Two extensions of the variational method with explicit energy functionals (EEFs) with respect to the spin-orbit force were performed. In this method, the energy per nucleon of nuclear matter is explicitly expressed as a functional of various two-body distribution functions, starting from realistic nuclear forces. The energy was then minimized by solving the Euler–Lagrange equation for the distribution functions derived from the EEF. In the first extension, an EEF of symmetric nuclear matter at zero temperature was constructed using the two-body central, tensor, and spin-orbit nuclear forces. The energy per nucleon calculated using the Argonne v8’ two-body nuclear potential was found to be lower than those calculated using other many-body methods, implying that the energy contribution caused by the spin-orbit correlation, whose relative orbital angular momentum operator acts on other correlations, is necessary. In a subsequent extension, the EEF of neutron matter at zero temperature, including the spin-orbit force, was extended to neutron matter at finite temperatures using the method by Schmidt and Pandharipande. The thermodynamic quantities of neutron matter calculated using the Argonne v8’ nuclear potential were found to be reasonable and self-consistent.

• Book : 8(1)
• Pub. Date : 2025
• Page : pp.11-11
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• Pub. Date : 2025
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Using (2712±14)×106 ψ(2S) events collected with the BESIII detector at the BEPCII collider, we search for the decays ηc(2S)→ωω and ηc(2S)→ωϕ via the process ψ(2S)→γηc(2S). No statistically significant signals are observed. The upper limits of their product branching fractions at the 90% confidence level are determined to be B(ψ(2S)→γηc(2S),ηc(2S)→ωω)<1.04×10−6 and B(ψ(2S)→γηc(2S),ηc(2S)→ωϕ)<1.85×10−7, respectively. We also update the branching fractions of χcJ→ωω and χcJ→ωϕ via the ψ(2S)→γχcJ transition. Their branching fractions are determined to be B(χc0→ωω)=(10.66±0.11±0.57)×10−4, B(χc1→ωω)=(6.43±0.07±0.31)×10−4, B(χc2→ωω)=(8.75±0.08±0.42)×10−4, B(χc0→ωϕ)=(1.18±0.03±0.07)×10−4, B(χc1→ωϕ)=(2.04±0.15±0.11)×10−5, and B(χc2→ωϕ)=(9.58±1.07±0.76)×10−6, where the first uncertainties are statistical and the second are systematic. Published by the American Physical Society 2025

• Book : 111(3)
• Pub. Date : 2025
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• Pub. Date : 2025
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Abstract Introduction The diagnosis of Growth Hormone Deficiency (GHD) during childhood has been the subject of much controversy over the last few years. Aiming to accurate medical treatment, there is a need for biomarker discovery. Objective To characterize the metabolic profile of GHD children, examine the effect of GH administration on the metabolic signature, and investigate the correlations between metabolites and IGF-1. Methods Nuclear Magnetic Resonance (NMR)-based untargeted and targeted metabolomic approach applied to study the metabolic profiles of children with GHD. Plasma, serum, and urine samples were collected from twenty-two children diagnosed with GHD and forty-eight age matched controls from the Pediatric Endocrinology Unit of the University Hospital of Patras. Experimental data were examined by both multivariate and univariate statistical analysis. Results The results of this pilot study revealed a different metabolic fingerprint of children with GHD in comparison to age-matched healthy individuals. However, the detected alterations in the metabolite patterns before and after GH treatment were subtle and of minor discriminative statistical power. Conclusions This study provides evidence that metabolome plays a pivotal role in GHD, but large-scale multicenter studies are warranted to validate the results.

• Book : 21(1)
• Pub. Date : 2025
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ABSTRACT We present a set of 11 two-temperature, radiative, general relativistic magnetohydrodynamic simulations of the black hole M87* in the magnetically arrested state, surveying different values of the black hole spin $a_*$. Our 3-D simulations self-consistently evolve the temperatures of separate electron and ion populations under the effects of adiabatic compression/expansion, viscous heating, Coulomb coupling, and synchrotron, bremsstrahlung, and inverse Compton radiation. We adopt a subgrid heating prescription from gyrokinetic simulations of plasma turbulence. Our simulations have accretion rates $\dot{M}=(0.5-1.5)\times 10^{-6}\dot{M}_{\rm Edd}$ and radiative efficiencies $\epsilon _{\rm rad}=$ 3–35 per cent. We compare our simulations to a fiducial set of otherwise identical single-fluid general relativistic magnetohydrodynamic (GRMHD) simulations and find no significant changes in the outflow efficiency or black hole spin-down parameter. Our simulations produce an effective adiabatic index for the two-temperature plasma of $\Gamma _{\rm gas}\approx 1.55$, larger than the $\Gamma _{\rm gas}=13/9$ value often adopted in single-fluid GRMHD simulations. We find moderate ion-to-electron temperature ratios in the 230 GHz emitting region of $R=T_{\rm i}/T_{\rm e}\,{\approx }\,5$. While total intensity 230 GHz images from our simulations are consistent with Event Horizon Telescope (EHT) results, our images have significantly more beam-scale linear polarization ($\langle |m|\rangle \approx 30~{{\rm per\ cent}}$) than is observed in EHT images of M87* ($\langle |m|\rangle \lt 10~{{\rm per\ cent}}$). We find a trend of the average linear polarization pitch angle $\angle \beta _2$ with black hole spin consistent with what is seen in single-fluid GRMHD simulations, and we provide a simple fitting function for $\angle \beta _2(a_*)$ motivated by the wind-up of magnetic field lines by black hole spin in the Blandford–Znajek mechanism.

• Book : 537(3)
• Pub. Date : 2025
• Page : pp.2496-2515
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AbstractBackgroundSpinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterized by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, and spinal cord are core features of SCA2; however, the evolution and pattern of whole‐brain atrophy in SCA2 remain unclear.ObjectiveWe undertook a multisite, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2.MethodsVoxel‐based morphometry analyses of 110 participants with SCA2 and 128 controls were undertaken to assess groupwise differences in whole‐brain volume. Correlations with clinical severity and genotype, and cross‐sectional profiling of atrophy patterns at different disease stages, were also performed.ResultsAtrophy in SCA2 versus controls was greatest (Cohen's d >2.5) in the cerebellar white matter (WM), middle cerebellar peduncle, pons, and corticospinal tract. Very large effects (d >1.5) were also evident in the superior cerebellar, inferior cerebellar, and cerebral peduncles. In the cerebellar gray matter (GM), large effects (d >0.8) were observed in areas related to both motor coordination and cognitive tasks. Strong correlations (|r| > 0.4) between volume and disease severity largely mirrored these groupwise outcomes. Stratification by disease severity exhibited a degeneration pattern beginning in the cerebellar and pontine WM in preclinical subjects; spreading to the cerebellar GM and cerebro‐cerebellar/corticospinal WM tracts; and then finally involving the thalamus, striatum, and cortex in severe stages.ConclusionThe magnitude and pattern of brain atrophy evolve over the course of SCA2, with widespread, nonuniform involvement across the brainstem, cerebellar tracts, and cerebellar cortex; and late involvement of the cerebral cortex and striatum. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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• Pub. Date : 2025
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Abstract Fine-grained nuclear emulsion films have been developed as a tracking detector with nanometric spatial resolution to be used in direction-sensitive dark matter searches, thanks to novel readout technologies capable of exploiting this unprecedented resolution. Emulsion detectors are time insensitive. Therefore, a directional dark matter search with such detector requires the use of an equatorial telescope to absorb the Earth rotation effect. We have conducted for the first time a directional dark matter search in an unshielded location, at the sea level, by keeping an emulsion detector exposed for 39 days on an equatorial telescope mount. The observed angular distribution of the data collected during an exposure equivalent to 0.59 g days agrees with the background model and an exclusion plot was then derived in the dark matter mass and cross-section plane: cross-sections higher than 9.2 × 10-29 cm2 and 1.2 × 10-31 cm2 were excluded for a dark matter mass of 10 GeV/c 2 and 100 GeV/c 2, respectively. This is the first direction sensitive search for dark matter with a solid-state, particle tracking detector.

• Book : 2025(02)
• Pub. Date : 2025
• Page : pp.012-012
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Abstract Background JCOG1212 is a dose-finding and efficacy confirmatory study of concurrent superselective intra-arterial infusion of cisplatin and radiotherapy (RADPLAT) for locally advanced primary squamous cell carcinoma of the maxillary sinus (cT4a,bN0M0). In this study, we report the results of the final analysis of the efficacy confirmation phase for the T4a cohort with 5-year follow-up data to evaluate the late adverse events and long-term efficacy. Methods Based on the results of the dose-finding phase, the efficacy confirmation phase consisted of seven weekly intra-arterial infusions of cisplatin 100 mg/m2 combined with radiotherapy (70 Gy). The 5-year prognosis and late adverse events were evaluated. Results Between April 2014 and August 2018, 64 patients were included in the analysis (one ineligible patient was excluded); 31 patients were treated with three-dimensional conformal radiation therapy (3D-CRT) and 33 with intensity modulated radiation therapy (IMRT). The 5-year overall survival, event-free survival, and local event-free survival was 71.9, 54.7, and 57.5%, respectively. In terms of late adverse events, grade 3 or higher non-hematologic toxicity was observed in 42.9% of 63 patients (retinopathy: 12, cataract: 10, osteonecrosis of mandible: 4, etc.). Grade 3 and 4 cataracts of affected side appeared in 22.6% (7/31) of the 3D-CRT group compared to 3.1% (1/32) in the IMRT group. Twenty-one patients had died, with 15 from the primary disease, 5 from other causes, and 1 from treatment-related cause. Conclusion The prognosis of RADPLAT was favorable after 5-year follow-up with acceptable late adverse events and low proportion of treatment related death.

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• Pub. Date : 2025
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Background: The nuclear-encoded enzyme polymerase gamma (Pol-γ) is crucial in the replication of the mitochondrial genome (mtDNA), which in turn is vital for mitochondria and hence numerous metabolic processes and energy production in eukaryotic cells. Variants in the POLG gene, which encodes the catalytic subunit of Pol-γ, can significantly impair Pol-γ enzyme function. Pol-γ-associated disorders are referred to as POLG-spectrum disorders (POLG-SDs) and are mainly autosomal-recessively inherited. Clinical manifestations include muscle weakness and fatigue, and severe forms of the disease can lead to premature death in infancy, childhood, and early adulthood, often associated with seizures, liver failure, or intractable epilepsy. Here, we analyzed fibroblasts from a compound heterozygous patient with the established pathogenic variant c.2419C>T; p.(Arg807Cys) and a previously undescribed variant c.678G>C; p.(Gln226His) with a clinical manifestation compatible with POLG-SDs, sensory ataxic neuropathy, and infantile muscular atrophy. We conducted a battery of functional studies for Pol-γ and mitochondrial dysfunction on the patient’s fibroblasts, to test whether the novel variant c.678G>C; p.(Gln226His) may be causative in human disease. Aims/Methods: We analyzed skin-derived fibroblasts in comparison to a first-degree relative (the mother of the patient), an asymptomatic carrier harboring only the established c.2419C>T; p.(Arg807Cys) mutation. Assessments of mitochondrial function included measurements of mtDNA content, mRNA levels of mitochondrial genes, mitochondrial mass, and mitochondrial morphology. Case Presentation and Results: A 13-year-old male presented with symptoms starting at three years of age, including muscle weakness and atrophy in the lower extremities and facial muscles, which later extended to the upper limbs, voice, and back muscles, without further progression. The patient also reported fatigue and muscle pain after physical activity, with no sensory deficits. Extensive diagnostic tests such as electromyography, nerve conduction studies, muscle biopsy, and MRI were unremarkable. Exome sequencing revealed that he carried the compound heterozygous variants in POLG c.678G>C; p.(Gln226His) and c.2419C>T; p.(Arg807Cys), but no other potential genetic pathogenic causes. In comparison to a first-degree relative (his mother) who only carried the c.2419C>T; p.(Arg807Cys) pathogenic mutation, in vitro analyses revealed a significant reduction in mtDNA content (~50%) and mRNA levels of mtDNA-encoded proteins. Mitochondrial mass was reduced by approximately 20%, and mitochondrial interconnectivity within cells was impaired, as determined by fluorescence microscopy and mitochondrial staining. Conclusions: Our findings suggest that the c.678G>C; p.(Gln226His) variant, in conjunction with the c.2419C>T; p.(Arg807Cys) mutation, may compromise mtDNA replication and mitochondrial function and could result in clinically significant mitochondriopathy. As this study is based on one patient compared to a first-degree relative (but with an identical mitochondrial genome), the pathogenicity of c.678G>C; p.(Gln226His) of POLG should be confirmed in future studies, in particular, in conjunction with other POLG-variants.

• Book : 16(2)
• Pub. Date : 2025
• Page : pp.198-198
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