1,198 research outputs found
Brain tumour diagnostics using a DNA methylation-based classifier as a diagnostic support tool
Aims: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. Methods: About 502 CNS tumour samples were analysed using (850 k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. Results: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score ≥0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect, the MP result predicted the right diagnosis for three of these cases. In six cases, the suggested class was interpreted as ‘discrepant but noncontributory’. The remaining 33.7% of cases (169/502) had a calibrated score <0.9, including 7.8% (39/502) for which no class indication was given at all (calibrated score <0.3). Conclusions: MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information
Clear cell chondrosarcoma in Von Hippel-Lindau disease
A diagnosis of clear cell chondrosarcoma of the ulna was made in a patient with Von Hippel-Lindau disease (VHL). After surgery, genetic analysis of the tumor tissue showed loss of heterozygosity at the VHL gene locus. Immunohistochemical analysis confirmed loss of expression of the VHL protein in the tumor cells. In addition, abundant Cyclin D1 expression in the tumor was observed. Chondrosarcoma has been described before in a VHL patient and VHL protein expression has been correlated to tumor grade in a series of sporadic chondrosarcomas. In this report, we show that clear cell chondrosarcoma may be a rare but canonical VHL manifestation through a cell-autonomous mechanism involving somatic loss-of-heterozygosity of the VHL tumor suppressor gene. We discuss the relevance of this observation with regard to the pathogenesis of clear cell chondrosarcoma in the context of VHL
Longitudinal characteristics of T2-FLAIR mismatch in IDH-mutant astrocytomas: Relation to grade, histopathology, and overall survival in the GLASS-NL cohort.
BACKGROUND: The T2-FLAIR mismatch sign is defined by signal loss of the T2-weighted hyperintense area with Fluid-Attenuated Inversion Recovery (FLAIR) on magnetic resonance imaging, causing a hypointense region on FLAIR. It is a highly specific diagnostic marker for IDH-mutant astrocytoma and is postulated to be caused by intercellular microcystic change in the tumor tissue. However, not all IDH-mutant astrocytomas show this mismatch sign and some show the phenomenon in only part of the lesion. The aim of the study is to determine whether the T2-FLAIR mismatch phenomenon has any prognostic value beyond initial noninvasive molecular diagnosis.
METHODS: Patients initially diagnosed with histologically lower-grade (2 or 3) IDH-mutant astrocytoma and with at least 2 surgical resections were included in the GLASS-NL cohort. T2-FLAIR mismatch was determined, and the growth pattern of the recurrent tumor immediately before the second resection was annotated as invasive or expansive. The relation between the T2-FLAIR mismatch sign and tumor grade, microcystic change, overall survival (OS), and other clinical parameters was investigated both at first and second resection.
RESULTS: The T2-FLAIR mismatch sign was significantly related to Grade 2 (80% vs 51%), longer post-resection median OS (8.3 vs 5.2 years), expansive growth, and lower age at second resection. At first resection, no relation was found between the mismatch sign and OS. Microcystic change was associated with areas of T2-FLAIR mismatch.
CONCLUSIONS: T2-FLAIR mismatch in IDH-mutant astrocytomas is correlated with microcystic change in the tumor tissue, favorable prognosis, and Grade 2 tumors at the time of second resection
LKB1 as the ghostwriter of crypt history
Familial cancer syndromes present rare insights into malignant tumor development. The molecular background of polyp formation and the cancer prone state in Peutz-Jeghers syndrome remain enigmatic to this day. Previously, we proposed that Peutz-Jeghers polyps are not pre-malignant lesions, but an epiphenomenon to the malignant condition. However, Peutz-Jeghers polyp formation and the cancer-prone state must both be accounted for by the same molecular mechanism. Our contribution focuses on the histopathology of the characteristic Peutz-Jeghers polyp and recent research on stem cell dynamics and how these concepts relate to Peutz-Jeghers polyposis. We discuss a protracted clonal evolution scenario in Peutz-Jeghers syndrome due to a germline LKB1 mutation. Peutz-Jeghers polyp formation and malignant transformation are separately mediated through the same molecular mechanism played out on different timescales. Thus, a single mechanism accounts for the development of benign Peutz-Jeghers polyps and for malignant transformation in Peutz-Jeghers syndrome
Explanations for the Lower Rates of Diabetic Neuropathy in Indian Asians Versus Europeans
OBJECTIVE - Risks of diabetes and cardiovascular disease are elevated worldwide in Indian Asians. However, risks of other diabetes-related complications, i.e., foot ulceration and amputation, also with a vascular basis, are substantially lower in Asians than in white Europeans in the U.K., possibly due to less neuropathy. We therefore compared signs, symptoms, and objective quantitative measures of diabetic neuropathy and their risk factors in Indian Asians and Europeans. RESEARCH DESIGN AND METHODS - This was a cross-sectional study of a population-based sample of age- and sex-matched adults with type 2 diabetes of European (95 male and 85 female) and Asian (96 male and 84 female) descent in the U.K. Patients were assessed for neuropathic symptoms, signs, nerve conduction, autonomic function, and quantitative sensory testing. Peripheral vascular function and other potential risk factors for neuropathy were measured. RESULTS - Mean nerve conduction velocity Z scores were better in Asians (mean ± SD 0.07 ± 0.62) than in Europeans (-0.11 ± 0.60; P = 0.007) and were explained by the shorter height, fewer pack-years smoked, and higher transcutaneous oxygen levels (TCpO2) in Indian Asians (P value for ethnic comparison attenuated to 0.2). Small fiber neuropathy was less prevalent in Indian Asians compared with Europeans (odds ratio 0.58 [95% CI 0.37-0.93]; P = 0.02) and was primarily accounted for by better TCpO2 (0.70 [0.40-1.21]; P = 0.2). CONCLUSIONS - Asians with diabetes have substantially less large and small fiber neuropathy than Europeans, despite comparable traditional risk factors. Independent from smoking, the lower risk of neuropathy in Asians is due to better skin microvascularization and may help explain the substantially reduced Asian foot ulcer risk. © 2010 by the American Diabetes Association
Study of
We present an analysis of the decay based
on data collected by the BESIII experiment at the resonance. Using
a nearly background-free sample of 18262 events, we measure the branching
fraction . For GeV/ the partial branching fraction is
. A partial wave analysis shows that the dominant
component is accompanied by an \emph{S}-wave contribution accounting for
of the total rate and that other components are
negligible. The parameters of the resonance and of the
form factors based on the spectroscopic pole dominance predictions are also
measured. We also present a measurement of the helicity
basis form factors in a model-independent way.Comment: 17 pages, 6 figure
Measurement of azimuthal asymmetries in inclusive charged dipion production in annihilations at = 3.65 GeV
We present a measurement of the azimuthal asymmetries of two charged pions in
the inclusive process based on a data set of 62
at the center-of-mass energy GeV collected with
the BESIII detector. These asymmetries can be attributed to the Collins
fragmentation function. We observe a nonzero asymmetry, which increases with
increasing pion momentum. As our energy scale is close to that of the existing
semi-inclusive deep inelastic scattering experimental data, the measured
asymmetries are important inputs for the global analysis of extracting the
quark transversity distribution inside the nucleon and are valuable to explore
the energy evolution of the spin-dependent fragmentation function.Comment: 7 pages, 5 figure
Study of and and
We study the decays of and to the final states
and based on a single
baryon tag method using data samples of
and events collected with
the BESIII detector at the BEPCII collider. The decays to
are observed for the first time. The
measured branching fractions of and
are in good agreement with, and much
more precise, than the previously published results. The angular parameters for
these decays are also measured for the first time. The measured angular decay
parameter for , , is found to be negative, different to the other
decay processes in this measurement. In addition, the "12\% rule" and isospin
symmetry in the and and
systems are tested.Comment: 11 pages, 7 figures. This version is consistent with paper published
in Phys.Lett. B770 (2017) 217-22
Measurement of the proton form factor by studying
Using data samples collected with the BESIII detector at the BEPCII collider,
we measure the Born cross section of at 12
center-of-mass energies from 2232.4 to 3671.0 MeV. The corresponding effective
electromagnetic form factor of the proton is deduced under the assumption that
the electric and magnetic form factors are equal . In
addition, the ratio of electric to magnetic form factors, , and
are extracted by fitting the polar angle distribution of the proton
for the data samples with larger statistics, namely at 2232.4 and
2400.0 MeV and a combined sample at = 3050.0, 3060.0 and 3080.0 MeV,
respectively. The measured cross sections are in agreement with recent results
from BaBar, improving the overall uncertainty by about 30\%. The
ratios are close to unity and consistent with BaBar results in
the same region, which indicates the data are consistent with the
assumption that within uncertainties.Comment: 13 pages, 24 figure
Confirmation of a charged charmoniumlike state in with double tag
We present a study of the process
using data samples of 1092~pb at ~GeV and 826~pb
at ~GeV collected with the BESIII detector at the BEPCII storage
ring. With full reconstruction of the meson pair and the bachelor
in the final state, we confirm the existence of the charged
structure in the system in the two
isospin processes and . By
performing a simultaneous fit, the statistical significance of
signal is determined to be greater than 10, and its pole mass and width
are measured to be
=(3881.71.6(stat.)1.6(syst.))~MeV/ and
=(26.62.0(stat.)2.1(syst.))~MeV, respectively.
The Born cross section times the branching fraction
() is measured to be
at
~GeV and
at
~GeV. The polar angular distribution of the
- system is consistent with the expectation of a
quantum number assignment of for
- …