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The peel represents a significant portion of the araticum fruit (about 40%), which becomes waste after its consumption or processing. Previous studies have shown that the araticum peel is rich in phenolic compounds; however, little is known about the ideal conditions for recovering these compounds. Therefore, response surface methodology, using a central composite rotatable design, was employed to optimize the extraction process to maximize the total phenolic compounds (TPCs) and enhance the Trolox equivalent antioxidant capacity (TEAC) from araticum peel. The variables optimized were ethanol concentration (EC; 20–80%, v/v), extraction time (ET; 5–45 min), and solid–solvent ratio (SSR; 10–100 mg/mL). Additionally, condensed tannins, antioxidant capacity against synthetic free radicals (TEAC and FRAP) and reactive oxygen species (ROS), and the phenolic compounds profile, were evaluated. Optimum extraction conditions were 50% (v/v) ethanol concentration, 5 min of extraction time, and 10 mg/mL solid–solvent ratio. Under these conditions, experimental TPCs and TEAC values were 70.16 mg GAE/g dw and 667.22 µmol TE/g dw, respectively, comparable with predicted models (68.47 mg GAE/g dw for TPCs and 677.04 µmol TE/g dw for TEAC). A high condensed tannins content (76.49 mg CE/g dw) was also observed and 12 phenolic compounds were identified, predominantly flavonoids (97.77%), including procyanidin B2, epicatechin, and catechin as the major compounds. Moreover, a potent antioxidant activity was observed against synthetic free radicals and ROS, especially in scavenging peroxyl and hydroxyl radicals. From this study, we obtained the ideal conditions for recovering phenolic compounds from araticum peel using a simple, fast, sustainable, and effective method, offering a promising opportunity for the management of this plant byproduct.

Cutaneous melanoma is an aggressive type of skin cancer that is recognized for its high metastatic potential and the challenges it presents in its treatment. There has been increasing interest in plant extracts and their potential applications in melanoma. The present study aimed to investigate the content of individual phenolic compounds in araçá-boi extract, evaluate their antioxidant activity, and explore their effects on cell viability, migration properties, oxidative stress levels, and protein expression in the human metastatic melanoma cell line SK-MEL-28. HPLC-DAD analysis identified 11 phenolic compounds in the araçá-boi extract. Trans-cinnamic acid was the main phenolic compound identified; therefore, it was used alone to verify its contribution to antitumor activities. SK-MEL-28 melanoma cells were treated for 24 h with different concentrations of araçá-boi extract and trans-cinnamic acid (200, 400, 600, 800, and 1600 µg/mL). Both the araçá-boi extract and trans-cinnamic acid reduced cell viability, cell migration, and oxidative stress in melanoma cells. Additionally, they modulate proteins involved in apoptosis and inflammation. These findings suggest the therapeutic potential of araçá-boi extract and its phenolic compounds in the context of melanoma, especially in strategies focused on preventing metastasis. Additional studies, such as the analysis of specific signaling pathways, would be valuable in confirming and expanding these observations.

Abstract A new species of Ancistrus is described from the rio Vacacaí drainage, rio Jacuí basin, laguna dos Patos system, southern Brazil. The new species differs from A. brevipinnis, the common species in the laguna dos Patos system, by having a dark brown to black background body color and dorsal and caudal fins plain dark, without lighter spots or bands. A morphometric and molecular comparison of different populations of A. brevipinnis from the laguna dos Patos system suggests that previously undetected species diversity is present in that basin. The type-locality of A. brevipinnis, originally described as Rio Grande do Sul State, is herein restricted to the rio Camaquã sub-basin of the laguna dos Patos system, and a redescription of A. brevipinnis is provided based on that population.

Abstract Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in vitro. 44 linear S-derived peptides were genetically fused with the RAD scaffold (RAD-SCoV-epitopes) and screened for antigenicity with sera collected from COVID-19-infected patients. In a second step, selected RAD-SCoV-epitopes were used to immunize mice and generate antibodies. Phenotypic screening showed that some of these antibodies were able to recognize replicating viral particles in VERO CCL-81 and most notably seven of the RAD-SCoV-epitopes were able to induce antibodies that inhibited viral infection. Our findings highlight the RAD display system as an useful platform for the immunological characterization of peptides and a potentially valuable strategy for the design of antigens for peptide-based vaccines, for epitope-specific antibody mapping, and for the development of antibodies for diagnostic and therapeutic purposes.

In this study, Eugenia calycina and Eugenia stigmatosa, native Brazilian berries, were explored regarding their proximal composition, bioactive compounds, and antioxidant activities. The edible parts of both fruits presented a low content of lipids, proteins, and carbohydrates, resulting in a low caloric value (E. stigmatosa fruit showed a high total fiber content (3.26 g/100 g fw), qualifying it as a source of dietary fiber. The sugar profile was mainly monosaccharides (glucose, fructose, and rhamnose). Significant contents of total phenolics and flavonoids, monomeric anthocyanins and, condensed tannins, were observed in both fruits. E. calycina contains a high level of anthocyanins, primarily cyanidin-3-glucoside (242.97 µg/g). Other phenolic compounds were also found, the main ones being rutin and ellagic acid. In contrast, E. stigmatosa is mainly composed of rutin and gallic acid. Furthermore, these fruits showed expressive antioxidant activity, evidenced by ORAC, FRAP, and ABTS. These Eugenia fruits are promising sources of bioactive compounds and have a low caloric and high dietary fiber content, making them interesting options for inclusion in a balanced diet, contributing to the promotion of health and the valorization and conservation of Brazilian biodiversity.

In 2019, the emergence of the seventh known coronavirus to cause severe illness in humans triggered a global effort towards the development of new drugs and vaccines for the SARS-CoV-2 virus. These efforts are still ongoing in 2024, including the present work where we conducted a ligand-based virtual screening of terpenes with potential anti-SARS-CoV-2 activity. We constructed a Quantitative Structure–Activity Relationship (QSAR) model from compounds with known activity against SARS-CoV-2 with a model accuracy of 0.71. We utilized this model to predict the activity of a series of 217 terpenes isolated from the Fabaceae family. Four compounds, predominantly triterpenoids from the lupane series, were subjected to an in vitro phenotypic screening in Vero CCL-81 cells to assess their inhibitory activity against SARS-CoV-2. The compounds which showed high rates of SARS-CoV-2 inhibition along with substantial cell viability underwent molecular docking at the SARS-CoV-2 main protease, papain-like protease, spike protein and RNA-dependent RNA polymerase. Overall, virtual screening through our QSAR model successfully identified compounds with the highest probability of activity, as validated using the in vitro study. This confirms the potential of the identified triterpenoids as promising candidates for anti-SARS-CoV-2 therapeutics.

Brazil is home to some of the world’s greatest biodiversity, providing an immeasurable number of new opportunities and unexplored sources of native plants for the development of products, extracts, foods, and compounds of social and economic interest. Among these, plants of the genus Eugenia stand out because of the large number of species found in Brazilian territory, many of which are endemic and exclusive to Brazil. These plants have emerged as potential sources for obtaining essential oils with relevant biological activities. In this context, the present review provides an overview of essential oils derived from the main native plants of Brazilian socio-biodiversity from the genus Eugenia with food value (Eugenia stipitata, Eugenia dysenterica, Eugenia involucrata, Eugenia brasiliensis, Eugenia klotzschiana, Eugenia uniflora, and Eugenia pyriformis) and their phytochemical profile and health beneficial effects. The compiled data showed that the essential oils of these plants are composed mainly of sesquiterpenes and, in smaller quantities, monoterpenes and other compounds. These compounds contribute to different biological activities, including antimicrobial, antioxidant, anticancer, and antiparasitic effects. These findings demonstrate that the essential oils of Brazilian native plants of the genus Eugenia can be a promising raw material for active ingredients to develop innovative and sustainable food products, drugs, and cosmetics.

Solanum is the largest genus within the Solanaceae family and has garnered considerable attention in chemical and biological investigations over the past 30 years. In this context, lobeira or “fruta-do-lobo” (Solanum lycocarpum St. Hill), a species predominantly found in the Brazilian Cerrado, stands out. Beyond the interesting nutritional composition of the fruits, various parts of the lobeira plant have been used in folk medicine as hypoglycemic, sedative, diuretic, antiepileptic, and antispasmodic agents. These health-beneficial effects have been correlated with various bioactive compounds found in the plant, particularly alkaloids. In this review, we summarize the alkaloid composition of the lobeira plant and its biological activities that have been reported in the scientific literature in the last decades. The compiled data showed that lobeira plants and fruits contain a wide range of alkaloids, with steroidal glycoalkaloid solamargine and solasonine being the major ones. These alkaloids, but not limited to them, contribute to different biological activities verified in alkaloid-rich extracts/fractions from the lobeira, including antioxidant, anti-inflammatory, anticancer, antigenotoxic, antidiabetic, antinociceptive, and antiparasitic effects. Despite the encouraging results, additional research, especially toxicological, pre-clinical, and clinical trials, is essential to validate these human health benefits and ensure consumers’ safety and well-being.

Amblyomma ticks are vectors of both Rickettsia rickettsii and R. parkeri in the Americas, where capybaras (Hydrochoerus hydrochaeris) are the main hosts in urban areas, thus contributing to the transmission of spotted fever. Herein, we studied: (i) the seasonal dynamics and abundance of ticks in areas where capybaras live, (ii) the effect of environmental variables on tick abundance, and (iii) the presence of Rickettsia-infected ticks. Between September 2021 and September 2022, we sampled ticks using cloth-dragging at 194 sites on the shore of Lake Paranoá in Brasília, Brazil. We measured environmental data (season, vegetation type, canopy density, temperature, humidity, and presence or vestige of capybara) at each site. Nymphs and adults were morphologically identified to the species level, and a selected tick sample including larvae was subjected to genotypic identification. We investigated Rickettsia-infected ticks by PCR (gltA, htrA, ompB, and ompA genes) and associations between tick abundance and environmental variables using Generalized Linear Models. A total of 30,334 ticks (96% larvae) were captured. Ticks were identified as Amblyomma, with A. sculptum comprising 97% of the adult/nymphs. Genotype identification of a larval sample confirmed that 95% belonged to A. dubitatum. Seasonal variables showed significant effects on tick abundance. Most larvae and nymphs were captured during the early dry season, while the adults were more abundant during the wet season. Vegetation variables and the presence of capybaras showed no association with tick abundance. Rickettsia parkeri group and R. bellii were identified in A. dubitatum, while A. sculptum presented R. bellii. We conclude that: (i) Amblyomma ticks are widely distributed in Lake Paranoá throughout the year, especially larvae at the dry season, (ii) the abundance of Amblyomma ticks is explained more by climatic factors than by vegetation or presence of capybaras, and (iii) A. dubitatum ticks are potential vectors of R. parkeri in Brasília.

The difficulty in obtaining a superconducting gap free of subgap states has hindered progress with hybrid superconductor-semiconductor devices in germanium. Here, this challenge is addressed by using a germanosilicide parent superconductor to contact high mobility planar germanium, facilitating scalable quantum information processing.

Glycosylation is one of the most structurally and functionally diverse co- and post-translational modifications in a cell. Addition and removal of glycans, especially to proteins and lipids, characterize this process which has important implications in several biological processes. In mammals, the repeated enzymatic addition of a sialic acid unit to underlying sialic acids (Sia) by polysialyltransferases, including ST8Sia2, leads to the formation of a sugar polymer called polysialic acid (polySia). The functional relevance of polySia has been extensively demonstrated in the nervous system. However, the role of polysialylation in infection is still poorly explored. Previous reports have shown that Trypanosoma cruzi (T. cruzi), a flagellated parasite that causes Chagas disease (CD), changes host sialylation of glycoproteins. To understand the role of host polySia during T. cruzi infection, we used a combination of in silico and experimental tools. We observed that T. cruzi reduces both the expression of the ST8Sia2 and the polysialylation of target substrates. We also found that chemical and genetic inhibition of host ST8Sia2 increased the parasite load in mammalian cells. We found that modulating host polysialylation may induce oxidative stress, creating a microenvironment that favors T. cruzi survival and infection. These findings suggest a novel approach to interfere with parasite infections through modulation of host polysialylation. Author summary: Glycosylation, the process of adding and removing sugar molecules from proteins, lipids, and small RNAs, plays a crucial role in numerous biological processes. Trypanosoma cruzi, the parasite responsible for Chagas disease affecting 6 to 8 million people globally, significantly alters the sialylation of host cell glycoproteins. In mammals, the enzyme ST8Sia2 is involved in forming polysialic acid (polySia), primarily studied in the nervous system, yet its role in infectious diseases remains poorly understood. In our study, we found that T. cruzi infection reduces the expression of ST8Sia2 in host cells, leading to decreased levels of polySia. This reduction also affects key proteins such as NCAM1 and SCN5A. Furthermore, experiments involving the removal of polySia, chemical inhibition of ST8Sia2, or genetic silencing of the enzyme resulted in increased intracellular parasites numbers. We propose that altering host polysialylation may induce oxidative stress, thereby favoring T. cruzi survival and infection. Our findings suggest that inhibiting ST8Sia2 enhances T. cruzi infection, providing new insights into Chagas disease mechanisms and highlighting the important role of host polysialylation. [ABSTRACT FROM AUTHOR]

In this work, we evaluated the extraction of nanocellulose from agro-industrial residue of yerba mate (YM, Ilex paraguariensis, St.Hil) sticks through chemical (bleaching and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation), physical (steam explosion) and mechanical (ultra-fine friction grinding) treatments, divided into three distinct sequences for method comparison. The results showed that steam explosion as the initial treatment step makes an increase of up to 23% in the crystallinity index of cellulose nanofiber (CNF) in relation to the raw sample. The TEMPO-mediated oxidation resulted in more dispersed CNF, verified by transmission electron microscopy (TEM). Samples treated by steam-explosion and ultrafine grinding showed a higher yield in relation to steam-explosion and oxidative treatment (24.3% versus 16.2% respectively). CNFs with a diameter of 6 nm and a length range of 2200 to 2600 nm were obtained.

Tobacco is a rich source of cellulosic material and one of the most cultivated non-food plants in the world with great potential for incorporation in polymeric matrices. The use of tobacco residues as reinforcing filler requires chemical/physical fiber treatment aiming to maximize compatibility with the polymer. In this study, tobacco residues were treated with two concentrations of NaOH (10 or 15 wt.%) at two-time exposures (3 or 5 h). Four distinct heating rates were used for each condition. It was applied an artificial neural network to model the thermogravimetric curves. After, the fitted ANN curves were used to create a 3D surface response. The equations from 3D surface response allowed the creation of thermogravimetric curves in any heating rate situated between the minimum and maximum range tested.

Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.

Over the past two decades, the application of nanostructured materials in construction, such as concrete, paint, coatings, glass, renders, plasters, thermal insulation, steel, and even sensors, has become increasingly prevalent. However, previous studies and reports have raised concerns about the ecotoxicity and long-term impact of nanomaterials on human health and the environment. National and international legislation and regulations are struggling to keep up with the rapid development of nanomaterials, taking into account their unique characteristics and essential requirements for application and commercialization. This paper, based on existing standards for conventional materials and bibliometric networks of papers focused on nanomaterials, conducts a critical review and proposes relevant indicators for the application of nanomaterials in the construction sector. These indicators should be mandatory and are divided into environmental, human health, and economic perspectives, providing a risk assessment framework for applying nanomaterial-based constructive solutions oriented to environmental, social, and economic sustainability.

Introduction: A timely diagnosis of osteoporosis is key to reducing its growing clinical and economic burden. Radiofrequency Echographic Multi Spectrometry (REMS), a new diagnostic technology using an ultrasound approach, has been recognized by scientific associations as a facilitator of patients’ care pathway. We aimed at evaluating the costs of REMS vs. the conventional ionizing technology (dual-energy X-ray absorptiometry, DXA) for the diagnosis of osteoporosis from the perspective of the Italian National Health Service (NHS) using a cost-minimization analysis (CMA). Methods: We carried out structured qualitative interviews and a structured expert elicitation exercise to estimate healthcare resource consumption with a purposeful sample of clinical experts. For the elicitation exercise, an Excel tool was developed and, for each parameter, experts were asked to provide the lowest, highest and most likely value. Estimates provided by experts were averaged with equal weights. Unit costs were retrieved using different public sources. Results: Considering the base-case scenario (most likely value), the cost of professionals amounts to €31.9 for REMS and €48.8 for DXA, the cost of instrumental examinations and laboratory tests to €45.1 for REMS and €68.2 for DXA. Overall, in terms of current costs, REMS is associated with a mean saving for the NHS of €40.0 (range: €27.6-71.5) for each patient. Conclusions: REMS is associated with lower direct healthcare costs with respect to DXA. These results may inform policy-makers on the value of the REMS technology in the earlier diagnosis for osteoporosis, and support their decision regarding the reimbursement and diffusion of the technology in the Italian NHS.

Epothilones are 16‐membered macrolides that act as microtubule‐targeting agents to tackle cancer. Many synthetic analogues have been investigated for their activity, yet often based on macrolide structures. A notable exception is Ixabepilone, an azalide whose metabolic stability and pharmacokinetics are significantly improved. Exploiting the amide‐triazole bioisosterism, in this work we report the synthesis of the first generation of epothilones lacking the macrolide or azalide structure, with the ester or amide linkage replaced by a triazole unit. Together with the synthesis of this new analogue, computational and biological evaluations have been performed too. [ABSTRACT FROM AUTHOR]

The peel represents a significant portion of the araticum fruit (about 40%), which becomes waste after its consumption or processing. Previous studies have shown that the araticum peel is rich in phenolic compounds; however, little is known about the ideal conditions for recovering these compounds. Therefore, response surface methodology, using a central composite rotatable design, was employed to optimize the extraction process to maximize the total phenolic compounds (TPCs) and enhance the Trolox equivalent antioxidant capacity (TEAC) from araticum peel. The variables optimized were ethanol concentration (EC; 20–80%, v/v), extraction time (ET; 5–45 min), and solid–solvent ratio (SSR; 10–100 mg/mL). Additionally, condensed tannins, antioxidant capacity against synthetic free radicals (TEAC and FRAP) and reactive oxygen species (ROS), and the phenolic compounds profile, were evaluated. Optimum extraction conditions were 50% (v/v) ethanol concentration, 5 min of extraction time, and 10 mg/mL solid–solvent ratio. Under these conditions, experimental TPCs and TEAC values were 70.16 mg GAE/g dw and 667.22 µmol TE/g dw, respectively, comparable with predicted models (68.47 mg GAE/g dw for TPCs and 677.04 µmol TE/g dw for TEAC). A high condensed tannins content (76.49 mg CE/g dw) was also observed and 12 phenolic compounds were identified, predominantly flavonoids (97.77%), including procyanidin B2, epicatechin, and catechin as the major compounds. Moreover, a potent antioxidant activity was observed against synthetic free radicals and ROS, especially in scavenging peroxyl and hydroxyl radicals. From this study, we obtained the ideal conditions for recovering phenolic compounds from araticum peel using a simple, fast, sustainable, and effective method, offering a promising opportunity for the management of this plant byproduct. [ABSTRACT FROM AUTHOR]

Hyperspectral image (HI) analysis approaches have recently become increasingly complex and sophisticated. Recently, the combination of spectral-spatial information and superpixel techniques have addressed some hyperspectral data issues, such as the higher spatial variability of spectral signatures and dimensionality of the data. However, most existing superpixel approaches do not account for specific HI characteristics resulting from its high spectral dimension. In this work, we propose a multiscale superpixel method that is computationally efficient for processing hyperspectral data. The Simple Linear Iterative Clustering (SLIC) oversegmentation algorithm, on which the technique is based, has been extended hierarchically. Using a novel robust homogeneity testing, the proposed hierarchical approach leads to superpixels of variable sizes but with higher spectral homogeneity when compared to the classical SLIC segmentation. For validation, the proposed homogeneity-based hierarchical method was applied as a preprocessing step in the spectral unmixing and classification tasks carried out using, respectively, the Multiscale sparse Unmixing Algorithm (MUA) and the CNN-Enhanced Graph Convolutional Network (CEGCN) methods. Simulation results with both synthetic and real data show that the technique is competitive with state-of-the-art solutions. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma is an aggressive type of skin cancer that is recognized for its high metastatic potential and the challenges it presents in its treatment. There has been increasing interest in plant extracts and their potential applications in melanoma. The present study aimed to investigate the content of individual phenolic compounds in araçá-boi extract, evaluate their antioxidant activity, and explore their effects on cell viability, migration properties, oxidative stress levels, and protein expression in the human metastatic melanoma cell line SK-MEL-28. HPLC-DAD analysis identified 11 phenolic compounds in the araçá-boi extract. Trans-cinnamic acid was the main phenolic compound identified; therefore, it was used alone to verify its contribution to antitumor activities. SK-MEL-28 melanoma cells were treated for 24 h with different concentrations of araçá-boi extract and trans-cinnamic acid (200, 400, 600, 800, and 1600 µg/mL). Both the araçá-boi extract and trans-cinnamic acid reduced cell viability, cell migration, and oxidative stress in melanoma cells. Additionally, they modulate proteins involved in apoptosis and inflammation. These findings suggest the therapeutic potential of araçá-boi extract and its phenolic compounds in the context of melanoma, especially in strategies focused on preventing metastasis. Additional studies, such as the analysis of specific signaling pathways, would be valuable in confirming and expanding these observations. [ABSTRACT FROM AUTHOR]

In this study, Eugenia calycina and Eugenia stigmatosa, native Brazilian berries, were explored regarding their proximal composition, bioactive compounds, and antioxidant activities. The edible parts of both fruits presented a low content of lipids, proteins, and carbohydrates, resulting in a low caloric value (<70 kcal/100 g fw). E. stigmatosa fruit showed a high total fiber content (3.26 g/100 g fw), qualifying it as a source of dietary fiber. The sugar profile was mainly monosaccharides (glucose, fructose, and rhamnose). Significant contents of total phenolics and flavonoids, monomeric anthocyanins and, condensed tannins, were observed in both fruits. E. calycina contains a high level of anthocyanins, primarily cyanidin-3-glucoside (242.97 µg/g). Other phenolic compounds were also found, the main ones being rutin and ellagic acid. In contrast, E. stigmatosa is mainly composed of rutin and gallic acid. Furthermore, these fruits showed expressive antioxidant activity, evidenced by ORAC, FRAP, and ABTS. These Eugenia fruits are promising sources of bioactive compounds and have a low caloric and high dietary fiber content, making them interesting options for inclusion in a balanced diet, contributing to the promotion of health and the valorization and conservation of Brazilian biodiversity. [ABSTRACT FROM AUTHOR]

Introduction: Health state valuation and diagnostic-therapeutic pathways at the junction between non-metastatic and metastatic castration-resistant prostate cancer (CRPC) are not well documented. We aimed at: (i) estimating the disability weights (DWs) for health states across a continuum of disease from asymptomatic non-metastatic (nmCRPC) to symptomatic metastatic state (mCRPC); (ii) mapping the diagnostic-therapeutic pathway of nmCRPC in Italy. Methods: Structured qualitative interviews were performed with clinical experts to gather information on nmCRPC clinical pathway. An online survey was administered to clinical experts to estimate DWs for four CRPC health states defined from interviews and literature review (i.e., nmCRPC, asymptomatic mCRPC, symptomatic mCRPC, mCRPC in progression during or after chemotherapy). Clinicians’ preferences for health states were elicited using the Person-Trade-Off (PTO) and Visual Analogue Scale (VAS) methods. DWs associated with each health state, from 0 (best imaginable health state) and 1 (worst imaginable health state), were estimated. Results: We found that the management of nmCRPC is heterogeneous across Italian regions and hospitals, especially with respect to diagnostic imaging techniques. DWs for PTO ranged from 0.415 (95% confidence interval [CI] 0.208-0.623) in nmCRPC to 0.740 (95% CI 0.560-0.920) in mCRPC, in progression during or after chemotherapy. DWs for VAS ranged between 0.246 (95% CI 0.131-0.361) in nmCRPC to 0.689 (95% CI 0.583-0.795) in mCRPC, in progression during or after chemotherapy. Conclusions: Estimated DWs suggest that delaying transition to a metastatic state might ease the disease burden at both patient and societal levels.

Advanced fabrication techniques enable a wide range of quantum devices, such as the realization of a topological qubit. Here, the authors introduce an on-chip fabrication technique based on shadow walls to implement topological qubits in an InSb nanowire without fabrication steps such as lithography and etching.