Recent publications
This study provides new mineral chemistry data together with micro‐thermometric measurements on fluid inclusions hosted in ultramafic xenoliths (lherzolite, wehrlite, and dunite) brought to the surface by the last Mt. Vulture volcano activity (140 ka; southern Italy), and fed by melilitite‐carbonatite magmas. Petrographic evidence and mineralogical compositions of Mt. Vulture xenoliths are consistent with an origin in the upper mantle. Fluid inclusions in rock‐forming minerals of lherzolite and wehrlite xenoliths are CO 2 ‐dominated. The equilibrium temperature calculated by geothermometric estimates ranges from 1039 C (±36°C) to 1142°C (±15°C), and entrapment pressures of fluid inclusions with post‐trapping re‐equilibration correspond to the local crust–mantle boundary (32 km depth), and to a shallow reservoir located at 12–14 km depth. These results contribute to constrain the origin of these xenoliths and the depth of storage of magmas erupted from Mt. Vulture, where carbonatite‐like metasomatism and mantle‐derived CO 2 degassing occur.
The tight and coordinated regulation of virulence gene expression is crucial to ensure the survival and persistence of bacterial pathogens in different contexts within their hosts. Considering this, bacteria do not express virulence factors homogenously in time and space, either due to their associated fitness cost or to their detrimental effect at specific infection stages. To efficiently infect and persist into their hosts, bacteria have thus to monitor environmental cues or chemical cell-to-cell signaling mechanisms that allow their transition from the external environment to the host, and therefore adjust gene expression levels, intrinsic biological activities, and appropriate behaviors. Listeria monocytogenes (Lm), a major Gram-positive facultative intracellular pathogen, stands out for its adaptability and capacity to thrive in a wide range of environments. Because of that, Lm presents itself as a significant concern in food safety and public health, that can lead to potentially life-threatening infections in humans. A deeper understanding of the intricate bacterial virulence mechanisms and the signals that control them provide valuable insights into the dynamic interplay between Lm and the host. Therefore, this review addresses the role of some crucial signals behind Lm pathogenic virulence mechanisms and explores how the ability to assimilate and interpret these signals is fundamental for pathogenesis, identifying potential targets for innovative antimicrobial strategies.
Epilepsy is a complex chronic brain disorder with diverse clinical features that can be caused by various triggering events, such as infections, head trauma, or stroke. During epileptogenesis, various abnormalities are observed, such as altered cellular homeostasis, imbalance of neurotransmitters, tissue changes, and the release of inflammatory mediators, which in combination lead to spontaneous recurrent seizures. Regulatory T cells (Tregs), a subtype of CD4⁺Foxp3⁺ T cells, best known for their key function in immune suppression, also seem to play a role in attenuating neurodegeneration and suppressing pathological inflammation in several brain disease states. Considering that epilepsy is also highly associated with neuronal damage and neuroinflammation, modulation of Tregs may be an interesting way to modify the disease course of epilepsy and needs further investigation. In this review, we will describe the currently available information on Tregs in epilepsy.
The Azores archipelago, situated east of the Mid-Atlantic Ridge, comprises volcanic islands arranged along sub-parallel spreading systems and rests on a thick oceanic crust. Magma is supplied directly from the roots of the volcanic systems. Located at or nearby the boundary between the crust and the mantle, they consist of mafic cumulates and mafic mush layers. This work focuses on tephra samples and a submarine lava younger than 40.000 years, collected from both central volcanoes and fissure zones. Our report details a new dataset of major, trace, and volatile elements analysed in glassy melt inclusions trapped in olivine (Fo75.8–85.6) which are extracted from cumulative bodies at the vicinity of the crust-mantle boundary. Their compositions cover a range from subalkaline to mildly alkaline basalt, and trachybasalt, which match those of Azores lavas. They registered a chemical evolution through fractional crystallisation of olivine alone, as well as olivine and clinopyroxene, as both the FeOt/MgO (1.4–3.1) and CaO/Al2O3 (0.4–1.0) ratios of the melt decrease. Incompatible element ratios of Zr (40–352 ppm), Ba (135–612 ppm), and Rb (5–77 ppm), as compared to Nb (5–82 ppm), exhibit variability within a limited but significant range of values. The ranges in the Nb/Zr, Ba/Nb and Rb/Nb ratios recorded by melt inclusions possibly reveal distinct geochemical sources (at least two), and mixing between partial melts as they move upward. The halogen signature is characteristic of the shallow mantle. The majority of melt inclusions show Cl/K ratio (0.06) similar to E-MORB, although some of them are comparable to N-MORB (Cl/K = 0.03). Their F/Nd ratio may achieve a rather high value (27.8).
Methamphetamine (Meth) use is known to induce complex neuroinflammatory responses, particularly involving astrocytes and microglia. Building upon our previous research, which demonstrated that Meth stimulates astrocytes to release tumor necrosis factor (TNF) and glutamate, leading to microglial activation, this study investigates the role of the anti‐inflammatory cytokine interleukin‐10 (IL‐10) in this process. Our findings reveal that the presence of recombinant IL‐10 (rIL‐10) counteracts Meth‐induced excessive glutamate release in astrocyte cultures, which significantly reduces microglial activation. This reduction is associated with the modulation of astrocytic intracellular calcium (Ca ²⁺ ) dynamics, particularly by restricting the release of Ca ²⁺ from the endoplasmic reticulum to the cytoplasm. Furthermore, we identify the small Rho GTPase Cdc42 as a crucial intermediary in the astrocyte‐to‐microglia communication pathway under Meth exposure. By employing a transgenic mouse model that overexpresses IL‐10 (pMT‐10), we also demonstrate in vivo that IL‐10 prevents Meth‐induced neuroinflammation. These findings not only enhance our understanding of Meth‐related neuroinflammatory mechanisms, but also suggest IL‐10 and Cdc42 as putative therapeutic targets for treating Meth‐induced neuroinflammation.
Carbon dioxide released permanently from soils in diffuse degassing areas may constitute a permanent hazard for the population. Several villages in the Azores archipelago (Portugal) are placed in areas with anomalous soil CO2 degassing and lethal indoor CO2 concentration (>10 vol%) has been already recorded in some buildings. The 2021-2022 dislodgements of population at Vulcano (Italy) and La Palma (Spain) volcanic islands due to high soil CO2 degassing highlight the importance of defining criteria to produce human CO2 exposure risk maps, which are useful to mitigate the risk and should constitute valuable tools for land-use planners. Risk is assessed in the current study by combining susceptibility, exposure, and vulnerability maps. The defined criteria were applied to two villages in Furnas Volcano (São Miguel Island, Azores), showing that 58% and 98% of the buildings, respectively, at Furnas and Ribeira Quente villages are at high risk of CO2 exposure.
The 2022’s seismo-volcanic crisis on São Jorge Island of the Azores archipelago has provided an opportunity to deploy a portable infrasound array as a collaborative work between the Research Institute for Volcanology and Risk Assessment (IVAR) of the University of the Azores (UAc) and the University of Florence (UniFI). The four-element array, SJ1, became operational on 2 April 2022. Despite being deployed in a first stage to monitor the activities related to the volcanic unrest on São Jorge Island, SJ1 worked as a supporting tool to the existing IMS infrasound station IS42, located on Graciosa Island at ~ 40 km distance, leading to an enhancement of the infrasonic monitoring network in the region. This work emphasises the importance of low-cost portable infrasound arrays to improve the coverage of infrasound observations for local and regional monitoring purposes in the Azores region. Two events recorded by both arrays are briefly exemplified: a low-magnitude earthquake on São Jorge Island and a fireball which crossed the North Atlantic Ocean. Infrasound data from both arrays are combined to obtain a fast but still accurate source localization of the analysed events.
Artificial intelligence (AI) applications in oncology are at the forefront of transforming healthcare during the Fourth Industrial Revolution, driven by the digital data explosion. This review provides an accessible introduction to the field of AI, presenting a concise yet structured overview of the foundations of AI, including expert systems, classical machine learning, and deep learning, along with their contextual application in clinical research and healthcare. We delve into the current applications of AI in oncology, with a particular focus on diagnostic imaging and pathology. Numerous AI tools have already received regulatory approval, and more are under active development, bringing clear benefits but not without challenges. We discuss the importance of data security, the need for transparent and interpretable models, and the ethical considerations that must guide AI development in healthcare. By providing a perspective on the opportunities and challenges, this review aims to inform and guide researchers, clinicians, and policymakers in the adoption of AI in oncology.
Background
The use of a smartphone built-in microphone for auscultation is a feasible alternative to the use of a stethoscope, when applied by physicians.
Objective
This cross-sectional study aims to assess the feasibility of this technology when used by parents—the real intended end users.
Methods
Physicians recruited 46 children (male: n=33, 72%; age: mean 11.3, SD 3.1 y; children with asthma: n=24, 52%) during medical visits in a pediatric department of a tertiary hospital. Smartphone auscultation using an app was performed at 4 locations (trachea, right anterior chest, and right and left lung bases), first by a physician (recordings: n=297) and later by a parent (recordings: n=344). All recordings (N=641) were classified by 3 annotators for quality and the presence of adventitious sounds. Parents completed a questionnaire to provide feedback on the app, using a Likert scale ranging from 1 (“totally disagree”) to 5 (“totally agree”).
Results
Most recordings had quality (physicians’ recordings: 253/297, 85.2%; parents’ recordings: 266/346, 76.9%). The proportions of physicians' recordings (34/253, 13.4%) and parents' recordings (31/266, 11.7%) with adventitious sounds were similar. Parents found the app easy to use (questionnaire: median 5, IQR 5-5) and were willing to use it (questionnaire: median 5, IQR 5-5).
Conclusions
Our results show that smartphone auscultation is feasible when performed by parents in the clinical context, but further investigation is needed to test its feasibility in real life.
Highlights
•Both primary endometrial cancers (ECs) and matched lung metastases shared a common ancestor with independent evolution at each site.
•The two endometrioid ECs studied acquired additional mutations during the distant metastatic process.
•Subclonal CTNNB1 hotspot mutations in the two primary ECs studied became clonal in the distant metastases.
Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.
The central nervous system (CNS) contains a diverse number of neuronal and non-neuronal cell types that physically interact with one another. It is these physical interactions which underlie many essential functions. For example, neurons communicate with each other at specialized structures called synapses. At a synapse, information is conveyed by the release of neurotransmitters from a presynaptic neuron, which diffuse across the synaptic cleft and bind receptors on the postsynaptic neuron, eliciting a response. Although most studies place the neuron at the center of the synapse, other cell types have recently been shown to play crucial roles at this structure. Astrocytes are the major non-neuronal cell type in the mammalian brain and play key roles in synapse formation, maintenance of synapse homeostasis, modulation of synaptic transmission, and provision of trophic support to neurons. In this chapter, we aim to describe methods used for in-depth analysis of the transcriptomic landscape of astrocytes at the single-cell level, to better understand the interaction(s) between astrocytes and neurons at synapses.
Volcano observatories (VOs) around the world are required to maintain surveillance of their volcanoes and inform civil protection and aviation authorities about impending eruptions. They often work through consolidated procedures to respond to volcanic crises in a timely manner and provide a service to the community aimed at reducing the potential impact of an eruption. Within the International Airways Volcano Watch (IAVW) framework of the International Civil Aviation Organisation (ICAO), designated State Volcano Observatories (SVOs) are asked to operate a colour coded system designed to inform the aviation community about the status of a volcano and the expected threats associated. Despite the IAVW documentation defining the different colour-coded levels, operating the aviation colour code in a standardised way is not easy, as sometimes, different SVOs adopt different strategies on how, when, and why to change it. Following two European VOs and Volcanic Ash Advisory Centres (VAACs) workshops, the European VOs agreed to present an overview on how they operate the aviation colour code. The comparative analysis presented here reveals that not all VOs in Europe use this system as part of their operational response, mainly because of a lack of volcanic eruptions since the aviation colour code was officially established, or the absence of a formal designation as an SVO. We also note that the VOs that do regularly use aviation colour code operate it differently depending on the frequency and styles of eruptions, the historical eruptive activity, the nature of the unrest, the monitoring level, institutional norms, previous experiences, and on the agreement they may have with the local Air Transport Navigation providers. This study shows that even though the aviation colour code system was designed to provide a standard, its usage strongly depends on the institutional subjectivity in responding to volcano emergencies. Some common questions have been identified across the different (S)VOs that will need to be addressed by ICAO to have a more harmonised approach and usage of the aviation colour code.
MicroRNA (miRNA) modulation has been identified as a promising strategy for improving the response of human prostate cancer (PCa) to radiotherapy (RT). Studies have shown that mimics or inhibitors of miRNAs could modulate the sensitivity of PCa cells to RT. In addition, pegylated gold nanoparticles have been studied as a therapeutic approach to treat PCa cells and/or vehicles for carrying miRNAs to the inside of cells. Therefore, we evaluated the capacity of hypofractionated RT and pegylated gold nanorods (AuNPr-PEG) to modulate the miRNA signature on PCa cells. Thus, RT-qPCR was used to analyze miRNA-95, miRNA-106-5p, miRNA-145-5p, and miRNA-541-3p on three human metastatic prostate cell lines (PC3, DU145, and LNCaP) and one human prostate epithelial cell line (HprEpiC, a non-tumor cell line) with and without treatment. Our results showed that miRNA expression levels depend on cell type and the treatment combination applied using RT and AuNPr-PEG. In addition, cells pre-treated with AuNPr-PEG and submitted to 2.5 Gy per day for 3 days decreased the expression levels of miRNA-95, miRNA-106, miRNA-145, and miRNA-541-3p. In conclusion, PCa patients submitted to hypofractionated RT could receive personalized treatment based on their metastatic cellular miRNA signature, and AuNPr-PEG could be used to increase metastatic cell radiosensitivity.
The fifth edition of the WHO classification of thyroid tumors stresses the prominence of (vascular) invasiveness and histological grading over cytomorphological features. Molecular data are useless regarding the identification of capsular and/or vascular invasion. Despite the growing importance of next-generation sequencing in numerous fields of oncology, the adequate preoperative diagnosis of thyroid tumors rests on a competent combination of imaging and cytology, hopefully supported in the future by artificial intelligence algorithms. For the moment, the gold standard of thyroid tumors goes on being based upon the careful articulation of clinical aspects with histology, enriched by immunohistochemistry and molecular data whenever appropriate.
Transition from optical to digital observation requires an additional procedure in the pathology laboratory, the scanning of glass slides, leading to increased time and digital archive consumption. Thyroid surgical samples often carry the need to collect several tissue fragments that generate many slides to be scanned. This study evaluated the impact of using different inking colours for the surgical margin, section thickness, and glass slide type, in the consumption of time and archive. The series comprehended 40 nodules from 30 patients, including 34 benign nodules in follicular nodular disease, 1 NIFTP, and 5 papillary carcinomas. In 12 nodules, the dominant pattern was microfollicular/solid and in 28 it was macrofollicular. Scanning times/mm² were longer in red-inked fragments in comparison to green (p = 0.04) and black ones (p = 0.024), and in blue-inked in comparison to green ones (p = 0.043). File sizes/mm² were larger in red-inked fragments in comparison to green (p = 0.008) and black ones (p = 0.002). The dominant pattern microfollicular/solid was associated with bigger file size/mm² in comparison with the macrofollicular one (p < 0.001). All scanner outputs increase significantly with the thickness of the section. All scanning outputs increase with the usage of adhesive glass slides in comparison to non-adhesive ones. Small interventions in thyroid sample management that can help optimizing the digital workflow include to prefer black and green inking colours for the surgical margins and 2 µm section in non-adhesive glass slides for increased efficiency.
Given the tubal origin of high-grade serous ovarian cancer (HGSC), we sought to investigate intrauterine lavage (IUL) as a novel method of biomarker detection. IUL and serum samples were collected from patients with HGSC or benign pathology. Although CA-125 and HE4 concentrations were significantly higher in IUL samples compared to serum, they were similar between IUL samples from patients with HGSC vs benign conditions. In contrast, CA-125 and HE4 serum concentrations differed between HGSC and benign pathology (P =.002 for both). IUL and tumor samples from patients with HGSC were subjected to targeted panel sequencing and droplet digital PCR (ddPCR). Tumor mutations were found in 75 % of matched IUL samples. Serum CA-125 and HE4 biomarker levels allowed for better differentiation of HGSC and benign pathology compared to IUL samples. We believe using IUL for early detection of HGSC requires optimization, and current strategies should focus on prevention until early detection strategies improve.
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