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BACKGROUND: The identification of specific circulating miRNAs has been proposed as a valuable tool for elucidating the pathophysiology of brain damage or injury and predicting patient outcomes. OBJECTIVE: This study aims to apply several bioinformatic tools in order to clarify miRNA interactions with potential genes involved in brain injury, emphasizing the need of using a computational approach to determine the most likely correlations between miRNAs and target genes. Specifically, this study centers on elucidating the roles of miR-34b, miR-34c, miR-135a, miR-200c, and miR-451a. METHODS: After a careful evaluation of different software available (analyzing the strengths and limitations), we applied three tools, one to perform an analysis of the validated targets (miRTarBase), and two to evaluate functional annotations (miRBase and TAM 2.0). RESULTS: Research findings indicate elevated levels of miR-135a and miR-34b in patients with traumatic brain injury (TBI) within the first day post-injury, while miR-200c and miR-34c were found to be upregulated after 7 days. Moreover, miR-451a and miR-135a were found overexpressed in the serum, while miRNAs 34b, 34c, and 200c, had lower serum levels at baseline post brain injury. CONCLUSION: This study emphasizes the use of computational methods in determining the most likely relationships between miRNAs and target genes by investigating several bioinformatic techniques to elucidate miRNA interactions with potential genes. Specifically, this study focuses on the functions of miR-34b, miR-34c, miR-135a, miR-200c, and miR-451a, providing an up-to-date overview and suggesting future research directions for identifying theranomiRNAs related to brain injury, both at the tissue and serum levels.
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The thermodynamic and dynamical conditions necessary to observe indefinite growth in homogeneous open chemical reaction networks (CRNs) satisfying mass action kinetics are presented in Srinivas et al. [Phys. Rev. Lett. 132, 268001 (2024)10.1103/PhysRevLett.132.268001]. Unimolecular CRNs can accumulate only equilibrium concentrations of species while multimolecular CRNs are needed to produce indefinite growth with nonequilibrium concentrations. Within multimolecular CRNs, pseudo-unimolecular CRNs produce nonequilibrium concentrations with zero efficiencies. Nonequilibrium growth with efficiencies greater than zero requires dynamically nonlinear CRNs. In this paper, we provide a detailed analysis supporting these results. Mathematical proofs are provided for growth in unimolecular and pseudo-unimolecular CRNs. For multimolecular CRNs, four models displaying very distinctive topological properties are extensively studied, both numerically and partly analytically.
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We identify the thermodynamic conditions necessary to observe indefinite growth in homogeneous open chemical reaction networks (CRNs) satisfying mass action kinetics. We also characterize the thermodynamic efficiency of growth by considering the fraction of the chemical work supplied from the surroundings that is converted into CRN free energy. We find that indefinite growth cannot arise in CRNs chemostatted by fixing the concentration of some species at constant values, or in continuous-flow stirred tank reactors. Indefinite growth requires a constant net influx from the surroundings of at least one species. In this case, unimolecular CRNs always generate equilibrium linear growth, i.e., a continuous linear accumulation of species with equilibrium concentrations and efficiency one. Multimolecular CRNs are necessary to generate nonequilibrium growth, i.e., the continuous accumulation of species with nonequilibrium concentrations. Pseudounimolecular CRNs-a subclass of multimolecular CRNs-always generate asymptotic linear growth with zero efficiency. Our findings demonstrate the importance of the CRN topology and the chemostatting procedure in determining the dynamics and thermodynamics of growth.
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Artificial intelligence (AI) is a multidisciplinary field intersecting computer science, cognitive science, and other disciplines, able to address the creation of systems that perform tasks generally requiring human intelligence. It consists of algorithms and computational methods that allow machines to learn from data, make decisions, and perform complex tasks, aiming to develop an intelligent system that can work independently or collaboratively with humans. Since AI technologies may help physicians in life-threatening disease prevention and diagnosis and make treatment smart and more targeted, they are spreading in health services. Indeed, humans and machines have unique strengths and weaknesses and can complement each other in providing and optimizing healthcare. However, the healthcare implementation of these technologies is related to emerging ethical and deontological issues regarding the fearsome reduction of doctors' decision-making autonomy and acting discretion, generally strongly conditioned by cognitive elements concerning the specific clinical case. Moreover, this new operational dimension also modifies the usual allocation system of responsibilities in case of adverse events due to healthcare malpractice, thus probably imposing a redefinition of the established medico-legal assessment criteria of medical professional liability. This article outlines the new challenges arising from AI healthcare integration and the possible ways to overcome them, with a focus on Italian legal framework. In this evolving and transitional context emerges the need to balance the human dimension with the artificial one, without mutual exclusion, for a new concept of medicine "with" machines and not "of" machines.
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BACKGROUND: Respect for human rights and bioethical principles in prisons is a crucial aspect of society and is proportional to the well-being of the general population. To date, these ethical principles have been lacking in prisons and prisoners are victims of abuse with strong repercussions on their physical and mental health. METHODS: A systematic review was performed, through a MESH of the following words (bioethics) AND (prison), (ethics) AND (prison), (bioethics) AND (jail), (ethics) AND (jail), (bioethics) AND (penitentiary), (ethics) AND (penitentiary), (prison) AND (human rights). Inclusion and exclusion criteria were defined and after PRISMA, 17 articles were included in the systematic review. RESULTS: Of the 17 articles, most were prevalence studies (n.5) or surveys (n.4), followed by cross-sectional studies (n.3), qualitative studies (n.1), retrospective (n.1) and an explanatory sequential mixed-methods study design (n.1). In most cases, the studies associated bioethics with prisoners' access to treatment for various pathologies such as vaccinations, tuberculosis, hepatitis, HIV, it was also found that bioethics in prisons was related to the mental health of prisoners, disability, ageing, the condition of women, the risk of suicide or with the request for end-of-life by prisoners. The results showed shortcomings in the system of maintaining bioethical principles and respect for human rights. CONCLUSIONS: Prisoners, in fact, find it difficult to access care, and have an increased risk of suicide and disability. Furthermore, they are often used as improper organ donors and have constrained autonomy that also compromises their willingness to have end-of-life treatments. In conclusion, prison staff (doctors, nurses, warders, managers) must undergo continuous refresher courses to ensure compliance with ethical principles and human rights in prisons.
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Derechos Humanos , Prisioneros , Prisiones , Humanos , Respeto , Discusiones Bioéticas , Bioética , Accesibilidad a los Servicios de Salud/éticaRESUMEN
Congenital Heart Diseases (CHDs) are a group of structural abnormalities or defects of the heart that are present at birth. CHDs could be connected to sudden death (SD), defined by the WHO (World Health Organization) as "death occurring within 24 h after the onset of the symptoms" in an apparently "healthy" subject. These conditions can range from relatively mild defects to severe, life-threatening anomalies. The prevalence of CHDs varies across populations, but they affect millions of individuals worldwide. This article aims to discuss the post-mortem investigation of death related to CHDs, exploring the forensic approach, current methodologies, challenges, and potential advancements in this challenging field. A further goal of this article is to provide a guide for understanding these complex diseases, highlighting the pivotal role of autopsy, histopathology, and genetic investigations in defining the cause of death, and providing evidence about the translational use of autopsy reports. Forensic investigations play a crucial role in understanding the complexities of CHDs and determining the cause of death accurately. Through collaboration between medical professionals and forensic experts, meticulous examinations, and analysis of evidence, valuable insights can be gained. These insights not only provide closure to the families affected but also contribute to the prevention of future tragedies.
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Autopsia , Causas de Muerte , Cardiopatías Congénitas , Humanos , Cardiopatías Congénitas/patología , Cardiopatías Congénitas/mortalidad , Cardiopatías Congénitas/genética , Medicina Legal/métodosRESUMEN
Sudden unexpected postnatal collapse (SUPC) is a sudden collapse of the clinical conditions of a full-term or near-term newborn, within the first 7 days of life, that requires resuscitation with positive ventilation and who either dies, has hypoxic-ischemic encephalopathy, or requires intensive care. The incidence of SUPC is very low, and most often presents a negative prognosis. The BUB1B gene is a mitotic checkpoint of serine/threonine kinase B that encodes a protein crucial for maintaining the correct number of chromosomes during cell division. Mutations in the BUB1B gene are linked to mosaic variegated aneuploidy syndrome 1 (MVA1), a rare autosomal recessive disorder characterized by diffuse mosaic aneuploidies involving several chromosomes and tissues. This paper discusses a case of a newborn who had a spontaneous delivery. After 2 h and 10 min, the infant showed generalized hypotonia and cyanosis, and his doctors performed orotracheal intubation, cardiac massage, pharmacological hemodynamic therapy, mechanical ventilation, antibiotic therapy, and hypothermic treatment. The newborn was discharged after 5 months with the diagnosis of hypoxic-ischemic encephalopathy. Suspecting an SUPC, a complete genetic analysis was performed demonstrating a compound heterozygous mutations in the BUB1B gene. The newborn died at 6 months of life, 1 month after discharge. A complete autopsy was performed, determining that the cause of death was due to sepsis starting from a brocopneumonic process, with outcomes of hypoxic-ischemic encephalopathy (HIE). In this scenario, it is not possible to demonstrate the causal effect of this mutation, considering that it could play a causal or concausal role in the onset of SUPC. Further research based on multicenter studies, as well as on animal models, could be very useful to clarify the pathological effect of this mutation.
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Mutación , Proteínas Serina-Treonina Quinasas , Humanos , Recién Nacido , Proteínas Serina-Treonina Quinasas/genética , Masculino , Proteínas de Ciclo Celular/genética , Hipoxia-Isquemia Encefálica/genética , Muerte Súbita/etiología , Trastornos de los Cromosomas/genética , Hipotonía Muscular/genética , Mosaicismo , Cianosis/genéticaRESUMEN
Generalizing response theory of open systems far from equilibrium is a central quest of nonequilibrium statistical physics. Using stochastic thermodynamics, we develop an algebraic method to study the static response of nonequilibrium steady state to arbitrary perturbations. This allows us to derive explicit expressions for the response of edge currents as well as traffic to perturbations in kinetic barriers and driving forces. We also show that these responses satisfy very simple bounds. For the response to energy perturbations, we straightforwardly recover results obtained using nontrivial graph-theoretical methods.
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Energy transduction is central to living organisms, but the impact of enzyme regulation and signaling on its thermodynamic efficiency is generally overlooked. Here, we analyze the efficiency of ATP production by the tricarboxylic acid cycle and oxidative phosphorylation, which generate most of the chemical energy in eukaryotes. Calcium signaling regulates this pathway and can affect its energetic output, but the concrete energetic impact of this cross-talk remains elusive. Calcium enhances ATP production by activating key enzymes of the tricarboxylic acid cycle while calcium homeostasis is ATP-dependent. We propose a detailed kinetic model describing the calcium-mitochondria cross-talk and analyze it using nonequilibrium thermodynamics: after identifying the effective reactions driving mitochondrial metabolism out of equilibrium, we quantify the mitochondrial thermodynamic efficiency for different conditions. Calcium oscillations, triggered by extracellular stimulation or energy deficiency, boost the thermodynamic efficiency of mitochondrial metabolism, suggesting a compensatory role of calcium signaling in mitochondrial bioenergetics.
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Progress in DNA profiling techniques has made it possible to detect even the minimum amount of DNA at a crime scene (i.e., a complete DNA profile can be produced using as little as 100 pg of DNA, equivalent to only 15-20 human cells), leading to new defense strategies. While the evidence of a DNA trace is seldom challenged in court by a defendant's legal team, concerns are often raised about how the DNA was transferred to the location of the crime. This review aims to provide an up-to-date overview of the experimental work carried out focusing on indirect DNA transfer, analyzing each selected paper, the experimental method, the sampling technique, the extraction protocol, and the main results. Scopus and Web of Science databases were used as the search engines, including 49 papers. Based on the results of this review, one of the factors that influence secondary transfer is the amount of DNA shed by different individuals. Another factor is the type and duration of contact between individuals or objects (generally, more intimate or prolonged contact results in more DNA transfer). A third factor is the nature and quality of the DNA source. However, there are exceptions and variations depending on individual characteristics and environmental conditions. Considering that secondary transfer depends on multiple factors that interact with each other in unpredictable ways, it should be considered a complex and dynamic phenomenon that can affect forensic investigation in various ways, for example, placing a subject at a crime scene who has never been there. Correct methods and protocols are required to detect and prevent secondary transfer from compromising forensic evidence, as well as the correct interpretation through Bayesian networks. In this context, the definition of well-designed experimental studies combined with the use of new forensic techniques could improve our knowledge in this challenging field, reinforcing the value of DNA evidence in criminal trials.
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Dermatoglifia del ADN , ADN , Humanos , Teorema de Bayes , ADN/genética , Crimen , Proyectos de InvestigaciónRESUMEN
We study an autonomous model of a Maxwell demon that works by rectifying thermal fluctuations of chemical reactions. It constitutes the chemical analog of a recently studied electronic demon. We characterize its scaling behavior in the macroscopic limit, its performances, and the impact of potential internal delays. We obtain analytical expressions for all quantities of interest: the generated reverse chemical current, the output power, the transduction efficiency, and correlation between the number of molecules. Due to a bound on the nonequilibrium response of its chemical reaction network, we find that, contrary to the electronic case, there is no way for the Maxwell demon to generate a finite output in the macroscopic limit. Finally, we analyze the information thermodynamics of the Maxwell demon from a bipartite perspective. In the limit of a fast demon, the information flow is obtained, its pattern in the state space is discussed, and the behavior of partial efficiencies related to the measurement and feedback processes is examined.
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Crime scene investigation (CSI) is the complex act of reconstructing the dynamics that led to a crime and the circumstances of its perpetration. Crystallizing the CSI is a difficult task for the forensic pathologist; however, it is often requested by the public prosecutor and many judicial cases remain unsolved precisely for this reason. Recent years have seen an improvement in the ability of 3D scanning technology to obtain dense surface scans of large-scale spaces, for surveying, engineering, archaeology, and medical purposes such as forensics. The applications of this new technology are growing every day: forensic measurement of wounds in clinical reports, for example, reconstruction of traffic accidents, bullet trajectory studies in gunshot wounds, and 3D bloodstain pattern analysis. A retrospective analysis was conducted across all crime scene investigations performed by the forensic staff of the Department of Forensic Pathology of the University of Catania from January 2019 to June 2022. Inclusion criteria were the use of a laser scanner (LS), the use of a camera, a full investigative scene, and collection of circumstantial data thanks to the help of the judicial police. Cases in which the LS was not used were excluded. Out of 200 CSIs, 5 were included in the present study. In case number 1, the use of the LS made it possible to create a complete scale plan of the crime scene in a few hours, allowing a ship to be quickly returned to the judicial police officer. In case 2 (fall from a height), the LS clarified the suicidal intent of the deceased. In case number 3 it was possible to reconstruct a crime scene after many years. In case 4, the LS provided a great contribution in making a differential diagnosis between suicide and homicide. In case 5, the LS was fundamental for the COVID team in planning the study of COVID-19 pathways and areas within a hospital with the aim of reduction of nosocomial transmission. In conclusion, the use of the LS allowed the forensic staff to crystallize the investigative scene, making it a useful tool.
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We develop a general classification of the nature of the instabilities yielding spatial organization in open nonideal reaction-diffusion systems, based on linear stability analysis. This encompasses dynamics where chemical species diffuse, interact with each other, and undergo chemical reactions driven out of equilibrium by external chemostats. We find analytically that these instabilities can be of two types: instabilities caused by intermolecular energetic interactions (E type), and instabilities caused by multimolecular out-of-equilibrium chemical reactions (R type). Furthermore, we identify a class of chemical reaction networks, containing unimolecular networks but also extending beyond them, that can only undergo E-type instabilities. We illustrate our analytical findings with numerical simulations on two reaction-diffusion models, each displaying one of the two types of instability and generating stable patterns.
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The entropy production of an open system coupled to a reservoir initialized in a canonical state can be expressed as a sum of two microscopic information-theoretic contributions: the system-bath mutual information and the relative entropy measuring the displacement of the environment from equilibrium. We investigate whether this result can be generalized to situations where the reservoir is initialized in a microcanonical or in a certain pure state (e.g., an eigenstate of a nonintegrable system), such that the reduced dynamics and thermodynamics of the system are the same as for the thermal bath. We show that while in such a case the entropy production can still be expressed as a sum of the mutual information between the system and the bath and a properly redefined displacement term, the relative weight of those contributions depends on the initial state of the reservoir. In other words, different statistical ensembles for the environment predicting the same reduced dynamics for the system give rise to the same total entropy production but to different information-theoretic contributions to the entropy production.
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Entropía , TermodinámicaRESUMEN
We study a model of a synthetic molecular motor-a [3]-catenane consisting of two small macrocycles mechanically interlocked with a bigger one-subjected to time-dependent driving using stochastic thermodynamics. The model presents nontrivial features due to the two interacting small macrocycles but is simple enough to be treated analytically in limiting regimes. Among the results obtained, we find a mapping into an equivalent [2]-catenane that reveals the implications of the no-pumping theorem stating that to generate net motion of the small macrocycles, both energies and barriers need to change. In the adiabatic limit (slow driving), we fully characterize the motor's dynamics and show that the net motion of the small macrocycles is expressed as a surface integral in parameter space, which corrects previous erroneous results. We also analyze the performance of the motor subjected to step-wise driving protocols in the absence and presence of an applied load. Optimization strategies for generating large currents and maximizing free energy transduction are proposed. This simple model provides interesting clues into the working principles of non-autonomous molecular motors and their optimization.
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We introduce a wide class of quantum maps that arise in collisional reservoirs and are able to thermalize a system if they operate in conjunction with an additional dephasing mechanism. These maps describe the effect of collisions and induce transitions between populations that obey detailed balance, but also create coherences that prevent the system from thermalizing. We combine these maps with a unitary evolution acting during random Poissonian times between collisions and causing dephasing. We find that, at a low collision rate, the nontrivial combination of these two effects causes thermalization in the system. This scenario is suitable for modeling collisional reservoirs at equilibrium. We justify this claim by identifying the conditions for such maps to arise within a scattering theory approach and provide a thorough characterization of the resulting thermalization process.
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Stochastic chemical processes are described by the chemical master equation satisfying the law of mass-action. We first ask whether the dual master equation, which has the same steady state as the chemical master equation, but with inverted reaction currents, satisfies the law of mass-action and, hence, still describes a chemical process. We prove that the answer depends on the topological property of the underlying chemical reaction network known as deficiency. The answer is yes only for deficiency-zero networks. It is no for all other networks, implying that their steady-state currents cannot be inverted by controlling the kinetic constants of the reactions. Hence, the network deficiency imposes a form of non-invertibility to the chemical dynamics. We then ask whether catalytic chemical networks are deficiency-zero. We prove that the answer is no when they are driven out of equilibrium due to the exchange of some species with the environment.
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This study aims to assess the situation of Italian hotspots for migrant reception during the COVID-19 pandemic, and specifically analyzing the situation of two hotspots located in the Sicily Region (Pozzallo harbor and Lampedusa Island), to identify critical issues. At the same time, we hypothesize solutions to guarantee the respect of human rights and suggest an operational protocol to be applied in similar situations, considering that the migration phenomenon is increasing and involving new geographical areas. Based on data obtained through the site inspections, the facilities of Pozzallo and Lampedusa exceeded their capacity to adequately contain the spread of the SARS-CoV-2 infection. Considering these findings, we suggest a practical workflow summarizing the main actions that should be applied to contain COVID-19, or other infectious disease, spreading in hotspots for migrants. The impact of the COVID-19 pandemic on migrants has received limited attention, although the migration phenomenon did not slow down during the pandemic period. Regarding the risk of spreading infectious diseases such as COVID-19, it is necessary that those countries who are most exposed to migration flows, such as Italy, plan dedicated strategies to minimize the possibility of transmission of SARS-CoV-2, using adequate protocols to monitor the possible insurgence of variants of interest (VOIs) or variants of concern (VOCs). Finally, it is important to state that these suggestions could be applied in any future pandemics.
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COVID-19 , Migrantes , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Pandemias/prevención & control , Mar Mediterráneo , Italia/epidemiologíaRESUMEN
There is ongoing controversy about whether a coherent superposition of the occupied states of two fermionic modes should be regarded entangled or not, that is, whether its intrinsic quantum correlations are operationally accessible and useful as a resource. This has been questioned on the basis that such an entanglement cannot be accessed by local operations on individual modes due to the parity superselection rule which constrains the set of physical observables. In other words, one cannot observe violations of Bell's inequality. Here, we show, however, that entanglement of a two-mode fermionic state can be used as a genuine quantum resource in open-system thermodynamic processes, enabling one to perform tasks forbidden for separable states. We thus demonstrate that quantum thermodynamics can shed light on the nature of fermionic entanglement and the operational meaning of the different notions used to define it.
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MiRNAs regulate both physiological and pathological heart functions. Altered expression of miRNAs is associated with cardiovascular diseases (CVDs), making miRNAs attractive therapeutic strategies for the diagnosis and treatment of heart diseases. A recent publication defined, for the first time, the term theranoMiRNA, meaning the miRNAs that may be used both for diagnosis and treatment. The use of in silico tools may be considered fundamental for these purposes, clarifying several molecular aspects, suggesting future directions for in vivo studies. This study aims to explore different bioinformatic tools in order to clarify miRNA interactions with candidate genes, demonstrating the need to use a computational approach when establishing the most probable associations between miRNAs and target genes. This study focused on the functions of miR-133a-3p, miR-21-5p, miR-499a-5p, miR-1-3p, and miR-126-3p, providing an up-to-date overview, and suggests future lines of research in the identification of theranoMiRNAs related to CVDs. Based on the results of the present study, we elucidated the molecular mechanisms that could be linked between miRNAs and CVDs, confirming that these miRNAs play an active role in the genesis and development of heart damage. Given that CVDs are the leading cause of death in the world, the identification of theranoMiRNAs is crucial, hence the need for a definition of in vivo studies in order to obtain further evidence in this challenging field of research.