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We study Shimura curves of PEL type in A g generically contained in the Prym locus. We study both the unramified Prym locus, obtained using étale double covers, and the ramified Prym locus, corresponding to double covers ramified at two points. In both cases, we consider the family of all double covers compatible with a fixed group action on the base curve. We restrict to the case where the family is one-dimensional and the quotient of the base curve by the group is ℙ 1 . We give a simple criterion for the image of these families under the Prym map to be a Shimura curve. Using computer algebra we check all the examples obtained in this way up to genus 28. We obtain 43 Shimura curves contained in the unramified Prym locus and 9 families contained in the ramified Prym locus. Most of these curves are not generically contained in the Jacobian locus. [ABSTRACT FROM AUTHOR]

• HTV delivers better target coverage uniformity than HDR-BT. • HDR-BT demonstrates superior performance in managing complex geometries, such as PTVs with concave surfaces. • HTV shows higher conformity indexes, with better sparing of optic nerve and lens. • Clinical judgements are more prone to prefer HTV treatments. This study aims to investigate and compare High Dose Rate Brachytherapy (HDR-BT) with Helical Tomotherapy (HT) treatment plans. The focus is on small target volumes near radiation-sensitive organs in the ocular region, to evaluate the advantages of these techniques in treating skin cancer. This retrospective observational analysis included patients who underwent skin cancer HDR-BT Freiburg flap treatment between 2019 and 2023. An expert radiation oncologist contoured the planning target volumes (PTVs) and marked their visible extension with a radio-opaque tin wire. Each patient had two treatment plans: an individually shaped HDR-BT surface mold and an HT calculation used specifically for this study. Quality assurance of treatment plan was performed in both HDR-BT and HT. The plans were then compared using organ at risk (OAR) maximum doses and the conformity index CI. Radiation oncologists assessed their quality using their routine workflow evaluation plan. Twelve patients were selected for the inclusion in this study. HT provided more consistent target coverage than HDR-BT, with a statistically significant difference (p < 0.05) at t -test. HT showed higher CIs and maximum dose for the optic nerve, optic chiasm, and lens in the homolateral part. Radiation oncologists preferred the overall quality of HT treatment due to its superior PTV coverage, especially for convex surfaces, while maintaining effective OAR sparing. HDR-BT is preferred when concave surfaces are present. HT offers more conformal treatment, although some OAR parameters are statistically significantly better with HDR-BT, which may also be superior for complex geometries. [ABSTRACT FROM AUTHOR]

Local management of adult soft tissue sarcoma of the extremities has evolved over the past decades. Until the 1970s, radical surgery (amputations) was the standard therapeutic procedure resulting in significant physical and psychological morbidity for the patients. In the present era, limb sparing surgery combined with radiotherapy represents the current standard of care for high grade and > 5 cm STSs. This approach guarantees high local control rate and function preservation. The aim of this paper is to summarize the current evidence for RT in STSs of the extremities. Outcomes, technical details (techniques, timing, dose, volumes of treatment) and the emerging role of RT in the management of oligometastatic disease will be analysed. Finally, results of the recent clinical trials testing new scenarios in RT of STSs will be described. [ABSTRACT FROM AUTHOR]

Aim: Current diagnostic systems, DSM‐5 and ICD‐10, still adopt a categorical approach to classify psychotic disorders. The present study was aimed at investigating the structure of psychotic symptomatology in both affective and non‐affective psychosis from a dimensional approach. Methods: Participants with a first episode psychosis (FEP) were recruited from a cluster‐randomized controlled trial (GET‐UP PIANO TRIAL), offered to all Community Mental Health Centres (CMHCs) located across two northern Italian regions. After clinical stabilization, patients were assessed with a comprehensive set of psychopathological measures including the Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale and the Bech‐Rafaelsen Mania Rating Scale. A two‐step cluster analysis was performed. Results: Overall, 257 FEP patients (male, n = 171, 66.5%; mean age = 24.96 ± 4.56) were included in the study. The cluster analysis revealed a robust four‐cluster solution: delusional‐persecutory (n = 82; 31.9%), depressed (n = 95; 37%), excited (n = 26; 10.1%) and negative‐disorganized (n = 54; 21%), thus suggesting a quadripartite structure with both affective and non‐affective dimensions. Among non‐affective dimensions, negative and disorganization symptoms constituted a unique construct apart from positive symptoms. Conclusions: Symptom dimensions may represent a useful tool for dissecting the indistinct and non‐specific psychopathology of FEP in order to better target specific interventions. [ABSTRACT FROM AUTHOR]

Background: Concurrent chemotherapy and radiation using conventional fractionation is the standard treatment for inoperable, locally advanced non-small-cell lung cancer (NSCLC). We tested accelerated hypofractionated radiotherapy (AHR) and chemotherapy for the treatment of locally advanced NSCLC.Methods: Eligible patients with locally advanced NSCLC were treated with induction chemotherapy (cisplatin and docetaxel), followed by AHR using tomotherapy and consolidation chemotherapy. The prescribed doses were 30 Gy/5 daily fractions at the reference isodose (60-70%) to the tumor, and 25 Gy/5 daily fractions to the clinically involved lymph nodes. The primary end-point was response rate (RR); the secondary end-points were acute and late side-effects, local progression-free survival (PFS), metastasis-free survival (MFS) and overall survival (OS). This trial closed before the first planned interim analysis due to poor accrual.Results: From January 2009 to January 2012, 17 of the 23 enrolled patients were evaluable. Treatment yielded an overall RR of 82%. Median follow-up was 87 months (range: 6-87), local PFS was 19.8 months (95% CI 9.7 - not reached), MFS was 9.7 months (95% CI 5.8-46.0) and OS was 23 months (95% CI 8.4-48.4). 70% of patients experienced acute G4 neutropenia, 24% G4 leukopenia, 24% G3 paresthesia, 4% G3 cardiac arrythmia, 4% underwent death after chemotherapy. Late toxicity was represented by 24% dyspnea G3.Conclusions: AHR combined with chemotherapy is feasible with no severe side-effects, and it appears highly acceptable by patients.Trial Registration: This study is registered with the EudractCT registration 2008-006525-14 . Registered on 9 December 2008. [ABSTRACT FROM AUTHOR]

Purpose The role played by radiation therapy after pleurectomy/decortication or surgical biopsy in malignant pleural mesothelioma is uncertain. We treated patients with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy in an attempt to keep lung toxicity to a minimum. The present study reports the feasibility and toxicity of this approach. Material and Methods Between 2008 and 2012, 36 patients with malignant pleural mesothelioma underwent accelerated hypofractionated radiotherapy to the hemithorax after pleurectomy/decortication (19 patients) or biopsy (17 patients). The prescription dose was 25 Gy in five fractions over 5 consecutive days. Results We observed three patients with G3 pneumonitis, five cases of grade 2 dyspnea and six cases of grade 2 cough. The median follow-up was 37 months (range: 3–54 months). The median overall survival for patients who underwent pleurectomy/decortication followed by radiotherapy was 21.6 months [95% confidence interval (95% CI): 15.5–24.1] compared to 19.4 months for patients not submitted to surgery. Conclusion Treatment of intact lung with pleural intensity-modulated arc irradiation in malignant pleural mesothelioma patients with malignant pleural mesothelioma proved safe and feasible, with an acceptable rate of pneumonitis. Survival rates were encouraging for both biopsy-only and pleurectomy/decortication groups. We are currently conducting a phase II dose escalation trial in a similar patient setting to prospectively evaluate the impact of radiotherapy on toxicity, disease-free survival and overall survival. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality globally, significantly influenced by modifiable risk factors, particularly hypercholesterolemia. Despite the availability of effective lipid-reducing drugs, achieving the low-density lipoprotein cholesterol (LDL-C) target levels remains a significant challenge in clinical practice, contributing to persistently high rates of cardiovascular events. The intEgrated multidiscipliNary pathway for large-scale maNagement of dyslipidemiA in high-risk patients (ENNA) Project was designed to address the alarming rates of suboptimal lipid management in patients at high and very-high risk in the province of Enna, Sicily. This program aims to optimize LDL-C control through an integrated care model that fosters collaboration among pharmacists, general practitioners, and cardiologists, ultimately promoting a patient-centered approach to therapy. The patients who are eligible are identified using data-driven methods through prescription claims, laboratory results, and hospital discharge data, facilitated by local pharmacies. General practitioners play a crucial role as the primary care providers for initiating or optimizing lipid-reducing therapy, whereas cardiologists are involved in managing more complex cases requiring specialized intervention. The primary objective of the ENNA Project is to increase the percentage of patients at great risk in whom LDL-C targets are achieved, improving overall lipid management and therapeutic adherence., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Varying light conditions elicit metabolic responses as part of acclimation with changes in ascorbate levels being an important component. Here, we adopted a genome-wide association-based approach to characterize the response in ascorbate levels on high light (HL) acclimation in a panel of 315 Arabidopsis (Arabidopsis thaliana) accessions. These studies revealed statistically significant SNPs for total and reduced ascorbate under HL conditions at a locus in chromosome 2. Ascorbate levels under HL and the region upstream and within PAS/LOV PROTEIN (PLP) were strongly associated. Intriguingly, subcellular localization analyses revealed that the PLPA and PLPB splice variants co-localized with VITAMIN C DEFECTIVE2 (VTC2) and VTC5 in both the cytosol and nucleus. Yeast 2-hybrid and bimolecular fluorescence complementation analyses revealed that PLPA and PLPB interact with VTC2 and that blue light diminishes this interaction. Furthermore, PLPB knockout mutants were characterized by 1.5- to 1.7-fold elevations in their ascorbate levels, whereas knockout mutants of the cry2 cryptochromes displayed 1.2- to 1.3-fold elevations compared to WT. Our results collectively indicate that PLP plays a critical role in the elevation of ascorbate levels, which is a signature response of HL acclimation. The results strongly suggest that this is achieved via the release of the inhibitory effect of PLP on VTC2 upon blue light illumination, as the VTC2-PLPB interaction is stronger under darkness. The conditional importance of the cryptochrome receptors under different environmental conditions suggests a complex hierarchy underpinning the environmental control of ascorbate levels. However, the data we present here clearly demonstrate that PLP dominates during HL acclimation., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Competing Interests: None.

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/aot-21-8). The authors have no conflicts of interest to declare.