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Abstract The sensitivity of radiochromic films to UV-blue light is increasingly considered for light dosimetry purposes, owing to their bidimensional detection capabilities and ease of use. While film response to radiation intensity has been widely investigated by commercial scanners, spatial resolution studies remain scarce, especially for small field-of-view applications. These are of growing interest due to the antimicrobial or photo-bio-stimulating effects of UV-blue light sources in in vitro, ex vivo and in vivo models, where precise knowledge of irradiation conditions with adequate spatial resolution is crucial. In this study, we report the spatial lateral resolution and contrast reproduction of GAFchromic EBT2 and EBT3 models. Upon film irradiation by a 405 nm laser source or 365 nm LED, a confocal microscope setup was employed to read the film response at 405, 470, 488, 532 and 570 nm wavelengths, with radiant exposure of 10–70 J/cm2. The measured lateral resolution ranged from 8 to 33 μm. The film capability to reproduce contrast across various spatial frequencies (4–14 lines/mm) was evaluated using modulation transfer function analysis with irradiation performed at 365 nm and 405 nm, revealing a pronounced dependency on both radiant exposure and reading wavelength. These results confirm the film capacity to detect and resolve light intensity variability with a ~ 10 μm resolution, with notable applications in micro-beam profiling and light dosimetry.

Abstract Aquatic species living in productive coastal habitats with abundant primary producers have evolved in highly dynamic diel and seasonally fluctuating environments in terms of, for example, water temperature and dissolved oxygen. However, how environmental fluctuations shape the thermal tolerance of marine species is still poorly understood. Here we hypothesize that the degree of predictability of the diel environmental fluctuations in the coastal area can explain the thermal response of marine species. To test this hypothesis, we measured the thermal tolerance of 17 species of marine ectotherm from tropical, warm temperate and cold temperate latitudes under two levels of oxygen (around saturation and at supersaturation), and relate the results to their site-specific temperature and oxygen fluctuation and their environmental predictability. We demonstrate that oxygen and temperature fluctuations at tropical latitudes have a higher predictability than those at warm and cold temperate latitudes. Further, we show that marine species that are adapted to high predictability have the potential to tune their thermal performance when exposed to oxygen supersaturation, despite being constrained within a narrow safety margin. We advocate that the predictability of the environmental fluctuation needs to be considered when measuring and forecasting the response of marine animals to global warming.

Abstract Global functional adaptation after local mechanical stimulation, as in mechanobiology and the mimosa plant, is fascinating and ubiquitous in nature. This is achieved by locally sensing mechanical deformation with precise thresholds, processing this information via biochemical circuits, followed by downstream actuation. The integration of such embodied intelligence allowing for mechano-to-chemo-to-function information-processing remains elusive in man-made systems. By merging the fields of chemical circuits and metamaterials, we introduce adaptive metamaterial hydrogels (meta-gels) that can accurately sense mechanical stimuli (local touch and global strain), transmit this information over long distances via reaction-diffusion signaling, and induce downstream mechanical strengthening by growing nanofibril networks, or soft robotic actuation through competitive swelling. All elements of the sensor-processor-actuator system are embedded in the device, functioning autonomously without external feeding reservoirs. Our concept enables designing advanced life-like materials systems that synergistically combine two worlds – chemical circuits for chemical information-processing and metamaterial unit cells for physical information-processing.

Abstract Animals likely use a variety of strategies to solve laboratory tasks. Traditionally, combined analysis of behavioral and neural recording data across subjects employing different strategies may obscure important signals and give confusing results. Hence, it is essential to develop techniques that can infer strategy at the single-subject level. We analyzed an experiment in which two male monkeys performed a visually cued rule-based task. The analysis of their performance shows no indication that they used a different strategy. However, when we examined the geometry of stimulus representations in the state space of the neural activities recorded in dorsolateral prefrontal cortex, we found striking differences between the two monkeys. Our purely neural results induced us to reanalyze the behavior. The new analysis showed that the differences in representational geometry are associated with differences in the reaction times, revealing behavioral differences we were unaware of. All these analyses suggest that the monkeys are using different strategies. Finally, using recurrent neural network models trained to perform the same task, we show that these strategies correlate with the amount of training, suggesting a possible explanation for the observed neural and behavioral differences.

Abstract Goal-directed tasks involve acquiring an internal model, known as a predictive map, of relevant stimuli and associated outcomes to guide behavior. Here, we identified neural signatures of a predictive map of task behavior in perirhinal cortex (Prh). Mice learned to perform a tactile working memory task by classifying sequential whisker stimuli over multiple training stages. Chronic two-photon calcium imaging, population analysis, and computational modeling revealed that Prh encodes stimulus features as sensory prediction errors. Prh forms stable stimulus-outcome associations that can progressively be decoded earlier in the trial as training advances and that generalize as animals learn new contingencies. Stimulus-outcome associations are linked to prospective network activity encoding possible expected outcomes. This link is mediated by cholinergic signaling to guide task performance, demonstrated by acetylcholine imaging and systemic pharmacological perturbation. We propose that Prh combines error-driven and map-like properties to acquire a predictive map of learned task behavior.

The therapeutic approach to many solid tumors, including non-small cell lung cancer (NSCLC), is mainly based on the use of platinum-containing anticancer agents and is often characterized by acquired or intrinsic resistance to the drug. Therefore, the search for safer and more effective drugs is still an open challenge.Two organometallic ruthenium(II)-cyclopentadienyl compounds [Ru(η5-C5H4CHO)(Me2bipy)(PPh3)]+ (RT150) and [Ru(η5-C5H4CH2OH)(Me2bipy)(PPh3)][CF3SO3] (RT151) were tested against a panel of cisplatin-resistant NSCLC cell lines and xenografts. They were more effective than cisplatin in inducing oxidative stress and DNA damage, affecting the cell cycle and causing apoptosis. Importantly, they were found to be inhibitors of drug efflux transporters. Due to this property, the compounds significantly increased the retention and cytotoxicity of cisplatin within NSCLC cells. Notably, they did not display high toxicity in vitro against non-transformed cells (red blood cells, fibroblasts, bronchial epithelial cells, cardiomyocytes, and endothelial cells). Both compounds induced vasorelaxation and reduced endothelial cell migration, suggesting potential anti-angiogenic properties. RT151 confirmed its efficacy against NSCLC xenografts resistant to cisplatin. Either alone or combined with low doses of cisplatin, RT151 showed a good biodistribution profile in the liver, kidney, spleen, lung, and tumor. Hematochemical analysis and post-mortem organ pathology confirmed the safety of the compound in vivo, also when combined with cisplatin.To sum up, we have confirmed the effectiveness of a novel class of drugs against cisplatin-resistant NSCLC. Additionally, the compounds have a good biocompatibility and safety profile.

Case summary Two 18-day-old domestic shorthair kittens presented with dyspnoea, mild cyanosis, heart murmur, lung pattern, abnormal crawling and a marked dorsoventral flattening of the thorax. Deformity of the thoracic wall without pectus excavatum was diagnosed. Cardboard corsets tailored to each kitten were applied. This gave immediate respiratory relief, easing distress and pain. After 10 days, clinical and radiographic monitoring revealed normalisation of the shape of the chest wall with an improvement in general condition. At 6 months of age, clinical examination showed normal growth and development of both kittens, with a normal thoracic profile and shape also seen on radiographs. Relevance and novel information Data about flat-chested kitten syndrome and its aetiopathogenesis, treatment and outcome are scarce, but there is significant experience among breeders that is shared through online communities. High mortality rates are reported. The use of a cardboard splint appears to be novel in the published literature; in this case report, it proved to be a rapid and easy solution. For this reason, cardboard splints could be considered as a first approach for the clinical management of flat-chested kitten syndrome.

Biomedical applications relying on optical radiation, particularly with the advent of lasers, have experienced exponential growth in the last 20 years. Powerful optical sources are now found not only in universities, hospitals, and industries but also in beauty centers, used for tasks such as tattoo removal, and even in our homes. Despite their widespread use, managing the risks associated with lasers, particularly in non-research contexts, has not kept pace with their proliferation. While the risks associated with direct exposure to radiation to the eye and skin are relatively well understood, the hazards posed by reflected and diffuse radiation remain less characterized and monitored. Therefore, there is a critical need to assess potential eye and skin hazards in spaces where lasers and non-coherent light sources are used. This necessitates a detailed analysis of reflective surfaces, with particular emphasis on evaluating their reflectance characteristics at relevant wavelength ranges. This study investigates the reflectance and transmittance (where relevant) properties of commonly used materials in biomedical settings, including fabrics, plastics, and metals, across a broad spectrum from 250 nm (UVA) to visible light and into the infrared (IR) region up to 25 μm. Both specular (at 45° incidence) and diffuse reflectance spectra were measured using spectrophotometric techniques and used to provide a straightforward parameter to classify the specular/diffusive behavior of the different surfaces. Besides, small-angle reflectance measurements in the IR range were performed by Fourier transform infrared spectrometry. The knowledge of the material optical properties used in environments where optical radiation is employed allows for accurate assessment of associated risks. This facilitates the determination of appropriate preventive measures and the establishment of safer protocols, for both operators and, where applicable, patients and the general public. For this scope, the creation of a database of material reflective properties has been initiated.

Ocean warming reduces O2 solubility and increases organismal O2 demand, endangering marine life. Coastal ecosystems, however, experience O2 supersaturation during peak daytime temperatures due to metabolic cycles. Recent discoveries show that this environmental supersaturation can reduce the vulnerability of tropical species to warming by satisfying their oxygen requirements. To test whether this also occurs within the cnidarian holobiont, we elevated internal O2 in Cassiopea andromeda at nighttime (i.e. holobiont respiration prevails on Symbiodniaceae O2 production) relying on bell pulsation for ventilation, then experimentally subjected them to thermal stress (+1°C day-1). Though ecologically unrealistic, this approach verified our hypothesis and eliminated confounding factors. Holobionts were exposed to either constant levels of 100% air saturation (100AS) or nighttime supersaturation (NSS; where 100% air saturation transitioned to O2 supersaturation at nighttime). At sublethal temperatures, supersaturation mitigated reductions in holobiont size of ~ 10.37% (-33.418% ± 0.345 under 100AS vs -23.039% ± 0.687 under NSS). Supersaturation alleviated chlorophyll-a loss by 42.73% until 34°C, when counteraction of this process could not be sustained due to excessive thermal stress. Supersaturation also enriched potentially beneficial bacterial taxa of the microbiome and selected a more consistent bacterial community. Although modest, the detected effects show that a O2 surplus increased the resistance of the holobionts to thermal stress.

Abstract Salt marshes occur globally across climatic and coastal settings, providing key linkages between terrestrial and marine ecosystems. However, salt marsh science lacks a unifying conceptual framework; consequently, historically well‐studied locations have been used as normative benchmarks. To allow for more effective comparisons across the diversity of salt marshes, we developed an integrative salt marsh conceptual framework. We review ecosystem‐relevant drivers from global to local spatial scales, integrate these multi‐scale settings into a framework, and provide guidance on applying the framework using specific variables on 11 global examples. Overall, this framework allows for appropriate comparison of study sites by accounting for global, coastal, inter‐, and intra‐system spatial settings unique to each salt marsh. We anticipate that incorporating this framework into salt marsh science will provide a mechanism to critically evaluate research questions and a foundation for effective quantitative studies that deepen our understanding of salt marsh function across spatial scales.

The Atti Chiari project, collecting the first large Italian corpus of judicial acts, presents strict legal requirements as well as many peculiarities in terms of language and content; to meet them, a number of processes and tools have been designed and implemented. The first issue is the requirement to remove any personal data from the documents, without however destroying their linguistic form, nor compromising their readability. To this end, a pseudonymisation procedure has been created based on a preliminary annotation stage, which adds information right in order to remove it in different ways, according to different purposes (linguistic analysis, legal analysis, etc.). At the same time, this light annotation provides data useful not only for pseudonymization, but also for the conversion of documents, from their original presentational format into a semantic one based on TEI. Once documents have been prepared in this way, they are then centralized in a corpus, ready to be indexed for linguistic research. Given the multiple search criteria that must be combined, whatever their origin and model, a new type of search engine, designed primarily in the philological field, has been used here to obtain the required openness and granularity of metadata.

In the present study, growth potential of Listeria monocytogenes in steak tartare samples taken at retail and belonging to 13 brands marketed in Northern Italy was investigated. The samples were submitted to microbiological and chemical-physical characterization. The data obtained were used as inputs for the application of the predictive microbiology software FSSP that allows the estimation of the growth of L. monocytogenes during the shelf-life. Lactic acid bacteria, the main component of the microflora, gave variable counts among the brands (from 3.38 to 6.24 log CFU/g). pH and aw values were always higher than 5.3 and 0.96, respectively, thus they could not be considered as single efficient hurdles to prevent the growth of L. monocytogenes according to the EC Reg. 2073/2005; the same was observed for salt content (constantly

Abstract Background The Covid-19 pandemic provided new challenges and opportunities for patients and healthcare providers while accelerating the trend of digital healthcare transformation. This study explores the perspectives of healthcare professionals and managers on (i) drivers to the implementation of telemedicine services and (ii) perceived benefits and challenges related to the use of telemedicine across the Italian National Health Service. Methods An online cross-sectional survey was distributed to professionals working within 308 healthcare organisations in different Italian regions. Quantitative and qualitative data were collected through a self-administered questionnaire (June-September 2021). Responses were analysed using summary statistics and thematic analysis. Results Key factors driving the adoption of telemedicine have been grouped into (i) organisational drivers (reduce the virus spread-80%; enhance care quality and efficiency-61%), (ii) technological drivers (ease of use-82%; efficacy and reliability-64%; compliance with data governance regulations-64%) and (iii) regulatory drivers (regulations’ semplification-84%). Nearly all respondents perceive telemedicine as useful in improving patient care (96%). The main benefits reported by respondents are shorter waiting lists, reduced Emergency Department attendance, decreased patient and clinician travel, and more frequent patient-doctor interactions. However, only 7% of respondents believe that telemedicine services are more effective than traditional care and 66% of the healthcare professionals believe that telemedicine can’t completely substitute in-person visits due to challenges with physical examination and patient-doctor relationships. Other reported challenges include poor quality and interoperability of telemedicine platforms and scarce integration of telemedicine with traditional care services. Moreover, healthcare professionals believe that some groups of patients experience difficulties in accessing and using the technologies due to socio-cultural factors, technological and linguistic challenges and the absence of caregivers. Conclusions Respondents believe that telemedicine can be useful to complement and augment traditional care. However, many challenges still need to be overcome to fully consider telemedicine a standard of care. Strategies that could help address these challenges include additional regulations on data governance and reimbursements, evidence-based guidelines for the use of telemedicine, greater integration of tools and processes, patient-centred training for clinicians, patient-facing material to assist patients in navigating virtual sessions, different language options, and greater involvement of caregivers in the care process.

Abstract Aging is the basis for several unfavorable conditions, including cardiovascular diseases (CVDs). In this sense, regular physical activity (regular PA) has been proven to delay cellular aging and prevent endothelial dysfunction related to CVDs. Despite numerous studies involving athletes, little is known about cellular and molecular mechanisms of regular PA among master athletes. The present study aimed at evaluating the effects of regular PA on local microcirculatory functions in elderly athletes as compared to age-matched sedentary controls. Moreover, molecular/epigenetic mechanisms (nitric oxide, oxidative stress, PGC-1α, SIRT1 and miR29) were also assessed. The results of the present study showed that regular PA significantly increased local blood flow in post-ischemia and post-heating conditions, as well as NO plasma concentrations, denoting a better endothelial function/microcirculatory efficiency. Moreover, athletes presented a greater plasma antioxidant and increased transcriptional levels of the metabolism regulator PGC-1α. Finally, regular PA enhanced plasma level of SIRT1 and miR29, suggested as epigenetic regulators of redox balance and cellular metabolism. In addition, stimulated local blood flow was directly related to plasma antioxidant capacity, and SIRT1 and miR29 levels. Overall, our data confirm the beneficial effects of regular PA on the cardiovascular profile in elderly athletes and shed light on molecular signals involved in the positive adaptations to exercise.

In Equids, undetected twin pregnancy represents the most important cause of abortion and is also associated with high neonatal mortality rates. Therefore, the detection and management of twin pregnancies is pivotal to allow the continuation of single pregnancies. Although pre-fixation manual crushing of one embryo is the most common management of twin pregnancies, and the impact of natural reduction has been reported in mares, very little is known about donkeys. The present study aimed to report results on the natural reduction occurrence and post-fixation manual crushing management of twin pregnancies in the Martina Franca donkey breed. Methods: Twenty-five twin pregnancies were detected at 11–13 days after ovulation. At 16 days after ovulation, twin pregnancies were classified as unilateral or bilateral and left untreated. The occurrence of natural reduction of one embryo was assessed at 20–21 days after ovulation, and post-fixation manual crushing of one embryo was performed in those cases in which natural reduction did not occur. The pregnancy rate at 28 days after ovulation and live foal rate were recorded. Result: Sixteen out of 25 twin pregnancies were unilateral and nine bilateral. At 20–21 days after ovulation, the natural reduction of one embryo occurred in 87.5% of the unilateral and in none of the bilateral twin pregnancies. The remaining twin pregnancies were treated by post-fixation manual crushing of one embryo. The 28-days-after-ovulation single embryo pregnancy rate was 93.8% for unilateral twin pregnancies and 88.9% for bilateral twin pregnancies, with an overall pregnancy rate of 92%. The live foal rate was 87%. Conclusions: The success rate of natural reduction within 20–21 days after ovulation, the 28-days-after-ovulation pregnancy rate, and the live foal rate suggest that waiting for the natural reduction of one embryo and choosing the post-fixation manual crushing of one embryo could be considered as an alternative to traditional early pre-fixation manual crushing in the Martina Franca donkey breed.

Abstract Background The transition from water to air is a key event in the evolution of many marine organisms to access new food sources, escape water hypoxia, and exploit the higher and temperature-independent oxygen concentration of air. Despite the importance of microorganisms in host adaptation, their contribution to overcoming the challenges posed by the lifestyle changes from water to land is not well understood. To address this, we examined how microbial association with a key multifunctional organ, the gill, is involved in the intertidal adaptation of fiddler crabs, a dual-breathing organism. Results Electron microscopy revealed a rod-shaped bacterial layer tightly connected to the gill lamellae of the five crab species sampled across a latitudinal gradient from the central Red Sea to the southern Indian Ocean. The gill bacterial community diversity assessed with 16S rRNA gene amplicon sequencing was consistently low across crab species, and the same actinobacterial group, namely Ilumatobacter, was dominant regardless of the geographic location of the host. Using metagenomics and metatranscriptomics, we detected that these members of actinobacteria are potentially able to convert ammonia to amino acids and may help eliminate toxic sulphur compounds and carbon monoxide to which crabs are constantly exposed. Conclusions These results indicate that bacteria selected on gills can play a role in the adaptation of animals in dynamic intertidal ecosystems. Hence, this relationship is likely to be important in the ecological and evolutionary processes of the transition from water to air and deserves further attention, including the ontogenetic onset of this association. Video Abstract

Oxygen availability is a pivotal factor for ecosystem functioning and the resistance of organisms to the effect of climate change in aquatic habitats. Although extensive work has been done to assess the effect of oxygen on marine and freshwater biota, many studies have not captured the ecological importance of oxygen variations. Overlooking the fluctuating nature of oxygen may cause potential biases in the design and implementation of management policies for aquatic habitats. Conceptual perspectives on the dynamic nature of oxygen fluctuations have been raised in the scientific community in order to enhance the understanding of the effect of oxygen on the physiology and the ecology of aquatic species as well as the biogeochemical functioning of their ecosystems. A growing number of empirical work has been outlining a novel conceptual framework that considers the magnitude of oxygen fluctuation as a key variable that explains adaptation to stress conditions. Oxygen in productive aquatic habitats shows large fluctuations at the diel scale, exposing aquatic species to conditions ranging from extreme supersaturation to anoxia. Recent research has indicated that such a fluctuation tunes the physiological plasticity of the animal in response to thermal stresses. In this paper, we provide compelling evidence based on current research that the fluctuating oxygen landscape, here defined as “oxyscape”, has an important role in aquatic animal physiology and adaptation as well as the ecosystem biogeochemistry. We propose that the oxyscape should be considered in the modelling and managing policies of aquatic ecosystems.

Abstract Aims Mechanical circulatory support (MCS) systems are increasingly employed in cardiogenic shock and advanced heart failure. A thorough understanding of the complex interactions occurring among heart, vasculature, and device is essential to optimize patient's management. The aim of this study is to explore non‐invasive haemodynamic profiling of patients undergoing MCS based on pressure–strain (PS) analysis. Methods Clinical and echocardiographic data from consecutive patients undergoing different MCS systems positioning/implantation admitted to the third level cardiological intensive care unit of Siena Hospital from August 2021 to November 2021 were retrospectively reviewed. Patients without a useful echocardiographic exam or without arterial blood pressure recording at the time of echocardiography were excluded. Myocardial work analysis was performed in the included patients. Results We reviewed 18 patients, of which nine were excluded. Included patients were three patients with intra‐aortic balloon pump (IABP), two patients with durable left ventricular assist device (dLVAD), two patients with Impella®, one patient with extracorporeal membrane oxygenation (ECMO), and one patient with ECMO and IABP. Myocardial work analysis was feasible in each included patient. The use of IABP shifted the PS curve rightward and downward. Global work index (GWI) and global wasted work (GWW) decreased after IABP positioning, whereas global work efficiency (GWE) increased. The use of continuous‐flow pumps, whether temporaneous (Impella®) or long term (dLVAD), induced a change in the PS loop morphology, with a shift towards a triangular shape. ECMO positioning alone resulted in a narrowing of the PS loop, with a decrease in GWI and GWE and an increase in GWW and mean arterial pressure. The combined used of IABP with ECMO widened the PS loop and improved GWI and GWE. Conclusions PS loops analysis in patients undergoing MCS seems to be feasible and may unveil MCS‐induced haemodynamic variations. Myocardial work could be used to monitor ventricular–arterial–device coupling and guide tailored MCS management.