We present phenomenological findings on charm quark transport while including its energy loss in both pre-equilibrium and hydrodynamic stages of the evolution. We employed the MARTINI event generator for the production and evolution of heavy quarks in the relativistic heavy-ion collisions. The sensitivity of the heavy meson nuclear modification factor and flow coeffcient to the early stage of heavy-ion collisions and bulk medium evolution is analyzed for Pb+Pb collisions at 5.02 TeV. Our study provides insights into the interaction strength of charm quarks during the early phase and within the quark-gluon plasma.

• Book : 316()
• Pub. Date : 2025
• Page : pp.04018-04018
• Keyword :

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

Abstract Introduction Giant prolactinomas are rare, especially in children and adolescents and often resistant to the recommended first-line cabergoline monotherapy. In addition, possible second line guideline treatment recommendations (surgery, radiotherapy, temozolomide) are not suitable. Clinical Case A 14-year-old girl (51kg/155,7cm/BMI 18.4 kg/m2, bone age 14.37) was referred to pediatric endocrinologist because of primary amenorrhea and delayed puberty. Two years earlier, she underwent a brief episode of anorectic behavior (rapid weight loss of 15.4 kg) but recovered before the age of 14. Results Clinical examination was normal, excluding Tanner stage M2P3. No galactorrhea was evident. Laboratory work-up revealed hyperprolactinemia (S-PRL 26 817 mU/l (86-324)). Estradiol and gonadotropins were consistent with the pubertal stage (S-Estdiol 0.02 nmol/l; S-FSH 3.2 U/l, S-LH <1.0 U/l). Thyroid function and cortisol secretion (P-Corsol 411 nmol/l, P-ACTH 21 ng/l) were normal, but S-TPOAb elevated at 350 kU/l (<34 kU/l). Genetic testing for AIP, MEN1, GNAS1, MAX, SDHA, SDHC, SDHD, SDHAF2, PRKAR1a mutations was negative. Abdominal ultrasound revealed a small uterus. Brain MRI showed a giant prolactinoma, (21x30x40 mm; Fig. 1A) which extended to the dorsum sellae, infiltrated the left cavernous sinus, filled the suprasellar cistern compressed the optic chiasm. Neuro-ophthalmological examination; visual acuity, fields was normal. Prolactin level was repeatedly high (30 210 mU/l; 78% (23 672 mU/l) biologically active. The patient was put on cabergoline (0,5mg/week) and the dose was doubled one month later as the prolactin remained high (14 509 mU/l). Tumor size was unchanged on 4 months follow-up MRI. The case was discussed at the multidisciplinary pituitary tumor board. Neither surgery nor radiotherapy were recommended and temozolomide was unsuitable. Cabergoline was increased to 1,5mg/week. At 5 months, the patient had primary hypothyroidism (P-TSH 5,00 mU/l, free-T4 11; S-PRL 4509 mU/l) and was put on L-T4 (50µg/day). 11C-methionine PET/MRI demonstrated significant uptake throughout the tumor tissue. Tumor size had decreased slightly. Cabergoline was increased to 3mg/week; 11 months after initiation of the treatment, S-PRL had decreased to 4800mU/l. Though no clinical signs of puberty were evident, estradiol and gonadotropin levels had risen (S-Estdiol 0.21 nmol/l, LH 18 IU/l, FSH 7.4 IU/l). Cabergoline was increased to 3.5mg/week. After 13 months of treatment, S-PRL was 3523, S-Estdiol 0.08, FSH 5.9, LH 7.7, TSH 0.08, free-T4 17. Cabergoline was increased to 4mg/week. Next examination, including MRI and laboratory tests, is scheduled 2 months later. Conclusion Treatment of adolescents with giant prolactinoma is challenging. There is an unmet need for second line tailored treatments, such as combined D2 and SST2&5 receptor agonist therapy (cabergoline+pasireotide), which, for this case, is the planned second line experimental treatment.Figure 1:

• Book : 3(Supplement_1)
• Pub. Date : 2025
• Page :
• Keyword :

Pediatric cancers, while rare, pose unique challenges due to the heightened sensitivity of developing tissues and the increased risk of long-term radiation-induced effects. Radiotherapy (RT) is a cornerstone in pediatric oncology, but its application is limited by concerns about toxicity, particularly secondary malignancies, growth abnormalities, and cognitive deficits. CyberKnife (CK), an advanced robotic radiosurgery system, has emerged as a promising alternative due to its precision, non-invasiveness, and ability to deliver hypofractionated, high-dose RT while sparing healthy tissues. This narrative review explores the existing evidence on CK application in pediatric patients, synthesizing data from case reports, small series, and larger cohort studies. All the studies analyzed reported cases of tumors located in the skull or in the head and neck region. Findings suggest CK’s potential for effective tumor control with favorable toxicity profiles, especially for complex or inoperable tumors. However, the evidence remains limited, with the majority of studies involving small sample sizes and short follow-up periods. Moreover, concerns about the “dose-bath” effect and limited long-term data on stochastic risks warrant cautious adoption. Compared to Linac-based RT and proton therapy, CK offers unique advantages in reducing session numbers and enhancing patient comfort, while its real-time tracking provides superior accuracy. Despite these advantages, CK is associated with significant limitations, including a higher potential for low-dose scatter (often referred to as the “dose-bath” effect), extended treatment times in some protocols, and high costs requiring specialized expertise for operation. Emerging modalities like π radiotherapy further underscore the need for comparative studies to identify the optimal technique for specific pediatric cases. Notably, proton therapy remains the benchmark for minimizing long-term toxicity, but its cost and availability limit its accessibility. This review emphasizes the need for balanced evaluations of CK and highlights the importance of planning prospective studies and long-term follow-ups to refine its role in pediatric oncology. A recent German initiative to establish a CK registry for pediatric CNS lesions holds significant promise for advancing evidence-based applications and optimizing treatment strategies in this vulnerable population.

• Book : 32(2)
• Pub. Date : 2025
• Page : pp.76-76
• Keyword :

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

AbstractObjectiveTo assess the pathological mechanisms contributing to white matter (WM) lesion expansion or contraction and remyelination in multiple sclerosis (MS).MethodsWe assessed 1,613 lesions in 49 people with relapsing–remitting MS in the CCMR‐One bexarotene trial (EudraCT 2014‐003145‐99). We measured lesion orientation relative to WM tracts, surface‐in gradients and veins. Jacobian deformation was used to assess lesion expansion over 6 months, while magnetization transfer ratio (MTR) imaging was used to assess remyelination.ResultsAt baseline, 33% of lesions were aligned with veins, 2% along WM tracts, 0% with surface‐in gradients, and 4% orthogonal to veins. No significant differences were observed in lesion shape, while lesions aligned with surface‐in gradients and with veins had lower volume compared to all remaining orientations. At follow‐up, 13% of lesions expanded and 7% contracted. The directions for both expansion and contraction were 18% and 8%, respectively, along WM tracts, 20% and 15% parallel to veins, 22% and 23% orthogonal to veins and 0% and 1% along surface‐in gradients. Bexarotene had no effect on lesion expansion or contraction, but MTR significantly increased in lesions aligned with surface‐in gradients and veins.InterpretationLesion expansion and shrinkage are affected by venous and WM tract factors, but these do not influence bexarotene's capacity to promote remyelination. This, instead, appears to be affected by surface‐in factors. To limit lesion expansion and maximize tissue repair, multiple processes may need to be targeted.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor, with fewer than 5% of patients surviving five years after diagnosis. The introduction of immune checkpoint inhibitors (ICIs), followed by chimeric antigen receptor (CAR) T-cell therapy, marked major advancements in oncology. Despite demonstrating efficacy in other blood and solid cancers, these therapies have yielded limited success in clinical trials for both newly diagnosed and recurrent GBM. A deeper understanding of GBM’s resistance to immunotherapy is essential for enhancing treatment responses and translating results seen in other cancer models. Objectives: In this review, we examine clinical trial outcomes involving ICIs and CAR-T for GBM patients and explore the evasive mechanisms of GBM and the tumor microenvironment. Findings and Discussion: Multiple clinical trials investigating ICIs in GBM have shown poor outcomes, with no significant improvement in progression-free survival (PFS) or overall survival (OS). Results from smaller case studies with CAR-T therapy have warranted further investigation. However, no large-scale trials or robust studies have yet established these immunotherapeutic approaches as definitive treatment strategies. Future research should shift focus from addressing the scarcity of functional T cells to exploiting the abundant myeloid-derived cells within the tumor microenvironment. Conclusions: Translating these therapies into effective treatments for glioblastoma in humans remains a significant challenge. The highly immunosuppressive nature of GBM and its tumor microenvironment continue to hinder the success of these innovative immunotherapeutic approaches. Targeting the myeloid-derived compartment may lead to more robust and sustained immune responses.

• Book : 17(3)
• Pub. Date : 2025
• Page : pp.462-462
• Keyword :

Abstract This paper explores the operational boundaries and power availability of the neutral beam injection (NBI) system in ITER, with a specific focus on shine-through loss prevention. Shine-through, a phenomenon where part of the injected neutral beam remains un-ionized in the plasma and directly impacts the first wall components, poses a significant risk to the lifetime of ITER’s plasma-facing components. The operational window for NBI is consequently constrained by these losses, which are influenced by factors such as plasma density, beam energy, and injection geometry. Leveraging advanced numerical simulations, we investigate these dependencies across various ITER plasma scenarios, particularly for the DT-1 phase, which will mark the first NBI operations. In light of recent ITER blanket design changes, our analysis refines previous estimates of the maximum acceptable shine-through power on plasma-facing components. We then present a new heuristic formula which permits the calculation of the shine-through fraction and the minimum plasma density that permits ITER NBI operations as a function of global variables. This allows for establishing operational limits for Hydrogen and Deuterium NBI in Hydrogen, Deuterium, and Deuterium-Tritium plasmas. Additionally, we compare commonly used beam ionisation codes for ITER and tokamak simulations, evaluating their reliability in the investigated parameter space. The findings of this study are crucial for ensuring the efficient operation of the NBI system during ITER's experimental phases. They define the conditions under which beam power can be fully utilised without compromising operational lifetime, thereby informing future plasma operation plans and contributing to the success of ITER's scientific objectives.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

Abstract In the initial stages of ITER operation, ELM mitigation systems need to be commissioned. This requires controlled flat-top operation in type-I ELMy H-mode regimes. Hydrogen or helium plasma discharges are used exclusively in these stages to ensure negligible production of neutrons from fusion reactions. With the expected higher L-H power threshold of hydrogen and helium plasmas compared to corresponding D and D/T plasmas, it is uncertain whether available auxiliary power systems are sufficient to operate in stable type-I ELMy H-mode. This has been investigated using integrated core and edge/SOL/divertor modelling with JINTRAC. Assuming that the L-H power threshold is well captured by the Martin08 scaling law, the presented simulations have found that 30 MW of ECRH power is likely required for the investigated hydrogen plasma scenarios, rather than the originally planned 20 MW in the 2016 Staged Approach ITER Baseline. However, past experiments have shown that a small helium fraction (~10 %) can considerably reduce the hydrogen plasma L-H power threshold. Assuming that these results extrapolate to ITER operation regimes, the 7.5MA/2.65T hydrogen plasma scenario is likely to access stable type-I ELMy H-mode operation also at 20 MW of ECRH.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :