Healthy Conditions Research Articles

Entropy Wavelet-Based Method to Increase Efficiency in Highway Bridge Damage Identification

Highway bridges are crucial civil constructions for the transport infrastructure, which require proper attention from the corresponding institutions of each country and constant financing for their adequate maintenance; this is important because different types of damage can be generated within these structures, caused by natural disasters, among other sources, and the heavy loads they transport every day. Therefore, the development of simple, efficient, and low-cost methods is of vital importance, allowing us to identify damage in a timely manner and avoid bridges collapsing. As reported in a previous work, the wavelet energy accumulation method (WEAM) and its corresponding application in the Rio Papaloapan Bridge (RPB) represented an important advance within the field. Despite identifying damage in bridges with precision and at a low cost, there are several aspects to improve in that method. Therefore, in this work, that method was improved, eliminating several steps, and meaningfully reducing the computational burden by implementing an algorithm based on the Shannon entropy, thus giving way to the new entropy wavelet-based method (EWM). This new method was applied directly with regard to the real-life RPB, in both its healthy and damaged conditions. Also, its corresponding numerical model based on the finite element method in its healthy condition and different damage scenarios were carried out. The results indicate that the new EWM retains the advantages of WEAM, and it allows for damage identification to be completed more efficiently, increasing the precision by approximately 0.11%, and significantly reducing the computing time required to obtain results by 5.67 times.

A novel algorithm for open switch fault detection and fault tolerant control of interleaved DC‐DC boost converters

AbstractThis paper presents a novel algorithm for fault diagnosis and fault tolerant control of interleaved boost converters (IBCs) in the presence of single or double simultaneous open‐circuit faults (OCFs) in power switches. An innovative diagnosis signal (recorded by a cheap current sensor) will be introduced whose waveform mainly depends on the healthy or faulty condition of the converter. Since the diagnosis signal is periodic in the steady‐state operation of the converters, its Fourier Series coefficients, together with the duty cycle of the converter are used as distinguishing features for fault diagnosis of the OCFs in the converter. The well‐known Kalman filter is utilized for robust estimation of the Fourier‐based features. Finally, the modulation of the remaining healthy phases is rearranged in a way that the pre‐fault performance recovers. The proposed algorithm is verified in a laboratory four‐phase IBC setup in which the experimental results show its satisfactory performance. Also, the structure of the proposed method is straightforward and can be implemented in the same microcontroller which is used for voltage and current regulation of the converter.

Waterfront developments and engineered canals in the UAE

Engineered canals and waterfront developments as a means to revitalize aging riverfront and coastal areas, dominated until the mid-thirties by industrial buildings and warehouses, have been at the forefront of many American and European cities. Urban revitalization is accomplished after prolonged public participation and has succeeded to transform abandoned areas to healthy public spaces, renovating old warehouses and industrial buildings to apartments with water views, and keeping alive the historical memory of a city. In contrast, in the United Arab Emirates (UAE), most of these waterfront developments, such as Al-Qana, a recent project in Abu Dhabi promote forms of modern, spectacular architecture that project a sense of departure from tradition, local culture and architecture. This is also visible in the area around the Dubai canal, which has opted for a modern development on its banks, replacing parts of an existing open park. A project that diverges from such an approach is the two-decades old waterfront project in the city of Sharjah, UAE. Al-Qasba in Sharjah aimed for a more balanced approach, intertwining new architectural forms with hybridized Islamic ornaments. The current article analyzes these three UAE waterfront development projects, focusing on the one in Abu Dhabi. In order to assess the water quality in these engineered canals on the long term we created simulation waterflow models using 2D Finite Element Surface Water Modelling System (FESWMS). Our hydrodynamic modeling results indicate that water velocities in some canals was better than others. Furthermore, on the long-term Al-Qana may require mechanical means in order to maintain healthy waterflow conditions.

Mathematical modeling of transdermal delivery of topical drug formulations in a dynamic microfluidic diffusion chamber in health and disease.

Mathematical models of epidermal and dermal transport are essential for optimization and development of products for percutaneous delivery both for local and systemic indication and for evaluation of dermal exposure to chemicals for assessing their toxicity. These models often help directly by providing information on the rate of drug penetration through the skin and thus on the dermal or systemic concentration of drugs which is the base of their pharmacological effect. The simulations are also helpful in analyzing experimental data, reducing the number of experiments and translating the in vitro investigations to an in-vivo setting. In this study skin penetration of topically administered caffeine cream was investigated in a skin-on-a-chip microfluidic diffusion chamber at room temperature and at 32°C. Also the transdermal penetration of caffeine in healthy and diseased conditions was compared in mouse skins from intact, psoriatic and allergic animals. In the last experimental setup dexamethasone, indomethacin, piroxicam and diclofenac were examined as a cream formulation for absorption across the dermal barrier. All the measured data were used for making mathematical simulation in a three-compartmental model. The calculated and measured results showed a good match, which findings indicate that our mathematical model might be applied for prediction of drug delivery through the skin under different circumstances and for various drugs in the novel, miniaturized diffusion chamber.

Impact of respiratory cycle during mechanical ventilation on beat-to-beat right ventricle stroke volume estimation by pulmonary artery pulse wave analysis.

The same principle behind pulse wave analysis can be applied on the pulmonary artery (PA) pressure waveform to estimate right ventricle stroke volume (RVSV). However, the PA pressure waveform might be influenced by the direct transmission of the intrathoracic pressure changes throughout the respiratory cycle caused by mechanical ventilation (MV), potentially impacting the reliability of PA pulse wave analysis (PAPWA). We assessed a new method that minimizes the direct effect of the MV on continuous PA pressure measurements and enhances the reliability of PAPWA in tracking beat-to-beat RVSV. Continuous PA pressure and flow were simultaneously measured for 2-3min in 5 pigs using a high-fidelity micro-tip catheter and a transonic flow sensor around the PA trunk, both pre and post an experimental ARDS model. RVSV was estimated by PAPWA indexes such as pulse pressure (SVPP), systolic area (SVSystAUC) and standard deviation (SVSD) beat-to-beat from both corrected and non-corrected PA signals. The reference RVSV was derived from the PA flow signal (SVref). The reliability of PAPWA in tracking RVSV on a beat-to-beat basis was enhanced after accounting for the direct impact of intrathoracic pressure changes induced by MV throughout the respiratory cycle. This was evidenced by an increase in the correlation between SVref and RVSV estimated by PAPWA under healthy conditions: rho between SVref and non-corrected SVSD -0.111 (0.342), corrected SVSD 0.876 (0.130), non-corrected SVSystAUC 0.543 (0.141) and corrected SVSystAUC 0.923 (0.050). Following ARDS, correlations were SVref and non-corrected SVSD -0.033 (0.262), corrected SVSD 0.839 (0.077), non-corrected SVSystAUC 0.483 (0.114) and corrected SVSystAUC 0.928 (0.026). Correction also led to reduced limits of agreement between SVref and SVSD and SVSystAUC in the two evaluated conditions. In our experimental model, we confirmed that correcting for mechanical ventilation induced changes during the respiratory cycle improves the performance of PAPWA for beat-to-beat estimation of RVSV compared to uncorrected measurements. This was demonstrated by a better correlation and agreement between the actual SV and the obtained from PAPWA.

Sustained Release of Salicylic Acid for Halting Peri-Implantitis Progression in Healthy and Hyperglycemic Systemic Conditions: A Gottingen Minipig Model.

To develop a peri-implantitis model in a Gottingen minipig and evaluate the effect of local application of salicylic acid poly(anhydride-ester) (SAPAE) on peri-implantitis progression in healthy, metabolic syndrome (MS), and type-2 diabetes mellitus (T2DM) subjects. Eighteen animals were allocated to three groups: (i) control, (ii) MS (diet for obesity induction), and (iii) T2DM (diet plus streptozotocin for T2DM induction). Maxillary and mandible premolars and first molar were extracted. After 3 months of healing, four implants per side were placed in both jaws of each animal. After 2 months, peri-implantitis was induced by plaque formation using silk ligatures. SAPAE polymer was mixed with mineral oil (3.75 mg/μL) and topically applied biweekly for up to 60 days to halt peri-implantitis progression. Periodontal probing was used to assess pocket depth over time, followed by histomorphologic analysis of harvested samples. The adopted protocol resulted in the onset of peri-implantitis, with healthy minipigs taking twice as long to reach the same level of probing depth relative to MS and T2DM subjects (∼3.0 mm), irrespective of jaw. In a qualitative analysis, SAPAE therapy revealed decreased levels of inflammation in the normoglycemic, MS, and T2DM groups. SAPAE application around implants significantly reduced the progression of peri-implantitis after ∼15 days of therapy, with ∼30% lower probing depth for all systemic conditions and similar rates of probing depth increase per week between the control and SAPAE groups. MS and T2DM conditions presented a faster progression of the peri-implant pocket depth. SAPAE treatment reduced peri-implantitis progression in healthy, MS, and T2DM groups.

Exploring neurodegenerative disorders using advanced magnetic resonance imaging of the glymphatic system

The glymphatic system, a macroscopic waste clearance system in the brain, is crucial for maintaining neural health. It facilitates the exchange of cerebrospinal and interstitial fluid, aiding the clearance of soluble proteins and metabolites and distributing essential nutrients and signaling molecules. Emerging evidence suggests a link between glymphatic dysfunction and the pathogenesis of neurodegenerative disorders, including Alzheimer’s, Parkinson’s, and Huntington’s disease. These disorders are characterized by the accumulation and propagation of misfolded or mutant proteins, a process in which the glymphatic system is likely involved. Impaired glymphatic clearance could lead to the buildup of these toxic proteins, contributing to neurodegeneration. Understanding the glymphatic system’s role in these disorders could provide insights into their pathophysiology and pave the way for new therapeutic strategies. Pharmacological enhancement of glymphatic clearance could reduce the burden of toxic proteins and slow disease progression. Neuroimaging techniques, particularly MRI-based methods, have emerged as promising tools for studying the glymphatic system in vivo. These techniques allow for the visualization of glymphatic flow, providing insights into its function under healthy and pathological conditions. This narrative review highlights current MRI-based methodologies, such as motion-sensitizing pulsed field gradient (PFG) based methods, as well as dynamic gadolinium-based and glucose-enhanced methodologies currently used in the study of neurodegenerative disorders.

Performance Evaluation of Deep, Shallow and Ensemble Machine Learning Methods for the Automated Classification of Alzheimer's Disease.

Artificial intelligence (AI)-based approaches are crucial in computer-aided diagnosis (CAD) for various medical applications. Their ability to quickly and accurately learn from complex data is remarkable. Deep learning (DL) models have shown promising results in accurately classifying Alzheimer's disease (AD) and its related cognitive states, Early Mild Cognitive Impairment (EMCI) and Late Mild Cognitive Impairment (LMCI), along with the healthy conditions known as Cognitively Normal (CN). This offers valuable insights into disease progression and diagnosis. However, certain traditional machine learning (ML) classifiers perform equally well or even better than DL models, requiring less training data. This is particularly valuable in CAD in situations with limited labeled datasets. In this paper, we propose an ensemble classifier based on ML models for magnetic resonance imaging (MRI) data, which achieved an impressive accuracy of 96.52%. This represents a 3-5% improvement over the best individual classifier. We evaluated popular ML classifiers for AD classification under both data-scarce and data-rich conditions using the Alzheimer's Disease Neuroimaging Initiative and Open Access Series of Imaging Studies datasets. By comparing the results to state-of-the-art CNN-centric DL algorithms, we gain insights into the strengths and weaknesses of each approach. This work will help users to select the most suitable algorithm for AD classification based on data availability.

Review on the Effect of An Ayurvedic Management Protocol in Chronic Obstructive Pulmonary Disease

Considering the similarities noticed in the etiology and clinical features, COPD can be correlated to Tamaka shvasa among the Pranavaha srotodushti vikara, a condition where Pitta is involved along with Kapha and Vata. Rasayana is the main intervention in such a chronic disease and considering the Doshas and Rasayana, Virecana is the best preparatory Shodhana here to be administered for the patients. In Ayurveda, drug is denoted by the term ‘Bheshaja’ which is defined as the substance through which we can overcome the fear of disease. The ‘Upakarana’ which helps physician for maintaining the healthy condition or to alleviate disorders is said to be Bheshaja. Physician accomplishes the object ‘Vikara shamana’, by giving the appropriate Bheshaja according to different stages and conditions of the patient and disease. According to Ayurveda, action of a drug is based on its Guna, Virya, Vipaka and Prabhava. Fate of the drug always depends on Rasapancaka and it goes in line with modern pharmacodynamics. Besides that, the drug action also depends on the action of agni on that particular drug. In this article, a management protocol review on Chronic Obstructive Pulmonary Disease was carried out. The protocol selected and reviewed was Dipana with Panchakola curna in hot water, Snehapana with Kantakari ghrta, Abhyanga with Tila taila followed by Ushmasveda, Virecana with Vidangatanduladi curna and finally Pippali Vardhamana rasayana.

Intein-mediated thyroid hormone biosensors: towards controlled delivery of hormone therapy

Although blood sampling and medical imaging are well-established techniques in clinical diagnostics, they often require long post-processing procedures. Fast and simple quantification of signaling molecules can enable efficient health monitoring and improve diagnoses. Thyroid hormones (THs) treatment relies on trial-and-error dose adjustments, and requires constant tracking via blood tests. Thus, a fast and reliable method that can constantly track THs levels could substantially improve patient quality of life by reducing their visits to doctors. Synthetic biosensors have shown to be inexpensive and easy tools for sensing molecules, with their use in healthcare increasing over time. This study describes the construction of an engineered THs bacterial biosensor, consisting of a split-intein-based TH receptor ligand binding domain (LBD) biosensor that reconstitutes green fluorescence protein (GFP) after binding to TH. This biosensor could quantitatively measure THs concentrations by evaluating fluorescence intensity. In vitro sensing using Escherichia coli produced GFP over a wide dynamic range. The biosensor was further optimized by adding a double LBD, which enhanced its dynamic range until it reached healthy physiological conditions. Moreover, a mathematical model was developed to assess the dynamic properties of the biosensor and to provide a basis for the characterization of other intein-mediated biosensors. This type of biosensor can be used as the basis for novel treatments of thyroid diseases and can be adapted to measure the concentrations of other hormones, giving rise to a series of mathematically characterized modular biosensors.

Exploring Mechanisms of Lipid Nanoparticle-Mucus Interactions in Healthy and Cystic Fibrosis Conditions.

Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR-based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerged as versatile non-viral gene delivery systems that could help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF). This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein-loaded LNP-mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics simulations. Taken together, this study identifies key mucus and LNP characteristics that are critical to enabling a rational LNP design for transmucosal delivery. This article is protected by copyright. All rights reserved.

Prevalence of skin and subcutaneous neoplasm in bovines at various districts of Chhattisgarh, India

The present study was undertaken to evaluate the prevalence of skin and subcutaneous tumours in bovines. Thirty cases of skin and subcutaneous tumours were studied and examined at the time of presentation and their age, sex, breed, species, clinical observation for the body condition, location, colour of tumour mass, consistency, weight, shape, peduncultion, presence of bleeding were recorded. Most of the animals were middle aged, ranging from 4 to 8 years. Breed wise prevalence was more in crossbred cattle than other breeds. Sex wise higher incidence in male than females. The eye, neck, and limb region (13.34%) were most common tumours. The red and black colour of masses accounted for 10 (33.33%) and weight ranges from 80 to 120 gms affected with skin and subcutaneous tumours were twelve (40%) whereas bleeding and infection found in eleven (36.66%) and eight (26.66%) respectively. On clinical examination, animals with healthy condition (73.34%), tumours with non-pedunculated (broad based) (73.34%). The hard consistency (46.66%) cases along with round shape of tumour mass were found in thirteen (43.34%) cases which contributed maximum number of skin and subcutaneous tumours.

Design of a flow modulation device to facilitate individualized ventilation in a shared ventilator setup.

This study aims to resolve the unmet need for ventilator surge capacity by developing a prototype device that can alter patient-specific flow in a shared ventilator setup. The device is designed to deliver a predictable tidal volume (VT), requiring minimal additional monitoring and workload. The prototyped device was tested in an in vitro bench setup for its performance against the intended use and design criteria. The ventilation parameters: VT and airway pressures, and ventilation profiles: pressure, flow and volume were measured for different ventilator and device settings for a healthy and ARDS simulated lung pathology. We obtained VTs with a linear correlation with valve openings from 10 to 100% across set inspiratory pressures (IPs) of 20 to 30 cmH2O. Airway pressure varied with valve opening and lung elastance but did not exceed set IPs. Performance was consistent in both healthy and ARDS-simulated lung conditions. The ventilation profile diverged from traditional pressure-controlled profiles. We present the design a flow modulator to titrate VTs in a shared ventilator setup. Application of the flow modulator resulted in a characteristic flow profile that differs from pressure- or volume controlled ventilation. The development of the flow modulator enables further validation of the Individualized Shared Ventilation (ISV) technology with individualization of delivered VTs and the development of a clinical protocol facilitating its clinical use during a ventilator surge capacity problem.

VSI: The Anoctamins: Structure and Function

When activated by increase in intracellular Ca2+, anoctamins (TMEM16 proteins) operate as phospholipid scramblases and as ion channels. Anoctamin 1 (ANO1) is the Ca2+-activated epithelial anion-selective channel that is coexpressed together with the abundant scramblase ANO6 and additional intracellular anoctamins. In salivary and pancreatic glands, ANO1 is tightly packed in the apical membrane and secretes Cl−. Epithelia of airways and gut use cystic fibrosis transmembrane conductance regulator (CFTR) as an apical Cl− exit pathway while ANO1 supports Cl− secretion mainly by facilitating activation of luminal CFTR and basolateral K+ channels. Under healthy conditions ANO1 modulates intracellular Ca2+ signals by tethering the endoplasmic reticulum, and except of glands its direct secretory contribution as Cl− channel might be small, compared to CFTR. In the kidneys ANO1 supports proximal tubular acid secretion and protein absorption and probably helps to excrete HCO3− in the collecting duct epithelium. However, under pathological conditions as in polycystic kidney disease, ANO1 is strongly upregulated and may cause enhanced proliferation and cyst growth. Under pathological condition, ANO1 and ANO6 are upregulated and operate as secretory channel/phospholipid scramblase, partly by supporting Ca2+-dependent processes. Much less is known about the role of other epithelial anoctamins whose potential functions are discussed in this review.

The Art of Eating Right: Ahara Vidhi Vidhana in Ayurvedic Perspective

Introduction : Maintaining health is influenced not only by the quantity and quality of food but also by the manner in which it is consumed. The processes of digestion, absorption, and assimilation involve intricate procedures influenced by physical, physiological, social, and emotional factors. To fully reap the benefits of food, adherence to specific guidelines is essential. Ayurveda provides insights into what, when, where, and how food should be consumed to optimize its effects on overall well-being. Aims and Objectives: To assess and compile information on diverse dietary and dining guidelines (Ahara Vidhi Vidhana) documented in Ayurvedic texts, examining their structure and effectiveness within the context of Charaka Samhita. Materials and Methods: The data for the review primarily collected from Ayurvedic Samhitas, including Charaka Samhita, Susrutha Samhita, Ashtanga Sangraha, Ashtanga Hridaya, and Sharangadhara Samhita. Observations: The guidelines are categorized into dietary rules and dining rules. The former outlines the types of food that should be consumed based on their quality and the individual's condition. The latter focuses on the manner in which food should be consumed, directly influencing both the hygiene of the food and the state of the mind. Conclusion: Both Ahara (diet) and Ahara Vidhi Vidhana (dietetic rules) are extremely significant in our day to day life . The appropriate application of both contributes to maintaining a healthy condition, while their improper utilization can lead to various diseases.

Single-Nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root.

Aortic root aneurysm is a potentially life-threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single-nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell-type-specific transcriptomic and cis-regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such as FOXN3, TEAD1, BACH2, and BACH1, are identified. In vitro experiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.

An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii

Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we established a gut epithelium-microbe-immune (GuMI) microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4+ naive T cells circulating underneath the colonic epithelium. In GuMI-APC condition, multiplex cytokine assays suggested that APCs contribute to the elevated level of cytokines and chemokines secreted into both apical and basolateral compartments compared to GuMI condition that lacks APC. In GuMI-APC with F. prausnitzii (GuMI-APC-FP), F. prausnitzii increased the transcription of pro-inflammatory genes such as toll-like receptor 1 (TLR1) and interferon alpha 1 (IFNA1) in the colonic epithelium, without a significant effect on cytokine secretion, compared to the GuMI-APC without bacteria (GuMI-APC-NB). In contrast, in the presence of CD4+ naive T cells (GuMI-APCT-FP), TLR1, IFNA1, and IDO1 transcription levels decreased with a simultaneous increase in F. prausnitzii-induced secretion of pro-inflammatory cytokines (e.g., IL8) compared to GuMI-APC-FP that lacks T cells. These results highlight the contribution of individual innate immune cells in regulating the immune response triggered by the gut commensal F. prausnitzii. The integration of defined populations of immune cells in the gut microphysiological system demonstrated the usefulness of GuMI physiomimetic platform to study microbe-epithelial-immune interactions in healthy and disease conditions.

Brain stars take the lead during critical periods of early postnatal brain development: relevance of astrocytes in health and mental disorders.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodeling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to "compute" the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions. Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodeling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events. From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

A Framework to Assure the Trustworthiness of Physical Model-Based Digital Twins for Marine Engines

Digital twins (DTs) are gradually employed in the maritime industry to represent the physical systems and generate datasets, among others. However, the trustworthiness of both the digital twins and datasets must be assured. This study aims at developing a framework to assure the trustworthiness of marine engines DTs based on first-principle models. This framework considers the phases of the DT development, progressivity, and trustworthiness assurance, the latter being based on three steps, namely validation, verification, and robustness. Subsequently, a methodology is applied to develop the DT of a marine engine for healthy conditions, which is extended to represent a wider operating envelope considering systematically identified anomalies. The results demonstrate that the developed DT trustworthiness is assured, as the validation step provided errors within ±3%, the verification step provided sound trade-offs, whereas the robustness assessment step confirmed acceptable uncertainty ratios. Subsequently, the DT is employed to generate datasets required for developing a data-driven model for anomaly diagnosis, which exhibits an accuracy of 98.8% for anomaly detection, 97.6% for anomaly identification, and 90.1–91.8% for anomaly isolation. This is the first study addressing the trustworthiness of DTs for marine engines, and as such advances concepts of the fourth industrial revolution to the shipping industry.

Dynamic Changes of the Gut Microbiota and Its Functional Metagenomic Potential during the Development of Non-Small Cell Lung Cancer.

The gut microbiota plays a significant role in tumor pathogenesis by regulating the host metabolism and immune response, and there are few studies focused on tracking changes in the gut microbiota from the onset of lung cancer. Therefore, the aim of our study is combining preclinical and clinical research to thoroughly analyze the signatures of fecal microbiota in lung cancer, which will be useful for early diagnosis and predicting the therapeutic efficacy of lung cancer. The first part of this study analyzed the fecal metagenomic differences between patients with non-small cell lung cancer and healthy subjects, and the second part of this work constructed a murine lung cancer model to monitor changes in mouse fecal metagenomics and T cell immunology during lung cancer progression. We found that the fecal microbiota was altered in both humans and mice with lung cancer, characterized by a significantly reduced microbial diversity and number of beneficial microbes, with increases in potential pathogens. The fecal level of Akkermansia muciniphila and the gut metabolic module of the secondary bile acid metabolism were diminished in both humans and mice with lung cancer compared with healthy subjects. Splenomegaly was observed in the lung cancer mice. Flow cytometer analysis of the splenocytes revealed substantial alterations in the proportions of T cell subsets in the lung cancer mice, characterized by significant increases in CD4+Foxp3+CD25+ T regulatory cells (p < 0.05) while significant decreases in CD3+ T cells (p < 0.001), CD4+ T cells (p < 0.001), and the CD4+/CD8+ ratio (p < 0.01). Vertical and longitudinal analyses of the fecal microbiota of the two mouse groups identified some lung cancer biomarkers (including Acutalibacter timonensis, Lachnospiraceae bacterium NSJ-38 sp014337195, etc.). The fecal microbiota of the lung cancer mice had a reduced metagenomic potential for neurotransmitters (melatonin, γ-aminobutyric acid, and histamine) compared with healthy mice. In summary, this study found that the diversity, structure, and composition of gut microbiota vary between cancer and healthy conditions, ultimately leading to changes in the potential for functional metagenomics.