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Abstract The Triassic red beds of the Tabular Cover of the Iberian Meseta are an excellent reservoir outcrop analogue, a direct consequence of high‐quality exposures, which offer exceptional three‐dimensional outcrops, as well as a wide variability of depositional environments. Fluvial and transitional with tide‐influenced and wave‐influenced settings are recognised. Three point bar geobodies of similar scale, but influenced by different processes, were selected from this succession. Point bar geobody 1 was influenced by purely fluvial processes while geobodies 2 and 3 were tide‐influenced. Both types of geobody were developed as point bar deposits in sinuous channels. A fully integrated study was carried out on these geobodies, utilising both outcrop and subsurface‐based approaches, to characterise the key differences between fluvial and tidal point bars in the sedimentary record. The outcrop‐based component involved traditional field data collection methods alongside digital techniques and data capture, including the use of digital outcrop models. Additionally, subsurface‐based methods were employed, utilising core and wireline logs obtained from wells drilled in close proximity to the outcrop. The integration of these approaches aims to accurately differentiate the depositional settings of the three different geobodies, which while apparently very similar in many key respects also exhibit considerable differences when considered from the perspective of subsurface management of potentially similar geobodies. This study also emphasises the need to clearly distinguish high‐sinuosity deposits based on their depositional sub‐environment in order to properly evaluate their potential for subsurface management. Additionally, it highlights the presence and importance of internal baffles that may well influence fluid migration and indeed even compartmentalise geobodies. Three point bar geobodies of similar scale, but influenced by different processes, have been selected in this succession. A fully integrated study was carried out on these geobodies, utilising both outcrop‐based and subsurface‐based approaches, to characterise the key differences between fluvial and tidal point bars in the sedimentary record.

Abstract Objective People with multiple sclerosis (MS) might experience symptoms that are usually underestimated. Dysphagia should be evaluated within the Expanded Disability Status Scale (EDSS), but clinicians often do not assess it properly. The objectives of this study are as follows: To assess the prevalence of dysphagia in patients with MS utilizing the Swallowing Disturbance Questionnaire (SDQ); to examine the correlation with the EDSS; to investigate the relationship between dysphagia and clinico‐demographic characteristics of MS. Methods In total, 177 MS patients underwent evaluations with EDSS, SDQ, cognitive functions, anxiety, depression, fatigue, and sleep quality tests. We compared clinico‐demographic data of patients with and without dysphagia and native‐EDSS to SDQ‐EDSS. Results Out of the 177 MS patients, 56% of individuals were identified having dysphagia according to the SDQ with 41 patients exhibiting mild dysphagia, 31 showing moderate dysphagia and 27 patients having severe dysphagia. Only 6 patients had dysphagia recorded in the EDSS. SDQ‐EDSS scores were significantly higher than native scores. Dysphagia was associated with depressive symptoms and sleep quality. Interpretation Dysphagia affects up to 56% of MS patients. The SDQ questionnaire is useful for identifying dysphagia, which can help in capturing disease progression and preventing complications like aspiration pneumonia. The SDQ‐EDSS was higher than the native‐EDSS, reflecting the poor ability of the native‐EDSS to evaluate certain symptoms such as dysphagia. The SDQ correlated with depressive symptoms, which are associated with a greater perception of MS symptoms, and poor sleep quality, which could be associated with the triggering of pathogenic mechanisms responsible for disease progression.

Abstract Prompt Gamma Imaging (PGI) is a promising technique for range verification in Particle Therapy. This technique was already tested in clinical environment with a knife-edge-collimator camera for proton treatments but remains relatively unexplored for Carbon Ion Radiation Therapy (CIRT). Previous FLUKA simulations suggested that PG profile shifts could be detected in CIRT with a precision of $$\sim$$ 4 mm ( $$2 \sigma$$ ) for a particle statistic equal to $$5 \cdot 10^{7}$$ C-ions using a 10 × 10 cm2 camera. An experimental campaign was carried out at CNAO (Pavia, Italy) to verify these results, using a knife-edge-collimator camera prototype based on a 5 × 5 cm2 pixelated LYSO crystal. PG profiles were measured irradiating a plastic phantom with a C-ion pencil beam at clinical energies and intensities, also moving the detector to extend the FOV to 13 × 5 cm2. The prototype detected Bragg-peak shifts with $$\sim$$ 4 mm precision for a statistic of $$\sim 4 \cdot 10^{8}$$ C-ions ( $$3 \cdot 10^{8}$$ for the extended FOV), slightly larger than expected. Nevertheless, the detector demonstrated significant potential for verifying the precision in dose delivery following a treatment fraction, which remains fundamental in the clinical environment. For the first time to our knowledge, range verification based on PGI was applied to a C-ion beam at clinical energy and intensities.

Abstract Lipid nanoparticles (LNPs) play a crucial role in addressing genetic disorders, and cancer, and combating pandemics such as COVID-19 and its variants. Yet, the ability of LNPs to effectively encapsulate large-size DNA molecules remains elusive. This is a significant limitation, as the successful delivery of large-size DNA holds immense potential for gene therapy. To address this gap, the present study focuses on the design of PEGylated LNPs, incorporating large-sized DNA, departing from traditional RNA and ionizable lipids. The resultant LNPs demonstrate a unique particle morphology. These particles were further engineered with a DNA coating and plasma proteins. This multicomponent bionanoconstruct exhibits enhanced transfection efficiency and safety in controlled laboratory settings and improved immune system evasion in in vivo tests. These findings provide valuable insights for the design and development of bionanoarchitectures for large-size DNA delivery, opening new avenues for transformative gene therapies.

The research workflow employed in the SOSGAS project is presented, aimed at the Quality Assessment as a reservoir of CO2 and green H2 in heterogeneous Mesozoic and Cenozoic fluvial and deltaic formations of the Iberian Plateau and the Ebro and Graus-Tremp Basins. Through the integrated study of outcrop and subsurface data (derived from boreholes drilled behind the outcrops), conceptual models are developed for each examined case, describing variations in sedimentary heterogeneities. These models contribute to the static modeling of different geobodies and their petrophysical properties. Finally, dynamic modeling, based on gas injection simulation experiments (CO2 and H2) into static models, enables the analysis of the sustainability of geo-storage projects for these key fluids in the energy transition.

In recent years, significant advancements have been made in utilizing nanoparticles (NPs) to modulate immune responses within the central nervous system (CNS), offering new opportunities for nanotherapeutic interventions in neurological disorders. NPs can serve as carriers for immunomodulatory agents or platforms for delivering nucleic acid-based therapeutics to regulate gene expression and modulate immune responses. Several studies have demonstrated the efficacy of NP-mediated immune modulation in preclinical models of neurological diseases, including multiple sclerosis, stroke, Alzheimer’s disease, and Parkinson’s disease. While challenges remain, advancements in NPs engineering and design have led to the development of NPs using diverse strategies to overcome these challenges. The nano-bio interface with the immune system is key in the conceptualization of NPs to efficiently act as nanotherapeutics in the CNS. The biomolecular corona plays a pivotal role in dictating NPs behavior and immune recognition within the CNS, giving researchers the opportunity to optimize NPs design and surface modifications to minimize immunogenicity and enhance biocompatibility. Here, we review how NPs interact with the CNS immune system, focusing on immunosurveillance of NPs, NP-induced immune reprogramming and the impact of the biomolecular corona on NPs behavior in CNS immune responses. The integration of NPs into CNS nanotherapeutics offers promising opportunities for addressing the complex challenges of acute and chronic neurological conditions and pathologies, also in the context of preventive and rehabilitative medicine. By harnessing the nano-bio immune interface and understanding the significance of the biomolecular corona, researchers can develop targeted, safe, and effective nanotherapeutic interventions for a wide range of CNS disorders to improve treatment and rehabilitation. These advancements have the potential to revolutionize the treatment landscape of neurological diseases, offering promising solutions for improved patient care and quality of life in the future.

Parasitic otitis is an inflammatory process that can affect the external to internal cattle ear, causing discomfort in animals, impairing performance, and even leading to animal death. The infection was initially associated with nematodes of the Rhabditis genus in tropical and subtropical regions. Currently, the nematode species described as associated with bovine otitis are Metarhabditis costai, Metarhabditis freitasi, and, more recently, M. blumi. It is worth highlighting that there is still a lack of robust information regarding the morphological details, ultrastructural aspects, and molecular biology data of these species. The Metarhabditis genus is composed of seven species and two more have recently been added. The objective of this study is to update the morphological data using advanced microscopy techniques to emphasize and clarify the main morphological differences between three species of Metarhabditis currently associated with parasitic otitis. Samples of inflammatory exudate were collected from four adult female Gir cattle (Bos taurus indicus) on a farm in Itabira, Minas Gerais state, Brazil. Specimens were analyzed using light microscopy and scanning electron microscopy. Two species, M. costai and M. freitasi, were morphologically identified, consistent with previous reports. Scanning electron microscopy revealed new structural characteristics of the nematode species involved in parasitic otitis compared with M. blumi obtained from the CGC Center. Significant differences were observed in the male posterior region, bursa, and tail. Molecular analysis was conducted to differentiate these three species, and it was observed that the species first associated with otitis formed distinct clusters compared to M. blumi. However, it is important to note that further studies are needed to genetically characterize species of the Metarhabditis genus.

Abstract Pancreatic cancer (PC) is a clinically challenging tumor to combat due to its advanced stage at diagnosis as well as its resistance to currently available therapies. The absence of early symptoms and known detectable biomarkers renders this disease incredibly difficult to detect/manage. Recent advances in the understanding of PC biology have highlighted the importance of cancer-immune cell interactions, not only in the tumor micro-environment but also in distant systemic sites, like the bone marrow, spleen and circulating immune cells, the so-called macro-environment. The response of the macro-environment is emerging as a determining factor in tumor development by contributing to the formation of an increasingly immunogenic micro-environment promoting tumor homeostasis and progression. We will summarize the key events associated with the feedback loop between the tumor immune micro-environment (TIME) and the tumor immune macroenvironment (TIMaE) in pancreatic precancerous lesions along with how it regulates disease development and progression. In addition, liquid biopsy biomarkers capable of diagnosing PC at an early stage of onset will also be discussed. A clearer understanding of the early crosstalk between micro-environment and macro-environment could contribute to identifying new molecular therapeutic targets and biomarkers, consequently improving early PC diagnosis and treatment.

Abstract Consumers are demonstrating increasing awareness towards initiatives promoting sustainable practices in the food sector. This is particularly pronounced among university students, a segment known for its receptivity to sustainability initiatives. Utilizing a choice experiment, this study examines the Italian students’ preferences for fruit juice produced by a hypothetical company. Specifically, the research explicitly assesses the premium price attributable to a circular economy certification—a relatively new standard—in comparison with the widely recognized and appreciated organic certification. Furthermore, the study evaluates the potential additive value of possessing both certifications jointly. Results indicate that consumers are willing to pay a premium for products labelled with circular economy attributes. However, in the presence of an organic certification, the additive value of the circular economy certification is diminished by more than half. Finally, consumers who have received environmental training demonstrate a higher premium for such products, highlighting the role of education in promoting sustainable choices. These findings suggest that a potential market exists for circular economy-certified products, providing an incentive for businesses to adopt circular economy practices. Environmental training plays a relevant role in fostering sustainable transitions, thereby underscoring the significance of education in shaping conscious consumer behaviour.

The successful trajectory of liposome-encapsulated doxorubicin (e.g., Doxil, which has been approved by the U.S. Food and Drug Administration) as an anticancer nanodrug in clinical applications is contradicted by in vitro cell viability data that highlight its reduced efficacy in promoting cell death compared with non-encapsulated doxorubicin. No reports to date have provided a mechanistic explanation for this apparently discordant evidence. Taking advantage of doxorubicin intrinsic fluorescence and time-resolved optical microscopy, we analyze the uptake and intracellular processing of liposome-encapsulated doxorubicin (L-DOX) in several in vitro cellular models. Cell entry of L-DOX was found to lead to a rapid (seconds to minutes), energy- and temperature-independent release of crystallized doxorubicin nanorods into the cell cytoplasm, which then disassemble into a pool of fibril-shaped derivatives capable of crossing the cellular membrane while simultaneously releasing active drug monomers. Thus, a steady state is rapidly established in which the continuous supply of crystal nanorods from incoming liposomes is counteracted by a concentration-guided efflux in the extracellular medium of fibril-shaped derivatives and active drug monomers. These results demonstrate that liposome-mediated delivery is constitutively less efficient than isolated drug in establishing favorable conditions for drug retention in the cell. In addition to explaining previous contradictory evidence, present results impose careful rethinking of the synthetic identity of encapsulated anticancer drugs.

Objective WHO recommends the use of the Robson’s ‘Ten Groups Classification’ for monitoring and assessing caesarean section (CS) rates. The aim of this study was to investigate the rates, indications and outcomes of CS using Robson classification in a tertiary hospital in Sierra Leone.Design Cross-sectional study.Setting Princess Christian Maternity Hospital (PCMH), Freetown, Sierra Leone.Participants All women who gave birth in PCMH from 1 October 2020 to 31 January 2021.Primary and secondary outcome measures Primary outcome: CS rate by Robson group. Secondary outcomes: indications for CS and the newborn outcomes for each Robson group.Results 1998 women gave birth during the study period and 992 CS were performed, with a CS rate of 49.6%. Perinatal mortality was 7.8% and maternal mortality accounted for 0.5%. Two-thirds of the women entered labour spontaneously and were considered at low risk (groups 1 and 3). CS rates in these groups were very high (43% group 1 and 33% group 3) with adverse outcomes (perinatal mortality, respectively, 4.1% and 6%). Dystocia was the leading indication for CS accounting for about two-thirds of the CS in groups 1 and 3. Almost all women with a previous CS underwent CS again (95%). The group of women who give birth before term (group 10) represents 5% of the population with high CS rate (50%) mainly because of emergency conditions.Conclusion Our data reveals a notably high CS rate, particularly among low-risk groups according to the Robson classification. Interpretation must consider PCMH as a referral hospital within an extremely low-resourced healthcare system, centralising all the complicated deliveries from a vast catchment area. Further research is required to assess the impact of referred obstetrical complications on the CS rate and the feasibility of implementing measures to improve the management of women with dystocia and previous CS.

Introduction: Peritoneal Ultrafiltration (PUF) has been proposed as an additional therapeutic option for Refractory Congestive Heart Failure (RCHF) patients. Despite promising observational studies and/or case report results, limited clinical trials data exist, and so far, PUF solutions remain only indicated for chronic kidney diseases (CKD). In this article, we describe a multicenter, randomized, controlled, unblinded, adaptive design clinical trial, about to start, investigating the effects of PolyCore™, an innovative PUF solution, in the treatment of RCHF patients. Methods: The Peritoneal Ultrafiltration in Cardiorenal Syndrome (PURE) study is a Phase II, multicenter, randomized, controlled, unblinded, adaptive design clinical trial that aims to evaluate the safety and efficacy of PUF, using PolyCore™ as the investigational solution, in the treatment of RCHF patients who present with prominent right ventricular failure due to afterload mismatch, functional tricuspid regurgitation and enlarged cava vein consequent to intravascular fluid overload. Approximately 84 patients will be randomized 1:1 either to continue with their prescribed guidelines-directed medical therapy or to add the PUF treatment on top of it. The primary objective is to evaluate if PUF treatment has an impact on the composite endpoint of the patient’s mortality or worsening of the patient’s condition such as hospitalization for cardiovascular causes, increasing the initial daily dose of loop diuretic or worsening of renal function. Statistical analysis for the primary endpoint will be standard survival analysis to estimate the failure rate at month 7 for each group via Kaplan-Meier curves. Sensitivity analysis and various secondary analyses, including a multiple events analysis, will be conducted to evaluate the robustness of the primary endpoint results. Safety will be evaluated for up to 12 months. Conclusion: The PURE Study was designed to evaluate the safety and efficacy of peritoneal ultrafiltration with PolyCore™ on top of guidelines-directed medical therapy in patients with RCHF, assuming a combined clinical endpoint of mortality or worsening patients’ condition. If successful, the treatment should allow for an improvement of the RCHF symptoms, decreasing hospitalization rate of patients. ClinicalTrials.gov Identifier: NCT03994874

Abstract Background The development and physiology of plants are influenced by light intensity and its changes. Despite the significance of this phenomenon, there is a lack of understanding regarding the processes light regulates. This lack of understanding is partly due to the complexity of plant’s responses, but also due to the limited availability of light setups capable of producing specific light patterns. Results While unraveling the complexities of plant responses will require further studies, this research proposes a simple method to implement dynamic light setups. In this study, we introduce two distinct electronic circuits that are cost-effective and enable the control of a dimmable power supply. Conclusion This method enables the generation of intricate light patterns and rapid intensity fluctuations, providing a means to investigate how plants respond and develop when exposed to dynamic light conditions.