Abstract
For further sensitivity improvement in the KOTO experiment, we studied the origin and mechanism of accidental hits of the VETO counters. A simulation study shows that a half of the counts of ...Front-Barrel (FB) VETO counter is stemmed from “delayed photons”, which is produced by the (n,
γ
) reaction due to the thermal neutrons moderated in the KOTO detector. A boron-carbide absorber is a possible candidate to suppress the delayed photons.
Summary
Background
Interleukin (IL)‐31 affects the inflammatory response, is involved in epidermal barrier disruption in atopic dermatitis (AD) and plays a key role in pruritus. Nemolizumab, a ...humanized monoclonal antibody against IL‐31 receptor A, reduced pruritus in patients with AD after a 16‐week administration period.
Objectives
To examine the long‐term effectiveness and safety of nemolizumab in patients aged ≥ 13 years with AD and inadequately controlled moderate‐to‐severe pruritus.
Methods
In two long‐term phase III studies, nemolizumab 60 mg every 4 weeks (Q4W) was administered subcutaneously, concomitantly with topical treatments. Study‐JP01 patients received double‐blind nemolizumab or placebo for 16 weeks, and then entered a 52‐week extension period in which all patients received nemolizumab (nemolizumab/nemolizumab and placebo/nemolizumab groups). Study‐JP02 patients received nemolizumab for 52 weeks. Both studies included an 8‐week follow‐up period.
Results
Study‐JP01 nemolizumab/nemolizumab and placebo/nemolizumab, and Study‐JP02 nemolizumab groups comprised 143, 72 and 88 patients, respectively. In the nemolizumab/nemolizumab group, there were clinically meaningful improvements from the start of treatment to week 68 in the pruritus visual analogue scale (66% decrease) and Eczema Area and Severity Index (78% decrease). Quality of life (QoL) indicators improved after the first nemolizumab dose; improvements were maintained during the follow‐up period. The long‐term safety profile was consistent with previous studies, with no unexpected late‐onset adverse events.
Conclusions
Nemolizumab 60 mg Q4W with concomitant topical treatments in patients with AD and inadequately controlled moderate‐to‐severe pruritus produced a continuous improvement in pruritus, signs of AD, and QoL for up to 68 weeks, with a favourable safety profile.
What is already known about this topic?
Pruritus, a characteristic symptom of atopic dermatitis (AD), causes distress to patients, reducing quality of life and affecting sleep and daily activities.
Nemolizumab (plus topical agents) has previously been shown to reduce pruritus associated with AD to a greater extent than placebo over 16 weeks.
As patients with AD suffer from repeated phases of relapse and remission, it is important to extend the periods of relief from pruritus and rash.
What does this study add?
Data from two long‐term (≥ 52 weeks) phase III studies confirmed that nemolizumab plus topical agents increased or maintained effectiveness through the study duration, with continuous improvement after week 16.
Acute itchiness or flare of AD were rarely observed during the 8‐week follow‐up period.
The results support the long‐term use of nemolizumab with concomitant topical agents in patients with AD and inadequately controlled moderate‐to‐severe pruritus.
Linked Comment: S. Barbarot. Br J Dermatol 2022; 186:608.
Plain language summary available online
Functional microRNAs (miRNAs) in exosomes have been recognised as potential stable biomarkers in cancers. The aim of this study is to identify specific miRNAs in exosome as serum biomarkers for the ...early detection of recurrence in human colorectal cancer (CRC).
Serum samples were sequentially obtained from six patients with and without recurrent CRC. The miRNAs were purified from exosomes, and miRNA microarray analysis was performed. The miRNA expression profiles and copy number aberrations were explored using microarray and array CGH analyses in 124 CRC tissues. Then, we validated exosomal miRNAs in 2 serum sample sets (90 and 209 CRC patients) by quantitative real-time RT-PCR.
Exosomal miR-17-92a cluster expression level in serum was correlated with the recurrence of CRC. Exosomal miR-19a expression levels in serum were significantly increased in patients with CRC as compared with healthy individuals with gene amplification. The CRC patients with high exosomal miR-19a expression showed poorer prognoses than the low expression group (P<0.001).
Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients.
We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. ...PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.
We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT-PCR.
CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-β signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients.
PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.
Abstract
The characterization and modeling of polarized foregrounds has become a critical issue in the quest for primordial
B
-modes. A typical method to proceed is to factorize and parametrize the ...spectral properties of foregrounds and their scale dependence (i.e. assuming that foreground spectra are well described everywhere by their sky average). Since in reality foreground properties vary across the Galaxy, this assumption leads to inaccuracies in the model that manifest themselves as biases in the final cosmological parameters (in this case the tensor-to-scalar ratio
r
). This is particularly relevant for surveys over large fractions of the sky, such as the Simons Observatory (SO), where the spectra should be modeled over a distribution of parameter values. Here we propose a method based on the existing “moment expansion” approach to address this issue in a power-spectrum-based analysis that is directly applicable in ground-based multi-frequency data. Additionally, the method uses only a small set of parameters with simple physical interpretation, minimizing the impact of foreground uncertainties on the final
B
-mode constraints. We validate the method using SO-like simulated observations, recovering an unbiased estimate of the tensor-to-scalar ratio
r
with standard deviation σ(
r
) ≃ 0.003, compatible with official forecasts. When applying the method to the public BICEP2/
Keck
data, we find an upper bound
r
< 0.06 (95% C.L.), compatible with the result found by BICEP2/
Keck
when parametrizing spectral index variations through a scale-independent frequency decorrelation parameter. We also discuss the formal similarities between the power spectrum-based moment expansion and methods used in the analysis of CMB lensing.
Predictive biomarkers for the recurrence of hepatocellular carcinoma (HCC) have great benefit in the selection of treatment options, including liver transplantation (LT), for HCC. The purpose of this ...study was to identify specific microRNAs (miRs) in exosomes from the serum of patients with recurrent HCC and to validate these molecules as novel biomarkers for HCC recurrence.
We employed microarray-based expression profiling of miRs derived from exosomes in the serum of HCC patients to identify a biomarker that distinguishes between patients with and without HCC recurrence after LT. This was followed by the validation in a separate cohort of 59 HCC patients who underwent living related LT. The functions and potential gene targets of the recurrence-specific miRs were analysed using a database, clinical samples and HCC cell lines.
We found that miR-718 showed significantly different expression in the serum exosomes of HCC cases with recurrence after LT compared with those without recurrence. Decreased expression of miR-718 was associated with HCC tumour aggressiveness in the validated cohort series. We identified HOXB8 as a potential target gene of miR-718, and its upregulation was associated with poor prognosis.
Circulating miRs in serum exosomes have potential as novel biomarkers for predicting HCC recurrence.
The neutron escape probability from a rectangular cell is investigated for the collision probability method. Since the numerical calculation of the escape probability requires multiple integrations, ...resulting in a long computing time, semianalytical approximation of the multiple integrations is proposed to reduce the computing time. By approximating the result of integration in the z-direction by a polynomial expression divided into ranges, it is possible to perform the integrations in the x- and y-directions analytically. The computing time of the present semianalytical approximation is reduced by one to two orders of magnitude compared with that required for the conventional numerical integration. Moreover, a lookup escape probability table for rectangular cells calculated using the semianalytical approximation enables the calculation of the escape probability for an arbitrary rectangle with a much shorter computing time and practical precision (<0.1% error). In addition, a method of applying the semianalytical approximation and a lookup table to the collision probability calculation for an x-y geometry is discussed.
•Reduction of PMMoV and human enteric viruses in four full-scale DWTPs was evaluated.•The developed virus concentration method achieved high recovery (>30%) of PMMoV.•CS–RSF and C–MF reduced PMMoV by ...about 1–3-log10.•Low coagulant dosage led to low reduction ratios (1-log10) of PMMoV in C–MF.•Reduction ratios of EVs and HuNoV GII were higher than those of PMMoV in CS–RSF.
Here, we evaluated the reduction efficiencies of indigenous pepper mild mottle virus (PMMoV, a potential surrogate for human enteric viruses to assess virus removal by coagulation-sedimentation–rapid sand filtration CS–RSF and coagulation–microfiltration C–MF) and representative human enteric viruses in four full-scale drinking water treatment plants that use CS–RSF (Plants A and B) or C–MF (Plants C and D). First, we developed a virus concentration method by using an electropositive filter and a tangential-flow ultrafiltration membrane to effectively concentrate and recover PMMoV from large volumes of water: the recovery rates of PMMoV were 100% when 100-L samples of PMMoV-spiked dechlorinated tap water were concentrated to 20 mL; even when spiked water volume was 2000 L, recovery rates of >30% were maintained. The concentrations of indigenous PMMoV in raw and treated water samples determined by using this method were always above the quantification limit of the real-time polymerase chain reaction assay. We therefore were able to determine its reduction ratios: 0.9–2.7-log10 in full-scale CS–RSF and 0.7–2.9-log10 in full-scale C–MF. The PMMoV reduction ratios in C–MF at Plant C (1.0 ± 0.3-log10) were lower than those in CS–RSF at Plants A (1.7 ± 0.5-log10) and B (1.4 ± 0.7-log10), despite the higher ability of MF for particle separation in comparison with RSF owing to the small pore size in MF. Lab-scale virus-spiking C–MF experiments that mimicked full-scale C–MF revealed that a low dosage of coagulant (polyaluminum chloride PACl) applied in C–MF, which is determined mainly from the viewpoint of preventing membrane fouling, probably led to the low reduction ratios of PMMoV in C–MF. This implies that high virus reduction ratios (>4-log10) achieved in previous lab-scale virus-spiking C–MF studies are not necessarily achieved in full-scale C–MF. The PMMoV reduction ratios in C–MF at Plant D (2.2 ± 0.6-log10) were higher than those at Plant C, despite similar coagulant dosages. In lab-scale C–MF, the PMMoV reduction ratios increased from 1-log10 (with PACl basicity 1.5, as at Plant C) to 2–4-log10 (with high-basicity PACl basicity 2.1, as at Plant D), suggesting that the use of high-basicity PACl probably resulted in higher reduction ratios of PMMoV at Plant D than at Plant C. Finally, we compared the reduction ratios of indigenous PMMoV and representative human enteric viruses in full-scale CS–RSF and C–MF. At Plant D, the concentrations of human norovirus genogroup II (HuNoV GII) in raw water were sometimes above the quantification limit; however, whether its reduction ratios in C–MF were higher than those of PMMoV could not be judged since reduction ratios were >1.4-log10 for HuNoV GII and 2.3–2.9-log10 for PMMoV. At Plant B, the concentrations of enteroviruses (EVs) and HuNoV GII in raw water were above the quantification limit on one occasion, and the reduction ratios of EVs (>1.2-log10) and HuNoV GII (>1.5-log10) in CS–RSF were higher than that of PMMoV (0.9-log10). This finding supports the usefulness of PMMoV as a potential surrogate for human enteric viruses to assess virus removal by CS–RSF.
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Current and future Cosmic Microwave Background (CMB) Radiation experiments are targeting the polarized B-mode signal. The small amplitude of this signal makes a successful measurement challenging for ...current technologies. Therefore, very accurate studies to mitigate and control possible systematic effects are vital to achieve a successful observation. An additional challenge is coming from the presence of polarized Galactic foreground signals that contaminate the CMB signal. When they are combined, the foreground signals dominate the polarized CMB signal at almost every relevant frequency. Future experiments, like the LiteBIRD space-borne mission, aim at measuring the CMB B-mode signal with high accuracy to measure the tensor-to-scalar ratio r at the 10−3 level. We present a method to study the photometric calibration requirement needed to minimize the leakage of polarized Galactic foreground signals into CMB polarization maps for a multi-frequency CMB experiment. We applied this method to the LiteBIRD case, and we found precision requirements for the photometric calibration in the range ∼10−4–2.5×10−3 depending on the frequency band. Under the assumption that the detectors are uncorrelated, we found requirements per detector in the range ∼0.18×10−2–2.0×10−2. Finally, we relate the calibration requirements to the band-pass resolution to define constraints for a few representative band-pass responses: Δν∼0.2–2 GHz.
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