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Synthetic polymer scaffolds can encapsulate transition metal catalysts (TMCs) to provide bioorthogonal nanocatalysts. These “polyzymes” catalyze the in situ generation of therapeutic agents without disrupting native biological processes. The design and modification of polymer scaffolds in these polyzymes can enhance the catalytic performance of TMCs in biological environments. In this study, we explore the hydrophobic design space of an oxanorborneneimide‐based polymer by varying the length of its carbon side chain to engineer bioorthogonal polyzymes. Activity studies indicate that modulating the hydrophobicity of the polymer scaffold can be used to enhance the catalyst loading efficacy, catalytic activity, and serum stability of polyzymes. These findings provide insight into the structural elements contributing to improving polymeric nanocatalysts for a variety of applications.

The Spectrometer/Telescope for Imaging X-rays (STIX) is a hard X-ray imaging spectrometer on board the ESA and NASA heliospheric mission Solar Orbiter. STIX has been operational for three years and has observed X-ray emission from ${\sim }35\,000$ solar flares. Throughout its lifetime, Solar Orbiter has been frequently struck by a high flux of energetic particles usually of flare origin, or from coronal mass ejection (CME) shocks. These solar energetic particles (SEPs) are detected on board by the purpose-built energetic particle detector (EPD) instrument suite. During SEP events, the X-ray signal is also contaminated in STIX. This work investigates the effect of these particles on the STIX instrument for two events. The first event occurred during an interplanetary shock crossing and the second event occurred when solar orbiter passed through Earth’s radiation belts while performing a gravity assist maneuver. The induced spectra consist of tungsten fluorescence emission lines and secondary Bremsstrahlung emission produced by incident particles interacting with spacecraft components. For these two events, we identify >100 keV electrons as significant contributors to the contamination via Bremsstrahlung emission and tungsten fluorescence.

The present study applies Game Theory to study public investment at tourist destinations to determine the ‘best action’ for tourist destinations in competitive scenarios. This study proves that the higher the probability that the public sector of the destination will invest in tourism promotion, the greater the expected financial benefits for the destination. Furthermore, the research results show that the higher the probability of tourists traveling to the destination, the greater the expected financial return for the Destination’s Public Sector (DPS) investing. Notably, the findings prove the positive impact of reducing information asymmetry between tourists and destinations. Results from applying Game Theory to the tourist industry show that spending on advertising may be motivated by more than just increasing visitor numbers. Finally, this article’s main contribution is offering a theoretical-mathematical framework applicable to any tourist destination.

Purpose To report and document a case of torpedo maculopathy found in a patient affected by keratoconus. Case report: An healthy 16-year-old male patient, affected by keratoconus in both eyes, was referred to the cornea service of our hospital for a follow-up visit. During the dilated fundus examination of the left eye, an oval, well-demarcated, hypopigmented lesion was observed in the juxtafoveal temporal region, pointing towards the center of the macula. Multimodal imaging of the lesion was performed, and the diagnosis of Torpedo Maculopathy was established based on the clinical picture.Conclusion This is the first case of torpedo maculopathy described in a patient affected by keratoconus. This association may be merely fortuitous or the result of developmental abnormalities affecting both corneal and retinal structures.

Learning and learning to regulate more than one language is shown to have an impact on the structural connectivity of the brain in networks related to language processing and executive control. The available evidence remains however variable in terms of the occurrence, localization and extent of these effects. Variability likely depends on the fact that grouping heterogeneous linguistic profiles under a dichotomous condition (bilingualism vs. monolingualism) may obscure critical aspects of language experience underlying white matter changes. Here, we treated the main quantifiable features in which bilingual experience can be partitioned—that is, age of acquisition, proficiency and use of a second language—as continuous variables, and tested their effects on a sample of young adult participants. Findings indicate that the time spent using a second language, rather than the age of acquisition or knowledge of that language, significantly modulates white matter microstructure in a bilateral cingulo-frontal cluster encompassing structures primarily related to language control. Taken together, these data point to a usage-dependent remodeling of cingulo-frontal connections, and substantiate the conceptualization of bilingualism as a complex and dynamic experience.

Magnetic biomaterials are multifunctional tools currently under investigation as theranostic platforms for biomedical applications. They can be implanted in bone tissue after bone cancer resection to perform local interstitial hyperthermia treatment. Given the requirements of high quality treatment, the hyperthermia therapy should be performed monitoring the system temperature, to avoid hot spots and control the treatment outcome. It is known that the magnetic properties of such implants vary with temperature. It is hypotesized that the treatment dynamic could be monitored using a microwave monitoring system. The variation of the electromagnetic properties of the biological tissues and the magnetic implant during the therapy would result in a different propagation of the microwave signal. This work investigates the feasibility of using microwaves to non-invasively monitor hyperthermia treatments with a simplified monodimensional propagation model. The forward problem is solved to identify the working frequencies, the matching medium properties and study several candidate materials. By using the numerical solutions from nonlinear and multiphysics simulations of the bone tumor hyperthermia treatment using magnetic scaffolds, the microwave signal propagation dynamic is studied. From our feasibility analysis, we found that it is possible to correlate the average tumor temperature with significant ($\sim$20 dB) variations in the transmission coefficient during a typical interstitial hyperthermia session using magnetic scaffolds. Our work brings together, for the first time, the electromagnetic material properties, the physio-pathology and physics of the hyperthermia treatment and the microwave propagation problem, thus paving the route for the development of an innovative theranostic system.

Distribution drift is an important issue for practical applications of machine learning (ML). In particular, in streaming ML, the data distribution may change over time, yielding the problem of concept drift, which affects the performance of learners trained with outdated data. In this article, we focus on supervised problems in an online nonstationary setting, introducing a novel learner-agnostic algorithm for drift adaptation, namely importance weighting for drift adaptation (IWDA), with the goal of performing efficient retraining of the learner when drift is detected. IWDA incrementally estimates the joint probability density of input and target for the incoming data and, as soon as drift is detected, retrains the learner using importance-weighted empirical risk minimization. The importance weights are computed for all the samples observed so far, employing the estimated densities, thus, using all available information efficiently. After presenting our approach, we provide a theoretical analysis in the abrupt drift setting. Finally, we present numerical simulations that illustrate how IWDA competes and often outperforms state-of-the-art stream learning techniques, including adaptive ensemble methods, on both synthetic and real-world data benchmarks.

Hepatobiliary resections are among the most complex and technically challenging surgical procedures. Even though robust evidence showed that complex surgical procedures such as hepatobiliary surgery have better short- and long-term outcomes and lower mortality rate when performed in high-volume centers, the minimal criteria of centers that can perform hepatobiliary activity are not clearly defined. We conducted a retrospective population study of patients who underwent hepatobiliary surgery for malignant disease in a single Italian administrative region (Veneto) from 2010 to 2021 with the aim to investigate the hospitals annual surgical volume for hepatobiliary malignant diseases and the effect of hospital volume on in-hospital, 30- and 90-day postoperative mortality. The centralization process of hepatobiliary surgery in Veneto is rapidly increasing over the past 10 years (rate of performed in highly specialized centers increased from 62% in 2010 to 78% in 2021) and actually it is really established. The crude and adjusted (for age, sex, Charlson Index) mortality rate after hepatobiliary surgery resulted significantly lower in centers with high-volume activity compared to them with low-volume activity. In the Veneto region, the “Hub and Spoke” model led to a progressive centralization of liver and biliary cancer treatment. High surgical volume has been confirmed to be related to better outcomes in terms of mortality rate after hepatobiliary surgical procedures. Further studies are necessary to clearly define the minimal criteria and associated numerical cutoffs that can help define the characteristics of centers that can perform hepatobiliary activities.

We report the experimental generation of a broadband and flat mid-infrared supercontinuum in a silicon-germanium-on-silicon two-stage waveguide. Our particular design combines a short and narrow waveguide section for efficient supercontinuum generation, and an inverse tapered section that promotes the generation of two spectrally shifted dispersive waves along the propagation direction, leading to an overall broader and flatter supercontinuum. The experimentally generated supercontinuum extended from 2.4 to 5.5 μm, only limited by the long wavelength detection limit of our spectrum analyzer. Numerical simulations predict that the supercontinuum actually extends to 7.8 μm. We exploit the enhanced flatness of our supercontinuum for a proof-of-principle demonstration of free-space multi-species gas spectroscopy of water vapor and carbon dioxide.

Background: Despite substantial research, the mechanisms behind stress Tako-tsubo cardiomyopathy (TTC) remain rather elusive. Objective: The purpose of this paper was to provide a detailed review of the mainstream factors underlying the pathophysiology of TTC, highlighting the novel contributions of molecular pathology and in-vivo molecular imaging. Methods: A careful literature review selected all papers discussing TTC, specifically those providing novel insights from myocardial pathology and cardiac molecular imaging. Results: Results concerning myocardial pathology, defect extension, sites and relationships between functional parameters underline the existence of a causal relationship between a determinant (e.g., the release of catecholamines induced by stress) and an outcome for TTC, which is not limited to a reversible contractile cardiomyopathy, but it includes reversible changes in myocardial perfusion and a long-lasting residual deficit in sympathetic function. Besides, they reinforce the hypothesis that sympathetic nerves may exert a complex control on cardiac contractile function, which is likely to be direct or indirect through metabolism and microvascular perfusion changes during anaerobic and aerobic conditions. Conclusion: TTC is characterized by acute transient left ventricular systolic dysfunction, which can be challenging to distinguish from myocardial infarction at presentation. Catecholamineinduced myocardial injury is the most established theory, but other factors, including myocardial metabolism and perfusion, should be considered of utmost importance. Each effort to clarify the numerous pathways and emerging abnormalities may provide novel approaches to treat the acute episode, avoid recurrences, and prevent major adverse cardiovascular events.

In this letter, a microwave imaging strategy based on an artificial neural network (ANN) is applied, for the first time, to experimental data gathered from simplified neck phantoms. The ANN is used for solving the underlying inverse scattering problem, with the aim of retrieving the dielectric properties of the neck for monitoring and diagnostic purposes. The ANN is trained using simulated phantoms, to overcome the limited availability of experimental data. First, a simple configuration with a liquid-filled glass beaker is tested. Then, simplified 3-D-printed models of the human neck are considered. The preliminary findings indicate the possibility of training the network with numerical simulations and testing it against experimental measurements.

The paper presents the skeletal remains of an adult male of 30–40 years with bone lesions and deformity on the left hip, recovered during the archaeological excavation below the former Basilica of San Dionigi, dated to Late Antiquity (3rd – 5th century AD) Milan. Biological profile and paleopathological analysis were performed following standard references and the bones underwent radiological examination. Differential diagnosis included congenital anomaly, active rickets, infectious diseases, femoral neck trauma, Legg-Carvé-Perthes disease, Slipped Capital Femoral Epiphysis (SFCE), osteogenesis imperfecta and osteoporosis. While the lesions were highly consistent with Legg-Calvé-Perthes disease, they were typical of SFCE, complicated by an avascular necrosis and secondary osteoarthrosis. The alteration of the femoral head led to a 7.8% leg-length discrepancy, causing gait alteration with partial compensation though increased muscular activity on the right leg, reduced mobility of the joint and potentially hip pain, difficulty in walking and running and even limping. This paper explores a case of physical disability from the Roman era found near a Christian place of worship and represents a rare case of SFCE in the paleopathological record.

Bioorthogonal catalysis using transition-metal catalysts (TMCs) provides a toolkit for the in situgeneration of imaging and therapeutic agents in biological environments. Integrating TMCs with nanomaterials mimics key properties of natural enzymes, providing bioorthogonal “nanozymes”. ZnS nanoparticles provide a platform for bioorthogonal nanozymes using ruthenium catalysts embedded in self-assembled monolayers on the particle surface. These nanozymes uncage allylated profluorophores and prodrugs. The ZnS core combines the non-toxicity and degradability with the enhancement of Ru catalysis through the release of thiolate surface ligands that accelerate the rate-determining step in the Ru-mediated deallylation catalytic cycle. The maximum rate of reaction (Vmax) increases ∼2.5-fold as compared to the non-degradable gold nanoparticle analogue. The therapeutic potential of these bioorthogonal nanozymes is demonstrated by activating a chemotherapy drug from an inactive prodrug with efficient killing of cancer cells.

Recounts the career and contributions of (Matteo Pastorino).

The reactor is one of the most important equipment to be designed for optimal process operations. An appropriate reactor modeling leads to an efficient and optimal process conceptual design, simulation, and eventually construction. The key for success in this step is mainly related to kinetics. The present work is centered toward process simulation and aims at comparing three different kinetic models for methanol synthesis. The comparison shows how the refitted Graaf model, presented in a previous study, effectively predicts the performance of modern methanol synthesis loops. To pursue this objective, we simulated in Aspen HYSYS three methanol synthesis technologies (the most popular technologies in modern plants) and compared the results with industrial data. The proposed case study demonstrates that the refitted Graaf model is more accurate in output prediction than the well-established original Graaf and Vanden Bussche–Froment models, which are currently considered the industrial benchmark, thus showing how the refitted Graaf model is a potential candidate for future industrial applications.

Purpose: Diabetes is a growing health problem. The aim of this study was to capture time trends in mortality associated with diabetes. Methods: The mortality database of the Veneto region (Italy) includes both the underlying causes of death, and all the diseases mentioned in the death certificate. The annual percent change (APC) in age-standardized rates from 2008 to 2017 was computed by the Joinpoint Regression Program. Results: Overall 453,972 deaths (56,074 with mention of diabetes) were observed among subjects aged ≥ 40 years. Mortality rates declined for diabetes as the underlying cause of death and from diabetes-related circulatory diseases. The latter declined especially in females − 4.4 (CI 95% − 5.3/− 3.4), while in males the APC was − 2.8 (CI 95% − 4.0/− 1.6). Conclusion: We observed a significant reduction in mortality during the period 2008–2017 in diabetes either as underlying cause of death or when all mentions of diabetes in the death certificate were considered.

The South African fruit industry is concerned with increasing losses, both financially and of the produce itself, linked to temperature breaks in the export cold chain. To determine the cause(s) of temperature breaks along their export cold chains of table grapes, Company X, a prominent fruit exporter, requested an independent enquiry be conducted from the Western Cape, South Africa to the United Kingdom.

With the release of several COVID-19 vaccines, hopes for ending the pandemic have emerged. However, the uptake of the vaccines is largely voluntary and depends on the intentions of the public. From a social marketing perspective, this study takes the case of Italy to identify and test factors that are likely to increase COVID-19-vaccine intention. A sample of 3893 respondents was collected throughout Italy and a model empirically tested by structural equation modeling. The findings suggest that a social marketing campaign for undertaking COVID-19 vaccines should educate the public, going beyond just safety and efficacy, and create positive social norms by combatting misinformation on various platforms, including social media. Furthermore, it was found that economic hardship from COVID-19 does not automatically translate to vaccination intention and that social marketing campaigns should particularly target economically vulnerable and important segments. Also, instilling a craving for travel could potentially stimulate citizens to undertake COVID-19 inoculation. Finally, contributions and implications for social marketing COVID-19 vaccines in Italy and elsewhere are addressed.

Formally describing and assessing the difficulty of learning and teaching material is important for quality assurance in university teaching, for aligning teaching and learning activities, and for easing communications among stakeholders such as teachers and students. We propose a novel taxonomy to describe and quantify the difficulty levels of exam questions and exercises encountered in engineering-related contexts, together with its development and piloting processes. The taxonomy consists of two dimensions which separately and independently describe the difficulty in understanding / explaining and using / applying a content unit. The piloting phase included 10 purposefully selected experts in the field of control engineering, external to the project, that tested its performance, utility, ease of use, and clarity. The results indicate that the users were able to provide consistent and coherent assessments of the difficulty levels of 15 selected exam questions. The paper further discusses suggestions for improvement voiced by the participants in order to promote an even more consistent and coherent assessment of engineering students’ mastery of the subject.

Purpose: The possibility to provide answers from morphological imaging to neurosurgeon needs in patients with high- and low-grade gliomas relies on FLAIR images and percentage increase of contrast enhancement on T1-weighted images. Molecular imaging investigating the functionality of tumor cells has been progressively introduced in surgery planning to overcome limitations of conventional MRI. The purpose is to highlight the potential diagnostic and prognostic role of 18F-FET PET in gliomas. Methods: We performed a literature review for articles on the topic in PubMed, Google Scholar, and Web of Science until January 2022. Search keywords included “glioma”, “glioblastoma”, “tumor biology” “18F-FET”, “MRI”, “surgery”. Results: This review provides evidence of the potential of molecular imaging with 18F-FET to address the surgeon diagnosticand prognosticneeds, including the knowledge of precise burden of cancer to guide biopsy or maximal safe resection, tumor grade and residual disease. The main cornerstones underlying the capacity of molecular imaging to provide information concerning tumor biology are deeply discussed to make the reader confident with the role of 18F-FET as a reliable imaging bio-marker in gliomas. Conclusion: Although conventional MRI has been shown to be reliable technique to identify gliomas in terms of morphological concerns, some important limitations depending on the incapacity to reveal the tumor biology have emerged. The 18F-FET PET has been established to provide early information of functional nature including real tumor extension, grade, and metabolic residual disease. Therefore, the use of 18F-FET PET has progressively increased suggesting a potential shift from a morphological to functional plus morphological neurosurgery.

AbstractThe Ospedale Maggiore,known as Ca’ Granda, was founded in 1456 by will of Francesco Sforza, Duke of Milan, and was considered for almost five centuries a model for Milanese, Italian and even European healthcare. Attracting patients from all over Europe, the Ca’ Grandadistinguished itself for the introduction of new treatments and innovative health reforms. In the burial ground of the hospital still lie the bodies of the deceased patients, who came from the poorest strata of the population. The study of their remains aims to give back a general identity and a story to each of these persons as well as reconstruct a fraction of the sixteenth century population of Milano as concerns lifestyle and disease and examine practises and therapy of this exceptional hospital. It is estimated that about two million commingled bones and articulated skeletons rest in the crypt, together with other types of findings (e.g., ceramic, coins, clothing). These remains are the object of a large project involving various disciplines ranging from humanities to hard sciences. The aim of this paper is to bring this historical gem to the attention of scholars and provide a glimpse of what its contents have already revealed.

IntroductionCardiovascular benefits deriving from physical activity are well known, but it is unclear whether physical activity trajectories in late life are associated with different risks of cardiovascular diseases.MethodsProgetto Veneto Anziani (Pro.V.A.) is a cohort study of 3099 Italians aged ≥65 years with baseline assessment in 1995–1997 and follow-up visits at 4 and 7 years. Surveillance was extended to 2018 by linkage with hospital and mortality records. Prevalent and incident cardiovascular diseases (coronary heart disease, heart failure and stroke) were identified through clinical examination, questionnaire, or hospital records. Moderate to vigorous physical activity was considered as a time-varying variable. Physical activity trajectories were categorised as: stable-low, high-decreasing, low-increasing and stable-high. Exposure was also assessed at 70, 75, 80 and 85 years.ResultsOverall, physical activity was associated with lower rates of incident cardiovascular diseases. A significant risk reduction was present among men and was stronger earlier in late life (70–75 years). Trajectories of stable-high physical activity were associated with a significantly lower risk of cardiovascular outcomes among men (HR 0.48, 95% CI 0.27 to 0.86) compared with those with stable-low trajectories (p for trend 0.002). No significant association was found with stroke. The greatest cardiovascular risk reduction was observed for >20 min/day of physical activity, and was more marked at 70 years.ConclusionIncreasingly active trajectories of physical activity were associated with lower rates of cardiovascular diseases and overall mortality. Promoting at least 20 min/day of physical activity early in late life seems to provide the greatest cardiovascular benefits.