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Abstract Gyrate atrophy of choroid and retina (GACR) is a chorioretinal degeneration caused by pathogenic variants in the gene encoding ornithine aminotransferase (OAT), an enzyme mainly expressed in liver. Affected patients have increased ornithine concentrations in blood and other body fluids and develop progressive constriction of vision fields leading to blindness. Current therapies are unsatisfactory and better treatments are highly needed. In two mouse models of OAT deficiency that recapitulates biochemical and retinal changes of GACR, we investigated the efficacy of an intravenously injected serotype 8 adeno‐associated (AAV8) vector expressing OAT under the control of a hepatocyte‐specific promoter. Following injections, OAT‐deficient mice showed reductions of ornithine concentrations in blood and eye cups compared with control mice injected with a vector expressing green fluorescent protein. AAV‐injected mice showed improved electroretinogram response and partial restoration of retinal structure up to one‐year post‐injection. In summary, hepatic OAT expression by AAV8 vector was effective at correction of hyperornithinemia and improved function and structure of the retina. In conclusion, this study provides proof‐of‐concept of efficacy of liver‐directed AAV‐mediated gene therapy of GACR.

The prognostic and predictive role of specific gene mutations in Waldenström Macroglobulinemia (WM) is well-ascertained whereas the clinical impact of chromosome aberrations is far less known. Recent work has provided initial evidence for an adverse prognostic impact of some aberrations, such as del(6q), while other studies suggest a possible relationship between some clinical features (e.g. advanced age and/or inflammatory status) and specific cytogenetic abnormalities. To add to the still limited knowledge on WM cytogenetics and its clinical implications, we herein report our experience in a cohort of WM patients across 23 years. Based on our retrospective study, we found that abnormal karyotype was more represented in older patients and maintained a statistically significant independence from other molecular, clinical, and biological features related to WM. The presence and number of cytogenetic aberrations correlated with inferior overall and progression-free survival outcomes regardless of the type of single chromosome aberration. Our data suggests that the role of the altered karyotype deserves to be further clarified especially in elderly WM patients, in whom cytogenetic abnormalities and disease biology appear to be characterized by a higher degree of complexity. [ABSTRACT FROM AUTHOR]

Objectives: Combined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle. Materials and methods: Between January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded. Results: 128 patients (mean age, 69.3 years ± 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360° had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360° also showed to be an independent protective factor against residual tumor at multivariate analysis. Conclusion: Unenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360° was detected. [ABSTRACT FROM AUTHOR]

The bin packing is a well-known NP-Hard problem in the domain of artificial intelligence, posing significant challenges in finding efficient solutions. Conversely, recent advancements in quantum technologies have shown promising potential for achieving substantial computational speedup, particularly in certain problem classes, such as combinatorial optimization. In this study, we introduce QAL-BP, a novel Quadratic Unconstrained Binary Optimization (QUBO) formulation designed specifically for bin packing and suitable for quantum computation. QAL-BP utilizes the Augmented Lagrangian method to incorporate the bin packing constraints into the objective function while also facilitating an analytical estimation of heuristic, but empirically robust, penalty multipliers. This approach leads to a more versatile and generalizable model that eliminates the need for empirically calculating instance-dependent Lagrangian coefficients, a requirement commonly encountered in alternative QUBO formulations for similar problems. To assess the effectiveness of our proposed approach, we conduct experiments on a set of bin packing instances using a real Quantum Annealing device. Additionally, we compare the results with those obtained from two different classical solvers, namely simulated annealing and Gurobi. The experimental findings not only confirm the correctness of the proposed formulation, but also demonstrate the potential of quantum computation in effectively solving the bin packing problem, particularly as more reliable quantum technology becomes available. [ABSTRACT FROM AUTHOR]

Effective String Theory (EST) represents a powerful non-perturbative approach to describe confinement in Yang-Mills theory that models the confining flux tube as a thin vibrating string. EST calculations are usually performed using the zeta-function regularization: however there are situations (for instance the study of the shape of the flux tube or of the higher order corrections beyond the Nambu-Goto EST) which involve observables that are too complex to be addressed in this way. In this paper we propose a numerical approach based on recent advances in machine learning methods to circumvent this problem. Using as a laboratory the Nambu-Goto string, we show that by using a new class of deep generative models called Continuous Normalizing Flows it is possible to obtain reliable numerical estimates of EST predictions. [ABSTRACT FROM AUTHOR]

Background: Forest ecosystems undergo significant transformations due to harvesting and climate fluctuations, emphasizing the critical role of seeding in natural regeneration and long-term structural preservation. Climate change further amplifies these dynamics, affecting phenology across species and regions. In Tierra del Fuego (Argentina), Nothofagus pumilio (lenga) forests represent the most important timber resource, and it is managed through different silvicultural strategies. This species demonstrates notable post-disturbance regeneration, yet seed fall exhibits significant variability, leading to variations in seed quality (e.g., viability). This study aims to assess fluctuations in N. pumilio seed quality, determine how it varies concerning forest management strategies, annual productivity, and the co-occurrence of climatic phenomena including El Niño-Southern Oscillation (ENSO) and the Southern Annular Mode (SAM). Results: Viable seeds represented 18.4% of the total, notably higher in unharvested than in managed areas. Conversely, empty seeds were more prevalent in harvested areas (> 75%). Seed quality exhibited significant differences across silvicultural treatments, except for insect-predated seeds, which had similar proportions across all areas, though dispersed retention showed higher predation. When considering years with varying production levels, high-production years favoured full and viable seeds, particularly in unharvested forests and aggregated retention, while low-production years saw reduced viability across all treatments. Quadratic models revealed that viability increased with seed production, where unharvested forests achieved the highest values. Climate variability influenced seed proportions, where ENSO+/SAM+ promoting more full and viable seeds, while ENSO–/SAM+ favoured non-predated seeds, especially in unharvested stands. Conclusions: Seed quality varies among treatments and years with different levels of seeding. Variations in seed quality, linked to climatic events, influence seed viability. Seed quality plays a critical role in forest regeneration, ensuring a seedling bank for harvested stands to face climate variability. These findings are relevant for forest management and ecosystem services, considering the increasing climate variability and extreme events. Understanding these influences is crucial for Nothofagus pumilio forests' sustainability and global forest adaptation strategies. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether perioperative and functional outcomes of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) may be affected by large prostate sizes (PS). Methods: All patients treated with RS-RARP were identified and compared according to PS. The definition of PS relied on the prostatic weight at final pathology (PS < 100 g vs ≥ 100 g). Multivariable logistic regression models tested immediate and 12-month urinary continence recovery (UCR, namely, 0–1 safety pad per-day), and positive surgical margins (PSM). Multivariable Poisson log-linear regression analyses tested operative time (OT), estimated blood loss (EBL), and length of stay (LOS). The analyses relied on the database of a high-volume European institution (2010–2022). Results: Of 1,555 overall patients, 1503 (96.7%) had a PS < 100 g and 52 (3.3%) had a PS ≥ 100 g. No differences were recorded in LOS (3 days), and intraoperative (1.9 vs 2.3%) as well as postoperative complications (13 vs 12%; all p values > 0.05). No significant difference was recorded in PSM (25 vs 23%, p = 0.6). In patients with PS ≥ 100 g vs < 100 g, immediate UCR rate was 42 vs 64% (p = 0.002), and 12-month UCR rate was 87 vs 88% (p = 0.3). PV ≥ 100 g independently predicted worse immediate UCR (odds ratio 0.55, 95% CI 0.30–0.98, p = 0.044), but not worse 12-month UCR (p = 0.3) or higher PSM (p = 0.7). PV ≥ 100 g independently predicted longer OT (incidence rate ratio [IRR] 1.12, 95% CI 1.10–1.15, p < 0.001) and higher EBL (IRR 1.26, 95% CI 1.24–1.28, p < 0.001), but not longer LOS (p = 0.3). Conclusions: RS-RARP is a valid option for prostate cancer treatment, even in case of very large prostates. Specifically, no significant association was recognized between PS ≥ 100 g and PSM or 12-month UCR. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by respiratory failure due to a vicious cycle of defective Cystic Fibrosis Transmembrane conductance Regulator (CFTR) function, chronic inflammation and recurrent bacterial and fungal infections. Although the recent introduction of CFTR correctors/potentiators has revolutionized the clinical management of CF patients, resurgence of inflammation and persistence of pathogens still posit a major concern and should be targeted contextually. On the background of a network-based selectivity that allows to target the same enzyme in the host and microbes with different outcomes, we focused on sphingosine-1-phosphate (S1P) lyase (SPL) of the sphingolipid metabolism as a potential candidate to uniquely induce anti-inflammatory and antifungal activities in CF. As a feasibility study, herein we show that interfering with S1P metabolism improved the immune response in a murine model of CF with aspergillosis while preventing germination of Aspergillus fumigatus conidia. In addition, in an early drug discovery process, we purified human and A. fumigatus SPL, characterized their biochemical and structural properties, and performed an in silico screening to identify potential dual species SPL inhibitors. We identified two hits behaving as competitive inhibitors of pathogen and host SPL, thus paving the way for hit-to-lead and translational studies for the development of drug candidates capable of restraining fungal growth and increasing antifungal resistance. [ABSTRACT FROM AUTHOR]

In the investigation of moral judgments of autonomous vehicles (AVs), the paradigm of the sacrificial dilemma is a widespread and flexible experimental tool. In this context, the sacrifice of the AV's passenger typically occurs upon enactment of the utilitarian option, which differs from traditional sacrificial dilemmas, in which the moral agent's life is often jeopardized in the non-utilitarian counterpart. The present within-subject study (n = 183) is aimed at deepening the role of self-sacrifice framing, comparing autonomous- and human-driving text-based moral dilemmas in terms of moral judgment and intensity of four moral emotions (shame, guilt, anger, and disgust). A higher endorsement of utilitarian behavior was observed in human-driving dilemmas and for self-protective utilitarian behaviors. Interestingly, the utilitarian option was considered less moral, shameful, and blameworthy in the case of concurrent self-sacrifice. The present study collects novel information on how different levels of driving automation shape moral judgment and emotions, also providing new evidence on the role of self-sacrifice framing in moral dilemmas. [ABSTRACT FROM AUTHOR]

Distortions of duration perception are often observed in response to highly arousing stimuli, but the exact mechanisms that evoke these variations are still under debate. Here, we investigate the effect of induced physiological arousal on time perception. Thirty-eight university students (22.89 ± 2.5; 28 females) were tested with spontaneous finger-tapping tasks and a time bisection task (with stimuli between 300 and 900 ms). Before the time bisection task, half of the participants (STRESS group) performed a stress-inducing task, i.e., the Paced Auditory Serial Addition Test (PASAT), whereas the other participants (CONTROL group) performed a control task, the Paced Auditory Number Reading Task (PANRAT). The PASAT induced a greater heart rate, but not electrodermal, increase, as well as a more unpleasant and arousing state compared to the PANRAT. Moreover, although the two groups presented a similar performance at the finger-tapping tasks, participants in the STRESS group showed better temporal performance at the time bisection task (i.e., lower constant error) than the controls. These results indicate that psychophysiological stress may alter the subsequent perception of time. [ABSTRACT FROM AUTHOR]

Petrol stations emit benzene and other contaminants that have been associated with an increased risk of childhood leukemia. We carried out a population-based case-control study in two provinces in Northern Italy. We enrolled 182 cases of childhood leukemia diagnosed during 1998–2019 and 726 age- and sex-matched population controls. We geocoded the addresses of child residences and 790 petrol stations located in the study area. We estimated leukemia risk according to distance from petrol stations within a 1000 m buffer and amount of supplied fuel within a buffer of 250 m from the child's residence. We used conditional logistic regression models to approximate risk ratios (RRs) and 95% confidence intervals (CIs) for associations of interest, adjusted for potential confounders. We also modeled non-linear associations using restricted cubic splines. In secondary analyses, we restricted to acute lymphoblastic leukemia (ALL) cases and stratifed by age (<5 and ≥5 years). Compared with children who lived≥1000 m from a petrol station, the RR was 2.2 (95% CI 0.5–9.4) for children living<50 m from nearest petrol station. Associations were stronger for the ALL subtype (RR=2.9, 95% CI 0.6–13.4) and among older children (age≥5 years: RR=4.4, 95% CI 0.6–34.1; age<5 years: RR=1.6, 95% CI 0.1–19.4). Risk of leukemia was also greater (RR=1.6, 95% CI 0.7–3.3) among the most exposed participants when assigning exposure categories based on petrol stations located within 250 m of the child's residence and total amount of gasoline delivered by the stations. Overall, residence within close proximity to a petrol station, especially one with more intense refueling activity, was associated with an increased risk of childhood leukemia, though associations were imprecise. [ABSTRACT FROM AUTHOR]

The growing interest in the subject of moral judgment in driver and autonomous vehicle behavior highlights the importance of investigating the suitability of sacrificial dilemmas as experimental tools in the context of traffic psychology. To this aim a set of validated sacrificial trolley problems and a new set of trolley-like driving dilemmas were compared through an online survey experiment, providing normative values for rates of participants' choices; decision times; evaluation of emotional valence and arousal experienced during the decision process; and ratings of the moral acceptability. Results showed that while both sets of dilemmas led to a more frequent selection of utilitarian outcomes, the driving-type dilemmas seemed to enhance faster decisions mainly based on the utilitarian moral code. No further differences were observed between the two sets, confirming the reliability of the moral dilemma tool in the investigation of moral driving behaviors. We suggest that as moral judgments and behaviors become more lifelike, the individual's moral inclination emerge more automatically and effectively. This new driving-type dilemma set may help researchers who work in traffic psychology and moral decision-making to approach the complex task of developing realistic moral scenarios more easily in the context of autonomous and nonautonomous transportation. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic body radiotherapy is increasingly used for the treatment of oligometastatic disease. Magnetic resonance-guided stereotactic radiotherapy (MRgSBRT) offers the opportunity to perform dose escalation protocols while reducing the unnecessary irradiation of the surrounding organs at risk. The aim of this retrospective, monoinstitutional study is to evaluate the feasibility and clinical benefit (CB) of MRgSBRT in the setting of oligometastatic patients. Materials and methods: Data from oligometastatic patients treated with MRgSBRT were collected. The primary objectives were to define the 12-month progression-free survival (PFS) and local progression-free survival (LPFS) and 24-month overall survival (OS) rate. The objective response rate (ORR) included complete response (CR) and partial response (PR). CB was defined as the achievement of ORR and stable disease (SD). Toxicities were also assessed according to the CTCAE version 5.0 scale. Results: From February 2017 to March 2021, 59 consecutive patients with a total of 80 lesions were treated by MRgSBRT on a 0.35 T hybrid unit. CR and PR as well as SD were observed in 30 (37.5%), 7 (8.75%), and 17 (21.25%) lesions, respectively. Furthermore, CB was evaluated at a rate of 67.5% with an ORR of 46.25%. Median follow-up time was 14 months (range: 3–46 months). The 12-month LPFS and PFS rates were 70% and 23%, while 24-month OS rate was 93%. No acute toxicity was reported, whereas late pulmonary fibrosis G1 was observed in 9 patients (15.25%). Conclusion: MRgSBRT was well tolerated by patients with reported low toxicity levels and a satisfying CB. [ABSTRACT FROM AUTHOR]

Moral decision-making depends on the interaction between emotional and cognitive control processes, which are also affected by sleep. Here we aimed to assess the potential role of sleep in the modulation of moral decisions over time by testing the change in behavioral responses to moral dilemmas over time (1 week). Thirty-five young adults were tested twice, with one week between the sessions. In each session, participants were presented with 24 sacrificial (12 Footbridge- and 12 Trolley-type) and 6 everyday-type moral dilemmas. In sacrificial dilemmas, participants had to choose whether or not to kill one person to save more people (utilitarian choice), to judge how morally acceptable the proposed solution was, and how they felt in terms of valence and arousal during the decision. In everyday-type dilemmas, they had to decide whether to pursuit moral violations involving dishonest behavior. Between the sessions, the participants' sleep pattern was assessed via actigraphy. We observed that participants reduced the utilitarian choices in the second session, and this effect was more pronounced for the Trolley-type dilemmas. We also showed that after a week participants judged the utilitarian choices as less morally acceptable, but there was no change in self-reported emotional reactivity (i.e., valence, and arousal). Moreover, sleep efficiency was mildly negatively associated with the changes in decision choices and moral acceptability for the Footbridge-type dilemmas. Taken together, our data suggest that dealing with a moral situation engages several interacting factors that seem to go beyond the competing roles of cognitive and emotional processes. [ABSTRACT FROM AUTHOR]

Key Message: Seed fall and leaf litter production are linked by a source–sink limitation relationship in unharvested areas. The magnitude of these relationships varied differently according to the retention levels over the years-after-harvesting. Seed fall and leaf litter influence forest regeneration, nutrient cycling, and other key ecological processes closely related to forest management. In Patagonian forests, variation of both managed and unmanaged forests over the years can influence their resilience, where the sustainability implications of harvesting are not fully understood. The aim was to analyse the relationship between seed fall and leaf litter in variable retention harvesting and unmanaged Nothofagus pumilio forests in the medium term. Seed production (S) and leaf litter (LL) in primary unmanaged forests and three retention types were measured over the years after harvesting (YAH). Two indexes (SI, LLI) were calculated based on basal area for both S and LL. Due to harvesting, forest structure varied between retention levels. Both seed production and leaf litter decreased in managed forests, but statistical differences were not found when comparing SI. In addition, LLI was higher in the harvested areas. Forest harvesting progressively showed an increase in LLI values over the YAH, but SI maintained similar values. For all forest types, LLI presented higher values for years with low SI, and this could be linked with a source–sink limitation relationship. Finally, managed forests provide higher values of LLI for similar values of SI, contributed mainly by unmanaged areas. Seed fall and leaf litter production evidenced alterations in the medium term after harvesting. These findings have important implications for the adjustment of forest management practices, and for the understanding of the regulation and support of ecosystem service provision. [ABSTRACT FROM AUTHOR]

Aim: This survey derived from the collaboration between the Palliative Care and Reirradiation Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Its aim was to obtain a real "snapshot" on the treatments of spinal metastases, focusing on reirradiation, among radiation oncologists in Italy. Methods: The survey was elaborated on SurveyMonkey's online interface and was sent via e-mail to all Radiation Oncologists of AIRO that were invited to anonymously fill in the electronic form within 60 days. The questionnaire was prepared by the AIRO "Palliative care" and "Reirradiation" Study Groups and it consisted of 36 questions, 19 single-choice questions, 10 multiple-choice questions and 6 open questions. The data were analyzed and represented with tables and graphs. Results: The survey shows that palliative radiotherapy remains a field of interest for most ROs in the Italian centers. 3D Conventional Radiation Therapy (3DCRT) alone or in combination with other techniques is the primary choice for patients with a life expectancy of less than 6 months. For patients with a life expectancy of more than six months, there is an increased use of new technologies, such as Volumetric Modulated Arc Therapy (VMAT). Factors considered for retreatment are time between first and second treatment, dose delivered to spine metastasis and spinal cord in the first treatment, vertebral stability, symptoms, and/or performance status. The most feared complication are myelopathy followed by vertebral fracture and local recurrence. This explain an increasing focus on patient selection and the use of high technology in the treatment of metastatic patients. Conclusion: Stereotactic body radiotherapy (SBRT) and image-guided radiotherapy allow the administration of ablative RT doses while sparing the constraints of healthy tissue in spinal metastases. However, there is still an unclear and heterogeneous reality in the reirradiation of spinal metastases. A national registry with the aim of clarifying the most controversial aspects of vertebral metastasis retreatments will enable better management of these patients and design more targeted study designs. [ABSTRACT FROM AUTHOR]

Background: It is necessary to determine the implications for managing forest stands using variable retention harvesting for maintaining carbon and for calculating the effects of different harvesting practices on above- and below-ground carbon balance in forest ecosystems. In this context, forest carbon management has gained more attention among managers and policy-makers during recent years. The aim of this study was to determine carbon pool dynamics in different forest ecosystem components after variable retention harvesting (VRH) to characterize the ecological stability and quantify the recovery rate through the years-after-harvesting (YAH). Methods: Carbon pool compartmentalization of 14 different components was determined in 60 harvested and primary unmanaged forests during the first 18 YAH in Tierra del Fuego (Argentina). We compared them using uni- and multi-variate methods, relativizing the outputs with primary unmanaged forests. Results: We determined the effectiveness to retain carbon components in post-harvested stands under different retention strategies (aggregated vs. dispersed). The balance among carbon pool components changed between managed and unmanaged stands across the YAH, and was directly related to the impact magnitude. Aggregated retention improved the ecological stability of the harvested areas, where the below-ground components were more stable than the above-ground components. The recovery rate was directly related to the post-harvesting natural dynamics of the stands. The studied period was not enough to fully recover the C levels of primary unmanaged forests, but VRH showed advantages to increase the C pools in the managed stands. Conclusions: Promoting VRH can improve sustainable forestry at the landscape level and in the long term, generating positive synergies with biodiversity and the provision of ecosystem services. This study provides important new insights into forest carbon management, in particular to setting standards in carbon projects and sets the groundwork for analysing the economics of the mentioned harvesting systems. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT). Methods: The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of 18 F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed 18 F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m2 twice daily orally) was prescribed for the entire treatment duration. Results: Eighteen patients (13 males, 5 females; median age 55 years [range, 41–77 years]) were enrolled in the trial. Patients underwent surgical resection at 8–9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal–Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. 18 F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT. Conclusions: Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate. [ABSTRACT FROM AUTHOR]

Production of value-added compounds from waste materials is of utmost importance for the development of a sustainable society especially regarding their use as catalysts in industrially relevant synthetic reactions. Herein, we show the production of laccases from four white-rot fungi, which were grown on agricultural residues, specifically Trametes versicolor 11269, Pleurotus ostreatus 1020, Panus tigrinus 707 and Lentinula edodes SC-495. The produced laccases were tested on a laccase-mediator system (LMS) for the biocatalytic oxidation of the model substrate benzyl alcohol into benzaldehyde. The LMS was carried out in the presence both of tetrahydrofuran as co-solvent and of the mediator 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) due to its high redox potential and its ability to perform the oxidation. Tolerance studies showed that the dialyzed solutions were able to tolerate 1% (99:1 v/v) of co-solvent, whereas a concentration of 10% v/v had a detrimental activity. Performances in the biocatalytic oxidation of laccase solutions from different purification steps were compared. Similar conversion was observed for laccase in dialysis (raw) and gel filtration (GF) product versus commercial T. versicolor laccase. The latter oxidized almost 99% of substrate while the other laccase solutions were able to reach a conversion from 91% for the laccase solution from P. tigrinus 707 after dialysis, to 50% for the laccase solution from P. ostreatus 1020 after gel filtration. This work highlights the potential of unpurified laccase solutions to be used as catalysts in synthetic reactions. [ABSTRACT FROM AUTHOR]

Previous trials showed the tolerability and efficacy of a palliative radiotherapy (RT) regimen (SHARON) based on the 4 fractions delivered in 2 days in different oncological settings. In order to identify possible predictors of symptomatic response, the purpose of this study is to perform a pooled analysis of previous trials. We analyzed the impact on symptomatic response of the following parameters: tumor site, histological type, performance status (ECOG), dominant symptom, and RT dose using the Chi-square test and Fisher's exact test. One-hundred-eighty patients were analyzed. Median RT dose was 20 Gy (range: 14–20 Gy). The overall response rate was 88.8% (95% CI 83.3–92.7%) while pre- and post-treatment mean VAS was 5.3 (± 7.7) and 2.2 (± 2.2), respectively (p < 0.001). The overall response rate of pain, dyspnea, bleeding, dysphagia, and other symptoms was 86.2%, 90.9%, 100%, 87.5%, and 100%, respectively. Comparing the symptomatic effect based on the analyzed parameters no significant differences were recorded. However, patients with locally advanced disease showed a higher rate of symptomatic responses than metastatic ones (97.3% vs 83.0%; p = 0.021). Finally, the complete pain response rate was more than double in patients with mild to moderate (VAS: 4–7) compared to those with severe (VAS > 7) pain (36.0% vs 14.3%; p = 0.028). This pooled analysis showed high efficacy of the SHARON regimen in the relief of several cancer-related symptoms. The markedly and significantly higher complete pain response rate, in patients with mild-moderate pain, suggests early referral to palliative RT for patients with cancer-related pain. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or switch of systemic treatments and allow local control (LC) and prolonged progression-free survival (PFS), particularly in patients with lymph nodes (LN) oligometastases. We performed a systematic review on stereotactic body radiotherapy (SBRT) in this setting. Papers reporting LC and/or PFS were selected. Data on ADT-free survival, overall survival, and toxicity were also collected from the selected studies. Fifteen studies were eligible (414 patients), 14 of them were retrospective analyses. A high heterogeneity was observed in terms of patient selection and treatment. In one study SBRT was delivered as a single 20 Gy fraction, while in the others the median total dose ranged between 24 and 40 Gy delivered in 3–6 fractions. LC and PFS were reported in 15 and 12 papers, respectively. LC was reported as a crude percentage in 13 studies, with 100% rate in seven and 63.2–98.0% in six reports. Five studies reported actuarial LC (2-year LC: 70.0–100%). PFS was reported as a crude rate in 11 studies (range 27.3–68.8%). Actuarial 2-year PFS was reported in four studies (range 30.0–50.0%). SBRT tolerability was excellent, with only two patients with grade 3 acute toxicity and two patients with grade 3 late toxicity. SBRT for LN oligorecurrences from PCa in safe and provides optimal LC. However, the long-term effect on PFS and OS is still unclear as well as which patients are the best candidate for this approach. [ABSTRACT FROM AUTHOR]

Sustainable forest management is proposed as a solution for many ecological and socio-economic trade-offs associated with different forest uses. In Patagonia, silvopastoral systems were proposed to balance provisioning ecosystem services and other natural values. However, the design of these practices needs a better understanding of livestock production. The objective of this study was to determine changes in the understory forage value and livestock occurrence in Nothofagus antarctica forests of Tierra del Fuego (Argentina) growing under a natural dynamic and in stands with impacts generated by harvesting, fires and silvopastoral uses. We sampled 145 areas determining forest structure, understory forage value (cover, biomass, forage quality) and livestock occurrence (wild and domestic stocking rate), including different forest conditions: (i) six phases of the natural forest cycle (even- and uneven-aged stands), (ii) four types of management and conversion alternatives (different thinning intensities, clear-cuts, and fires), and (iii) three associated environments (forest edges and grasslands). Main results showed that understory cover and biomass did not differ along the natural forest phases, but varied across management alternatives and associated environments. The magnitude of these changes was directly related to the impact degree. Forage quality did not change across the factors and levels. Livestock occurrence is related to the observed changes in the understory; however, a different behaviour was observed between wild and domestic herbivores. The different analyses highlighted the similarities in forage value and livestock occurrence among the different natural forest phases, and showed how the stands with different impacts differed from the control stands. The outputs could be used to improve forest management strategies in the framework of silvopastoral systems at landscape level. [ABSTRACT FROM AUTHOR]

This paper proposes a generalization of Shleifer's (RAND J Econ 16:319–327, 1985) model of yardstick competition to a dynamic framework. In a differential game setting, we show that the yardstick mechanism effectively replicates the first-best solution if players adopt open-loop behaviour rules and are symmetric at the initial time; in the absence of initial symmetry, the social efficiency is reached only in the asymptotic steady state. On the contrary, if players adopt Markovian behaviour rules, then the yardstick pricing rule cannot achieve the first-best solution along the equilibrium path of any Markov Perfect Nash Equilibrium. [ABSTRACT FROM AUTHOR]

COVID-19 has a mild clinical course with low mortality rate in general pediatric population, while variable outcomes have been described in children with cancer. Infectious diseases working party of the AIEOP collected data on the clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric oncology/hematology patients from April 2020 to May 2021, including the second and the third waves of the pandemic in Italy. Factors potentially associated with moderate, severe, or critical COVID-19 were analyzed. Of the 153 SARS-Cov2 infections recorded, 100 were asymptomatic and 53 symptomatic. The course of COVID-19 was mild in 41, moderate in 2, severe in 5, and critical in 5 children. A total of 40.5% of patients were hospitalized, ten requiring oxygen support and 5 admitted to the intensive care unit. Antibiotics and steroids were the most used therapies. No patient died due to SARS-CoV-2 infection. Infections occurring early (< 60 days) after the diagnosis of the underlying disease or after SCT were associated to moderate, severe, and critical disease compared to infections occurring late (> 60 days) or during maintenance therapy. In the patients on active chemotherapy, 59% withdrew the treatment for a median of 15 days. SARS-CoV-2 presented a favorable outcome in children with cancer in Italy during the pandemic. Modification of therapy represents a major concern in this population. Our findings suggest considering regular chemotherapy continuation, particularly in patients on maintenance therapy or infected late after the diagnosis. [ABSTRACT FROM AUTHOR]

Normalizing flows are a class of deep generative models that provide a promising route to sample lattice field theories more efficiently than conventional Monte Carlo simulations. In this work we show that the theoretical framework of stochastic normalizing flows, in which neural-network layers are combined with Monte Carlo updates, is the same that underlies out-of-equilibrium simulations based on Jarzynski's equality, which have been recently deployed to compute free-energy differences in lattice gauge theories. We lay out a strategy to optimize the efficiency of this extended class of generative models and present examples of applications. [ABSTRACT FROM AUTHOR]

Of all the socio-economic changes caused by the Covid-19 pandemic, the disruption to workforce organizations will probably leave the largest indelible mark. The way work will be organized in the future will be closely linked to the experience of working under the same institution's response to the pandemic. This paper aims to fill the gap in knowledge about smart working (SW) in public organizations, with a focus on the experience of the employees of two Italian research organizations, CNR and INGV. Analysing primary data, it explored and assessed how SW had been experienced following the implementation of governmental measures aimed at limiting the spread of COVID-19. [ABSTRACT FROM AUTHOR]

Both anxiety and autism spectrum disorder (ASD) are associated with atypical physiological activity. Few studies have systematically assessed the resting physiological activity in ASD with co-occurring anxiety disorders. We tested 75 participants divided in four groups: youth with ASD, with (ASD + Anxiety = 22, 6F, 12.29 ± 2.83 years old) and without co-occurring anxiety (ASD Alone = 15, 6F, 11.59 ± 2.85 years old) and compared their physiological profile with that of matched typically developing controls (TDC) with (Anxiety Alone = 16, 6F, 11.24 ± 3.36 years old) and without co-occurring anxiety disorders (TDC = 22, 8F, 11.88 ± 2.88 years old). Results indicated reduced sympathetic and parasympathetic activity at rest in ASD as compared to TDC youth. ASD + Anxiety and Anxiety Alone groups showed different sympathetic, but similar parasympathetic activity. These findings suggest that autonomic profile-based approaches may advance research, diagnosis, and treatment of ASD and anxiety. [ABSTRACT FROM AUTHOR]

Treatment discontinuation due to adverse events (AEs) occurred more frequently in patients treated with ITd (17%), mostly due to PN (6%), as compared with those who received Id (10%), ICd (12%), or IBd (9%; Fig. Id ixazomib-dexamethasone, ICd ixazomib-cyclophosphamide-dexamethasone, ITd ixazomib-thalidomide-dexamethasone, IBd ixazomib-bendamustine-dexamethasone. Bortezomib is a backbone of induction therapies for older patients with multiple myeloma (MM), either in combination with lenalidomide-dexamethasone (VRd) or with daratumumab-melphalan-prednisone (DVMP) [[1]]. During the induction phase, ixazomib dose reductions were more common in patients receiving triplets (ICd, 24%; ITd, 20%; IBd, 18%) than in those treated with Id (2%). [Extracted from the article]

Introduction: The COVID-19 pandemic has challenged healthcare systems worldwide over the last few months, and it continues to do so. Although some restrictions are being removed, it is not certain when the pandemic is going to be definitively over. Pandemics can be seen as a highly complex logistic scenario. From this perspective, some of the indications provided for palliative radiotherapy (PRT) during the COVID-19 pandemic could be maintained in the future in settings that limit the possibility of patients achieving symptom relief by radiotherapy. This paper has two aims: (1) to provide a summary of the indications for PRT during the COVID-19 pandemic; since some indications can differ slightly, and to avoid any possible contradictions, an expert panel composed of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) and the Palliative Care and Supportive Therapies Working Group (AIRO-palliative) voted by consensus on the summary; (2) to introduce a clinical care model for PRT [endorsed by AIRO and by a spontaneous Italian collaborative network for PRT named "La Rete del Sollievo" ("The Net of Relief")]. The proposed model, denoted "No cOmpRoMise on quality of life by pALliative radiotherapy" (NORMALITY), is based on an AIRO-palliative consensus-based list of clinical indications for PRT and on practical suggestions regarding the management of patients potentially suitable for PRT but dealing with highly complex logistics scenarios (similar to the ongoing logistics limits due to COVID-19). Material and Methods: First, a summary of the available literature guidelines for PRT published during the COVID-19 pandemic was prepared. A systematic literature search based on the PRISMA approach was performed to retrieve the available literature reporting guideline indications fully or partially focused on PRT. Tables reporting each addressed clinical presentation and respective literature indications were prepared and distributed into two main groups: palliative emergencies and palliative non-emergencies. These summaries were voted in by consensus by selected members of the AIRO and AIRO-palliative panels. Second, based on the summary for palliative indications during the COVID-19 pandemic, a clinical care model to facilitate recruitment and delivery of PRT to patients in complex logistic scenarios was proposed. The summary tables were critically integrated and shuffled according to clinical presentations and then voted on in a second consensus round. Along with the adapted guideline indications, some methods of performing the first triage of patients and facilitating a teleconsultation preliminary to the first in-person visit were developed. Results: After the revision of 161 documents, 13 papers were selected for analysis. From the papers, 19 clinical presentation items were collected; in total, 61 question items were extracted and voted on (i.e., for each presentation, more than one indication was provided from the literature). Two tables summarizing the PRT indications during the COVID-19 pandemic available from the literature (PRT COVID-19 summary tables) were developed: palliative emergencies and palliative non-emergencies. The consensus of the vote by the AIRO panel for the PRT COVID-19 summary was reached. The PRT COVID-19 summary tables for palliative emergencies and palliative non-emergencies were adapted for clinical presentations possibly associated with patients in complex clinical scenarios other than the COVID-19 pandemic. The two new indication tables (i.e., "Normality model of PRT indications") for both palliative emergencies and palliative non-emergencies were voted on in a second consensus round. The consensus rate was reached and strong. Written forms facilitating two levels of teleconsultation (triage and remote visits) were also developed, both in English and in Italian, to evaluate the patients for possible indications for PRT before scheduling clinical visits. Conclusion: We provide a comprehensive summary of the literature guideline indications for PRT during COVID-19 pandemic. We also propose a clinical care model including clinical indications and written forms facilitating two levels of teleconsultation (triage and remote visits) to evaluate the patients for indications of PRT before scheduling clinical visits. The normality model could facilitate the provision of PRT to patients in future complex logistic scenarios. [ABSTRACT FROM AUTHOR]

Italy has been the first nation outside of Asia to face the COVID-19 outbreak. To limit viral transmission of infection, by March 10th, 2020, the Italian Government has ordered a national lockdown, which established home confinement, home (smart) working, and temporary closure of non-essential businesses and schools. The present study investigated how these restrictive measures impacted mothers and their pre-school children's behavioral habits (i.e., sleep timing and quality, subjective time experience) and psychological well-being (i.e., emotion regulation, self-regulation capacity). An online survey was administered to 245 mothers with pre-school children (from 2 to 5 years). Mothers were asked to fill the survey thinking both on their habits, behaviors, and emotions and on those of their children during the quarantine, and retrospectively, before the national lockdown (i.e., in late February). A general worsening of sleep quality and distortion of time experience in both mothers and children, as well as increasing emotional symptoms and self-regulation difficulties in children, was observed. Moreover, even when the interplay between the behavioral and psychological factors was investigated, the factor that seems to mostly impact both mothers' and children's psychological well-being was their sleep quality. Overall, central institutions urgently need to implementing special programs for families, including not only psychological support to sustain families with working parents and ameliorating children's management. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) in early stages benefits from local ablative treatments such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). In this context, radiotherapy (RT) has shown promising results but has not been thoroughly evaluated. Magnetic resonance-guided RT (MRgRT) may represent a paradigm shifting improvement in stereotactic body radiotherapy (SBRT) for liver tumors. Methods: We retrospectively evaluated HCC patients treated on a hybrid low-tesla MRgRT unit. A total biologically effective dose (BED) > 100 Gy was delivered in 5 consecutive fractions, respecting the appropriate organs-at-risk constraints. Hybrid MR scans were used for treatment planning and cine MR was used for delivery gating. Patients were followed up for toxicity and treatment–response assessment. Results: Ten patients were enrolled, with a total of 12 lesions. All the lesions were irradiated with no interruptions. Six patients had already performed previous local therapies. Median follow-up after SBRT was 6.5 months (1–25). Two cases of acute toxicity were reported (G ≤ 2 according to CTCAE v4.0). At the time of the analysis, 90% of the population presented local control. Child–Pugh before and after treatment remained unchanged in all but one patient. Conclusion: MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the potential benefits of a hypofractionated radiotherapy boost (HRB) after chemotherapy (CT) and concomitant chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) patients. Primary endpoints were early and late toxicity, local control (LC) and pain-free progression (PFP) assessment. Two-years overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were secondary endpoints. Materials and methods: Patients (pts) affected by unresectable non-metastatic LAPC, previously treated with CT and CRT in upfront or sandwich setting, were selected for sequential HRB. Total prescribed dose was 30 Gy in 5 fractions (fr) to pancreatic primary lesion. Dose de-escalation was allowed in case of failure in respecting organs at risk constraints. Early and late toxicity were assessed according to CTCAE v.4.0 classification. The Kersh-Hazra scale was used for pain assessment. Local Control, PFP, MFS and DFS were calculated from the date of HRB to the date of relapse or the date of the last follow-up. Results: Thirty-one pts affected by unresectable, non-metastatic LAPC were consecutively enrolled from November 2004 to October 2019. All pts completed the planned HRB. Total delivered dose varied according to duodenal dose constraint: 20 Gy in 5 fr (N: 6; 19.4%), 20 Gy in 4 fr (N: 5; 16.2%), 25 Gy in 5 fr (N: 18; 58.0%) and 30 Gy in 6 fr (N: 2; 6.4%). Early and late toxicity were assessed in all pts: no Grade 3 or 4 acute gastrointestinal toxicity and no late gastrointestinal complications occurred. Median LC was 19 months (range 1–156) and 1- and 2-year PFP were 85% and 62.7%, respectively (median 28 months; range 2–139). According to the Kersh-Hazra scale, four pts had a Grade 3 and four pts had a Grade 1 abdominal pain before HRB. At the last follow-up only 3/31 pts had residual Grade 1 abdominal pain.Median MFS was 18 months (range 1–139). The 2-year OS after HRB was 57.4%, while 2-year OS from diagnosis was 77.3%. Conclusion: Treatment intensification with hypofractionated radiotherapy boost is well tolerated in pts affected by unresectable LAPC previously treated with CT/CRT. Its rates of local and pain control are encouraging, supporting its introduction in clinical practice. Timing, schedule and dose of HRB need to be further investigated to personalize therapy and optimize clinical advantages. [ABSTRACT FROM AUTHOR]

The aim of this analysis was to assess the efficacy of stereotactic body radiotherapy (SBRT) in terms of local control (LC) and progression-free survival (PFS) in patients with lymph node metastases (NMs) from solid tumors. A systematic literature search from the earliest date to July 25th, 2019 was performed following PRISMA guidelines. Papers reporting LC and/or PFS of NMs using SBRT (< 10 fractions) were selected. The clinical outcomes rates were pooled by means of a random or fixed-effect model. Twenty-nine studies were eligible (969 patients: 938 (LC) and 698 (PFS)). LC and PFS results were reported in 28 and 18 papers, respectively. Heterogeneity was observed in terms of patient and treatment characteristics. Pooled 2-year LC reported in 11 studies was 79.3% (95%CI, 72.8%–85.7%) with substantial heterogeneity between studies (Q2 test: p = 0.0083; I2 = 57.9%), while pooled 2-year PFS reported in 8 studies was 35.9% (95%CI, 22.1%–49.7%) with very high heterogeneity between studies (Q2 test: p < 0.0001; I2 = 86.1%). Grade ≥ 3 and Grade 5 toxicity rates were 2.0% and 0.2%, respectively. SBRT of NMs seems to be safe and effective in terms of LC. However, due to the marked heterogeneity of the included series, prospective studies are required. [ABSTRACT FROM AUTHOR]

In this paper we investigate whether the services offered by museums are affected by the choices of neighbors, and we discuss whether the evidence can document that competition processes are at work. Specifically, we take into account the Italian case, where governmental and private museums coexist. Resorting to spatial auto-regressive models, we show that the choices of a museum concerning services' supply are significantly influenced by the choices of its neighbors. However, we cast several doubts that this piece of evidence can be solely due to sound competition among museums. [ABSTRACT FROM AUTHOR]

Usually, stands with aging trees are considered forests with higher conservation values, regardless their structural diversity and other functional attributes. Natural stands present a wide range of age structures, from even-aged stands growing at different development growth phases (e.g. CO = stands at initial or final optimum development growth phase, MD = stands at mature or decaying development growth phases) to uneven-aged stands with mixed development growth phases (e.g. UOG = stands combining mature or decaying development growth phases with initial or final optimum development growth phases, UMD = stands combining only mature and decaying development growth phases). The aim of this work was to compare richness and cover of understory vascular plants of even- and uneven-aged stands of Nothofagus antarctica (ñire) forests in Tierra del Fuego (Argentina), and relate these characteristics with abiotic, soil and forest structure variables. A total of 75 stands were sampled across the natural range distribution of the forests, where understory (point intercept method), forest structure (angle count sampling and eye-fish photos) and environmental (soil) variables were measured. 17 one-way ANOVAs were conducted using Tukey test at p < 0.05 to compare the means. Among forest structure and environmental variables, cover (F = 4.3, p = 0.007), radiation (F = 4.4, p = 0.006), phosphorous (F = 3.9, p = 0.012), tree density (F = 10.3, p < 0.001), tree diameter (F = 10.3, p < 0.001) and stand growth (F = 4.9, p = 0.004) showed significant differences, and in general with a positive or negative trend across the MD—UMD—UOG—CO gradient. Total (F = 6.5, p < 0.001) and native species richness of the understory (F = 7.2, p < 0.001) were significantly different among forest types, where UMD > UOG > MD > CO (17–28 total, and 13–24 native species, respectively). Neither exotic species richness (4–5 species) nor understory cover significantly changed among treatments (total, dicots, ferns and bryophytes). However, monocots cover significantly differed among treatments (F = 3.9, p = 0.012), where UMD > MD > UOG > CO. Finally, indicator species cover for environmental degradation did not present significant differences (F = 2.1, p = 0.106), but they were positive related to forests growing in mature stages. We concluded that uneven-aged stands presented significantly higher conservation values compared to even-aged stands, where mature/decay stands have better conservation values than optimum growth development phases. These findings can be used for better silviculture practices that combine silvopastoral use and conservation strategies. [ABSTRACT FROM AUTHOR]

Since 2008, the kiwifruit industry has been devastated by a pandemic outbreak of Pseudomonas syringae pv. actinidiae (Psa), the causal agent of bacterial canker. This disease has become the most significant limiting factor in kiwifruit production. Psa colonizes different organs of the host plant, causing a specific symptomatology on each of them. In addition, the systemic invasion of the plant may quickly lead to plant death. Despite the massive risk that this disease poses to the kiwifruit industry, studies focusing on Psa ecology have been sporadic, and a comprehensive description of the disease epidemiology is still missing. Optimal environmental conditions for infection, dispersal and survival in the environment, or the mechanisms of penetration and colonization of host tissues have not been fully elucidated yet. The present work aims to provide a synthesis of the current knowledge, and a deeper understanding of the epidemiology of kiwifruit bacterial canker based on new experimental data. The pathogen may survive in the environment or overwinter in dormant tissues and be dispersed by wind or rain. Psa was observed in association with several plant structures (stomata, trichomes, lenticels) and wounds, which could represent entry points for apoplast infection. Environmental conditions also affect the bacterial colonization, with lower optimum values of temperature and humidity for epiphytic than for endophytic growth, and disease incidence requiring a combination of mild temperature and leaf wetness. By providing information on Psa ecology, these data sets may contribute to plan efficient control strategies for kiwifruit bacterial canker. [ABSTRACT FROM AUTHOR]