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The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in tissues of individuals with type 2 diabetes. Moreover, transgenic mice ubiquitously overexpressing ped/pea-15 feature impaired glucose tolerance and insulin resistance. We have now generated transgenic mice with beta-cell specific overexpressing of ped/pea-15 (beta-tg). Beta-tg mice exhibited decreased glucose tolerance but were not insulin-resistant. However, they showed impaired insulin response to hyperglycemia. Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Surl and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. Overexpression of ped/pea-15 inhibited the induction of the atypical PKCzeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. Rescue of PKCzeta activity elicited recovery of the expression of the Sur1, Kir6.2 and Foxa2 genes and of glucose-induced insulin-secretion in PED/PEA- 15 overexpressing beta-cells. Islets from ped/pea-15 null mice exhibited a 2-fold increased activation of PKCzeta by glucose and increased abundance of the Surl, Kir6.2 and Foxa2 mRNAs and enhanced glucose effect on insulin secretion. In conclusion, ped/pea-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. Overexpression of ped/pea-15 dysregulates beta-cell function and is sufficient to impair glucose tolerance in mice. [ABSTRACT FROM AUTHOR]

DJ-1 is a multifunctional protein associated with pathomechanisms implicated in different chronic diseases including neurodegeneration, cancer and diabetes. Several of the physiological functions of DJ-1 are not yet fully understood; however, in the last years, there has been increasing evidence for a potential role of DJ-1 in the regulation of cellular metabolism. Here, we summarize the current knowledge on specific functions of DJ-1 relevant to cellular metabolism and their role in modulating metabolic pathways. Further, we illustrate pathophysiological implications of the metabolic effects of DJ-1 in the context of neurodegeneration in Parkinson´s disease. [ABSTRACT FROM AUTHOR]

Marine environments represent an incredible source of biopolymers with potential biomedical applications. Recently, drug delivery studies have received great attention for the increasing need to improve site specificity, therapeutic value, and bioavailability, reducing off-target effects. Marine polymers, such as alginate, carrageenan, collagen, chitosan, and silica, have reported unique biochemical features, allowing an efficient binding with drugs, and a controlled release to the target tissue, also obtainable through "green processes". In the present review, we i) analysed the last ten years of scientific peer-reviewed literature; ii) divided the articles based on the achieved experimental phases, tagged as chemistry, drug release, and drug delivery, and iii) compared the best performances among marine polymers extracted from micro- and macro-organisms. Many reviews describe drug carriers from marine organisms, focusing on a single biopolymer or a chemical class. Our study is a groundbreaking literature collection, representing the first thorough investigation of all marine biopolymers described. Most articles report experimental results on the chemical characterisation of marine biopolymers and their in vitro behaviour as drug carriers, although development processes and commercial applications are still in the early stages. Hence, the next efforts should be focused on the sustainable production of marine polymers and final product development. [Display omitted] • The review summarizes the discovery of marine polymers as drug delivery carriers. • Macroalgae and invertebrates showed the strongest potential as source of polymers. • Polysaccharides represent the most isolated and investigated class of polymers. • Future efforts in the use of cultivable microorganisms for polymer production. [ABSTRACT FROM AUTHOR]

Abstract Understanding community assembly and processes driving diversity in deep-sea environments is a major challenge in marine ecosystems. In this paper, we investigated the importance of environmental gradients at different spatial scales in structuring deep-sea canyon and continental slope meiobenthic nematode communities in the NW Mediterranean Sea. Three scales were investigated 1) Ecosystem: Blanes Canyon vs. adjacent open slope; 2) Water-depth within each ecosystem: 1500, 1750 and 2000 m; and 3) Vertical profile (three layers within the first 5 cm of sediment). Nematode communities were analysed in terms of density, biomass, diversity and community structure. Grain size, Chl a , Chl a : phaeopigments, CPE, organic carbon and total nitrogen were measured to assess the relationships with nematode assemblages. Blanes Canyon harbours more abundant and diverse assemblages than the slope, particularly at 1750 m and 2000 m depth respectively. The higher canyon values may be related to the higher food availability there, which can be a consequence of the so-called "canyon effect". Slope assemblages were overall more uniform than those in the canyon, where there were greater bathymetrical differences in community structure. Densities in the canyon peaked at 1750 m depth, which did not correspond with the bathymetric gradient in food availability. The deepest canyon station was the most similar to the slope stations in terms of both environmental conditions and nematode communities, suggesting it lie outside the canyon influence. The higher habitat heterogeneity of the canyon (indicated by its greater vertical sediment and water depth differences) played a key role in structuring nematode spatial distribution. Independently of the ecosystem, however, the vertical sediment profile was the most determinative factor for density, community structure, and diversity. Highlights • Nematode community (standing stocks, diversity and community structure) differed between canyon and slope. • Blanes Canyon harbours more spatially heterogeneous and diverse nematode communities than its adjacent open slope. • Vertical sediment profile was significantly affecting the community structure and diversity, both in canyon and slope. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 5 (IRF5) modulates the expression of genes controlling cell growth and apoptosis. Previous findings have suggested a lack of IRF5 transcripts in both acute and chronic leukemias. However, to date, IRF5 expression and function have not been investigated in chronic myeloid leukemia (CML). We report that IRF5 is expressed in CML cells, where it interacts with the BCR-ABL kinase that modulates its expression and induces its tyrosine phosphorylation. Tyrosine-phosphorylated IRF5 displayed reduced transcriptional activity that was partially restored by imatinib mesylate (IM). Interestingly, a mutant devoid of a BCR-ABL consensus site (IRF5Y104F) still presented significant tyrosine phosphorylation. This finding suggests that the oncoprotein phosphorylates additional tyrosine residues or induces downstream signaling pathways leading to further IRF5 phosphorylation. We also found that ectopic expression of IRF5 decreases the proliferation of CML cell lines by slowing their S-G2 transition, increasing the inhibition of BCR-ABL signaling and enhancing the lethality effect observed after treatment with IM, α-2-interferon and a DNA-damaging agent. Furthermore, IRF5 overexpression successfully reduced the clonogenic ability of CML CD34-positive progenitors before and after exposure to the above-indicated cytotoxic stimuli. Our data identify IRF5 as a downstream target of the BCR-ABL kinase, suggesting that its biological inactivation contributes to leukemic transformation. [ABSTRACT FROM AUTHOR]

Sarcomas are mesenchymal-derived cancers with overlapping clinical and pathologic features and a remarkable histological heterogeneity. While a precise diagnosis is often challenging to achieve, systemic treatment of sarcomas is still quite uniform. In this scenario, next generation sequencing (NGS) may be exploited to assist diagnosis and to identify specific targetable alterations. However, the precise role of genomic characterization in these diseases is still debated. In the present study, we analyzed 18 samples from 11 low-incidence sarcomas using NGS technology. We also used an in-silico prediction tool to reclassify variants of unknown significance and then looked for potentially druggable alterations to match with targeted therapies. Our cohort presented several predictable findings (e.g. MYC amplification in radio-induced angio-sarcoma, COL1A1-PDGFB rearrangements in dermatofibrosarcoma protuberans) along with unexpected results (e.g. the reciprocal WT1-EWSR1 fusion in a desmoplastic small round cell tumor). One third of patients (6/18) displayed at least one actionable molecular alterations. Our experience confirms the potential role of NGS in the management of rare sarcomas. This tool may support the diagnostic process, but also detect targets for personalized therapies. [ABSTRACT FROM AUTHOR]

Abstract: The distribution of megabenthic epifauna (invertebrates) in the Balearic Basin (western Mediterranean) has been analyzed at depths between 427 and 2265 m after compiling samplings performed in 1985–1992 and 2007–2008 with an OTSB-14 bottom trawl. 84 epibenthic taxa of invertebrates (excluded decapod crustaceans) were collected. Epibenthic assemblages were organized in five groups (n-MDS analyses) as a function of increasing depth: upper slope assemblage, U, hauls between 427 and 660 m; middle slope assemblages M1 and M2, hauls between 663–876 m and 864–1412 m, respectively; lower slope assemblages L1 and L2, hauls between 1488–1789 m and 1798–2265 m, respectively). We found significant differences in assemblage composition between all depth-adjacent pairs of groups. Trends in the distribution of biomass vs. depth and within assemblages varied when hauls taken over insular were compared to those over mainland slopes. Over insular slopes we found (n-MDS) only four distinct depth assemblages, with significant differences between all depth-adjacent group pairs, except between L1 and L2. Over the mainland slope, two peaks of biomass situated at U (427–660 m) and at L1 (1488–1789 m) were clearly identified, attributable to the echinoid Brissopsis lyrifera and holothurian Molpadia musculus at U and to the synallactid holothurian Mesothuria intestinalis at L1. The distribution of biomass vs. depth on insular slopes did not follow this pattern, showing no significant biomass peak below 1000 m and a total biomass an order of magnitude lower than adjacent to the mainland. After compiling available environmental data over the mainland slope off Barcelona, we found coincidence between the peak biomass of Mesothuria intestinalis and: i) a significant increase of labile OM (%OrgC, C/N, hydrolizable aminoacids–EHAA, and the EHAA/THAA-total hydrolizable aminoacids-ratio) over 1600 m; and ii) an increase of turbidity and T at 1500–1600 m in February 2008. We suggest that such OM inputs must likely be associated to the formation of nepheloid layers close to submarine canyons, probably associated with oceanographic processes in deep water masses in the area. This would explain why aggregations of M. intestinalis were linked to the mainland part of the Balearic basin, with highest densities located south of canyons. If hotspots of biomass as cited here for M. intestinalis are regulated by factors such as river inputs, both natural climatic changes (e.g. changes in rainfall regimes) and human impact (e.g. river damming) may affect deep-Mediterranean communities below 1000 m. [Copyright &y& Elsevier]

Molecular testing of the BCR-ABL1 transcript via real-time quantitative-polymerase-chain-reaction is the most sensitive approach for monitoring the response to tyrosine-kinase-inhibitors therapy in chronic myeloid leukaemia (CML) patients. Each stage of the molecular procedure has been standardized and optimized, including the total white blood cells (WBCs) and RNA isolation methods. Here, we compare the performance of our current manual protocol to a newly semiautomatic method based on the Biomek i-5 Automated Workstations integrated with the CytoFLEX Flow Cytometer, followed by the automatic QIAsymphony system to facilitate high-throughput processing samples and reduce the hands-on time and the risk associated with SARS-CoV-2. The recovery efficiency was investigated in blood samples from 100 adults with CML. We observe a 100% of concordance between the two methods, with similar total WBCs isolated (median 1.137 × 106 for manual method vs. 1.076 × 106 for semiautomatic system) and a comparable quality and quantity of RNA extracted (median 103 ng/μL with manual isolation kit vs. 99.95 ng/μL with the QIAsymphony system). Moreover, by stratifying patients according to their BCR-ABL1 transcript levels, we obtained similar BCR-ABL1/ABL1IS values and ABL1 copies, and matched samples were assigned to the same group of molecular response. We conclude that this newly semiautomatic workflow has a performance comparable to our more laborious standard manual, which can be replaced, particularly when specimens from patients with suspected or confirmed SARS-CoV-2 infection need to be processed. [ABSTRACT FROM AUTHOR]

Hypereosinophilia (HE) is a heterogeneous condition with a persistent elevated eosinophil count of >350/mm3, which is reported in various (inflammatory, allergic, infectious, or neoplastic) diseases with distinct pathophysiological pathways. HE may be associated with tissue or organ damage and, in this case, the disorder is classified as hypereosinophilic syndrome (HES). Different studies have allowed for the discovery of two major pathogenetic variants known as myeloid or lymphocytic HES. With the advent of molecular genetic analyses, such as T-cell receptor gene rearrangement assays and Next Generation Sequencing, it is possible to better characterize these syndromes and establish which patients will benefit from pharmacological targeted therapy. In this review, we highlight the molecular alterations that are involved in the pathogenesis of eosinophil disorders and revise possible therapeutic approaches, either implemented in clinical practice or currently under investigation in clinical trials. [ABSTRACT FROM AUTHOR]

The introduction of ABL Tyrosine Kinase Inhibitors (TKIs) has significantly improved the outcome of Chronic Myeloid Leukemia (CML) patients that, in large part, achieve satisfactory hematological, cytogenetic and molecular remissions. However, approximately 15–20% fail to obtain optimal responses according to the current European Leukemia Network recommendation because of drug intolerance or resistance. Moreover, a plethora of evidence suggests that Leukemic Stem Cells (LSCs) show BCR-ABL1-independent survival. Hence, they are unresponsive to TKIs, leading to disease relapse if pharmacological treatment is discontinued. All together, these biological events generate a subpopulation of CML patients in need of alternative therapeutic strategies to overcome TKI resistance or to eradicate LSCs in order to allow cure of the disease. In this review we update the role of “non ABL-directed inhibitors” targeting signaling pathways downstream of the BCR-ABL1 oncoprotein and describe immunological approaches activating specific T cell responses against CML cells. [ABSTRACT FROM AUTHOR]

Playing music is a complex task that relies on the combination of musicians' technical and expressive skills. While the literature has investigated the effects of musical expressivity on the listeners, the way how technical difficulty and emotional expressivity affect musicians during playing has surprisingly received no attention. In an attempt to fill this gap in the literature, we collected behavioral and physiological data from twelve violinists playing 29 pieces that included both technical exercises and excerpts from classical repertoire for violin. After playing each stimulus, participants rated it for emotional expressivity and technical difficulty. During the entire session, cardiac parameters and electrodermal activity were collected, together with the kinematic parameters of the bowing gesture. A set of Linear Mixed-Effect (LME) models suggested that emotional expressivity attributed to music affected the fluidity of bowing (i.e., smoothness), with the excerpts rated as more expressive being performed in a less smooth way. In contrast, LME models revealed no effects of expressivity and technical difficulty on any of the physiological parameters of violinists. Our results offer novel insights into the psychophysiological dynamics that link motor parameters with musical expressivity. These findings could influence educational practices in music and deepen our understanding of aesthetic emotions., (© 2024. The Author(s).)

From 1 January 2022 to 31 May 2024, the World Health Organization (WHO) reported 97,745 laboratory-confirmed Mpox cases, including 203 deaths, across 116 countries. Despite a 2.3% decrease in new cases in May 2024 compared to April 2024, significant regional variations persist. The African Region reported the highest proportion of new cases, while other regions experienced mixed trends. Phylogenomic analyses of the Mpox virus Clade IIb lineage B.1 reveal stable genetic variability with minimal diversification. The Bayesian Skyline Plot indicates a generally stable viral population size with a modest peak in late 2023, followed by a decline. In general, the data indicate that the MPXV outbreak is primarily localized within a few consistent geographic clusters. The virus's evolution is relatively slow, as indicated by its stable genetic variability, and Clade IIb lineage B.1 does not currently show signs of rapid genetic changes or population growth. The current low level of genetic diversity should not lead to complacency. Ongoing genomic surveillance is essential for effective outbreak management and understanding. This monitoring is crucial for identifying any shifts in the virus's behavior or transmission, allowing for prompt public health responses and adjustments. In addition, continued vigilance is necessary to detect any new variants that might influence the outbreak's trajectory.

Viral hepatitis is a major cause of liver illness worldwide. Despite advances in the understanding of these infections, the pathogenesis of hepatitis remains a complex process driven by intricate interactions between hepatitis viruses and host cells at the molecular level. This paper will examine in detail the dynamics of these host-pathogen interactions, highlighting the key mechanisms that regulate virus entry into the hepatocyte, their replication, evasion of immune responses, and induction of hepatocellular damage. The unique strategies employed by different hepatitis viruses, such as hepatitis B, C, D, and E viruses, to exploit metabolic and cell signaling pathways to their advantage will be discussed. At the same time, the innate and adaptive immune responses put in place by the host to counter viral infection will be analyzed. Special attention will be paid to genetic, epigenetic, and environmental factors that modulate individual susceptibility to different forms of viral hepatitis. In addition, this work will highlight the latest findings on the mechanisms of viral persistence leading to the chronic hepatitis state and the potential implications for the development of new therapeutic strategies. Fully understanding the complex host-pathogen interactions in viral hepatitis is crucial to identifying new therapeutic targets, developing more effective approaches for treatment, and shedding light on the mechanisms underlying progression to more advanced stages of liver damage.

Despite Parvovirus B19 (B19V) generally causing mild or asymptomatic infections, and only certain high-risk groups such as hematological or immunocompromised patients and pregnant women tending to develop complications, several factors challenge the assumption of a "benign" clinical course in immunocompetent adults and adolescents. A significant proportion of the population may harbor undiagnosed health conditions or genetic predispositions that could render them more susceptible to severe B19V complications. These could include mild hematological disorders, immune dysregulation not resulting in overt immunodeficiency, or underlying cardiac conditions. Concurrent infections with other pathogens, even seemingly minor ones, could synergistically increase the severity of B19V infection, leading to more pronounced clinical manifestations. While not definitively proven, the possibility of emerging B19V strains with increased virulence or altered tissue tropism cannot be entirely discounted. Additionally, the period of pandemic-related restrictions likely led to reduced B19V circulation, potentially resulting in a cohort of young adults with limited natural immunity, making them more vulnerable to infection. Potential clinical consequences include atypical and severe presentations, even in individuals without known risk factors. The traditional focus on B19V primarily as a pediatric concern might lead to underdiagnosis or delayed diagnosis in adults, potentially hindering timely intervention and management. A surge in B19V-related complications, even if individually mild, could collectively strain healthcare resources, particularly in settings with limited capacity or pre-existing pressures. Possible recommendations are to heighten clinical awareness with a high index of suspicion for B19V infection in adults and adolescents presenting with compatible symptoms, even in the absence of classic risk factors. Additionally, expanding testing criteria and enhancing public health surveillance efforts would be prudent.

The COVID-19 pandemic underscored the critical importance of vaccination to global health security and highlighted the potential of digital health solutions to improve immunization strategies. This article explores integrating digital health technologies with immunization programs to improve coverage, monitoring, and public health outcomes. It examines the current landscape of digital tools used in immunization initiatives, such as mobile health apps, electronic health records, and data analytics platforms. Case studies from different regions demonstrate the effectiveness of these technologies in addressing challenges such as vaccine hesitancy, logistics, and real-time monitoring of vaccine distribution and adverse events. The paper also examines ethical considerations, data privacy issues, and the need for a robust digital infrastructure to support these innovations. By analyzing the successes and limitations of digital health interventions in immunization campaigns during and after the COVID-19 pandemic, we provide recommendations for future integration strategies to ensure resilient and responsive immunization systems. This research aims to guide policymakers, health professionals, and technologists in leveraging digital health to strengthen immunization efforts and prepare for future public health emergencies.

Growing evidence suggests that respiratory frequency ( f R ) is a valid marker of effort during high-intensity exercise, including sports of an intermittent nature, like soccer. However, very few attempts have been made so far to monitor f R in soccer with unobtrusive devices. This study assessed the validity of three strain-based commercial wearable devices measuring f R during soccer-specific movements. On two separate visits to the soccer pitch, 15 players performed a 30 min validation protocol wearing either a ComfTech ® (CT) vest or a Bioharness TM (BH) 3.0 strap and a Tyme Wear TM (TW) vest. f R was extracted from the respiratory waveform of the three commercial devices with custom-made algorithms and compared with that recorded with a reference face mask. The f R time course of the commercial devices generally resembled that of the reference system. The mean absolute percentage error was, on average, 7.03% for CT, 8.65% for TW, and 14.60% for BH for the breath-by-breath comparison and 1.85% for CT, 3.27% for TW, and 7.30% for BH when comparison with the reference system was made in 30 s windows. Despite the challenging measurement scenario, our findings show that some of the currently available wearable sensors are indeed suitable to unobtrusively measure f R in soccer.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Cyclooxygenase-2 (COX-2) is an enzyme that plays a pivotal role in peripheral inflammation and pain via the prostaglandin pathway. In the central nervous system (CNS), COX-2 is implicated in neurodegenerative and psychiatric disorders as a potential therapeutic target and biomarker. However, clinical studies with COX-2 have yielded inconsistent results, partly due to limited mechanistic understanding of how COX-2 activity relates to CNS pathology. Therefore, developing COX-2 positron emission tomography (PET) radiotracers for human neuroimaging is of interest. This study introduces [ 11 C]BRD1158, which is a potent and uniquely fast-binding, selective COX-2 PET radiotracer. [ 11 C]BRD1158 was developed by prioritizing potency at COX-2, isoform selectivity over COX-1, fast binding kinetics, and free fraction in the brain. Evaluated through in vivo PET neuroimaging in rodent models with human COX-2 overexpression, [ 11 C]BRD1158 demonstrated high brain uptake, fast target-engagement, functional reversibility, and excellent specific binding, which is advantageous for human imaging applications. Lastly, post-mortem samples from Huntington's disease (HD) patients and preclinical HD mouse models showed that COX-2 levels were elevated specifically in disease-affected brain regions, primarily from increased expression in microglia. These findings indicate that COX-2 holds promise as a novel clinical marker of HD onset and progression, one of many potential applications of [ 11 C]BRD1158 human PET., Competing Interests: The authors declare the following competing financial interest(s): Dr. Jacob Hooker discloses the following relationships: Massachusetts Institute of Technology Consultant; American Chemical Society (ACS), ACS Publications, ACS Chemical Neuroscience Editorial Role; Eikonizo Therapeutics Co-Founder, Advisor; Sensorium Therapeutics Co-Founder, Advisor; Psy Therapeutics Consultant; Delix Therapeutics Advisor; Fuzionaire Diagnostics Advisor; Arclight Therapeutics Advisor; Proximity Therapeutics Advisor; Human Health Advisor, Rocket Science Health Advisor; Atai Life Sciences Sponsored research, training grant/gift. Dr. Beth Stevens discloses the following relationships: Beth Stevens serves on the scientific advisory board of Annexon Biosciences and is a minor shareholder of this company., (© 2024 The Authors. Published by American Chemical Society.)

The influenza A(H1N1) pdm09 virus, which emerged in 2009, has been circulating seasonally since then. In this study, we conducted a comprehensive genome-based investigation to gain a detailed understanding of the genetic and evolutionary characteristics of the hemagglutinin (HA) and neuraminidase (NA) surface proteins of A/H1N1pdm09 strains circulating in Italy over a fourteen-year period from 2009 to 2023 in relation to global strains. Phylogenetic analysis revealed rapid transmission and diversification of viral variants during the early pandemic that clustered in clade 6B.1. In contrast, limited genetic diversity was observed during the 2023 season, probably due to the genetic drift, which provides the virus with a constant adaptability to the host; furthermore, all isolates were split into two main groups representing two clades, i.e., 6B.1A.5a.2a and its descendant 6B.1A.5a.2a.1. The HA gene showed a faster rate of evolution compared to the NA gene. Using FUBAR, we identified positively selected sites 41 and 177 for HA and 248, 286, and 455 for NA in 2009, as well as sites 22, 123, and 513 for HA and 339 for NA in 2023, all of which may be important sites related to the host immune response. Changes in glycosylation acquisition/loss at prominent sites, i.e., 177 in HA and 248 in NA, should be considered as a predictive tool for early warning signs of emerging pandemics, and for vaccine and drug development.

Measles, a highly contagious disease primarily affecting children, carries serious health risks, including complications and mortality. Vaccination remains the most effective preventive measure against measles transmission. The COVID-19 pandemic has exacerbated challenges in surveillance and immunization efforts, leaving millions of people exposed to preventable diseases such as measles. Globally accelerated immunization campaigns are critical for achieving regional elimination goals and mitigating the risk of outbreaks. Our team has developed an open-access database for global measles monitoring, facilitating standardized data collection and analysis. The analysis of measles cases from 2011 to 2023 reveals fluctuating trends, with notable increases in Africa in 2019 and 2023, indicating potential gaps in control strategies. Using an automated signal detection tool developed by the European Centre for Disease Prevention and Control (ECDC) team, we identified significant variations between World Health Organization (WHO) regions, underscoring the importance of continuous monitoring to detect epidemiological changes early. These results underscore the need for robust surveillance systems and accelerated vaccination efforts to safeguard public health.

Mpox, caused by viruses of the genus Orthopoxvirus, is an emerging threat to human and animal health. With increasing urbanization and more frequent interaction between humans and wild animals, the risk of Mpox transmission to humans has increased significantly. This review aims to examine in depth the epidemiology, pathogenesis, and diagnosis of Mpox, with a special focus on recent discoveries and advances in understanding the disease. Molecular mechanisms involved in viral replication will be examined, as well as risk factors associated with interspecific transmission and spread of the disease in human populations. Currently available diagnostic methods will also be discussed, with a critical analysis of their limitations and possible future directions for improving the accuracy and timeliness of diagnosis. Finally, this review will explore the public health implications associated with Mpox, emphasizing the importance of epidemiological surveillance, vaccination, and emergency preparedness to prevent and manage possible outbreaks. Understanding the epidemiology and control strategies for Mpox is critical to protecting the health of human and animal communities and mitigating the risk of interspecific transmission and spread of the disease.

Respiratory rate (fR) monitoring through wearable devices is crucial in several scenarios, providing insights into well-being and sports performance while minimizing interference with daily activities. Strain sensors embedded into garments stand out but require thorough investigation for optimal deployment. Optimal sensor positioning is often overlooked, and when addressed, the quality of the respiratory signal is neglected. Additionally, sensor metrological characterization after sensor integration is often omitted. In this study, we present the design, development, and feasibility assessment of a smart t-shirt embedded with two flexible sensors for fR monitoring. Guided by a motion capture system, optimal sensor design and position on the chest wall were defined, considering both signal magnitude and quality. The sensors were developed, embedded into the wearable system, and metrologically characterized, demonstrating a remarkable response to both static (sensitivity 9.4 Ω⋅%-1 and 9.1 Ω⋅%-1 for sensor A and sensor B, respectively) and cyclic loads (min. hysteresis span 20.4% at 36 bpm obtained for sensor A). The feasibility of the wearable system was assessed on healthy volunteers both under static and dynamic conditions (such as running, walking, and climbing stairs). A mean absolute error of 0.32 bpm was obtained by averaging all subjects and tests using the combination of the two sensors. This value was lower than that obtained using both sensor A (0.53 bpm) and sensor B (0.78 bpm) individually. Our study highlights the importance of signal amplitude and quality in optimal sensor placement evaluation, as well as the characterization of the embedded sensors for metrological assessment.

Our knowledge regarding the role of the microbiome in fish health has been steadily increasing in the last decade, especially for species of commercial interest. Conversely, relatively few studies focus on the microbiomes of wild fish, especially apex predators like sharks, due to lower economic interest and greater difficulty in obtaining samples. Studies investigating microbiome differences between diverse anatomical locations of sharks are limited, and the majority of the available studies are focused on the microbial diversity present on shark teeth, with the aim of preventing infections due to bites of these animals or evaluating the presence of certain pathogens in healthy or diseased specimens. Here, we investigated the skin, mouth, gills, and cloaca microbiomes of five individuals of two phylogenetically distant species of sharks ( Prionace glauca and Somniosus rostratus ) to obtain a better understanding of the diversity regarding the microbiomes of these animals, how they change throughout different body parts, and how much they are influenced and determined by the ecology and evolutionary relationship between host and microbiome. To confirm the taxonomy of the sharks under study, we barcoded the specimens by sequencing the mtDNA COI from a biopsy of their skin. Microbial diversity based on the 16S rRNA gene reveals that partially overlapping microbiomes inhabit different body parts of each shark species, while the communities are distinct between the two species. Our results suggest that sharks' microbiome species-specific differences are controlled by the ecology of the shark species. This is the first study comparatively analyzing the microbiome diversity of different anatomical locations in two shark species of the Mediterranean Sea.

Background: Influenza viruses are etiological agents which cause contagious respiratory, seasonal epidemics and, for influenza A subtypes, pandemics. The clinical picture of influenza has undergone continuous change over the years, due to intrinsic viral evolution as well as "reassortment" of its genomic segments. The history of influenza highlights its ability to adapt and to rapidly evolve, without specific circumstances. This reflects the complexity of this pathology and poses the fundamental question about its assumption as a "common illness" and its impact on public health., Summary: The global influenza epidemics and pandemics claimed millions of deaths, leaving an indelible mark on public health and showing the need for a better comprehension of the influenza virus. The clear understanding of genetic variations during the influenza seasonal epidemics is a crucial point for developing effective strategies for prevention, treatment, and vaccine design. The recent advance in next-generation sequencing approaches, model systems to virus culture, and bioinformatics pipeline played a key role in the rapid characterization of circulating influenza strains. In particular, the increase in computational power allowed the performance of complex tasks in healthcare settings through machine learning algorithms, which analyze different variables, such as medical and laboratory outputs, to optimize medical research and improve public health systems. The early detection of emerging and reemerging pathogens is a matter of importance to prevent future pandemics., Key Messages: The perception of influenza as a "trivial flu" or a more serious public health concern is a subject of ongoing debate, reflecting the multifaceted nature of this infectious disease. The variability in the severity of influenza sheds light on the unpredictability of the viral characteristics, coupled with the challenges in accurately predicting circulating strains. This adds complexity to the public health burden of influenza and highlights the need for targeted interventions., (© 2024 S. Karger AG, Basel.)

The intercalibration of age readings represents a crucial step in the ageing procedure; the use of different sampling methods, structures, preparation techniques, and ageing criteria can significantly affect age and growth data. This study evaluated the precision and accuracy of ageing for the most important North Atlantic (NA) and Mediterranean (M) ray species, Raja clavata , Raja brachyura , Torpedo marmorata , and Dipturus oxyrinchus , through exchange exercises carried out by readers from different laboratories. In addition, growth parameters were estimated from the obtained data. A total of 663 individual batoids were analysed. R. clavata and R. brachyura samples were obtained from both the NA and the M, while vertebral centra of T. marmorata and D. oxyrinchus were only available for the M. High reading variability was observed for all four evaluated species in terms of CV, APE, and PA. D. oxyrinchus and T. marmorata showed relatively slow growth and the von Bertalanffy model with fixed t 0 and Gompertz's model were, respectively, the most precise models for each of these species. In R. brachyura , females had a faster growth rate compared to combined sexes. The vbt0p proved the most precise model for describing growth in this species, and no statistical differences were found between the NO and the M. For R. clavata , the best-fitting model was the vbt0p for females and males in the NO and for females from the M, while the best-fitting model for males from the M and sexes combined for both areas was log.p. Distinct growth patterns were observed between the two study areas.

Purpose: Chronic Myeloid Leukemia (CML) is a clonal disorder of the hematopoietic stem cell caused by expression of the BCR::ABL1 oncoprotein. High BCR::ABL1 levels have been associated to proliferative advantage of leukemic cells, blast crisis progression and tyrosine kinase inhibitors (TKIs) inefficacy. We have previously shown that high BCR::ABL1/GUS IS transcripts measured at diagnosis are associated with inferior responses to standard dose Imatinib (IM). However, the mechanisms underlying the higher rates of disease progression and development of TKIs resistance dependent on elevated BCR::ABL1 levels remain unclear., Methods: Leukemic cells were collected from CML patients showing, at diagnosis, high or low BCR::ABL1/GUS IS . BCR::ABL1 expression levels were measured using real-time PCR. Short-term culture and long-term culture-initiating cells assays were employed to investigate the role of BCR::ABL1 gene-expression levels on proliferation, clonogenicity, signal transduction, TKIs responsiveness and self-renewal ability. Cell division was performed by carboxyfluorescein-succinimidyl ester (CFSE) assay., Results: We found that BCR::ABL1 oncogene expression levels correlate in both PMNs and CD34+ cells. Furthermore, high oncogene levels increased both proliferation and anti-apoptotic signaling via ERK and AKT phosphorylation. Moreover, high BCR::ABL1 expression reduced the clonogenicity of leukemic CD34+ cells and increased their sensitivity to high doses IM but not to those of dasatinib. Furthermore, we observed that high BCR::ABL1 levels are associated with a reduced self-renewal of primitive leukemic cells and, also, that these cells showed comparable TKIs responsiveness with cells expressing lower BCR::ABL1 levels. Interestingly, we found a direct correlation between high BCR::ABL1 levels and reduced number of quiescent leukemic cells caused by increasing their cycling., Conclusion: Higher BCR::ABL1 levels improving the proliferation, anti-apoptotic signaling and reducing self-renewal properties cause an increased expansion of leukemic clone., Competing Interests: Fabio Stagno reports personal fees from Pfizer, Novartis, and Incyte, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Massimino et al.)

Environmental pollution, particularly in the marine environment, has become a significant concern due to the increasing presence of pollutants and their adverse effects on ecosystems and human health. This study focuses on the bioaccumulation of trace elements in the muscle tissue of the blackmouth catshark ( Galeus melastomus ) from different areas in the Mediterranean Sea. Trace elements are of interest due to their persistence, toxicity, and potential for bioaccumulation. This research aims to assess the distribution and accumulation of trace elements in the muscle tissue of G. melastomus and investigate their potential impact on the deep-sea environment of the Mediterranean. The focused areas include the Ligurian Sea, the northern and central Tyrrhenian Sea, the southern Tyrrhenian Sea, the Ionian Sea, the Pantelleria Waters, and the Gela Waters. Samples were collected following established protocols, and trace element analysis was conducted using inductively coupled plasma mass spectrometry. The study provides data on the concentrations of 17 trace elements, namely aluminum, arsenic, cadmium, cobalt, copper, manganese, molybdenum, nickel, zinc, selenium, strontium, lead, chromium, iron, barium, bismuth, and uranium. The findings contribute to a better understanding of trace element bioaccumulation patterns in elasmobranch species, specifically G. melastomus , and highlight the potential risks associated with chemical contamination in the Mediterranean Sea. This research emphasizes the importance of studying the impacts of pollutants on marine organisms, particularly those occupying key ecological roles, like sharks, to support effective conservation and management strategies.

Natural polymers are extensively utilized as scaffold materials in tissue engineering and 3D disease modeling due to their general features of cytocompatibility, biodegradability, and ability to mimic the architecture and mechanical properties of the native tissue. A major limitation of many polymeric scaffolds is their autofluorescence under common imaging methods. This autofluorescence, a particular challenge with silk fibroin materials, can interfere with the visualization of fluorescently labeled cells and proteins grown on or in these scaffolds, limiting the assessment of outcomes. Here, Sudan Black B (SBB) was successfully used prefixation prior to cell seeding, in various silk matrices and 3D model systems to quench silk autofluorescence for live cell imaging. SBB was also trialed postfixation in silk hydrogels. We validated that multiple silk scaffolds pretreated with SBB (hexafluoro-2-propanol-silk scaffolds, salt-leached sponges, gel-spun catheters, and sponge-gel composite scaffolds) cultured with fibroblasts, adipose tissue, neural cells, and myoblasts demonstrated improved image resolution when compared to the nonpretreated scaffolds, while also maintaining normal cell behavior (attachment, growth, proliferation, differentiation). SBB pretreatment of silk scaffolds is an option for scaffold systems that require autofluorescence suppression.

Emerging evidence suggests that respiratory frequency ( f R ) is a valid marker of physical effort. This has stimulated interest in developing devices that allow athletes and exercise practitioners to monitor this vital sign. The numerous technical challenges posed by breathing monitoring in sporting scenarios (e.g., motion artifacts) require careful consideration of the variety of sensors potentially suitable for this purpose. Despite being less prone to motion artifacts than other sensors (e.g., strain sensors), microphone sensors have received limited attention so far. This paper proposes the use of a microphone embedded in a facemask for estimating f R from breath sounds during walking and running. f R was estimated in the time domain as the time elapsed between consecutive exhalation events retrieved from breathing sounds every 30 s. Data were collected from ten healthy subjects (both males and females) at rest and during walking (at 3 km/h and 6 km/h) and running (at 9 km/h and 12 km/h) activities. The reference respiratory signal was recorded with an orifice flowmeter. The mean absolute error (MAE), the mean of differences (MOD), and the limits of agreements (LOAs) were computed separately for each condition. Relatively good agreement was found between the proposed system and the reference system, with MAE and MOD values increasing with the increase in exercise intensity and ambient noise up to a maximum of 3.8 bpm (breaths per minute) and -2.0 bpm, respectively, during running at 12 km/h. When considering all the conditions together, we found an MAE of 1.7 bpm and an MOD ± LOAs of -0.24 ± 5.07 bpm. These findings suggest that microphone sensors can be considered among the suitable options for estimating f R during exercise.

Galeus melastomus is the most common Pentanchidae in the Mediterranean Sea. A scavenger and opportunistic feeder, and despite the wide distribution, little is known about its feeding habits in Italian waters. The main purpose of this study was to investigate the diet of the blackmouth catshark by analysing the stomach contents. The specimens analysed were obtained from five populations of the Tyrrhenian and of the Ionian Seas, collected from a depth between 40 and 700 m. A total of 259 stomachs were analysed. The stomach contents were grouped into macro-categories and identified to the lowest taxonomic level possible. Crustaceans such as Parapenaeus longirostris , the Cephalopods Heteroteuthis dispar and Onychoteuthis banksii , and Osteichthyes, mostly Myctophidae, were identified. Plastic debris was also found among the stomach contents and classified according to its colour and shape. Osteichthyes represent the most abundant item (44%), above all the Myctophidae family, except for the catshark population from Tuscany, in which the most frequent species were Cephalopods, such as Abralia veranyi and Heteroteuthis dispar . Differences in the plastic debris contents were also observed between the Tuscany population and other populations. These could be explained as a probable consequence of the different depths at which the blackmouth catshark populations were sampled.

Given the importance of respiratory frequency ( f R ) as a valid marker of physical effort, there is a growing interest in developing wearable devices measuring f R in applied exercise settings. Biosensors measuring chest wall movements are attracting attention as they can be integrated into textiles, but their susceptibility to motion artefacts may limit their use in some sporting activities. Hence, there is a need to exploit sensors with signals minimally affected by motion artefacts. We present the design and testing of a smart facemask embedding a temperature biosensor for f R monitoring during cycling exercise. After laboratory bench tests, the proposed solution was tested on cyclists during a ramp incremental frequency test (RIFT) and high-intensity interval training (HIIT), both indoors and outdoors. A reference flowmeter was used to validate the f R extracted from the temperature respiratory signal. The smart facemask showed good performance, both at a breath-by-breath level (MAPE = 2.56% and 1.64% during RIFT and HIIT, respectively) and on 30 s average f R values (MAPE = 0.37% and 0.23% during RIFT and HIIT, respectively). Both accuracy and precision (MOD ± LOAs) were generally superior to those of other devices validated during exercise. These findings have important implications for exercise testing and management in different populations.

Heart rate variability (HRV) indexes are becoming useful in various applications, from better diagnosis and prevention of diseases to predicting stress levels. Typically, HRV indexes are retrieved from the heart's electrical activity collected with an electrocardiographic signal (ECG). Heart-induced mechanical signals recorded from the body's surface can be utilized to record the mechanical activity of the heart and, in turn, extract HRV indexes from interbeat intervals (IBIs). Among others, accelerometers and gyroscopes can be used to register IBIs from precordial accelerations and chest wall angular velocities. However, unlike electrical signals, the morphology of mechanical ones is strongly affected by body posture. In this paper, we investigated the feasibility of estimating the most common linear and non-linear HRV indexes from accelerometer and gyroscope data collected with a wearable skin-interfaced Inertial Measurement Unit (IMU) positioned at the xiphoid level. Data were collected from 21 healthy volunteers assuming two common postures (i.e., seated and lying). Results show that using the gyroscope signal in the lying posture allows accurate results in estimating IBIs, thus allowing extracting of linear and non-linear HRV parameters that are not statistically significantly different from those extracted from reference ECG.

The demand for wearable devices to simultaneously monitor heart rate (HR) and respiratory rate (RR) values has grown due to the incidence increase in cardiovascular and respiratory diseases. The use of inertial measurement unit (IMU) sensors, embedding both accelerometers and gyroscopes, may ensure a non-intrusive and low-cost monitoring. While both accelerometers and gyroscopes have been assessed independently for both HR and RR monitoring, there lacks a comprehensive comparison between them when used simultaneously. In this study, we used both accelerometers and gyroscopes embedded in a single IMU sensor for the simultaneous monitoring of HR and RR. The following main findings emerged: (i) the accelerometer outperformed the gyroscope in terms of accuracy in both HR and RR estimation; (ii) the window length used to estimate HR and RR values influences the accuracy; and (iii) increasing the length over 25 s does not provide a relevant improvement, but accuracy improves when the subject is seated or lying down, and deteriorates in the standing posture. Our study provides a comprehensive comparison between two promising systems, highlighting their potentiality for real-time cardiorespiratory monitoring. Furthermore, we give new insights into the influence of window length and posture on the systems' performance, which can be useful to spread this approach in clinical settings.

Paratesticular liposarcomas are extremely rare malignant tumors originating from fat tissues, with an often-challenging diagnosis. We present here the case of a 76-year-old man with a giant paratesticular liposarcoma, initially misdiagnosed as a scrotal hernia. After two years, the progressively enlarging mass underwent surgical resection, and a diagnosis of well-differentiated liposarcoma (lipoma-like subtype) was made. Post-operative treatments were not indicated, and the patient remains relapse free. Next generation sequencing performed on the neoplastic tissue showed co-amplification of MDM2 and CDK4 . These alterations are molecular hallmarks of well-differentiated liposarcomas and corroborate the histological diagnosis. Clinical and molecular features of the presented case are in line with the majority of previously published experiences. In conclusion, the presence of a liposarcoma should be taken into account during the diagnostic workup of scrotal masses, in order to minimize the rate of misdiagnosis and improper management. Molecular analysis may support histological characterization of these rare entities and potentially disclose novel therapeutic targets.

Background: Multiple primary malignancies (MPM) are defined as tumors originating in the same individual without any correlation between them. In addition to morphological and immunohistochemical analyses, sensitive DNA sequencing methods such as next generation sequencing (NGS) may help to discriminate the common or different genetic alterations driving each malignancy, to better diagnose these uncommon cases., Methods and Results: Here we report the case of a man who developed a poorly differentiated gastric adenocarcinoma invading the pancreas followed, two years later, by a colorectal cancer involving also the kidney and the diaphragm. Despite the advanced stage of both diseases, adjuvant chemotherapy was successful. While the second tumor was initially interpreted as a relapse of his stomach cancer, NGS-based mutation profiling of the two carcinomas revealed two distinct malignances, independently developing in different times and indicative of metachronous MPM. Indeed, sequencing of cancer-associated genes identified somatic mutations only in the first gastric cancer, besides germline variants on three different genes (PDGFRA, APC and TP53). However, analysis of both somatic and germline mutations with bio-informatics prediction tools failed to find a correlation between these variants and the unexpectedly good prognosis of both cancers., Conclusions: In summary, NGS analysis contributed to defined different molecular profiles for two tumors developed in the span of two years, thus allowing diagnosing the case as MPN. However, NGS was unable to establish a direct correlation between the identified alterations and cancer development., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Fiber Bragg grating sensors (FBGs) are considered a valid sensing solution for a variety of medical applications. The last decade witnessed the exploitation of these sensors in applications ranging from minimally invasive surgery to biomechanics and monitoring physiological parameters. Recently, preliminary studies investigated the potential impact of FBGs in the management of epidural procedures by detecting when the needle reaches the epidural space with the loss of resistance (LOR) technique. In this article, we propose a soft and flexible FBG-based system capable of detecting the LOR, we optimized the solution by considering different designs and materials, and we assessed the feasibility of the optimized soft sensor (SS) in clinical settings. The proposed SS addresses some of the open challenges in the use of a sensing solution during epidural punctures: it has high sensitivity, it is non-invasive, the sensing element does not need to be inserted within the needle, and the clinician can follow the standard clinical practice. Our analysis highlights how the material and the design impact the system response, and thus its performance in this scenario. We also demonstrated the system's feasibility of detecting the LOR during epidural procedures.

Background: Detection of BCR-ABL1 transcript level via real-time quantitative-polymerase-chain reaction (Q-PCR) is a clinical routine for disease monitoring, assessing Tyrosine Kinase Inhibitor therapy efficacy and predicting long-term response in chronic myeloid leukemia (CML) patients. For valid Q-PCR results, each stage of the laboratory procedures need be optimized, including the cell-counting method that represents a critical step in obtaining g an appropriate amount of RNA and reliable Q-PCR results. Traditionally, manual or automated methods are used for the detection and enumeration of white blood cells (WBCs). Here, we compared the performance of the manual counting measurement to the flow cytometry (FC)-based automatic counting assay employing CytoFLEX platform., Methods: We tested five different types of measurements: one manual hemocytometer-based count and four FC-based automatic cell-counting methods, including absolute, based on beads, based on 7-amino actinomycin D, combining and associating beads and 7AAD. The recovery efficiency for each counting method was established considering the quality and quantity of total RNA isolated and the Q-PCR results in matched samples from 90 adults with CML., Results: Our analyses showed no consistent bias between the different types of measurements, with comparable number of WBCs counted for each type of measurement. Similarly, we observed a 100% concordance in the amount of RNA extracted and in the Q-PCR cycle threshold values for both BCR-ABL1 and ABL1 gene transcripts in matched counted specimens from all the investigated groups. Overall, we show that FC-based automatic absolute cell counting has comparable performance to manual measurements and allows accurate cell counts without the use of expensive beads or the addition of the time-consuming intercalator 7AAD., Conclusions: This automatic method can replace the more laborious manual workflow, especially when high-throughput isolations from blood of CML patients are needed.