fibrosis, DR, and transcriptional markers of fibrosis (ACTA2) and cholangiocytes (KRT7, KRT19) both at PE and after SPE. SCTR is a promising prognostic marker for PE outcomes and associates with liver injury in BA

    Enterococcal colonization of infants in a neonatal intensive care unit: associated predictors, risk factors and seasonal patterns

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    <p>Abstract</p> <p>Background</p> <p>During and shortly after birth, newborn infants are colonized with enterococci. This study analyzes predictors for early enterococcal colonization of infants in a neonatal intensive care unit and describes risk factors associated with multidrugresistant enterococci colonization and its seasonal patterns.</p> <p>Methods</p> <p>Over a 12-month period, we performed a prospective epidemiological study in 274 infants admitted to a neonatal intensive care unit. On the first day of life, we compared infants with enterococcal isolates detected in meconium or body cultures to those without. We then tested the association of enterococcal colonization with peripartal predictors/risk factors by using bivariate and multivariate statistical methods.</p> <p>Results</p> <p>Twenty-three percent of the infants were colonized with enterococci. The three most common enterococcal species were <it>E. faecium </it>(48% of isolates), <it>E. casseliflavus </it>(25%) and <it>E. faecalis </it>(13%). Fifty-seven percent of the enterococci found were resistant to three of five antibiotic classes, but no vancomycin-resistant isolates were observed. During winter/spring months, the number of enterococci and multidrug-resistant enterococci were higher than in summer/fall months (p = 0.002 and p < 0.0001, respectively). With respect to enterococcal colonization on the first day of life, predictors were prematurity (p = 0.043) and low birth weight (p = 0.011). With respect to colonization with multidrug-resistant enterococci, risk factors were prematurity (p = 0.0006), low birth weight (p < 0.0001) and prepartal antibiotic treatment (p = 0.019). Using logistic regression, we determined that gestational age was the only parameter significantly correlated with multidrug-resistant enterococci colonization. No infection with enterococci or multidrugresistant enterococci in the infants was detected. The outcome of infants with and without enterococcal colonization was the same with respect to death, necrotizing enterocolitis, intracerebral hemorrhage and bronchopulmonary dysplasia.</p> <p>Conclusion</p> <p>In neonatal intensive care units, an infant's susceptibility to early colonization with enterococci in general, and his or her risk for colonization with multidrug-resistant enterococci in particular, is increased in preterm newborns, especially during the winter/spring months. The prepartal use of antibiotics with no known activity against enterococci appears to increase the risk for colonization with multidrug-resistant enterococci.</p

    Novel composite implant in craniofacial bone reconstruction

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    Bioactive glass (BAG) and polymethyl methacrylate (PMMA) have been used in clinical applications. Antimicrobial BAG has the ability to attach chemically to surrounding bone, but it is not possible to bend, drill or shape BAG during the operation. PMMA has advantages in terms of shaping during the operation, but it does not attach chemically to the bone and is an exothermic material. To increase the usefulness of BAG and PMMA in skull bone defect reconstructions, a new composite implant containing BAG and PMMA in craniofacial reconstructions is presented. Three patients had pre-existing large defects in the calvarial and one in the midface area. An additive manufacturing (AM) model was used preoperatively for treatment planning and custom-made implant production. The trunk of the PMMA implant was coated with BAG granules. Clinical and radiological follow-up was performed postoperatively at 1 week, and 3, 6 and 12 months, and thereafter annually up to 5 years. Computer tomography (CT) and positron emission tomography (PET-CT) were performed at 12 and 24 months postoperatively. Uneventful clinical recovery with good esthetic and functional outcome was seen. CT and PET-CT findings supported good clinical outcome. The BAG–PMMA implant seems to be a promising craniofacial reconstruction alternative. However, more clinical experience is needed

    High cyclin B1 expression is associated with poor survival in breast cancer

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    Cyclin B1 regulates the G2-M transition of the cell cycle. Cyclin B1 expression is higher in premalignant and malignant than normal breast lesions. Correlation of cyclin B1 expression with other histopathological variables and prognostic role in breast cancer are not fully understood. Traditionally used prognostic criteria identify large subset of patients to receive adjuvant chemotherapy and to be exposed to adverse effects. A reliable and simple method helping prognostic evaluation in breast cancer is needed. We analysed cyclin B1 expression on 1348 invasive breast cancers and studied correlations with other histopathological variables and survival. High cyclin B1 correlated with high tumour grade, large tumour size and positive nodal status, oestrogen and progesterone receptor negativity, positive HER2 and p53 status, young age at diagnosis, and high cyclin E, cyclin A and Ki67 expression. Among patients not given adjuvant chemotherapy high cyclin B1 was a strong predictor of shorter overall and metastasis-free survival (RR 3.74, P<0.0005 and RR 3.51, P<0.0005, respectively), and remained as an independent prognostic factor also in multivariate analysis (RR 1.80, P=0.04 and RR 2.31, P=0.02, respectively). This study suggests high cyclin B1 associates with aggressive phenotype and is an independent prognostic factor in breast cancer

    Genome-wide association study identifies 48 common genetic variants associated with handedness

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    Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders

    Measurement report: Introduction to the HyICE-2018 campaign for measurements of ice-nucleating particles and instrument inter-comparison in the HyytiÀlÀ boreal forest

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    The formation of ice particles in Earth's atmosphere strongly influences the dynamics and optical properties of clouds and their impacts on the climate system. Ice formation in clouds is often triggered heterogeneously by ice-nucleating particles (INPs) that represent a very low number of particles in the atmosphere. To date, many sources of INPs, such as mineral and soil dust, have been investigated and identified in the low and mid latitudes. Although less is known about the sources of ice nucleation at high latitudes, efforts have been made to identify the sources of INPs in the Arctic and boreal environments. In this study, we investigate the INP emission potential from high-latitude boreal forests in the mixed-phase cloud regime. We introduce the HyICE-2018 measurement campaign conducted in the boreal forest of HyytiÀlÀ, Finland, between February and June 2018. The campaign utilized the infrastructure of the Station for Measuring Ecosystem-Atmosphere Relations (SMEAR) II, with additional INP instruments, including the Portable Ice Nucleation Chamber I and II (PINC and PINCii), the SPectrometer for Ice Nuclei (SPIN), the Portable Ice Nucleation Experiment (PINE), the Ice Nucleation SpEctrometer of the Karlsruhe Institute of Technology (INSEKT) and the Microlitre Nucleation by Immersed Particle Instrument (”L-NIPI), used to quantify the INP concentrations and sources in the boreal environment. In this contribution, we describe the measurement infrastructure and operating procedures during HyICE-2018, and we report results from specific time periods where INP instruments were run in parallel for inter-comparison purposes. Our results show that the suite of instruments deployed during HyICE-2018 reports consistent results and therefore lays the foundation for forthcoming results to be considered holistically. In addition, we compare measured INP concentrations to INP parameterizations, and we observe good agreement with the Tobo et al. (2013) parameterization developed from measurements conducted in a ponderosa pine forest ecosystem in Colorado, USA

    Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

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    A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

    Evidence for Top Quark Production in Nucleus-Nucleus Collisions

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    Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV

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    A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe

    Observation of the B-s(0) -> X(3872)phi Decay

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    Using a data sample of proton-proton collisions at root s = 13 TeV, corresponding to an integrated luminosity of 140 fb(-1) collected by the CMS experiment in 2016-2018, the B-s(0) -> X(3872)phi decay is observed. Decays into J/psi pi(+)pi(-) and K+K- are used to reconstruct, respectively, the X(3872) and phi. The ratio of the product of branching fractions B[B-s(0) -> X(3872)phi]B[X(3872) -> J/psi pi(+)pi(-)] to the product B[B-s(0) ->psi(2S)phi]B[psi(2S) -> J/psi pi(+)pi(-)] is measured to be [2.21 +/- 0.29(stat) +/- 0.17(syst)]%. The ratio B[B-s(0) -> X(3872)phi]/B[B-0 -> X(3872)K-0] is found to be consistent with one, while the ratio B[B-s(0) -> X(3872)phi]/B[B+-> X(3872)K+] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B-0 and B(0)s meson decays compared to B+. The reported observation may shed new light on the nature of the X(3872) particle.Peer reviewe
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