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2025
Abstract
The eigen-mode structure and distribution associated with the global dispersion are studied based on linear gyro-kinetic simulations in a global toroidal geometry using parameters and profiles modeled for JT-60U-like discharges with a strongly reversed magnetic shear configuration, which exhibit L-mode characteristics subject to a strong profile constraint. By incorporating the mode mismatch parameter ∆μ, related to the parallel wave number k_∥ (≡Δμ⁄R_0 ), and also the slab-to-toroidal ratio parameter X(≡(k_∥ R_0)⁄(k_θ ρ_i )), we identified two qualitatively distinct unstable branches. One is the density gradient driven trapped electron modes (∇n-TEMs) influenced by the ion temperature gradient with lower toroidal mode numbers n, while transited to weak toroidal-like ion temperature gradient modes (ITG modes) as n increases, in the inner negative magnetic shear region (s ̂<0). The other is the slab-like ITG modes with higher-n in the outer minimum safety factor region (q~q_min). These dynamics result in the separate radial location of the density and ion/electron temperature gradients, i.e. the former is inner region while the latter is outer region. These two branches are weakly connected through the boundary region inside the q_min surface, which leads to a discontinuity in the quasi-linear flux. Each branch is found to show approximately the similar level of peak growth rate in inner and outer regions, indicating that the constrained profiles are expected to be established such that linearly unstable free energy sources are globally balanced so as to maintain such profile in a quasi-steady state with a self-organized manner without causing unbalanced transport.- Book : ()
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2025
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2025
- Book : ()
- Pub. Date : 2025
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2025
Breast reconstruction after mastectomy improves the quality of life for many patients with breast cancer. There is uncertainty regarding eligibility criteria for reconstruction, timing (immediate or delayed—with or without radiotherapy), outcomes of nipple-sparing compared to skin-sparing mastectomy, selection criteria and surgical factors influencing outcomes of nipple-sparing mastectomy, prepectoral versus subpectoral implants, use of acellular dermal matrix, and use of autologous fat grafting. We conducted a systematic review of these topics to be used as the evidence base for an updated clinical practice guideline on breast reconstruction for Ontario Health (Cancer Care Ontario). The protocol was registered on PROSPERO, CRD42023409083. Medline, Embase, and Cochrane databases were searched until August 2024, and 229 primary studies met the inclusion criteria. Most studies were retrospective non-randomized comparative studies; 5 randomized controlled trials were included. Results suggest nipple-sparing mastectomy is oncologically safe, provided there is no clinical, radiological, or pathological indication of nipple-areolar complex involvement. Surgical factors, including incision location, may affect rates of complications such as necrosis. Both immediate and delayed reconstruction have similar long-term outcomes; however, immediate reconstruction may result in better short to medium-term quality of life. Evidence on whether radiotherapy should modify the timing of initial reconstruction or expander-implant exchange was very limited; studies delayed reconstruction after radiotherapy by at least 3 months and, more commonly, at least 6 months to avoid the period of acute radiation injury. Radiation after immediate reconstruction is a reasonable option. Surgical complications are similar between prepectoral and dual-plane or subpectoral reconstruction; prepectoral placement may give a better quality of life due to lower rates of long-term complications such as pain and animation deformity. Autologous fat grafting was found to be oncologically safe; its use may improve quality of life and aesthetic results.- Book : 32(4)
- Pub. Date : 2025
- Page : pp.231-231
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2025
ABSTRACT
Pseudorabies virus (PRV) is a porcine alphaherpesvirus that can infect different animal species and cause pruritus and lethal encephalitis. Stress granules (SGs) are membrane-free cytoplasmic structures formed by liquid-liquid phase separation of G3BP proteins during cell translation inhibition, which generally plays an antiviral role in various viral infections. In this study, we found that infection with different PRV strains inhibits the formation of SGs in host cells. We found that IE180, the only immediate early protein of PRV, has a distinct inhibitory effect on SG formation and colocalizes with SG-nucleating G3BP proteins (G3BP1/2) in the nucleus during PRV infection. Co-immunoprecipitation assays demonstrated an interaction between IE180 and G3BP1/G3BP2, and this interaction appears to depend on the Herpesvirus ICP4-like protein N-terminal (ICP4L-N) domain of IE180 and both NTF2L and RBD domains of G3BP1. Since G3BPs mainly function in the cytoplasm to induce SG formation, we constructed several IE180 protein truncations lacking a nuclear localization sequence to alter the subcellular localization of IE180 to the cytoplasm. Mutant IE180 protein was mainly expressed in the cytoplasm and still suppressed SG formation induced by arsenite or poly(I:C), but its ability to inhibit SG formation was weakened. Importantly, knockout of G3BPs facilitated PRV replication in H1299 cells, while exogenous expression of G3BPs and formation of SGs in wild-type H1299 cells suppressed PRV replication. In summary, our study indicates that PRV IE180 suppresses SG formation and hijacks G3BPs into the nucleus to benefit virus replication.
IMPORTANCE
Herpesviruses, including pseudorabies virus (PRV), have evolved different strategies to compromise host immune responses. Stress granules (SGs) are one of the targets that viruses can overcome in order to increase replication. The related herpes simplex virus 1 (HSV-1) inhibits SG formation to promote virus replication, but the underlying mechanisms remain unknown. In this study, we confirmed that infection with different PRV strains inhibits SG formation. Interestingly, we found that the PRV immediate early protein IE180 interacts with G3BP proteins and hijacks these proteins into the nucleus to prevent SG formation. In line with the antiviral effect of SGs on PRV replication, exogenous expression of G3BPs and formation of SGs in G3BP1/2 knockout H1299 cells significantly compromised PRV replication. The reported mechanism appears to be also utilized by HSV-1 to prevent SG formation. Therefore, our study elucidates a novel mechanism by which alphaherpesviruses inhibit SG formation, which provides a new perspective to inquire into the immune escape of PRV and other alphaherpesviruses.
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- Pub. Date : 2025
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2025
- Book : ()
- Pub. Date : 2025
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2025
The study examines a set of indicators characterizing the conditions for implementing the water-chemical regime of the secondary circuit in domestic nuclear power plants equipped with VVER-440 / VVER-1000 water-water energetic reactors. The presented research results are intended for use in software complexes for personnel training, specifically computer simulators. The reliable operation of nuclear power plants in any country depends on the proper functioning of all plant systems and the qualification of personnel. The study aims to assess the impact of deviations in the water-chemical regime and to develop decision-making algorithms for operational personnel managing the water-chemical regime. As part of the computer simulators for training operational personnel, structural and parametric identification of mathematical models for the time-dependent performance indicators of the water-chemical regime was carried out. The modeling primarily focused on the channels 'concentration of specific agents (hydrazine hydrate, morpholine) vs concentration of impurities (iron compounds, etc.) in the coolant', as these are closely associated with the corrosion processes of pipelines, primary, and auxiliary equipment in the secondary circuit of nuclear power plants. The study included modeling conditions for violations of the water-chemical regime in the secondary circuit using indicators such as electrical conductivity, mass concentration of oxygen, mass concentration of copper, and mass concentration of sodium. Experimental-statistical validation of the models was conducted, demonstrating that the developed mathematical models adequately describe the analyzed processes. Based on the obtained mathematical descriptions (a family of mathematical models in the form of ordinary differential equations), computer models were constructed. These models enable personnel to predict changes in the performance indicators of the investigated processes over time. Non-stationary process computer models for the water-chemical regime of the secondary circuit in nuclear power plants with VVER-1000 reactors, developed through the identification of extensive industrial data, facilitate the integration of new subsystems for modeling coolant composition management regimes into the computer simulator for operator training.- Book : (1)
- Pub. Date : 2025
- Page : pp.37-47
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2025
Haemophilia A (HA), defined by factor VIII (FVIII) levels ≤40 IU/dL, is a chronic condition with consequences beyond bleeding complications. Jan Astermark (Professor of Clinical Coagulation Medicine, Senior Consultant, and Head of Department of Translational Medicine, Lund University; and Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden) outlined the burden of HA on the quality of life (QoL) of patients, including bleeding, joint damage, pain, psychosocial wellbeing, and physical activity. He shared real-world evidence showing that current prophylactic regimens with FVIII or non-factor therapy (NFT) are not sufficient to eliminate all types of bleeds and that many challenges remain. Astermark presented several analyses highlighting that FVIII levels in the non-haemophilia range may be necessary to prevent residual bleeding. These analyses have informed recent treatment goals that transcend historical targets of converting severe HA (SHA) into moderate or mild forms and aim towards normalised haemostasis to eliminate bleeds. Maria Elisa Mancuso (Senior Consultant in Haematology, Centre for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital and Humanitas University, Milan, Italy) presented a patient case to illustrate the challenges that people with HA (PwHA) face over their lives and the evolution of treatment strategies to address unmet needs. Christoph Königs (Head of Clinical and Molecular Haemostasis at the Department of Paediatrics and Adolescent Medicine, Clinical and Molecular Haemostasis, Goethe University, University Hospital, Frankfurt, Germany) emphasised the unique challenges faced by children with HA and their caregivers, including restrictions in daily activities, regular evaluations for subclinical and evident bleeds, long-term joint protection, delayed inhibitor development, self-injection skills, and suboptimal adherence. He discussed how standard and extended half-life (SHL, EHL) therapies have improved care in children with HA but highlighted how prophylaxis with existing therapies is not sufficient to eliminate evident and subclinical bleeds. He concluded by sharing data on novel therapies that offer the potential to maintain FVIII levels in the non-haemophilia range (≥40 IU/dL) to help address these unmet needs. Robert Klamroth (Head of the Department of Internal Medicine, Vascular Medicine and Haematology, and Director of Haemophilia Treatment Centre, at Vivantes Klinikum Friedrichshain, Berlin, Germany) focused on the evolving challenges of HA in adulthood, including surgery and the need for anticoagulant or antiplatelet therapy for the management of comorbidities. Recent clinical data were shown to demonstrate how high sustained FVIII levels could minimise bleeding risk and improve joint health, surgical management, and overall QoL in adults with HA. In the panel discussion, two patient cases were reviewed to consider unmet needs in people with mild HA and in elderly people with HA, and the panel summarised how sustaining FVIII levels in the non-haemophilia range could help address these needs. The panel concluded by reviewing the evolution of treatment strategies and the importance of targeting normalised haemostasis in a new era of protection in HA.- Book : ()
- Pub. Date : 2025
- Page : pp.25-32
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2025
Dear Editor,
Magnetic resonance imaging (MRI) is an important diagnostic imaging modality, especially in children where radiation exposure is an important concern. As children undergoing MRI scans need to lie still for an extended period of time in an environment with loud noises, sedation is often required.1 However, its use comes with risks of adverse cardiorespiratory events2-3 and utilisation of hospital resources when children are admitted for monitoring post-sedation. Optimising the MRI environment, distraction techniques and the use of mock scanners minimises the need for sedation in children.4-8 A multi-faceted approach, which combines these components, has been shown to be effective in children as young as 4 years old.9-10- Book : ()
- Pub. Date : 2025
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2025
Abstract
Light-matter interaction is exploited in spectroscopic techniques to access information about molecular, atomic or nuclear constituents of a sample. While scattered light carries both amplitude and phase information of the electromagnetic field, the latter is lost in intensity measurements. However, often the phase information is paramount to reconstruct the desired information of the target, as it is well known from coherent x-ray imaging. Here we introduce a phase retrieval method which allows us to reconstruct the field phase information from two-dimensional time- and energy-resolved spectra. We apply this method to the case of x-ray scattering off Mössbauer nuclei at a synchrotron radiation source. Knowledge of the phase allows also for the reconstruction of energy spectra from two-dimensional experimental data sets with excellent precision, without theoretical modelling of the sample. Our approach provides an efficient and accurate data analysis tool which will benefit x-ray quantum optics and Mössbauer spectroscopy with synchrotron radiation alike.- Book : 16(1)
- Pub. Date : 2025
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