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Abstract Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant.

Lupinus gredensis is generally treated as an endemic species to the Iberian Peninsula, with some occurrences reported for the eastern Mediterranean, considered to be the result of an introduction. The finding of five populations attributable to L. gredensis on the south-eastern slopes of Mt. Etna (Sicily, Italy) is here reported for the first time. Lupinus gredensis samples from Mt. Etna were morphologically compared with fresh and herbarium preserved specimens of the related species L. luteus and L. hispanicus. The distribution and the ecology of the surveyed populations, as well as the phytosociological characterization of the plant communities hosting L. gredensis are defined. Finally, the chorological status of this species in Sicily is discussed through the review of the historical occurrence of L. luteus in the Mt. Etna area, providing new data on the putative distribution range of L. gredensis in the Mediterranean region.

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area > median) versus 5 ± 2.3 months (muscle area < median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population.

Abstract The effects of cosmological expansion on quantum bosonic states are investigated, using quantum information theory. In particular, a generic Bogoliubov transformation of bosonic field modes is considered and the state change on a single mode is regarded as the effect of a quantum channel. Properties and capacities of this channel are thus explored in the framework of f(Q) non-metric gravity. The reason is that non-metric gravity can be considered under the standard of gauge theories with all the advantages of such a formulation. As immediate result, we obtain that the information on a single-mode state appears better preserved, whenever the number of particles produced by the cosmological expansion is small. Specifically, we investigate a power law f(Q) model, leaving unaltered the effective gravitational coupling, and minimise the corresponding particle production. We thus show how to optimise the preservation of classical and quantum information, stored in bosonic mode states in the remote past. Finally, we compare our findings with those obtained in General Relativity.

Abstract Osteosarcoma (OS) is the most frequent primary malignant bone tumour, whose heterogeneity represents a major challenge for common antitumour therapies. Inflammatory cytokines are known to be necessary for OS progression. Therefore, to optimise therapy, it is important to discover reliable biomarkers by identifying the mechanism generating OS and investigating the inflammatory pathways that support the undifferentiated state. In this work, we highlight the differences of epigenetic activities of IL-1β and TNFα, and the susceptibility of TET-1 enzymatic inhibition, in tumour progression of three different OS cell lines. Investigating DNA methylation of IL-6 promoter and determining its expression, we found that TET enzymatic inhibition influences proliferation induced by inflammatory cytokines in OS cell lines. Moreover, Bobcat 339 treatment blocks IL-1β epigenetic action on IL-6 promoter, while only partially those of TNFα as well as inhibits IL-1β-dependent epithelial–mesenchymal transition (EMT) process, but only partially those of TNFα. In conclusion, this work highlights that IL-1β and TNFα have different effects on DNA demethylation in OS cell lines, making DNA methylation a potential biomarker of disease. Specifically, in IL-1β treatment, TET-1 inhibition completely blocks tumour progression, while in TNFα actions, it is only partially effective. Given that these two inflammatory pathways can be therapeutic targets for treating these tumours, knowledge of their distinct epigenetic behaviours can be useful for developing precise and specific therapeutic strategies for this disease.

Tuberculosis (TB) remains a significant global health challenge, particularly within pediatric populations. This article reports the case of a 7-year-old female patient admitted with massive fibrinous pleural effusion secondary to TB, highlighting the key role of ultrasound in disease monitoring and therapeutic guidance. The patient presented with fever, cough, and abdominal pain. Imaging confirmed the presence of pleural effusion and lymphadenopathy. Serial ultrasound assessments demonstrated superior sensitivity compared to CT in characterizing the pleural effusion, leading to the initiation of intrapleural urokinase therapy under ultrasound guidance. The treatment resulted in the successful dissolution of fibrin septations and marked clinical improvement. The discussion explores the diagnostic advantages of ultrasound in pediatric TB, its effectiveness in monitoring therapeutic response, and the utility of localized fibrinolytic therapy. This case highlights the value of ultrasound as a cost-effective, noninvasive, radiation-free tool in the management of pediatric TB, advocating for its increased integration into routine pediatric care.

Rocky habitats are suitable refuges for numerous rare and endemic plants. Due to their inaccessibility and the unreliability of traditional survey methods, assessing the survival status of these plants is quite a hard task. In order to address this sampling issue, we employed the drones and carried several field activities to investigate the vascular flora of Rocca di Novara massif located in Northeastern Sicily (NE Sicily hereafter). Located on the southern border of the Peloritani Mountains, Rocca di Novara, also known as Rocca Salvatesta, is a small carbonate massif and it represents one of the highest and most characteristic peaks in NE Sicily. According to our investigation, 300 taxa have been recorded, belonging to 189 genera and 51 different families. The results obtained show the presence of 13 endemic species to Italy (4.3%) and 12 strictly endemic to Sicily (4%). Some taxa of high phytogeographical value have been detected, such as Aubrieta columnae subsp. sicula, Daphne oleoides subsp. oleoides, Edraianthus graminifolius subsp. siculus, Fritillaria messanensis, Odontites bocconei subsp. bocconei, Phelipanche gussoneana, Saxifraga callosa subsp. australis. This latest species was rediscovered after 100 years on the high cliffs of Rocca di Novara thanks to the use of the drone imagery. Our results provide valuable insights into the floristic diversity of Rocca di Novara and offers a solid starting point for further phytogeographical and floristic studies on the vascular plants of the Peloritani district.

Abstract Background X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits. Methods We employed 4C/HiC-seq as a clinical tool to determine the functional impact of incidentally discovered GPR101 duplications on TAD integrity in three families. After defining duplications and breakpoints around GPR101 by clinical-grade and high-density aCGH, we constructed 4C/HiC chromatin contact maps for our study population and compared them with normal and active (X-LAG) controls. Results We showed that duplications involving GPR101 that preserved the centromeric invariant TAD boundary did not generate a pathogenic neo-TAD and that ectopic enhancers were not adopted. This allowed us to discount presumptive/suspected X-LAG diagnoses and GPR101 misexpression, obviating the need for intensive clinical follow-up. Conclusions This study highlights the importance of TAD boundaries and chromatin interactions in determining the functional impact of copy number variants and provides proof-of-concept for using 4C/HiC-seq as a clinical tool to acquire crucial information for genetic counseling and to support clinical decision-making in cases of suspected TADopathies.

Treatment of rectal cancer has improved over the years thanks to a multidisciplinary approach. A correct staging has a fundamental role for risk stratification and to define the best treatment for each patient. Unfortunately, approximately 30% of patients with locally advanced rectal cancers will experience tumor recurrence. Thus, the identification of novel clinical-pathological and radiological prognostic factors represents an urgent unmet clinical need. Here we report the case of a patient with radically resected localized rectal cancer who developed an impressive early pelvic recurrence. To better understand the clinical scenario, we have studied the possible factors related to the aggressiveness of the disease. The only poor prognosticfactor that was evidenced at histological report was perineural invasion. Therefore, we questioned whether we could evaluate perineural invasion with imaging, similar to head and neck tumors. Learning from this clinical case, we believe that improving the risk stratification and radiology reporting is necessary to provide the best care for the patient and allow for a better prognosis prediction. Of course, our data should be considered as hypothesis generating and should be further investigated and validated in larger and prospective studies.

The integration of multidisciplinary tumor boards (MTBs) is fundamental in delivering state-of-the-art cancer treatment, facilitating collaborative diagnosis and management by a diverse team of specialists. Despite the clear benefits in personalized patient care and improved outcomes, the increasing burden on MTBs due to rising cancer incidence and financial constraints necessitates innovative solutions. The advent of artificial intelligence (AI) in the medical field offers a promising avenue to support clinical decision-making. This review explores the perspectives of clinicians dedicated to the care of cancer patients—surgeons, medical oncologists, and radiation oncologists—on the application of AI within MTBs. Additionally, it examines the role of AI across various clinical specialties involved in cancer diagnosis and treatment. By analyzing both the potential and the challenges, this study underscores how AI can enhance multidisciplinary discussions and optimize treatment plans. The findings highlight the transformative role that AI may play in refining oncology care and sustaining the efficacy of MTBs amidst growing clinical demands.

Abstract We explore Noether symmetries of Horndeski gravity, extending the classification of general scalar–tensor theories. Starting from the minimally coupled scalar field and the first-generation scalar–tensor gravity, the discussion is generalised to kinetic gravity braiding and Horndeski gravity. We highlight the main findings by focusing on the non-minimally coupled Gauss–Bonnet term and the extended cuscuton model. Finally, we discuss how the presence of matter can influence Noether symmetries. It turns out that the selected Horndeski functions are unchanged with respect to the vacuum case.

Computed tomography (CT), magnetic resonance imaging (MRI), and radiography expose patients to electromagnetic fields (EMFs) and ionizing radiation. As an alternative, Electrical Impedance Tomography (EIT) offers a less EMF-influenced method for imaging by measuring superficial skin currents to provide a map of the body’s conductivity. EIT allows for functional monitoring of anatomical regions using low electromagnetic fields and minimal exposure times. This paper investigates the application of EIT for the morphological and functional assessment of tissues. Using the Finite Element Method (FEM) (Comsol 5.2), both two-dimensional and three-dimensional models and simulations of physiological and pathological tissues were developed to replicate EIT operations. The primary objective is to detect carcinoma by analysing the electrical impedance response to externally applied excitations. An eight-electrode tomograph was utilised for this purpose, specifically targeting epithelial tissue. The study allowed the characterisation of tomographs of any size and, therefore, the possibility to verify both their geometric profile and the ideal value of the excitation current to be delivered per second of the type of tissue to be analysed. Simulations were conducted to observe electrical impedance variations within a homogeneously modelled tissue and a carcinoma characterized by regular geometry. The outcomes demonstrated the potential of EIT as a viable technique for carcinoma detection, emphasizing its utility in medical diagnostics with reduced EMF exposure.

Abstract Potentialities and Criticalities of the Isole Ciclopi Marine Protected Area The paper analyses the Isole Ciclopi Marine Protected Area facing the hamlet of Aci Trezza within the municipality of Aci Castello in the Province of Catania, Italy. It aims to describe emerging potential and critical issues, posing the question of which actors are involved in the governance. Employing a qualitative methodology, the research revealed that the main problem is the non-implementation of the so-called command-and-control method. After establishing rules and prohibitions, resources for control and imposition of sanctions are lacking. A positive note is the increase in youth volunteer activities of cleaning the sea from plastics, showing a sound interest in the environmental education proposed by cultural and environmental associations.

Summary: A Delphi consensus-seeking procedure was conducted to validate a list of ICD-9-CM codes that could help identify hospital admissions in which antimicrobials are more likely to be prescribed. The panel agreed to include 2967 codes out of 16229 (18.28%). Such codes could support AMS strategies by large-scale monitoring of drug consumption.

This paper deals with the sensorless control of a Permanent Magnet Synchronous Motor (PMSM) to be employed on a turbo-generator to recover the exhaust gas energy of an Internal Combustion Engine (ICE). The main problem with this application is the high rotational speed required by the exhaust gas turbo-generator. Indeed, this implies the difficulty of installing an encoder for speed measurement and control. For this reason, sensorless control is highly recommendable, but, on the other hand, the main sensorless techniques could fail in this peculiar situation because of the high computational effort required compared with the other sensorless applications. Moreover, a good knowledge of the model parameters is necessary. Therefore, the main goal of this paper is to compare two main sensorless techniques for rotational speed measurement, both in the deterministic framework (Model Reference Adaptive System (MRAS) observer) and stochastic framework (Extended Kalman Filter (EKF)), to verify their effectiveness, their computational load, their sensitivity against parameter variation and noisy measurements, and, finally, to present the best solution for the exhaust gas energy recovery from the internal combustion engine.

Understanding how sea turtle species move through the environment and respond to environmental features is fundamental for sustainable ecosystem management and effective conservation. This study investigates the habitat suitability of the loggerhead sea turtle (Caretta caretta) in the Adriatic and Northern Ionian Seas (Central-Eastern Mediterranean) by developing and validating a multidisciplinary framework that leverages machine learning to investigate movement patterns collected by satellite tags Argos satellite tags. Satellite tracking data, enriched with sixteen environmental variables from the Copernicus Marine Service and EMODnet-bathymetry, were analyzed using Random Forest models, obtaining an accuracy of 80.9% when classifying presence versus pseudo-absence of loggerhead sea turtles. As main findings, sea bottom depth, surface chlorophyll (chl-a), and mixed layer depth (MLD) were identified as the most influential features in the habitat suitability of these specimens. Moreover, statistically significant differences, evaluated using t-test statistics, were found between coastal and pelagic locations, for the different seasons, in mixed layer depth, chl-a, 3D-clorophyll, salinity and phosphate. Although based on a limited sample of tagged animals, this study demonstrates that the distribution patterns of loggerhead sea turtles in Mediterranean coastal and pelagic areas are primarily influenced by sea water features linked to productivity and, consequently, to potential prey abundance. Additionally, this multidisciplinary framework presents a replicable approach that can be adapted for various species and regions.

Background The association between left ventricular ejection fraction (LVEF) change (ΔLVEF) following percutaneous coronary intervention (PCI) and the long‐term mortality rate in patients with coronary artery disease is incompletely investigated. We aimed to assess the impact of PCI on LVEF and the association of ΔLVEF after PCI with the long‐term mortality rate. Methods and Results This observational study included 8181 patients with paired angiographic LVEF measurements performed at baseline and 6 to 8 months following the index PCI. ΔLVEF was defined as LVEF measured on the 6‐ to 8‐month angiography minus LVEF measured on the baseline angiography. LVEF change was classified according to the following categories: reduced (ΔLVEF 0% to

Abstract We discuss spherically symmetric dynamical systems in the framework of a general model of $$f(\mathcal{R})$$ f ( R ) gravity, i.e. $$f(\mathcal{R})=\mathcal{R}e^{\zeta \mathcal{R}}$$ f ( R ) = R e ζ R , where $$\zeta $$ ζ is a dimensional quantity in squared length units [L $$^2$$ 2 ]. We initially assume that the internal structure of such systems is governed by the Krori–Barua ansatz, alongside the presence of fluid anisotropy. By employing astrophysical observations obtained from the pulsar SAX J1748.9-2021, derived from bursting X-ray binaries located within globular clusters, we determine that $$\zeta $$ ζ is approximately equal to $$\pm 5$$ ± 5 km $$^2$$ 2 . In particular, the model is capable of producing stable configurations for SAX J1748.9-2021, encompassing both its geometric and physical characteristics. We show that, within the framework of $$f(\mathcal{R})$$ f ( R ) gravity, the Krori–Barua ansatz establishes semi-analytical connections between the radial ( $$p_r$$ p r ) and tangential ( $$p_t$$ p t ) pressures, and the density ( $$\rho $$ ρ ). These relations are described as $$p_r\approx v_r^2 (\rho -\rho _{I})$$ p r ≈ v r 2 ( ρ - ρ I ) and $$p_t\approx v_t^2 (\rho -\rho _{II})$$ p t ≈ v t 2 ( ρ - ρ II ) . In this context, $$v_r$$ v r and $$v_t$$ v t denote the sound speeds in the radial and tangential directions, respectively. Meanwhile, $$\rho _I$$ ρ I pertains to the surface density, and $$\rho _{II}$$ ρ II is derived from the model parameters. These connections are consistent with the equations of state derived from the best-fit solutions identified in the ongoing investigation. Notably, within the framework of $$f(\mathcal{R})$$ f ( R ) gravity where $$\zeta $$ ζ is negative, the maximum compactness, denoted as C, is inherently limited to values that do not exceed the Buchdahl limit. This contrasts with general relativity or $$f(\mathcal{R})$$ f ( R ) gravity with $$\zeta $$ ζ positive, where the compactness has the potential to asymptotically reach the black hole threshold ( $$C\rightarrow 1$$ C → 1 ). The model predictions suggest a central density that largely exceeds the saturation nuclear density, which is $$\rho _{\text {nuc}} = 3\times 10^{14}$$ ρ nuc = 3 × 10 14 g/cm $$^3$$ 3 . Also the surface density $$\rho _I$$ ρ I surpasses $$\rho _{\text {nuc}}$$ ρ nuc . We obtain a mass-radius diagram, corresponding to the boundary density, which is consistent with other observational data.

While anterior cruciate ligament reconstruction (ACL-R) has been considered the gold standard for ACL tears, renewed interest in ACL repair has emerged. This review aims to examine the current knowledge regarding ACL repair. A comprehensive literature search was conducted on the PubMed, Web of Science, Scopus, and Embase databases, focusing on the most recent studies up to January 2024. Arthroscopic ACL repair has several advantages, such as resulting in a natural ligament with proprioceptive properties, preservation, and donor graft comorbidity absence. Several ACL repair surgical procedures have been developed thanks to the advancement in new fixation devices. The current literature showed that when performed on a suitable patient with the appropriate lesion type, corresponding to the proximal third with good tissue quality, ACL repair leads to satisfactory outcomes. Despite the benefits of ACL repair with promising results, ACL-R remains the gold standard for ACL lesions. There is still a lack of literature analyzing long-term outcomes; large series with homogenous populations and types of lesions are lacking. Based on the current evidence, further research and higher-quality studies investigating ACL repair will be necessary.

Abstract Actinobacillus pleuropneumoniae (APP) is a bacterium frequently associated with porcine pleuropneumonia. The acute form of the disease is highly contagious and often fatal, resulting in significant economic losses for pig farmers. Serotype diversity and antimicrobial resistance (AMR) of APP strains circulating in north Italian farms from 2015 to 2022 were evaluated retrospectively to investigate APP epidemiology in the area. A total of 572 strains isolated from outbreaks occurring in 337 different swine farms were analysed. The majority of isolates belonged to serotypes 9/11 (39.2%) and 2 (28.1%) and serotype diversity increased during the study period, up to nine different serotypes isolated in 2022. The most common resistances were against tetracycline (53% of isolates) and ampicillin (33%), followed by enrofloxacin, florfenicol and trimethoprim/sulfamethoxazole (23% each). Multidrug resistance (MDR) was common, with a third of isolates showing resistance to more than three antimicrobial classes. Resistance to the different classes and MDR varied significantly depending on the serotype. In particular, the widespread serotype 9/11 was strongly associated with florfenicol and enrofloxacin resistance and showed the highest proportion of MDR isolates. Serotype 5, although less common, showed instead a concerning proportion of trimethoprim/sulfamethoxazole resistance. Our results highlight how the typing of circulating serotypes and the analysis of their antimicrobial susceptibility profile are crucial to effectively manage APP infection and improve antimicrobial stewardship.

Abstract We address the galaxy rotation curves through the Yukawa gravitational potential emerging as a correction of the Newtonian potential in extended theories of gravity. On the one hand, we consider the contribution of the galactic bulge, galactic disk, and the dark matter halo of the Navarro–Frenk–White profile, in the framework of the standard $$\Lambda $$ Λ CDM model. On the other hand, we use modified Yukawa gravity to show that the rotational velocity of galaxies can be addressed successfully without the need for dark matter. In Yukawa gravity, we recover MOND and show that dark matter might be seen as an apparent effect due to the modification of the law of gravitation in terms of two parameters: the coupling constant $$\alpha $$ α and the characteristic length $$\lambda $$ λ . We thus test our theoretical scenario using the Milky Way and M31 rotation velocity curves. In particular, we place observational constraints on the free parameters of Yukawa cosmology through the Monte Carlo method and then compare our results with the predictions of the $$\Lambda $$ Λ CDM paradigm by making use of Bayesian information criteria. Specifically, we find that $$\lambda $$ λ is constrained to be of the order of kpc, while cosmological data suggest $$\lambda $$ λ of the order of Gpc. To explain this discrepancy, we argue that there is a fundamental limitation in measuring $$\lambda $$ λ due to the role of quantum mechanics on cosmological scales.

This work provides a comprehensive overview of the current landscape of lung cancer, emphasizing the global significance of the disease and the challenges associated with its diagnosis and treatment. The authors highlight the prevalence of lung cancer, with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCC) being the predominant histological subtypes. Advanced-stage diagnosis is common due to the asymptomatic nature of the disease, leading to a systemic treatment approach involving chemotherapy and radiotherapy.The authors discuss the evolution of treatment strategies, with a focus on the emergence of targeted therapies for advanced-stage NSCLC. A panel of predictive biomarkers, both DNA-based (e.g., EGFR, BRAF, KRAS) and RNA-based (e.g., ALK, ROS1, RET, MET), is highlighted as crucial for molecular analysis in diagnostic specimens. While advanced NSCLC patients benefit from targeted therapy, early-stage patients may undergo surgery followed by adjuvant cisplatin-based chemotherapy or stereotactic body radiotherapy (SBRT). The work emphasizes the importance of screening programs for early detection, with a particular focus on the Italian Lung Cancer Screening Network (RISP). RISP aims to recruit high-risk individuals for screening using low-dose computed tomography (LDCT) and implements primary prevention interventions, such as smoking cessation support. The program's objectives include reducing lung cancer mortality, developing a recruitment system for suitable candidates, and integrating radiological, clinical, and molecular data for individual risk profiling. The review also delves into the perspectives of clinicians, physicists, and biologists in the management of lung cancer. Clinicians focus on risk stratification and treatment options, physicists discuss the role of medical physicists in SBRT, and biologists explore precision medicine, biomarkers, and challenges inearly detection.The comparison between surgery and SBRT for early-stage NSCLC patients is discussed, emphasizing the efficacy of SBRT as a non-invasive approach for patients ineligible for surgery. The authors also touch upon ongoing trials addressing the clinical performance of SBRT in comparison to surgery and the challenges posed by preexisting treatment preferences. The physicist's perspective emphasizes the role of medical physicists in lung SBRT, covering aspects from treatment planning to quality assurance. The importance of radiation physics expertise, advanced imaging techniques, image-guided radiation therapy (IGRT), and adaptive radiotherapy is highlighted. Customized models for tumor control and toxicity evaluation, derived from dosimetric analysis, contribute to treatment optimization and patient care. The biologist's viewpoint explores precision medicine in advanced NSCLC treatment, emphasizing the role of somatic alterations as predictive biomarkers. Challenges in early detection are discussed, and the ideal screening tool is proposed to integrate radiological, pathological, and clinical data. Various blood-derived biomarkers and diagnostic assays, such as EarlyCDT-Lung, Nodify XL2, and miRNA-based signatures, are presented as potential tools for early-stage lung cancer detection. In conclusion, the review underscores the multidisciplinary approach required for effective lung cancer management. Advances in early detection, personalized treatment, and the integration of technology and biomarkers offer hope for improving outcomes and reducing the global burden of lung cancer.

In the field of veterinary medicine, the detection of parasite eggs in the fecal samples of livestock animals represents one of the most challenging tasks, since their spread and diffusion may lead to severe clinical disease. Nowadays, the scanning procedure is typically performed by physicians with professional microscopes and requires a significant amount of time, domain knowledge, and resources. The Kubic FLOTAC Microscope (KFM) is a compact, low-cost, portable digital microscope that can autonomously analyze fecal specimens for parasites and hosts in both field and laboratory settings. It has been shown to acquire images that are comparable to those obtained with traditional optical microscopes, and it can complete the scanning and imaging process in just a few minutes, freeing up the operator's time for other tasks. To promote research in this area, the first AI-KFM challenge was organized, which focused on the detection of gastrointestinal nematodes (GINs) in cattle using RGB images. The challenge aimed to provide a standardized experimental protocol with a large number of samples collected in a well-known environment and a set of scores for the approaches submitted by the competitors. This paper describes the process of generating and structuring the challenge dataset and the approaches submitted by the competitors, as well as the lessons learned throughout this journey.

Protein import and genome replication are essential processes for mitochondrial biogenesis and propagation. The J-domain proteins Pam16 and Pam18 regulate the presequence translocase of the mitochondrial inner membrane. In the protozoan Trypanosoma brucei, their counterparts are TbPam16 and TbPam18, which are essential for the procyclic form (PCF) of the parasite, though not involved in mitochondrial protein import. Here, we show that during evolution, the 2 proteins have been repurposed to regulate the replication of maxicircles within the intricate kDNA network, the most complex mitochondrial genome known. TbPam18 and TbPam16 have inactive J-domains suggesting a function independent of heat shock proteins. However, their single transmembrane domain is essential for function. Pulldown of TbPam16 identifies a putative client protein, termed MaRF11, the depletion of which causes the selective loss of maxicircles, akin to the effects observed for TbPam18 and TbPam16. Moreover, depletion of the mitochondrial proteasome results in increased levels of MaRF11. Thus, we have discovered a protein complex comprising TbPam18, TbPam16, and MaRF11, that controls maxicircle replication. We propose a working model in which the matrix protein MaRF11 functions downstream of the 2 integral inner membrane proteins TbPam18 and TbPam16. Moreover, we suggest that the levels of MaRF11 are controlled by the mitochondrial proteasome.

Site selection analysis is a fundamental methodology for the regeneration of Xylella fastidiosa subsp. pauca (Xfp) infected areas, with the introduction of Xfp immune/resistant tree crop species. The diffusion of these species could be assessed by combining ecological optima data, climate and soil attributes of the study area, and GIS tools. The study aimed to evaluate the potential suitability of eight Xfp immune tree crops, including Neglected and Underutilized Species (NUS) drought-resistant and new species, as follows: carob, hawthorn, prickly pear, mulberry, loquat, walnut, persimmon, and avocado. The use of GIS tools allowed the integration of different layers, such as climate and soil, to contribute to the identification of suitable areas for the cultivation of these tree crops helping the policy-makers to define plans for land use at a regional scale. Following the ecological optima, which represents the ideal environmental conditions for each species, this analysis provided valuable insights into the compatibility of the selected tree crops with the prevailing environmental factors in the affected area. Carob revealed its remarkable adaptability and drought resistance, presenting the broadest suitability. Hawthorn and Loquat also exhibited high adaptability, indicating their potential contribution to agricultural diversification and ecological balance. Conversely, crops like Avocado, Prickly pear, and Walnut, despite their economic value, demonstrated limited adaptability due to their specific soil and climate requirements. These findings can potentially contribute to the development of strategies for the policy-makers, aimed at diversifying and enhancing the resilience of agricultural systems, facing the problem of emerging quarantine pathogens and the incoming climate change, and highlighting the possibility of opening new cultivation scenarios in the zones affected by Xfp.

Objective: Monoclonal antibodies (mAbs) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reduced Coronavirus Disease 2019 (COVID-19) hospitalizations in people at risk of clinical worsening. Real-world descriptions are limited. Methods: CONDIVIDIAMO, a two-year multicenter observational study, consecutively enrolled SARS-CoV-2 outpatients with ≥1 risk factor for COVID-19 progression receiving mAbs. Demographic data, underlying medical condition, type of mAbs combination received, duration of symptoms before mAbs administration, COVID-19 vaccination history, were collected upon enrolment and centrally recorded. Data on outcomes (hospitalizations, reasons of hospitalization, deaths) were prospectively collected. The primary endpoint was the rate of hospitalization or death in a 28-day follow-up, whichever occurred first; subjects were censored at the day of last follow-up or up to 28 days. The Kaplan-Meier method was used to estimate the incidence rate curve in time. The Cox regression model was used to assess potential risk factors for unfavorable outcome. Results were shown as hazard ratio (HR) along with the corresponding 95 % Confidence Interval (95%CI). Results: Among 1534 subjects (median [interquartile range, IQR] age 66.5 [52.4–74.9] years, 693 [45.2 %] women), 632 (41.2 %) received bamlanivimab ± etesevimab, 209 (13.6 %) casirivimab/imdevimab, 586 (38.2 %) sotrovimab, 107 (7.0 %) tixagevimab/cilgavimab. After 28-day follow-up, 87/1534 (5.6 %, 95%CI: 4.4%–6.8 %) met the primary outcome (85 hospitalizations, 2 deaths). Hospitalizations for COVID-19 (52, 3.4 %) occurred earlier than for other reasons (33, 2.1 %), after a median (IQR) of 3.5 (1–7) versus 8 (3–15) days (p = 0.006) from mAbs administration.In a multivariable Cox regression model, factors independently associated with increased hospitalization risk were age (hazard ratio [HR] 1.02, 95%CI 1.00–1.03, p = 0.021), immunodeficiency (HR 1.78, 95%CI 1.11–2.85, p = 0.017), pre-Omicron calendar period (HR 1.66, 95%CI 1.02–2.69, p = 0.041). Conclusions: MAbs real-world data over a 2-year changing pandemic landscape showed the feasibility of the intervention, although the hospitalization rate was not negligible. Immunosuppressed subjects remain more at risk of clinical worsening.

In recent years, severe climate change leading to by water scarcity reduced water quality has increased the need for effective irrigation strategies for agricultural production. Among these, the reuse of reclaimed water represents a non-expensive and reliable solution. The effect of conventional or reclaimed water, applying convention or smart fertigation system, were investigated during two irrigation seasons on yield, qualitative and biochemical traits of pomegranates fruit (cv Wonderful One) at harvest, and after storage at 7 °C. The results of this study showed that using reclaimed waters with different fertigation systems did not affect the pH values, total soluble solids, and titratable acidity on pomegranates fruit showing slight decrease changes only during postharvest storage. On the other hand, the respiration rate was not affected by water quality. Furthermore, the antioxidant activity was also preserved during storage in pomegranates fruit from plants irrigated with reclaimed water by applying conventional or smart fertigation. The analysis also identified 52 compounds by UHPLC-MSn and HPLC-UV-Vis analyses. A slight decrease (about 17 %) at harvest and during storage in polyphenols content was shown in fruit grown using reclaimed water. The study demonstrates that using reclaimed water is a sustainable and effective way to limit the use of conventional water for irrigating pomegranate crops without significant reduction in yield, or in qualitative and nutritional values of the fruit at harvest and during storage.

This comprehensive review explores the pivotal role of radiotherapy in cancer treatment, emphasizing the diverse applications of genetic profiling. The review highlights genetic markers for predicting radiation toxicity, enabling personalized treatment planning. It delves into the impact of genetic profiling on radiotherapy strategies across various cancer types, discussing research findings related to treatment response, prognosis, and therapeutic resistance. The integration of genetic profiling is shown to transform cancer treatment paradigms, offering insights into personalized radiotherapy regimens and guiding decisions in cases where standard protocols may fall short. Ultimately, the review underscores the potential of genetic profiling to enhance patient outcomes and advance precision medicine in oncology.

IntroductionThe almond tree is a major global nut crop, and its production has surged dramatically in recent years. Super high-density (SHD) planting systems, designed to optimize resource efficiency and enhance precocity, have gained prominence in almond cultivation. A shift in cropping systems toward sustainable intensification (SI) pathways is imperative, and so maximizing branching density within the canopies of SHD trees is crucial to establish and maintain productive potential, especially for hedge-pruned trees. This study investigates the influence of different almond cultivars grafted onto a novel growth-controlling rootstock on tree architectural and growth parameters in a SHD orchard. This open field research provided valuable insights for the development and application of new tools and methods to increase productivity and sustainability in almond growing.MethodsThree cultivars (Lauranne® Avijour, Guara Tuono, and Filippo Cea) were evaluated in Gravina in Puglia (BA) over a two-year period. Canopy growth parameters, such as canopy volume and trunk cross-sectional area, and architectural traits, like branching density, branching angle, number and length of subterminal shoots, and number of brachyblasts, were measured through qualitative and quantitative measurements.Results and discussionResults revealed significant differences in tree height, canopy thickness, width, volume, and vigor among the cultivars. Architectural traits, including branch parameters, brachyblast parameters, and subterminal shoots, varied among the cultivars. Lauranne displayed a more compact well-distributed canopy and exhibited the lowest vigor. Filippo Cea showed the highest vigor and the greatest canopy volume. Tuono had a higher number of buds and bud density. The best ideotype for SHD orchards is a smaller tree, with high branching density and smaller trunk diameters, i.e. the vigor. Cv. Lauranne seemed to be the best cultivar, mostly with the lowest tree vigor of all the cultivars involved. These findings provide valuable insights for almond growers and breeders seeking to optimize orchard design and management for enhanced SHD orchards productivity and sustainability. Future research will explore the relationship between canopy architecture and yield parameters, considering different scion/rootstock combinations in different environmental conditions.

Abstract Background Cystadenoma of the salivary glands is a rare benign clinical condition affecting both major and minor salivary glands equally. It constitutes approximately 2% of total neoplasms and 4.2–4.7% of benign formations in minor salivary glands. Typically presenting as a slow-growing, painless neoplasm, it can be distinguished from Cystadenolymphoma (Whartin’s Tumor) by the absence of lymphoid elements in histological examination. While mostly located in the oral cavity and oropharynx, it can also be found in sinonasal mucosa, and rare cases have been identified in the larynx. Case presentation A 75-year-old Caucasian woman presented to the ear, nose, and throat department with complaints of dysphonia and headaches persisting for several months. Dysphonia had developed months after an unspecified vocal cord surgery elsewhere. Flexible laryngoscopy identified a left-sided cystic swelling affecting the supraglottic space, leading to respiratory obstruction and dysphonia. Head and neck computed tomography confirmed a 1.9 × 1.7 cm bilobed cystic mass originating from the left Morgagni ventricle. Microlaryngoscopy with CO2 laser excision and biopsy revealed a histopathological diagnosis of oncocytic papillary cystadenoma. Post-surgery, the patient fully recovered from dysphonia, with no significant complications noted. Long-term clinical surveillance was advised to detect potential recurrences promptly. Conclusion Ectopic minor salivary gland tumors, both benign and malignant, should be taken into consideration as potential differential diagnosis for any swelling arising within the upper digestive tract mucosa. Ears, nose, and throat clinical examination completed by videolaryngoscopy can easily point out the location of the mass. Imaging is mandatory for differential diagnosis and for surgical planning. Surgical excision can provide both diagnosis and definitive cure.

The GINGER (gyroscopes in general relativity) project foresees the construction of an array of large frame ring laser gyroscopes, rigidly connected to the Earth. Large frame ring laser gyroscopes are high-sensitivity instruments used to measure angular velocity with respect to the local inertial frame. In particular, they can provide sub-daily variations in the Earth rotation rate, a measurement relevant for geodesy and for fundamental physics at the same time. Sensitivity is the key point in determining the relevance of this instrument for fundamental science. The most recent progress in sensitivity evaluation, obtained on a ring laser prototype, indicates that GINGER should reach the level of 1 part in 1011 of the Earth’s rotation rate. The impact on fundamental physics of this kind of apparatus is reviewed.

Abstract Gravitational radiation-reaction phenomena occurring in the dynamics of inspiralling compact binary systems are investigated at the first post-Newtonian order beyond the quadrupole approximation in the context of Einstein–Cartan theory, where quantum spin effects are modeled via the Weyssenhoff fluid. We exploit balance equations for the energy and angular momentum to determine the binary orbital decay until the two bodies collide. Our framework deals with both quasi-elliptic and quasi-circular trajectories, which are then smoothly connected. Key observables like the laws of variation of the orbital phase and frequency characterizing the quasi-circular motion are derived analytically. We conclude our analysis with an estimation of the spin contributions at the merger, which are examined both in the time domain and the Fourier frequency space through the stationary wave approximation.

Objective To show the effectiveness of goal-oriented proprioceptive training in subacute stroke for balance, autonomy, and fall risk. Methods Out a total of 35 patients, consistent in age (75.31±8.65 years), type of stroke (ischemic, 3 to 11 weeks before), and motor impairment, 18 patients underwent solely proprioceptive rehabilitation, the other 17 dual task exercises. The study assessed autonomy using Barthel Index, fall risk with Timed Up and Go Test (TUG), balance through Berg Balance Scale (BBS) and Tinetti test. Results After two months, significant improvements were recorded in Barthel Index, BBS (p

Safe driving is a serious and challenging concern that is dependent on driver behaviors including aggressive, distracted, fatigued, and drowsy driving. In a smart society, in-vehicle monitoring of drivers and detecting abnormal driving behavior as anomalies can reduce the rate of road crashes. Existing surveys cover the various schemes for detecting on-road driver behaviors through sensing data. We have identified a gap in the linkage of driver’s health or vehicle conditions to abnormal behaviors that are not yet covered. This work presents a taxonomy of schemes, and the analytical evaluation and identifies the open research challenges. The work specifically investigates the modeling of driver behavior and the detection of abnormal behavior, utilizing techniques such as AI-based image processing, signal processing, and traditional algorithmic approaches. This analysis encompasses methods and features based on both driver health and vehicle monitoring with the ultimate goal of ensuring safe driving. More specifically, existing approaches are classified in a coherent taxonomy by reviewing traditional mathematical, machine learning, and deep learning-based schemes. Moreover, a summary of schemes is presented to highlight the key points followed by a comprehensive analytical discussion. It aids in pinpointing research issues by leveraging the insights gained from the comparison. Finally, the work highlights the open research challenges for the researchers to provide innovative solutions.

Abstract Background A significant number of individuals with alcohol use disorder remain unresponsive to currently available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study is set to evaluate the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy when incorporated as an auxiliary intervention during inpatient rehabilitation for severe alcohol use disorder. Moreover, it intends to pinpoint the modifications in the two core neurocognitive systems underscored by dual-process models of addiction. Methods In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21–64 years will be enrolled to undergo psilocybin-assisted therapy as part of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin (5 mg), both within the context of a brief standardized psychotherapeutic intervention drawing from key elements of acceptance and commitment therapy. The primary clinical outcome is the between-group difference regarding the change in percentage of heavy drinking days from baseline to four weeks posthospital discharge, while safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in (1) drinking behavior parameters up to six months posthospital discharge, (2) symptoms of depression, anxiety, trauma, and global functioning, (3) neuroplasticity and key neurocognitive mechanisms associated with addiction, and (4) psychological processes and alcohol-related parameters. Discussion The discussion outlines issues that might arise from our design. Trial registration EudraCT 2022-002369-14 and NCT06160232.

This paper presents the results of a phytosociological study on the Afroalpine vegetation of the Ruwenzori Mountains, one of the most prominent mountain ranges in Africa. This study marks the pioneering comprehensive investigation into the plant communities of this region, which holds significant phytogeographic importance. Through statistical analyses, eight distinct plant communities, three new alliances, two new orders, and one new class were identified within the altitudinal range of 3500 to 4600 m above sea level. These communities are well-defined from both floristic and ecological perspectives. Hierarchical classification was conducted using the quantitative Sørensen (Bray-Curtis) distance measure and the beta flexible linkage method. Furthermore, indicator species for each group were determined by calculating fidelity and constancy (occurrence frequency) within the classified dataset. To assess the validity of the classification results, non-metric multidimensional scaling (NMDS) was carried out. These analyses provide the first phytosociological arrangement of the Afroalpine vegetation of the Ruwenzori Mountains, providing a solid framework and valuable insights into its floristic and ecological characteristics.

A 79 year old female individual presented to the hospital and complained of 1 month melena and anemia due to chronic gastrointestinal bleeding because of cavernous hemangiomatosis of the small bowel. After undergoing an initial video laparoscopic jejunal–ileal resection surgery 7 days after first hospitalization, given the persistence of anemia, she underwent laparotomic duodenojejunal resection surgery again 2 months later. Multiple cavernous hemangiomatosis is a rare vascular disease (7–10% of all benign small bowel tumors), and it often manifests with bleeding, which may be occult or massive; more rarely, it manifests with intestinal occlusion or perforation. Diagnoses often require the use of multiple radiological and endoscopic methods; video capsule endoscopy has significantly increased the diagnostic rate. The gold standard of treatment is surgical resection, whenever possible, balancing the need for radicality with the possible metabolic consequences of massive small intestine resections.

Super high-density (SHD) planting systems are very efficient in terms of production and water use. In these orchards, water-saving irrigation strategies are used precisely to keep the best sustainability compared to traditional orchards. With agro-climatic and eco-physiological parameter monitoring, the SHD planting system has become even more efficient. SHD orchards, however, could also be more so affected by other pests and diseases than traditional systems, but field responses are still unknown when olive trees are grown in SHD groves. The goal of this two-year field research was to investigate the seasonal changes of the phytosanitary status of ‘Arbosana’ grown in an SHD orchard under both regulated deficit (RDI) and full irrigation regimes (FI). This study investigated the influence of the two different irrigation regimes on the infections of three olive tree key diseases: cercosporiosis (Pseudocercospora cladosporioides), cycloconium (Fusicladium oleagineum), and olive knot (Pseudomonas savastanoi pv. savastanoi). RDI significantly reduced the severity of cercosporiosis in 2020 compared to FI but not in 2021. Cycloconium was observed only as a latent infection during the two studied years and olive knot was not influenced by irrigation but only by weather conditions. These findings suggest that irrigation management can play a key role in controlling cercosporiosis effectively in SHD olive orchards, but also that weather conditions have an even higher impact on the tree key diseases.

In light of challenges like climate change, pollution, and depletion of fossil fuel reserves, governments and businesses prioritize renewable energy sources such as solar, wind, and hydroelectric power. Renewable energy forecasting models play a crucial role for energy market operators and prosumers, aiding in planning, decision-making, optimization of energy sales, and evaluation of investments. This study aimed to develop machine learning models for hydropower forecasting in plants integrated into Water Distribution Systems, where energy is generated from water flow used for municipal water supply. The study involved developing and comparing monthly and two-week forecasting models, utilizing both one-step-ahead and two-step-ahead forecasting methodologies, along with different missing data imputation techniques. The tested algorithms—Seasonal Autoregressive Integrated Moving Average, Random Forest, Temporal Convolutional Network, and Neural Basis Expansion Analysis for Time Series—produced varying levels of performance. The Random Forest model proved to be the most effective for monthly forecasting, while the Temporal Convolutional Network delivered the best results for two-week forecasting. Across all scenarios, the seasonal–trend decomposition using the LOESS technique emerged as the most successful for missing data imputation. The accurate predictions obtained demonstrate the effectiveness of using these models for energy planning and decision-making.

Xylella fastidiosa subsp. pauca (Xfp) is a significant threat to Mediterranean agriculture, particularly impacting olive trees in southern Italy, causing Olive Quick Decline Syndrome. Resistant olive cultivars, such as ‘Leccino’ and ‘Fs-17’, have been identified as alternatives to restore the oliviculture within the infected areas. ‘Frantoio’ and ‘Cipressino’ are included in ongoing studies on genetic resistance to Xfp. The mechanization of olive harvesting is essential for reducing production costs in the olive oil sector. Two systems, trunk shakers and over-the-row machines, are used depending on the tree density and canopy structure, with super-high-density systems offering advantages in terms of cost and efficiency. This study investigates the feasibility of using simple and non-destructive indices to assess the optimal mechanical harvesting time. Different physical ripening indices, including detachment force, fresh weight, pigmentation, and firmness, were measured on four olive cultivars (‘Fs-17’, ‘Leccino’, ‘Frantoio’, ‘Cipressino’) in southern Italy over two years. The study found that the pigmentation index had a strong relationship with the detachment index, particularly for ‘Fs-17’, and ‘Leccino’, providing a reliable non-destructive measure for optimal harvesting time. The results indicate that the optimal harvesting times for mechanical harvesting are early September for ‘Cipressino’, early October for ‘Fs-17’, and mid-October for ‘Frantoio’ and ‘Leccino’.

This study analyzed the past wave climate of the Black Sea region for the period from 1988 to 2021. The wave field has been simulated using the state-of-the-art, third-generation wave model WAVEWATCH III forced by the ECMWF reanalysis ERA5 winds, with the model resolution being the highest ever applied to the region in a basin-scale climate study. The surface currents provided by the Copernicus Marine Service have been included in the wave model to evaluate wave–current interactions. The wave model results have been validated with respect to satellite and buoy observations, showing that the simulation accurately reproduces the past evolution of the wave field, exceeding 0.9 correlation with respect to satellite data. The inclusion of wave–current interaction has been positively evaluated. Four statistics (significant wave height 5th and 95th percentiles, mean, and maxima) have been used to describe the wave field at seasonal timescale, showing a clear distinction between the Western (rougher sea conditions) and Eastern (calmer sea conditions) sub-basins. Furthermore, the intra-annual wave climate variability has been investigated using a Principal Component Analysis (PCA) and the Mann–Kendall test on significant wave height (SWH). This study represents the first time the PCA is applied to the region, identifying two main modes that highlight distinct features and seasonal trends in the Western and Eastern sub-basins. Throughout most seasons, the SWH trend is positive for the Eastern basin and negative for the Western basin. The PCA shows a regime shift with increasing eastward waves and decreasing north and north-eastward waves. Finally, SWH correlation (ρ) with four Teleconnection indexes (East Atlantic Pattern, Scandinavian Pattern, North Atlantic Oscillation, and East Atlantic/West Russia Pattern) revealed that the strongest ρ is observed with the Eastern–Atlantic–Western Russia teleconnection, with a peculiar spatial pattern of correlation, and is positive for the northwestern and negative for the southeastern sub-basin.

ABSTRACT: Untargeted metabolomic profiling, by ambient mass spectrometry and chemometric tools, has made a dramatic impact on human disease detection. In a similar vein, this study attempted the translation of this clinical human disease experience to farmed poultry for precise veterinary diagnosis. As a proof of principle, in this diagnostic/prognostic study, direct analysis in real-time high resolution mass spectrometry (DART-HRMS) was used in an untargeted manner to analyze fresh tissues (abdominal fat, leg skin, liver, and leg muscle) of pigmented and non-pigmented broilers to investigate the causes of lack of pigmentation in an industrial poultry farm. Afterwards, statistical analysis was applied to the DART-HRMS data to retrieve the molecular features that codified for 2 broiler groups, that is, properly pigmented and non-pigmented broilers. Higher abundance of oxidized lipids, high abundance of oxidized bile derivatives, and lower levels of tocopherol isomers (Vitamin E) and retinol (Vitamin A) were captured in nonpigmented than in pigmented broilers. In addition, conventional rapid analyses were used: 1) color parameters of the tissues of pigmented and non-pigmented broilers were measured to rationalize the color differences in abdominal fat, leg skin and leg muscle, and 2) macronutrients were determined in broiler leg muscle, to capture a detailed picture of the pathology and exclude other possible causes. In this study, the DART-HRMS system performed well in retrieving valuable chemical information from broilers that explained the differences between the 2 groups of broilers in absorption of xanthophylls and the subsequent lack of proper broiler pigmentation in affected broilers. The results suggest this technology could be useful in providing near real-time feedback to aid in veterinary decision-making in poultry farming.

Introduction: Out of hospital cardiac arrest (OHCA) remains one of the main causes of death among industrialized countries. The initiation of cardiopulmonary resuscitation (CPR) by laypeople before the arrival of emergency medical services improves survival. Mouth-to-mouth ventilation may constitute a hindering factor to start bystander CPR, while during continuous chest compressions (CCC) CPR quality decreases rapidly. The aim of this scoping review is to examine the existing literature on strategies that investigate the inclusion of intentional pauses during compression-only resuscitation (CO-CPR) to improve the performance in the context of single lay rescuer OHCA. Methods: The protocol of this Scoping review was prospectively registered in Open Science Framework (https://osf.io/rvn8j). A systematic search of PubMed, Scopus, EMBASE, CINAHL was performed. Results: Six articles were included. All studies were carried out on simulation manikins and involved a total of 1214 subjects. One study had a multicenter design. Three studies were randomized controlled simulation trials, the rest were prospective randomized crossover studies. The tested protocols were heterogeneous and compared CCC to CO-CPR with intentional interruptions of various length. The most common primary outcome was compressions depth. Compression rate, rescuers’ perceived exertion and composite outcomes were also evaluated. Compressions depth and perceived exertion improved in most study groups while compression rate and chest compression fraction remained within guidelines indications. Conclusions: In simulation studies, the inclusion of intentional interruptions during CO-CPR within the specific scenario of single rescuer bystander CPR during OHCA may improve the rate of compressions with correct depth and lower rate of perceived exertion. Further high-quality research and feasibility and safety of protocols incorporating intentional interruptions during CO-CPR may be justified.

Mycoplasmas are known as the minimalist microorganisms in the microbes’ world. Their minimalist nature makes them highly sensitive to the environmental conditions and limits their ability to survive for extended periods outside their animal host. Nevertheless, there are documented instances of mycoplasma transmission over significant distances and this phenomenon may be linked to relatively unexplored abilities of mycoplasmas, such as their capacity to synthesize biofilm—the predominant mode of bacterial growth in nature. The authors decided to establish a method aimed at inducing the clustering of mycoplasma planktonic cells within a biofilm in vitro and subsequently assess the capacity of certain avian mycoplasmas to synthesize a biofilm. A total of 299 avian mycoplasma isolates were included in the study, encompassing both pathogenic (Mycoplasma gallisepticum, M. synoviae, M. meleagridis, M. iowae) and non-pathogenic species (M. gallinaceum, M. gallinarum, M. iners and M. pullorum). The authors successfully demonstrated the feasibility of inducing avian mycoplasmas to synthetize in vitro a biofilm, which can be visually quantified. The only species that did not produce any biofilm was M. iowae. In general, the pathogenic mycoplasmas produced greater quantities of biofilm compared to the non-pathogenic ones. Furthermore, it was observed that the ability to produce biofilm appeared to vary, both qualitatively and quantitatively, not only among different species but also among isolates of a single species. Future studies will be necessary to determine whether biofilm production plays a pivotal epidemiological role for the pathogenic avian mycoplasmas.

Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue, bone marrow and placenta. MSCs have gained importance in the field of regenerative medicine because of their promising role in cell therapy and their regulatory abilities in tissue repair and regeneration. However, a better characterization of these cells and their products is necessary to further potentiate their clinical application. In this study, we used unbiased high-resolution mass spectrometry-based proteomic analysis to investigate the impact of distinct priming strategies, such as hypoxia and IFN-γ treatment, on the composition and therapeutic functionality of the secretome produced by MSCs derived from the amniotic membrane of the human placenta (hAMSCs). Our investigation revealed that both types of priming improved the therapeutic efficacy of hAMSCs, and these improvements were related to the secretion of functional factors present in the conditioned medium (CM) and exosomes (EXOs), which play crucial roles in mediating the paracrine effects of MSCs. In particular, hypoxia was able to induce a pro-angiogenic, innate immune response-activating, and tissue-regenerative hAMSC phenotype, as highlighted by the elevated production of regulatory factors such as VEGFA, PDGFRB, ANGPTL4, ENG, GRO-γ, IL8, and GRO-α. IFN-γ priming, instead, led to an immunosuppressive profile in hAMSCs, as indicated by increased levels of TGFB1, ANXA1, THBS1, HOMER2, GRN, TOLLIP and MCP-1. Functional assays validated the increased angiogenic properties of hypoxic hAMSCs and the enhanced immunosuppressive activity of IFN-γ-treated hAMSCs. This study extends beyond the direct priming effects on hAMSCs, demonstrating that hypoxia and IFN-γ can influence the functional characteristics of hAMSC-derived secretomes, which, in turn, orchestrate the production of functional factors by peripheral blood cells. This research provides valuable insights into the optimization of MSC-based therapies by systematically assessing and comparing the priming type-specific functional features of hAMSCs. These findings highlight new strategies for enhancing the therapeutic efficacy of MSCs, particularly in the context of multifactorial diseases, paving the way for the use of hAMSC-derived products in clinical practice.

Background The ORCHESTRA project, funded by the European Commission, aims to create a pan-European cohort built on existing and new large-scale population cohorts to help rapidly advance the knowledge related to the prevention of the SARS-CoV-2 infection and the management of COVID-19 and its long-term sequelae. The integration and analysis of the very heterogeneous health data pose the challenge of building an innovative technological infrastructure as the foundation of a dedicated framework for data management that should address the regulatory requirements such as the General Data Protection Regulation (GDPR). Methods The three participating Supercomputing European Centres (CINECA - Italy, CINES - France and HLRS - Germany) designed and deployed a dedicated infrastructure to fulfil the functional requirements for data management to ensure sensitive biomedical data confidentiality/privacy, integrity, and security. Besides the technological issues, many methodological aspects have been considered: Berlin Institute of Health (BIH), Charité provided its expertise both for data protection, information security, and data harmonisation/standardisation. Results The resulting infrastructure is based on a multi-layer approach that integrates several security measures to ensure data protection. A centralised Data Collection Platform has been established in the Italian National Hub while, for the use cases in which data sharing is not possible due to privacy restrictions, a distributed approach for Federated Analysis has been considered. A Data Portal is available as a centralised point of access for non-sensitive data and results, according to findability, accessibility, interoperability, and reusability (FAIR) data principles. This technological infrastructure has been used to support significative data exchange between population cohorts and to publish important scientific results related to SARS-CoV-2. Conclusions Considering the increasing demand for data usage in accordance with the requirements of the GDPR regulations, the experience gained in the project and the infrastructure released for the ORCHESTRA project can act as a model to manage future public health threats. Other projects could benefit from the results achieved by ORCHESTRA by building upon the available standardisation of variables, design of the architecture, and process used for GDPR compliance.

This study investigates breast cancer survival rates between 2000 and 2022 in northern Israel, focusing on ethnicity, socioeconomic status, age at diagnosis, and the Charlson Comorbidity Index. Analyzing data from Clalit Health Services, we studied 8,431 breast cancer patients (6,395 Jewish, 2,036 Arab). We compared five- and ten-year survival rates across different demographics. Ethnicity showed a minor impact on survival (OR 1.12, 95% CI: 0.93 - 1.35). Socioeconomic status had a significant effect, with a higher level of improving survival (OR 2.50, 95% CI: 2.04 – 3.08). Age was crucial; women 18-39 had better survival than 60-100, but no significant difference was found between the 18-39 and 40-59 age groups [OR (CI 0.90 – 1.53, p = 0.231)]. For the Charlson Comorbidity Index, women with scores of 3-10 showed lower survival compared to scores of 0 and 1-2. There was a notable improvement in five-year survival rates among patients aged 18-59 diagnosed from 2009-2018 (90.7%) compared to 2000-2008 (86.9%) (p = 0.0046), but not in patients aged 60-100. The study highlights that socioeconomic status, age, and comorbidity scores are significant in determining survival rates for breast cancer. The improvement in survival rates for younger patients diagnosed more recently reflects advancements in treatment and care. This research provides valuable insights into the factors affecting breast cancer survival rates, underscoring the role of socioeconomic status, age, and comorbidities while also highlighting the progress in breast cancer treatment over recent years.