Low‐grade epilepsy‐associated brain tumours (LEAT) are the second most common cause for drug‐resistant, focal epilepsy, that is ganglioglioma (GG) and dysembryoplastic neuroepithelial tumours (DNT). ...However, molecular pathogenesis, risk factors for malignant progression and their frequent association with drug‐resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular‐genetic basis and targeted treatment options in diffuse gliomas. The Neuropathology Task Force of the International League Against Epilepsy examined available literature to identify common obstacles in diagnosis and research of LEAT. Analysis of 10 published tumour series from epilepsy surgery pointed to poor inter‐rater agreement for the histopathology diagnosis. The Task Force tested this hypothesis using a web‐based microscopy agreement study. In a series of 30 LEAT, 25 raters from 18 countries agreed in only 40% of cases. Highest discordance in microscopic diagnosis occurred between GG and DNT variants, when oligodendroglial‐like cell patterns prevail, or ganglion cells were difficult to discriminate from pre‐existing neurons. Suggesting new terminology or major histopathological criteria did not satisfactorily increase the yield of histopathology agreement in four consecutive trials. To this end, the Task Force applied the WHO 2016 strategy of integrating phenotype analysis with molecular‐genetic data obtained from panel sequencing and 450k methylation arrays. This strategy was helpful to distinguish DNT from GG variants in all cases. The Task Force recommends, therefore, to further develop diagnostic panels for the integration of phenotype‐genotype analysis in order to reliably classify the spectrum of LEAT, carefully characterize clinically meaningful entities and make better use of published literature.
Patients with cortical dysplasia (CD) are difficult to treat because the MRI abnormality may be undetectable. This study determined whether fluorodeoxyglucose (FDG)-PET/MRI coregistration enhanced ...the recognition of CD in epilepsy surgery patients.
Patients from 2004-2007 in whom FDG-PET/MRI coregistration was a component of the presurgical evaluation were compared with patients from 2000-2003 without this technique. For the 2004-2007 cohort, neuroimaging and clinical variables were compared between patients with mild Palmini type I and severe Palmini type II CD.
Compared with the 2000-2003 cohort, from 2004-2007 more CD patients were detected, most had type I CD, and fewer cases required intracranial electrodes. From 2004-2007, 85% of type I CD cases had normal non-University of California, Los Angeles (UCLA) MRI scans. UCLA MRI identified CD in 78% of patients, and 37% of type I CD cases had normal UCLA scans. EEG and neuroimaging findings were concordant in 52% of type I CD patients, compared with 89% of type II CD patients. FDG-PET scans were positive in 71% of CD cases, and type I CD patients had less hypometabolism compared with type II CD patients. Postoperative seizure freedom occurred in 82% of patients, without differences between type I and type II CD cases.
Incorporating fluorodeoxyglucose-PET/MRI coregistration into the multimodality presurgical evaluation enhanced the noninvasive identification and successful surgical treatment of patients with cortical dysplasia (CD), especially for the 33% of patients with nonconcordant findings and those with normal MRI scans from mild type I CD.
Abstract Purpose Although stage IV colorectal cancer (CRC) encompasses a wide variety of clinical conditions with diverse prognoses, no statistical model for predicting the postoperative prognosis of ...stage IV CRC has been established. Thus, we here aimed to construct a predictive model for disease-free survival (DFS) and overall survival (OS) after curative surgery for stage IV CRC using nomograms. Methods The study included 1133 stage IV CRC patients who underwent curative surgical resection in 19 institutions. Patients were divided into derivation (n = 586) and validation (n = 547) groups. Nomograms to predict the 1- and 3-year DFS rates and the 3- and 5-year OS rates were constructed using the derivation set. Calibration plots were constructed, and concordance indices (c-indices) were calculated. The predictive utility of the nomogram was validated in the validation set. Results The postoperative carcinoembryonic antigen (CEA) level, depth of tumor invasion (T factor), lymph node metastasis (N factor), and number of metastatic organs were adopted as variables for the DFS-predicting nomogram, whereas the postoperative CEA level, T factor, N factor, and peritoneal dissemination were adopted for the nomogram to predict OS. The nomograms showed moderate calibration, with c-indices of 0.629 and 0.640 in the derivation set and 0.604 and 0.637 in the validation set for DFS and OS, respectively. Conclusions The nomograms developed were capable of estimating the probability of DFS and OS on the basis of only 4 variables, and may represent useful tools for postoperative surveillance of stage IV CRC patients in routine practice.
We present the first measurements of absolute branching fractions of Ξ_{c}^{0} decays into Ξ^{-}π^{+}, ΛK^{-}π^{+}, and pK^{-}K^{-}π^{+} final states. The measurements are made using a dataset ...comprising (772±11)×10^{6} BBover ¯ pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. We first measure the absolute branching fraction for B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0} using a missing-mass technique; the result is B(B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0})=(9.51±2.10±0.88)×10^{-4}. We subsequently measure the product branching fractions B(B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→Ξ^{-}π^{+}), B(B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→ΛK^{-}π^{+}), and B(B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+}) with improved precision. Dividing these product branching fractions by the result for B^{-}→Λover ¯_{c}^{-}Ξ_{c}^{0} yields the following branching fractions: B(Ξ_{c}^{0}→Ξ^{-}π^{+})=(1.80±0.50±0.14)%, B(Ξ_{c}^{0}→ΛK^{-}π^{+})=(1.17±0.37±0.09)%, and B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+})=(0.58±0.23±0.05)%. For the above branching fractions, the first uncertainties are statistical and the second are systematic. Our result for B(Ξ_{c}^{0}→Ξ^{-}π^{+}) can be combined with Ξ_{c}^{0} branching fractions measured relative to Ξ_{c}^{0}→Ξ^{-}π^{+} to yield other absolute Ξ_{c}^{0} branching fractions.
The dark photon A^{'} and the dark Higgs boson h^{'} are hypothetical constituents featured in a number of recently proposed dark sector models. Assuming prompt decays of both dark particles, we ...search for their production in the so-called Higgstrahlung channel e^{+}e^{-}→A^{'}h^{'}, with h^{'}→A^{'}A^{'}. We investigate ten exclusive final states with A^{'}→e^{+}e^{-}, μ^{+}μ^{-}, or π^{+}π^{-} in the mass ranges 0.1 GeV/c^{2} <m_{A^{'}}<3.5 GeV/c^{2} and 0.2 GeV/c^{2} <m_{h^{'}}<10.5 GeV/c^{2}. We also investigate three inclusive final states 2(e^{+}e^{-})X, 2(μ^{+}μ^{-})X, and (e^{+}e^{-})(μ^{+}μ^{-})X, where X denotes a dark photon candidate detected via missing mass, in the mass ranges 1.1 GeV/c^{2} <m_{A^{'}}<3.5 GeV/c^{2} and 2.2 GeV/c^{2} <m_{h^{'}}<10.5 GeV/c^{2}. Using the entire 977 fb^{-1} data set collected by Belle, we observe no significant signal. We obtain individual and combined 90% credibility level upper limits on the branching fraction times the Born cross section, B×σ_{Born}, on the Born cross section σ_{Born}, and on the dark photon coupling to the dark Higgs boson times the kinetic mixing between the standard model photon and the dark photon, α_{D}×ε^{2}. These limits improve upon and cover wider mass ranges than previous experiments. The limits from the final states 3(π^{+}π^{-}) and 2(e^{+}e^{-})X are the first placed by any experiment. For α_{D} equal to 1/137, m_{h^{'}}< 8 GeV/c^{2}, and m_{A^{'}}<1 GeV/c^{2}, we exclude values of the mixing parameter ε above ∼8×10^{-4}.
Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for ...metastatic urothelial carcinoma (UC).
Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences.
The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC.
In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.
Si0.5Ge0.5 crystals were grown at two different temperature gradients on board the International Space Station (ISS) using the traveling liquidus-zone (TLZ) method and effects of temperature gradient ...on crystal quality were investigated. Although average axial Ge concentration profile was not affected by the temperature gradient, crystal quality was affected greatly. Single crystal length was shortened and constitutional supercooling (CS) is shown to occur more easily at higher temperature gradient. The calculated degree of CS based on the solute concentration profile in the melt and phase diagram data is about 4 times larger when the temperature gradient is twice, which supports the experimental results. Instability at high temperature gradient is unique to the TLZ method and is not common to other crystal growth methods such as the directional solidification method and Czochralski method.
•Homogeneous Si0.5Ge0.5 crystal growth in microgravity.•Effects of temperature gradient on crystal quality.•Constitutional supercooling unique to the TLZ growth.•Critical degree of constitutional supercooling.
Background Cognitive impairment is difficult to improve after shunt operation in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to identify cerebrospinal fluid (CSF) ...biomarkers predictive of improvement in cognitive function. Methods This study was conducted between January 2008 and December 2010 on consecutive, unselected admissions to our program for the treatment of patients with clinically suspected iNPH. Lumbar CSF concentrations of total tau (Tau), tau phosphorylated at threonine 181 (p-tau), soluble amyloid precursor protein (sAPP), sAPPalpha, sAPPbeta, and beta-amyloid1-42 (Abeta42) were analyzed by ELISA. Results Concentrations of p-tau, sAPP, sAPPalpha, and sAPPbeta were strong diagnostic biomarkers for distinguishing between iNPH and Alzheimer's disease (AD). sAPPalpha exhibited the highest accuracy in differentiating iNPH from patients with AD and normal controls, with an area under the curve value of 0.994. We examined the prognostic value of p-tau and sAPPalpha for cognition function after surgery. With a cutoff value of 198 ng/ml or less for sAPPalpha, sensitivity and specificity are 66.7% and 82.9%, respectively, whilst the Mini-Mental State Examination score at 6 months after surgery is expected to be 25 or more. Conclusion Our results show that sAPPalpha is a suitable biomarker for the diagnosis and prognosis of iNPH. PUBLICATION ABSTRACT
Background
Cognitive impairment is difficult to improve after shunt operation in patients with idiopathic normal pressure hydrocephalus (iNPH). This study aims to identify cerebrospinal fluid (CSF) ...biomarkers predictive of improvement in cognitive function.
Methods
This study was conducted between January 2008 and December 2010 on consecutive, unselected admissions to our program for the treatment of patients with clinically suspected iNPH. Lumbar CSF concentrations of total tau (Tau), tau phosphorylated at threonine 181 (p‐tau), soluble amyloid precursor protein (sAPP), sAPPα, sAPPβ, and β‐amyloid1‐42 (Aβ42) were analyzed by ELISA.
Results
Concentrations of p‐tau, sAPP, sAPPα, and sAPPβ were strong diagnostic biomarkers for distinguishing between iNPH and Alzheimer's disease (AD). sAPPα exhibited the highest accuracy in differentiating iNPH from patients with AD and normal controls, with an area under the curve value of 0.994. We examined the prognostic value of p‐tau and sAPPα for cognition function after surgery. With a cutoff value of 198 ng/ml or less for sAPPα, sensitivity and specificity are 66.7% and 82.9%, respectively, whilst the Mini‐Mental State Examination score at 6 months after surgery is expected to be 25 or more.
Conclusion
Our results show that sAPPα is a suitable biomarker for the diagnosis and prognosis of iNPH.
Summary
Reasons for performing study
Although satellite cells are well known as muscle stem cells capable of adding myonuclei during muscle repair and hypertrophy, the response of satellite cells in ...horse muscles to a run to exhaustion is still unknown.
Objectives
To investigate the time course of satellite cell activation in Thoroughbred horse muscle after running to exhaustion. We hypothesised that this type of intense exercise would induce satellite cell activation in skeletal muscle similar to a resistance exercise.
Methods
Nine de‐trained Thoroughbred horses (6 geldings and 3 mares) aged 3–6 years were studied. Biopsy samples were taken from the gluteus medius muscle of the horses before and 1 min, 3 h, 1 day, 3 days, 1 week and 2 weeks after a treadmill run to exhaustion. The numbers of satellite cells for each fibre type were determined by using immunofluorescence staining. Total RNA was extracted from these samples, and the expressions of interleukin (IL)‐6, paired box transcriptional factor (Pax) 7, myogenic differentiation 1 (MyoD), myogenin, proliferating cell nuclear antigen (PCNA), insulin‐like growth factor (IGF)‐I and hepatocyte growth factor (HGF) mRNA were analysed using real‐time reverse transcription‐PCR.
Results
The numbers of satellite cells were significantly increased in type I and IIa fibres at 1 week and in type IIa/x fibre at 2 weeks post exercise. The expression of IL‐6 mRNA increased significantly by 3 h post exercise. The expression of PCNA mRNA also increased by 1 day after running, indicating that running can initiate satellite cell proliferation. The expression of Pax7, MyoD, myogenin, IGF‐I and HGF mRNA peaked at 1 week post exercise.
Conclusion
Satellite cell activation and proliferation could be enhanced after a run to exhaustion without detectable injury as assessed by the histochemical analysis. Understanding the response of satellite cell activation to running exercise provides fundamental information about the skeletal muscle adaptation in Thoroughbred horses.
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