• Book : ()
• 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.

• Book : ()
• 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.

• Book : ()
• 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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이 연구는 니가타현에 위치한 도쿄전력 가시와자키 가리와 원전 재가동을 둘러싼 원전 입지 지역의 현황을 희생의 시스템 논의를 토대로 검토했다. 원전 입지 지역에 대해서는 위험을 감수하는 희생을 강요당하는 반면, 그에 응당한 경제적인 혜택을 받는다는 등 쟁점이 존재하기 때문에, 사회적인 갈등을 야기하고 있는 해당 원전과 지역의 현황을 논할 필요가 있다. 주요 결과로는 첫 번째, 전력생산과 소비 측면에서 가시와자키 가리와 원전 입지 지역과 그 주변 지역에서는 불평등을 인식하고 있었으며, 원전에 대한 영향력이 제한된 상황에서 이를 극복하기 위한 움직임이 지역 정치와 시민사회 차원에서 관찰되었다. 두 번째, 일본 정부는 해당 원전의 안전성을 강조하며 재가동을 추진하려 하지만 원전의 위험은 이미 가시화된 상태이며, 이는 지자체와 시민들이 원전 관련 의사결정에 대한 참여를 요구하는 기제가 되고 있다. 세 번째, 원전이 지역경제에 어떠한 영향을 주는가에 대해서는 논쟁이 전개되고 있으며 지역 시민들의 인식도 혼란이 있었다. 이는 경제적 혜택과의 비교대상이 위험이라는 특성에서 기인한다. 이 연구에서는 원전 입지 지역과 주변 지역을 포함하여 ‘원전 영향 지역’이라는 개념을 제안했고, 가시와자키 가리와 원전 영향 지역 사례를 통해 지역과 주민 차원에서 기존의 수동적인 위치를 탈피하려는 실천이 이루어지고 있음을 확인할 수 있었다.

• Pub. Date : 2025
• Page : pp.280-311
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• Book : 34()
• Pub. Date : 2025
• Page :
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Abstract In the case of neonates, especially low birth weight preterm and high-risk infants, portable X-rays are frequently used. However, the image quality of portable X-rays is significantly lower compared to standard adult or pediatric X-rays, leading to considerable challenges in identifying abnormalities. Although attempts have been made to introduce deep learning to address these image quality issues, the poor quality of the images themselves hinders the training of deep learning models, further emphasizing the need for image enhancement. Additionally, since neonates have a high cell division rate and are highly sensitive to radiation, increasing radiation exposure to improve image quality is not a viable solution. Therefore, it is crucial to enhance image quality through preprocessing before training deep learning models. While various image enhancement methods have been proposed, Contrast Limited Adaptive Histogram Equalization (CLAHE) has been recognized as an effective technique for contrast-based image improvement. However, despite extensive research, the process of setting CLAHE’s hyperparameters still relies on a brute force, manual approach, making it inefficient. To address this issue, we propose a method called Bayesian Optimization CLAHE(BO-CLAHE), which leverages Bayesian optimization to automatically select the optimal hyperparameters for X-ray images used in diagnosing lung diseases in preterm and high-risk neonates. The images enhanced by BO-CLAHE demonstrated superior performance across several classification models, with particularly notable improvements in diagnosing Transient Tachypnea of the Newborn (TTN). This approach not only reduces radiation exposure but also contributes to the development of AI-based diagnostic tools, playing a crucial role in the early diagnosis and treatment of preterm and high-risk neonates.

• Book : 15(1)
• Pub. Date : 2025
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