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Institute
Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (~ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.
EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50–69 years taking up the invitation while the probability of false-positive needle biopsy is <1 % per round and overdiagnosis is only 1–10 % for a 20-year screening. Mortality reduction was also observed for the age groups 40–49 years and 70–74 years, although with “limited evidence”. Thus, we firstly recommend biennial screening mammography for average-risk women aged 50–69 years; extension up to 73 or 75 years, biennially, is a second priority, from 40–45 to 49 years, annually, a third priority. Screening with thermography or other optical tools as alternatives to mammography is discouraged. Preference should be given to population screening programmes on a territorial basis, with double reading. Adoption of digital mammography (not film-screen or phosphor-plate computer radiography) is a priority, which also improves sensitivity in dense breasts. Radiologists qualified as screening readers should be involved in programmes. Digital breast tomosynthesis is also set to become “routine mammography” in the screening setting in the next future. Dedicated pathways for high-risk women offering breast MRI according to national or international guidelines and recommendations are encouraged.
Polygenic risk scores, based on risk variants identified in genome-wide-association-studies (GWAS), explain a considerable portion of the heritability for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about the combined effects of these variants, although polygenic neuroimaging has developed into a powerful tool of translational neuroscience. In this study, we used genome wide significant SZ risk variants to test the predictive capacity of the polygenic model and explored potential associations with white matter volume, a key candidate in imaging phenotype for psychotic disorders.
By calculating the combined additive schizophrenia risk of seven SNPs (significant hits from a recent schizophrenia GWAS study), we show that increased additive genetic risk for SZ was associated with reduced white matter volume in a group of participants (n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ patients and BD patients. This effect was also seen in a second independent sample of healthy individuals (n = 89). We suggest that a moderate portion of variance (~4%) of white matter volume can be explained by the seven hits from the recent schizophrenia GWAS.
These results provide evidence for associations between cumulative genetic risk for schizophrenia and intermediate neuroimaging phenotypes in models of psychosis. Our work contributes to a growing body of literature suggesting that polygenic risk may help to explain white matter alterations associated with familial risk for psychosis.
By analyzing 6.32 fb − 1 of e+ e− annihilation data collected at the center-of-mass energies between 4.178 and 4.226 GeV with the BESIII detector, we determine the branching fraction of the leptonic decay D + s → τ + ντ, with τ+ → π + π0¯ντ, to be B D + s → τ + ν τ = (5.29 ± 0.25 stat ± 0.20 syst) %. We estimate the product of the Cabibbo-Kobayashi-Maskawa matrix element |Vcs|and the D + s decay constant f D + s to be f D + s|Vcs| = (244.8 ± 5.8 stat ± 4.8syst) MeV, using the known values of the τ + and D + s masses as well as the D + s lifetime, together with our branching fraction measurement. Combining the value of |Vcs| obtained from a global fit in the standard model and f D + s from lattice quantum chromodynamics, we obtain f D + s = (251.6 ± 5.9 stat ± 4.9syst) MeV and |Vcs| = 0.980 ± 0.023 stat ± 0.019 syst. Using the branching fraction of B D + s → μ + νμ = (5.35±0.21)×10−3, we obtain the ratio of the branching fractions B D + s → τ + ντ/B D +s → μ+νμ = 9.89±0.71, which is consistent with the standard model prediction of lepton flavor universality.
We report a measurement of the observed cross sections of e+ e− → J/ψX based on 3.21 fb − 1 of data accumulated at energies from 3.645 to 3.891 GeV with the BESIII detector operated at the BEPCII collider. In analysis of the cross sections, we measured the decay branching fractions of B(ψ(3686) → J/ψX) = (64.4 ± 0.6 ± 1.6)% and B(ψ(3770) → J/ψX) = (0.5 ± 0.2 ± 0.1)% for the first time. The energy-dependent line shape of these cross sections cannot be well described by two Breit-Wigner (BW) amplitudes of the expected decays ψ (3686) → J/ψX and ψ(3770) → J/ψX. Instead, it can be better described with one more BW amplitude of the decay R(3760)→ J/ψX. Under this assumption, we extracted the R (3760) mass M R (3760 ) = 3766.2 ± 3.8 ± 0.4 MeV/c2, total width Γ tot R ( 3760 ) = 22.2 ± 5.9 ± 1.4 MeV, and product of leptonic width and decay branching fraction
ΓeeR(3760) B[R(3760) → J/ψX] = (79.4 ± 85.5 ± 11.7) eV. The significance of the R(3760) is 5.3σ. The first uncertainties of these measured quantities are from fits to the cross sections and second systematic.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
Acute calculus cholecystitis is a very common disease with several area of uncertainty. The World Society of Emergency Surgery developed extensive guidelines in order to cover grey areas. The diagnostic criteria, the antimicrobial therapy, the evaluation of associated common bile duct stones, the identification of “high risk” patients, the surgical timing, the type of surgery, and the alternatives to surgery are discussed. Moreover the algorithm is proposed: as soon as diagnosis is made and after the evaluation of choledocholitiasis risk, laparoscopic cholecystectomy should be offered to all patients exception of those with high risk of morbidity or mortality. These Guidelines must be considered as an adjunctive tool for decision but they are not substitute of the clinical judgement for the individual patient.
Non-forest ecosystems, dominated by shrubs, grasses and herbaceous plants, provide ecosystem services including carbon sequestration and forage for grazing, and are highly sensitive to climatic changes. Yet these ecosystems are poorly represented in remotely sensed biomass products and are undersampled by in situ monitoring. Current global change threats emphasize the need for new tools to capture biomass change in non-forest ecosystems at appropriate scales. Here we developed and deployed a new protocol for photogrammetric height using unoccupied aerial vehicle (UAV) images to test its capability for delivering standardized measurements of biomass across a globally distributed field experiment. We assessed whether canopy height inferred from UAV photogrammetry allows the prediction of aboveground biomass (AGB) across low-stature plant species by conducting 38 photogrammetric surveys over 741 harvested plots to sample 50 species. We found mean canopy height was strongly predictive of AGB across species, with a median adjusted R2 of 0.87 (ranging from 0.46 to 0.99) and median prediction error from leave-one-out cross-validation of 3.9%. Biomass per-unit-of-height was similar within but different among, plant functional types. We found that photogrammetric reconstructions of canopy height were sensitive to wind speed but not sun elevation during surveys. We demonstrated that our photogrammetric approach produced generalizable measurements across growth forms and environmental settings and yielded accuracies as good as those obtained from in situ approaches. We demonstrate that using a standardized approach for UAV photogrammetry can deliver accurate AGB estimates across a wide range of dynamic and heterogeneous ecosystems. Many academic and land management institutions have the technical capacity to deploy these approaches over extents of 1–10 ha−1. Photogrammetric approaches could provide much-needed information required to calibrate and validate the vegetation models and satellite-derived biomass products that are essential to understand vulnerable and understudied non-forested ecosystems around the globe.