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Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumors anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.

Abstract Background Neuropathic pain (NP) is a chronic and disabling condition, caused by a lesion or disease of the somatosensory nervous system, characterized by a systemic inflammatory state. Signs and associated symptoms are rarely recognized, and response to usual analgesic drugs is poor. Antidepressant drugs are first-line agents for the treatment of NP. This narrative review aims to summarize the role of antidepressant drugs in treating NP and their mechanism of action, focusing on the effects on inflammatory cytokines. Main text. Peripheral nerve injury leads to a local inflammatory response and to the disruption of the blood-medullary barrier, allowing the influx of peripheral immune cells into the central nervous system. Antidepressants have antinociceptive effects because they recruit long-term neuronal plasticity. Amitriptyline modulates the inflammatory response due to the reduction of the mRNA of pro-inflammatory cytokines acting as an adenosine agonist and leading to the activation of the A3AR receptor. Through toll-like receptors, local inflammation determines the release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) that drives and stimulates the hyperflammation in NP. Nortriptyline has an important antiallodynic effect in NP as it determines the recruitment of norepinephrine in the dorsal root ganglia. By modulating the β2-adrenoreceptors expressed by non-neuronal satellite cells, it inhibits the local production of TNF-α and determines a reduction of NP symptoms. Following the administration of antidepressants, there is a reduction in the production of TNF-α in the brain which in turn transforms the function of the α2-adrenergic receptor from an inhibitor to an activator of the release of norepinephrine. This is important to prevent the development of chronic pain. Conclusion Inflammatory cytokines are the main players in a bidirectional communication between the central and peripheral nervous system and the immune system in NP. Antidepressants have an important role in NP. Further research should explore the interaction between neuroinflammation in NP, the effects of antidepressants and the clinical relevance of this interaction.

Abstract Fiddler crabs, as coastal ecosystem engineers, play a crucial role in enhancing biodiversity and accelerating the flow of material and energy. Here we show how widespread crab burrows modify the carbon sequestration capacity of different habitats across a large climatic gradient. The process of crab burrowing results in the reallocation of sediment organic carbon and humus. Crab burrows can increase more greenhouse gases emissions compared to the sediment matrix (CO2: by 17–30%; CH4: by 49–141%). Straightforward calculations indicate that these increased emissions could offset 35–134% of sediment carbon burial in these two ecosystems. This research highlights the complex interactions between crab burrows, habitat type, and climate which reveal a potential lower carbon sink function of blue carbon ecosystems than previously expected without considering crab burrows.

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2–8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1-year OS was 70 %, and the median was 20.8 months (17–36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0–7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

Abstract The distribution and intensity of fault damage zones provides insight into fault activity and its relationship to fluid flow in the crust. Presently, measures of the in‐situ distribution of fault damage remain limited and along‐strike studies are rare. This study focuses on an offshore section Palos Verdes Fault damage zone that spans 28 km, near Los Angeles, California. To investigate the previously unresolved shallow (∼400 m below the seafloor) fault damage zone we use densely spaced (∼500 m line separation) newly collected sparker multichannel seismic lines and sub‐bottom profiles. The combination of high‐resolution acquisition methods and specialized seismic processing workflows provide improved imaging of shallow faulting. We apply a multi‐trace similarity technique to identify discontinuities in the seismic data that may be attributed to faults and fractures. This fault detection approach reveals diverse fault damage patterns on adjacent seismic profiles. However, a discernible damage zone pattern emerges by stacking multiple damage detection profiles along strike. We find that peak damage identified in this way corresponds to the active main fault strand, confirmed in this study, and thus the technique may be useful for identifying active fault strands elsewhere. Additionally, we observe that the variable width of the damage zone along strike is controlled by fault obliquity. Furthermore, our observations reveal a correlation between fault damage and seafloor fluid seeps visible in the water column, suggesting that damage plays a role in controlling fluid flow around the fault.

Abstract The tumor microenvironment is a complex ecosystem that plays a critical role in cancer progression and treatment response. Recently, extracellular amyloid fibrils have emerged as novel components of the tumor microenvironment; however, their function remains elusive. In this study, we establish a direct connection between the presence of amyloid fibrils in the secretome and the activation of YAP, a transcriptional co-activator involved in cancer proliferation and drug resistance. Furthermore, we uncover a shared mechano-signaling mechanism triggered by amyloid fibrils in both melanoma and pancreatic ductal adenocarcinoma cells. Our findings highlight the crucial role of the glycocalyx protein Agrin which binds to extracellular amyloid fibrils and acts as a necessary factor in driving amyloid-dependent YAP activation. Additionally, we reveal the involvement of the HIPPO pathway core kinase LATS1 in this signaling cascade. Finally, we demonstrate that extracellular amyloid fibrils enhance cancer cell migration and invasion. In conclusion, our research expands our knowledge of the tumor microenvironment by uncovering the role of extracellular amyloid fibrils in driving mechano-signaling and YAP activation. This knowledge opens up new avenues for developing innovative strategies to modulate YAP activation and mitigate its detrimental effects during cancer progression.

A unique acoustic call type was identified and attributed to Bryde’s whales in the central North Pacific in 2015, but little is known about the distribution, calling behavior, or swimming behavior of Bryde’s whales in the region. Acoustic detections attributed to Bryde’s whales were used to localize and track individual whales on the U.S. Pacific Missile Range Facility (PMRF) in Kaua‘i, Hawai‘i. This study included 150 acoustically derived tracks from recordings spanning the years 2011–2022 with recording effort in nearly every month. Bryde’s whale movement was examined relative to calendar year, day of year, hour of day, wind speed, and acoustic calling rate. Hidden Markov models were used to identify two kinematic states (slower, less directional movement and faster, more directional movement). The findings indicate that Bryde’s whales were more likely to travel in a faster and more directional state during the daytime than at night and between May and August when compared to other times of year. The along-track acoustic cue rate was examined for 118 tracks, and the findings indicate a possible lengthening of the median inter-call interval over the duration of the study period. These results are an important first step in understanding more about behavior in Bryde’s whales, a relatively under-studied species.

Objective: To evaluate the impact of metastases-directed stereotactic body radiotherapy (SBRT) on health-related quality of life (HRQoL) in men with oligometastatic prostate cancer (PCa) using real-world data from the OligoCare cohort. Materials and methods: OligoCare is a pragmatic, observational cohort designed to assess the impact of metastases-directed SBRT on patients with oligometastatic disease (OMD). We report an interim analyses of the secondary endpoint HRQoL, assessed using the EORTC QLQ-C30, within six months of metastases-directed SBRT for oligometastatic disease in men with PCa among the first 1600 registered patients. HRQoL data collection was optional within the OligoCare cohort. To compare HRQoL between baseline and first follow-up assessment, a Wilcoxon signed-rank test was used. A multiple linear regression model was used to explore the HRQoL associations with predefined factors. Results: Out of the 1600 registered patients, 658 were treated for oligometastatic PCa, of which 233 had baseline QoL data and 132 patients had both baseline and follow-up HRQoL data. At baseline, most patients had a WHO performance status of 0 or 1 (87 %), were de-novo oligometastatic (79 %), had one metastasis (90 %), and had a good overall global health status (mean 80.81, SD16.11, IQR 75–92). 51 % received hormonal therapy as concomitant systemic treatment. Patients with comorbidities as assessed by the Charlson Comorbidity index had a worse global health status at baseline (-4.88, 95 % CI:-9.35, −0.42). No clinically meaningful significant difference in global health status was observed at first assessment following SBRT (median 3.0 months) compared with baseline (mean difference 2.27, 95 % CI:-1.54, 6.08). Upon evaluating the proportions, meaningful clinically important differences (a 10-point or more difference) was observed in, 17 % and 11 % of the patients reporting deterioration and improvement of global health status, respectively. Conclusion: Metastases-directed stereotactic body radiotherapy had no negative impact on global HRQoL within the first six months after treatment.

The aquatic ecotoxicity of three α-amino acid-derived polyamidoamines (PAAs) was studied using zebrafish embryos as a viable vertebrate model organism. The PAAs examined were water-soluble amphoteric polyelectrolytes with a primarily negative charge, which were efficient flame retardants for cotton. The fish embryo acute toxicity test performed with PAA water solutions using 1.5–500 mg L−1 concentrations showed that toxicity did not statistically differ from the control. The survival rates were indeed >90%, even at the highest concentration; the hatching rates were >80%; and the numbers of morphological defects were comparable to those of the control. Tests using transgenic zebrafish lines indicated that the numbers of microscopic vascular and musculoskeletal defects were comparable to the control, with one random concentration showing doubled alterations. Sensory–motor tests in response to visual and tactile stimuli were also performed. In the presence of PAAs, embryos exposed to alternating light/dark cycles showed an insignificant mobility reduction during the dark phase. Touch-evoked response tests revealed a mild effect of PAAs on the neuromotor system at concentrations > 10 mg L−1. The cystine/glycine copolymer at 100 mg L−1 exhibited the greatest effect. Overall, the studied PAAs showed a minimal impact on aquatic systems and should be further considered as promising ecofriendly materials.

Six differently charged amphoteric polyamidoamines, synthesized by the polyaddition of N,N′-methylenebisacrylamide to alanine, leucine, serine, arginine (M-ARG), glutamic acid (M-GLU) and a glycine/cystine mixture, were screened for their short-term phytotoxicity using a seed germination test. Lepidium sativum L. seeds were incubated in polyamidoamine water solutions with concentrations ranging from 0.156 to 2.5 mg mL−1 at 25 ± 1 °C for 120 h. The seed germination percentage (SG%), an indicator of acute toxicity, and both root and shoot elongation, related to plant maturation, were the considered endpoints. The germination index (GI) was calculated as the product of relative seed germination times relative radical growth. The SG% values were in all cases comparable to those obtained in water, indicating no detectable acute phytotoxicity of the polyamidoamines. In the short term, the predominantly positively charged M-ARG proved to be phytotoxic at all concentrations (GI < 0.8), whereas the predominantly negatively charged M-GLU proved to be biostimulating at intermediate concentrations (GI > 1) and slightly inhibitory at 2.5 mg mL−1 (0.8 < GI < 1). Overall, polyamidoamine phytotoxicity could be correlated to charge distribution, demonstrating the potential of the test for predicting and interpreting the eco-toxicological behavior of water-soluble polyelectrolytes.

Background: Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed on the surface of tumor cells in most of the patients affected by prostate adenocarcinoma (PCa). However, PSMA expression has also been demonstrated in the endothelial cells of newly formed vessels of various solid tumors, suggesting a role for PSMA in neoangiogenesis. In this scenario, gallium-68 (68Ga) or fluoro-18 (18F)-labeled PSMA positron emission tomography (PET) may play a role in tumors other than PCa, generally evaluated employing other radiopharmaceuticals targeting different pathways. This review aims to investigate the detection rate of PSMA-PET compared to other radiopharmaceuticals (especially [18F]FDG) in non-prostate tumors to identify patients who may benefit from the use of such a theragnostic agent. Methods: We performed a bibliographic search on three different databases until February 2024 using the following terms: “positron emission tomography”, “PET”, “PET/CT”, “Prostate-specific membrane antigen”, “PSMA”, “non-prostate”, “not prostate cancer”, “solid tumor”, “FDG”, “Fluorodeoxyglucose”, “FAPi”, “FET”, “MET”, “DOPA”, “choline”, “FCH”, “FES”, “DOTATOC”, “DOTANOC”, and “DOTATATE”. Only original articles edited in English with at least 10 patients were included. Results: Out of a total of 120 articles, only 25 original articles comparing PSMA with other radiotracers were included in this study. The main evidence was demonstrated in renal cell carcinoma, where PSMA showed a higher detection rate compared to [18F]FDG PET/CT, with implications for patient management. PSMA PET may also improve the assessment of other entities, such as gliomas, in defining regions of early neoangiogenesis. Further data are needed to evaluate the potential role of PSMA-PET in triple-negative breast cancer as a novel therapeutic vascular target. Finally, unclear applications of PSMA-PET include thyroid and gastrointestinal tumors. Conclusions: The present review shows the potential use of PSMA-labeled PET/CT in solid tumors beyond PCa, underlining its value over other radiopharmaceuticals (mainly [18F]FDG). Prospective clinical trials with larger sample sizes are crucial to further investigate these possible clinical applications.

Abstract Introduction Cardiac arrhythmias, including ventricular tachycardia (VT), stand as a significant threat to health, often leading to mortality and sudden cardiac death. While conventional treatments for VT exhibit efficacy, cases of refractory VT pose challenges. Stereotactic Arrhythmia Radioablation (STAR) offers a novel approach, delivering precise high‐dose radiation to well‐defined targets with minimal collateral damage. This study explores the potential of STAR as an alternative therapy, especially for high‐risk patients or those with refractory VT. Methods This research reviews ongoing studies and preliminary investigations into the evaluation of the efficacy and safety of STAR. The method involves targeted radiation delivery, assessing reductions in VT recurrence and the early safety profile in refractory VT patients. However, given STAR's early stage and limited clinical evidence, cautious interpretation is advised. Results Preliminary findings indicate a reduction in VT recurrence with STAR, suggesting promise as a therapeutic option. Early safety profiles are encouraging, but definitive statements on efficacy and safety require further investigation. Positive initial outcomes underscore the need for additional data and long‐term studies. Conclusion Stereotactic Arrhythmia Radioablation is recently emerging as a promising treatment for refractory VT. While early results are encouraging, careful interpretation is needed, due to STAR's early stages. Ongoing investigations are critical for a comprehensive understanding of its long‐term efficacy and tolerability. This review provides fundamental insights into STAR's background, principles, pre‐treatment procedures, clinical implications, and toxicity, setting the stage for future research in this evolving therapeutic field.

IntroductionPhenolic compounds in lettuce can increase by the application of positive stress (eustress) such as moderate saline stress. Phenolic compounds possess antioxidant capacity that is a key factor in the detoxification of excess reactive oxygen species. A double-blinded randomized interventional and placebo- controlled study design was carried out to compare the effect of daily dietary eustress lettuce ingestion in hepatic, lipid, bone, glucose, and iron metabolism.MethodsForty-two healthy volunteers, 19 female and 23 male participants, were divided into two groups. Participants were randomized into a polyphenol-enriched treatment (PET) arm or control arm. Each arm consumed 100 g/day of control or eustress (polyphenols enriched treatment = PET) lettuce for 12 days. Primary study outcomes were serological analysis for assessing hepatic, lipid, bone, iron, and glucose markers at baseline and after 12 days. Secondary outcomes assessed body composition.ResultsSalinity stress reduced plant yield but increased caffeic acid (+467%), chlorogenic acid (+320%), quercetin (+538%), and rutin (+1,095%) concentrations. The intake of PET lettuce reduced PTH, low-density lipoprotein (LDL), cholesterol, alanine transaminase (ALT), and aspartate transaminase (AST) enzyme levels and increased vitamin D and phosphate levels, while iron and glucose metabolism were unaffected.DiscussionSupplementation with eustress lettuce by increasing polyphenols concentration ameliorates hepatic, lipid, and bone homeostasis. Body composition was not affected.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT06002672, identifier: NCT06002672.

This study aimed to assess the effect of unroasted, dark and very dark roasted coffee on obesity and metabolic disorders in obese rats. All coffee samples significantly reduced weight gain (∼17%) compared to obese control. Coffee reduced glucose levels (∼17%) upon a glucose tolerance test in all cases compared to the control, while fasting glucose only decreased (∼26%) with very dark coffee. Insulin levels and insulin resistance significantly decreased (∼77% and 65% respectively) with all coffee samples compared to the control. Unroasted and dark roasted coffee decreased triglycerides (∼21% and ∼ 11%, respectively), and unroasted coffee also reduced free fatty acids (∼43%) and adipocyte size. Coffee decreased liver steatosis (∼55%) and Caspase-3 levels (∼27%), regardless of the roasting degree. Overall, coffee plays a positive role in restraining obesity and related metabolic disorders but, depending on the metabolic pathway and relevant marker, an effect of roasting could be either found or not.

Marine environmental monitoring is essential to ensure that heavy-metal (HM) concentrations remain within safe limits. Most seawater analyses currently consider sediment or water samples, but this approach does not apply to rocky substrates, where water samples can only indicate immediate contamination. We used two common Mediterranean algae species, Cystoseira compressa and Ericaria mediterranea, as bioindicators living in the intertidal zone on rocky substrates along the seacoast. HM concentrations were assessed over a one-year period in the perennial base crust and in the seasonal frond, considering marine sites characterised by different contamination risks. Both algae showed that HMs accumulate mainly in the perennial base rather than in the seasonal frond. Furthermore, the algae species always showed a different order of bioaccumulation factors: Cd > Ni > Pb > Cr > Cu > Mn > Zn for the frond and Pb > Cr > Ni > Cd > Mn > Cu > Zn for the base. Our study shows that C. compressa and E. mediterranea accumulate HM consistently with the types of sites analysed and differentially with respect to the part of the thallus. These results demonstrate that these algae can be effectively used as reliable bioindicators to assess the presence of HM in marine environments with rocky substrates, providing both short- and long-term monitoring.

Background and purpose: The 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL) provides an innovative modality for improved cardiac imaging when planning radiation treatment. No MRL based cardiac atlases currently exist, thus, we sought to comprehensively characterize cardiac substructures, including the conduction system, from cardiac images acquired using a 1.5 T MRL and provide contouring guidelines. Materials and methods: Five volunteers were enrolled in a prospective protocol (NCT03500081) and were imaged on the 1.5 T MRL with Half Fourier Single-Shot Turbo Spin-Echo (HASTE) and 3D Balanced Steady-State Free Precession (bSSFP) sequences in axial, short axis, and vertical long axis. Cardiac anatomy was contoured by (AS) and confirmed by a board certified cardiologist (JR) with expertise in cardiac MR imaging. Results: A total of five volunteers had images acquired with the HASTE sequence, with 21 contours created on each image. One of these volunteers had additional images obtained with 3D bSSFP sequences in the axial plane and additional images obtained with HASTE sequences in the key cardiac planes. Contouring guidelines were created and outlined. 15–16 contours were made for the short axis and vertical long axis. The cardiac conduction system was demonstrated with eleven representative contours. There was reasonable variation of contour volume across volunteers, with structures more clearly delineated on the 3D bSSFP sequence. Conclusions: We present a comprehensive cardiac atlas using novel images acquired prospectively on a 1.5 T MRL. This cardiac atlas provides a novel resource for radiation oncologists in delineating cardiac structures for treatment with radiotherapy, with special focus on the cardiac conduction system.

IntroductionPlacentas of term infants with birth asphyxia are reported to have more lesion such as maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM) and chorioamnionitis with fetal response (FIR) than those of term infants without birth asphyxia. We compared the placental pathology of asphyxiated newborns, including those who developed hypoxic-ischemic encephalopathy (HIE), with non-asphyxiated controls.MethodsWe conducted a retrospective case–control study of placentas from neonates with a gestational age ≥ 35 weeks, a birthweight ≥ 1,800 g, and no malformations. Cases were asphyxiated newborns (defined as those with an umbilical artery pH ≤ 7.0 or base excess ≤ −12 mMol, 10-minute Apgar score ≤ 5, or the need for resuscitation lasting >10 min) from a previous cohort, with (n=32) and without (n=173) diagnosis of HIE. Controls were non-asphyxiated newborns from low-risk l (n= 50) or high-risk (n= 68) pregnancies. Placentas were analyzed according to the Amsterdam Placental Workshop Group Consensus Statement 2014.ResultsCases had a higher prevalence of nulliparity, BMI>25, thick meconium, abnormal fetal heart monitoring, and acute intrapartum events than controls (p

Luca Nicosia,1 Claudio Vitale,1 Francesco Cuccia,1 Vanessa Figlia,1 Niccolò Giaj-Levra,1 Rosario Mazzola,1 Francesco Ricchetti,1 Michele Rigo,1 Ruggero Ruggieri,1 Stefano Cavalleri,2 Filippo Alongi1,3 1Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Verona, Negrar, Italy; 2Urology Division, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Negrar, Italy; 3University of Brescia, Brescia, ItalyCorrespondence: Luca Nicosia, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Verona, Negrar, Italy, Tel +39 045-6014800, Fax +045-60148071, Email lucanicosia.rg@gmail.comAim: To evaluate the impact of Ialuril soft Gels® (HA) in reducing acute genito-urinary (GU) toxicity in patients treated with adjuvant or salvage radiotherapy for a prostate cancer relapse.Material and Methods: The data of 305 patients were retrospectively collected. One hundred and five patients underwent adjuvant radiotherapy (aRT), while 200 a salvage treatment (sRT). GU toxicity was evaluated according to CTCAE v5.0. Every patient received RT combined with HA.Results: Grade 1– 2 GU toxicity during RT was represented by: urgency (36%), dysuria (23%), increased urinary frequency (12.1%), and urinary retention (11.8%). Nevertheless, the majority of symptoms were present at the baseline. Grade 3 severe toxicity was represented by 10 (3.2%) cases of incontinence and 3 (1%) cases of urgency. The incidence of any-grade RT-related GU toxicity was significantly higher in the aRT group than the salvage group (esRT + sRT) (83.8% versus 64.5%). When comparing the incidence of any-grade RT-related GU toxicity in the aRT, esRT, and sRT groups we observed a significant correlation favoring sRT, over esRT, and aRT.Conclusion: Postoperative hypofractionated radiotherapy is safe and not correlated with increase of unexpected toxicity when administered with oral hyaluronic acid. A prospective study is necessary to confirm these results.Keywords: prostate cancer, hyaluronic acid, postoperative radiotherapy, salvage radiotherapy, hypofractionation, toxicity

Green roofs have been widely recognized as sustainable nature-based solutions to mitigate floods in urban areas, which, in the last decades, are increasing due to the combination of intense worldwide urbanization and climate change. Besides flood mitigation, green roofs provide additional benefits for the urban environment (e.g., reducing the urban heat island and ensuring energy saving for the underneath building). Moreover, green roofs facilitate the increase of urban biodiversity, attracting different species of small animals, and upgrade the city aesthetic value. Among the different types of green roofs, multilayer blue-green roofs present an additional layer to store water during rainfall events. As part of the Polder Roof field lab project, prototypes of multilayer blue-green roof developed by the Dutch company Metropolder were installed in four Italian cities: Cagliari, Palermo, Perugia, and Viterbo. The four prototypes and the experimental set up are described and the potential benefits of this innovative solution are discussed. Preliminary analyses, from December 2020 to December 2021, enable to estimate runoff reduction and thermal properties of multilayer blue-green roofs, underlying the high potential of this nature-based solution, which allows to retain most of the rainfall events and to mitigate the daily temperature variability. HIGHLIGHTS Description of multilayer blue-green roofs installed in four Italian cities.; Analysis of the multilayer blue-green roof retention capacity.; Analysis of the multilayer blue-green roof thermal insultation properties.;

Abstract Background Brainstem metastases (BSM) are associated with a poor prognosis and their management represents a therapeutic challenge. BSM are often inoperable and, in absence of randomized trials, the optimal radiation treatment of BSM remains to be defined. We evaluated the efficacy and toxicity of linear accelerator (linac)-based stereotactic radiosurgery (SRS) and hypofractionated steretotactic radiotherapy (HSRT) in the treatment of BSM in a series of patients treated in different clinical centers. Methods We conducted a multicentric retrospective study of patients affected by 1–2 BSM from different histologies who underwent SRS/HSRT. Freedom from local progression (FLP), cancer-specific survival (CSS), overall survival (OS), and treatment-related toxicity were evaluated. In addition, predictors of treatment response and survivals were evaluated. Results Between 2008 and 2021, 105 consecutive patients with 111 BMS who received SRS or HSRT for 1–2 BSM were evaluated. Median follow-up time was 10 months (range 3–130). One-year FLP rate was 90.4%. At the univariate analysis, tumor volume ≤ 0.4 cc, and concurrent targeted therapy were associated with longer FLP, with combined treatment that remained a significant independent predictor [0.058, HR 0.139 (95% CI 0.0182–1.064]. Median OS and CSS were 11 months and 14.6 months, respectively. At multivariate analysis, concurrent targeted therapy administration was significantly associated with longer OS [HR 0.514 (95%CI 0.302–0.875); p = 0.01]. Neurological death occurred in 30.4% of patients, although this was due to local progression in only 3 (2.8%) patients. Conclusion Linac-based SRS/HSRT offers excellent local control to patients with BSM, with low treatment-related toxicity and no apparent detrimental effects on OS. When treated with ablative intent, BSM are an uncommon cause of neurological death. The present results indicates that patients with BSM should not be excluded a priori from clinical trials.

In the CodeBreaK 100 phase 2 study, sotorasib was active for patients with metastatic non-small cell lung cancer (NSCLC) harboring Kirsten rat sarcoma viral oncogene homologue (KRAS) p.G12C mutation. However, patients with untreated and/or active brain metastases were excluded from the trial, and the activity of sotorasib in the setting of brain metastases should be further investigated. Here we report the case of a KRAS p.G12C mutant NSCLC patient with three brain metastases, of whom one was untreated and the other two had progressed after radiotherapy with symptoms requiring steroids, that responded to sotorasib. Our report suggests that sotorasib may be active against untreated or progressive brain metastases, supporting further evaluation of sotorasib in this setting.

Aims: The introduction of on-line magnetic resonance image-guided radiotherapy (MRIgRT) has led to an improvement in the therapeutic workflow of radiotherapy treatments thanks to the better visualization of therapy volumes assured by the higher soft tissue contrast. Magnetic Resonance contrast agents (MRCA) could improve the target delineation in on-line MRIgRT planning as well as reduce inter-observer variability and enable innovative treatment optimization protocols. The aim of this survey is to investigate the utilization of MRCA among centres that clinically implemented on-line MRIgRT technology. Methods: In September 2021, we conducted an online survey consisting of a sixteen-question questionnaire that was distributed to the all the hospitals around the world equipped with MR Linacs. The questionnaire was developed by two Italian 0.35 T and 1.5 T MR-Linac centres and was validated by four other collaborating centres, using a Delphi consensus methodology. Results: The survey was distributed to 52 centres and 43 centres completed it (82.7%). Among these centres, 23 institutions (53.5%) used the 0.35T MR-Linac system, while the remaining 20 (46.5%) used the 1.5T MR-Linac system.According to results obtained, 25 (58%) of the centres implemented the use of MRCA for on-line MRIgRT. Gadoxetate (Eovist®; Primovist®) was reported to be the most used MRCA (80%) and liver the most common site of application (58%). Over 70% of responders agreed/strongly agreed to the need for international guidelines. Conclusions: The use of MRCA in clinical practice presents several pitfalls and future research will be necessary to understand the actual advantage derived from the use of MRCA in clinical practice, their toxicity profiles and better define the need of formulating guidelines for standardising the use of MRCA in MRIgRT workflow.

Abstract Plant survival during environmental stress greatly affects ecosystem carbon (C) cycling, and plant–microbe interactions are central to plant stress survival. The release of C-rich root exudates is a key mechanism plants use to manage their microbiome, attracting beneficial microbes and/or suppressing harmful microbes to help plants withstand environmental stress. However, a critical knowledge gap is how plants alter root exudate concentration and composition under varying stress levels. In a greenhouse study, we imposed three drought treatments (control, mild, severe) on blue grama (Bouteloua gracilis Kunth Lag. Ex Griffiths), and measured plant physiology and root exudate concentration and composition using GC–MS, NMR, and FTICR. With increasing drought severity, root exudate total C and organic C increased concurrently with declining predawn leaf water potential and photosynthesis. Root exudate composition mirrored the physiological gradient of drought severity treatments. Specific compounds that are known to alter plant drought responses and the rhizosphere microbiome mirrored the drought severity-induced root exudate compositional gradient. Despite reducing C uptake, these plants actively invested C to root exudates with increasing drought severity. Patterns of plant physiology and root exudate concentration and composition co-varied along a gradient of drought severity.

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value.

Background: One of the main challenges in the management of COVID-19 patients is to early assess and stratify them according to their risk of developing severe pneumonia. The alveolar–arterial oxygen gradient (D(A-a)O2) is defined as the difference between the alveolar and arteriolar concentration of oxygen, an accurate index of the ventilatory function. The aim of this study is to evaluate D(A-a)O2 as a marker for predicting severe pneumonia in COVID-19 patients, in comparison to the PaO2/FiO2. Methods: This retrospective, multicentric cohort study included COVID-19 patients admitted to two Italian hospitals between April and July 2020. Clinical and laboratory data were retrospectively collected at the time of hospital admission and during hospitalization. The presence of severe COVID-19 pneumonia was evaluated, as defined by the Infectious Diseases Society of America (IDSA) criteria for community-acquired pneumonia (CAP). Patients were divided in severe and non-severe groups. Results: Overall, 53 COVID-19 patients were included in the study: male were 30/53 (57%), and 10/53 (19%) had severe pneumonia. Patients with severe pneumonia reported dyspnea more often than non-severe patients (90% vs. 39.5%; p = 0.031). A history of chronic obstructive pulmonary disease (COPD) was recalled by 5/10 (50%) patients with severe pneumonia, and only in 6/43 (1.4%) of non-severe cases (p = 0.023). A ROC curve, for D(A-a)O2 >60 mmHg in detecting severe pneumonia, showed an area under the curve (AUC) of 0.877 (95% CI: 0.675–1), while the AUC of PaO2/FiO2 < 263 mmHg resulted 0.802 (95% CI: 0.544–1). D(A-a)O2 in comparison to PaO2/FiO2 had a higher sensibility (77.8% vs. 66.7%), positive predictive value (75% vs. 71.4%), negative predictive value (94% vs. 91%), and similar specificity (94.4% vs. 95.5%). Conclusions: Our study suggests that the D(A-a)O2 is more appropriate than PaO2/FiO2 to identify COVID-19 patients at risk of developing severe pneumonia early.

Summary: The treatment of oligometastatic disease using MR guidance is an evolving field. Since August 2018 patients are treated on a 1.5 Tesla MR-Linac (MRL). We present current workflows and practice standards from seven institutions for the initial patients treated for lymph node and liver metastases.

Behavioral responses to sonar have been observed in a number of baleen whales, including minke whales (Balaenoptera acutorostrata). Previous studies used acoustic minke whale boing detections to localize and track individual whales on the U.S. Pacific Missile Range Facility (PMRF) in Kaua ‘i, Hawai‘i before, during, and after Navy training activities. These analyses showed significant changes in central North Pacific minke whale distribution and swimming behavior during Navy sonar events. For the purposes of contextualizing changes in animal movement relative to Navy sonar, we expanded on this research to examine the natural variation in minke whale movement when Navy sonar was not present. This study included 2,245 acoustically derived minke whale tracks spanning the years 2012–2017 over all months that minke whales were detected (October–May). Minke whale movement was examined relative to calling season, day of the year, hour of day, wind speed, calling state (nominal or rapid), and distance to the nearest calling conspecific. Hidden Markov models were used to identify two kinematic states (slower, less directional movement and faster, more directional movement). The findings indicate that minke whales were more likely to travel in a faster and more directional state when they were calling rapidly, when other vocalizing minke whales were nearby, during certain times of the day and calling seasons, and in windier conditions, but these changes in movement were less intense than the changes observed during exposure to Navy sonar, when swim speeds were the fastest. These results start to put behavioral responses to Navy sonar into an environmental context to understand the severity of responses relative to natural changes in behavior.

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients. Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2–3, and 4–5; cumGTV was dichotomized to the value of 10 cc. Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1–3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1–3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4–5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000). Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution.