Today, we are all threatened by an unprecedented pandemic: COVID-19. How different is it from other coronaviruses? Will it be attenuated or become more virulent? Which animals may be its original host? In this study, we analyzed 377 publicly available complete genome sequences for the COVID-19 virus, the previously known flu-causing coronaviruses (HCov-229E, HCov-OC43, HCov-NL63 and HCov-HKU1) and the lethal, pathogenic P3/P4 viruses, SARS, MERS, Victoria, Lassa, Yamagata, Ebola, and Dengue. We found strong similarities between the current circulating COVID-19 and SARS and MERS, as well as COVID-19 in rhinolophines and pangolins. On the contrary, COVID-19 shares little similarity with the flu-causing coronaviruses and the other P3/P4 viruses. Strikingly, we observed divergence of COVID-19 strains isolated from human hosts has steadily increased from December 2019 to March 2020, suggesting COVID-19 is actively evolving in human hosts. From all existing human COVID-19 genome sequences, we calculated the first common model that represents the shared sequences of the human COVID-19 strains, which provides important information for vaccine and antibody development. Geographic and time-course analysis of the evolutionary trees of the human COVID-19 reveals possibly heterogeneous evolutional paths among strains from 21 countries. This finding has important implications to the management of COVID-19 and the development of vaccines.

Over the last decade, the field of Human Attribute Recognition (HAR) has dramatically changed, mainly due to the improvements brought by deep learning solutions. This survey reviews the progress obtained in HAR, considering the transition from the traditional hand-crafted to deep-learning approaches. The most relevant works on the field are analyzed concerning the advances proposed to address the HAR's typical challenges. Furthermore, we outline the applications and typical evaluation metrics used in the HAR context. Finally, we provide a comprehensive review of the publicly available datasets for the development and evaluation of novel HAR approaches.

This study introduces a compact Raman spectrometer with a 1064 nm excitation laser coupled with a fiber probe and an inexpensive motorized stage, offering a promising alternative to widely used Raman imaging instruments with 785 nm excitation lasers. The benefits of 1064 nm excitation for biomedical applications include further suppression of fluorescence background and deeper tissue penetration. The performance of the 1064 nm instrument in detecting cancer in human bladder resectates is demonstrated. Raman images with 1064 nm excitation were collected ex vivo from 10 human tumor and non-tumor bladder specimens and the results are compared to previously published Raman images with 785 nm excitation. K-Means cluster (KMC) analysis is used after pre-processing to identify Raman signatures of control, tumor, necrosis, and lipid-rich tissues. Hierarchical cluster analysis (HCA) groups the KMC centroids of all specimens as input. The tools for data processing and hyperspectral analysis were compiled in an open source Python library called SpectraMap (SpMap). In conclusion, the 1064 nm Raman system can differentiate between tumor and non-tumor bladder tissues in a similar way to 785 nm Raman spectroscopy. These findings hold promise for future clinical hyperspectral imaging.

Citrus fruits are extensively cultivated worldwide, with Italy and Spain being major producers. Southern Italy, particularly in Reggio Calabria, a typical citrus fruit is produced, namely, bergamot (Citrus bergamia Risso et Poiteau), known for its mysterious origins and exceptional quality essential oil protected by the EU's PDO designation. Despite historical challenges, bergamot has regained prominence for its nutraceutical potential, especially its flavonoid-rich juice, offering significant health benefits. However, little attention has been paid to understanding the qualitative and quantitative differences of bergamot juice in Calabrian production areas. For this reason, this work aims to investigate the quality characteristics of bergamot juice produced in different areas of Ca-labria sites. The results showed the best quality attributes of bergamot fruits harvested in the DPO area. In particular, higher levels of total soluble solids, stable acidity and higher juice were found. In addition, higher contents of ascorbic and citric acids, which are nutritionally valuable and tasteful, were found. The phenolic profile, characterized by the key compounds of bergamot, highlighted the better nutraceutical potential of the fruit grown in the DPO area.

Intrauterine growth restriction (IUGR) pigs are characterized by long-term growth failure, metabolic disorders, and intestinal microbiota imbalance. The characteristics of the negative effects of IUGR at different swine growth stages are still unclear. Therefore, this study explored whether intrauterine growth restriction (IUGR) model damaged the intestinal barrier function and altered the colonization and metabolic profiles of the colonic microbiota in growing-finishing pigs by the multi-omics method. Seventy-two piglets (36 IUGR and 36 NBW) were selected for this trial to analyze physiological and plasma biochemical parameters, oxidative damage, and inflammatory response in the colon. Moreover, the colonic microbial communities were examined using 16s rRNA sequencing and metabolomics to reveal the intestinal characteristics of pigs at different growth stages (25, 50, and 100 kg). IUGR altered the plasma concentrations of glucose, total protein triglyceride, and cholesterol. Colonic tight junction proteins were markedly inhibited by IUGR. IUGR decreased plasma T-AOC, SOD, and GSH levels, and colonic SOD-1, SOD-2, and GPX4 expressions by restraining the Nrf2/Keap1 signaling pathway. Moreover, IUGR increased the colonic IL-1β and TNF-α levels while reducing IL-10, possibly activating the TLR4-NF-κB/ERK pathways. Notably, IUGR pigs had lower colonic Streptococcus abundance and Firmicutes-to-Bacteroidetes ratio at the 25 kg BW stage while having higher Firmicutes abundance at the 100 kg BW stage; moreover, IUGR pigs had lower SCFAs concentrations. Metabolomics analysis showed that IUGR increased colonic lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic concentrations and enriched three differential metabolic pathways, including linoleic acid, sphingolipid, and purine metabolisms throughout the trial. Collectively, IUGR altered the nutrient metabolism, redox status, and colonic microbial community and metabolite profiles of pigs and continued to disrupt colonic barrier function by reducing antioxidant capacity via the Nrf2/Keap1 pathway and activating inflammation via the TLR4-NF-κB/ERK pathway during the growing-finishing stage. Colonic Firmicutes and Streptococcus could be potential regulatory targets for modulating the metabolism and health of IUGR pigs.

Abstract: Antimicrobial peptides (AMPs) are short peptides, usually made up of less than 100 amino acid residues. They are found in many living organisms and are an important factor in their innate immune systems. AMPs can be extracted from various living sources including bacteria, plants, animals and even humans. They are usually cationic peptides with an amphiphilic structure, which allows them to easily bind and interact with the cellular membranes of viruses, bacteria, fungi and other pathogens. They can act against both Gram-negative and Gram-positive pathogens and have various modes of action against them. Some attack the pathogens membrane, while others target their intracellular organelles as well as their nucleic acids, proteins and metabolic pathways. A crucial area of use of AMPs is in their ability to help with emerging antibiotic resistance: some AMPs are active against resistant strains and are susceptible to peptide engineering. This review considers AMPs from three key sources: plants, animals and humans, as well as their modes of action and some AMPs sequences.

Mint and to a lesser extent menthol have been used since antiquity for medicinal purposes. Key components of mint and menthol use such as composition and intake, safety and traditional uses are discussed prior to a review of clinical and human performance outcomes in the areas of digestive and respiratory health; antibacterial and anti-fungal properties, nocioception, migraine and headache and emerging evidence regarding COVID 19. Evidence suggests benefit for patients with irritable bowel syndrome and related digestive issues, with analgesic and respiratory effects also noted. Perceptual characteristics relating to thermal comfort and sensation, taste sensitivity and alertness are also considered; these effects are predominantly driven by stimulation of transient receptor potential melastatin 8 (TRPM8) activity resulting in sensations of cooling and freshness, with lesser influence on thirst. Finally, sport performance is considered as a domain that may further elucidate some of the aforementioned underpinning outcomes due to its systemic and dynamic nature, especially when performed in hot environmental conditions.

Mounting evidence supports the connections between exposure to environment types––such as green spaces and biodiversity––and human health. However, the mechanistic links that connect biodiversity (the variety of life) and human health, plus the level of supporting evidence, are less clear. Here, we undertook a scoping review to map the links between biodiversity and human health and summarise the levels of associated evidence using an established weight of evidence framework. Distinct from other reviews, we provide additional context regarding the environment-microbiome-health axis, evaluate the environmental buffering pathway (e.g., biodiversity impacts on air pollution), and draw upon expert opinion to provide case studies on three underrepresented linkages. The case studies include (1) biodiversity and Indigenous Peoples’ health, (2) biodiversity and urban social equity, and (3) biodiversity and COVID-19. We observed a moderate level of evidence to support the environmental microbiota-human health pathway and a moderate-high level of evidence to support broader nature pathways (e.g., green space) to various health outcomes, from stress reduction to enhanced wellbeing and improved social cohesion. However, studies of broader nature pathways did not typically include specific biodiversity metrics, indicating clear research gaps. Further research is required to understand the connections and causative pathways between biodiversity (e.g., using metrics such as taxonomy, diversity/richness, structure, and function) and health outcomes. There are well-established frameworks to assess the effects of broad classifications of nature on human health. These can assist future research in linking biodiversity metrics to human health outcomes. Our case studies on underrepresented linkages highlight the roles of biodiversity and its loss on urban lived experiences, infectious diseases, and Indigenous Peoples’ sovereignty and livelihoods. More research and awareness of these socioecological interconnections are needed.

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction. Single nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples have revealed alterations in communication between various cell types but a direct and integrated comparison between the two HCM phenotypes has not been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication and in endothelial cell communication to other cell types, largely through changes in expression of integrin-b1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for personalized management of different HCM phenotypes.

Human detection from Unmanned Aerial Vehicles (UAV) is gaining popularity in the field of disaster management, crowd counting, people monitoring. Real time human detection from UAV is a challenging task, because of many constraints involved. This study proposes a system for real time detection of humans on videos captured from UAVs addressing three of these constraints namely, flying height, computation time and scale of viewing. The proposed method integrated an android application with a binary classifier based on Haar-features to automatically detect human / non-human class from UAV images. The video frames were parsed and detected humans from image frames were geo-localized and visualized on Google Earth. The performance was evaluated for geo-localization accuracy, computation time and detection accuracy, considering human coverage – pixel size relationship for various heights and scale factor. Based on flying height - human size relationship and tradeoff between detection accuracy vs computation time, the study came up with optimal parameters for OpenCV’s cv2.cascadeClassifier. detectMultiScale function. This paper establishes a strong ground for further research relating to real time human detection from UAV.

This research concerns in to understand the link between urban heat and cool island, the Local Climatic Zones (LCZ) and atmospheric systems during the winter season in the city of Balneário Camboriú, Southern Brazil. To collect meteorological data on urban environmental, 11 permanent points in the Balneário Camboriú metropolitan region were installed. To understand the atmos-pheric systems operating in the region, a synoptic analysis of the dates was performed, and then, the LCZs map created for the city in World Urban Database and Acess Portal Tools was used to cor-relate the magnitudes of the heat and cool islands found in Balneário Camboriú in the winter period. The results indicate that the increasing verticalization with the construction of skyscrapers in Balneário Camboriú has a significant influence on local conditions for the occurrence of heat and cold islands. The findings indicate that LCZs with sparsely distributed buildings (LCZs 6, 8 and 9) and LCZs with dense vegetation (LCZ A) have lower intensity magnitudes of heat and cool con-ditions. The biggest magnitudes of heat and cool islands were reported in LCZs 1 and 3 during the timeframe. The synoptic analysis supports earlier researches that points to atmospheric stability (Anticyclonic domain) as a favorable atmospheric setting for the emergence of urban hear and coolness islands.

The health status of Hungary's population is unfavorable, with significant differences in health indicators not only compared to the EU15 but also to the Visegrad countries. Unfavorable health indicators can be disproportionate and particularly affect vulnerable groups, such as people with disabilities. The aim of the present study is to compare the health behaviour and indicators of adolescents with disabilities in Hungary with those of the HBSC survey in the Visegrad countries, and to compare the results of the Hungarian special needs adolescent population with those of the Visegrad countries. Eating habits are unfavourable for both the Visegrad countries and the young people we studied. Children with disabilities have significantly higher rates of schoolwork stress compared to other countries. Significantly higher prevalence of somatic complaints and worse mental well-being parameters higher in Hungary than in the other Visegrad countries. The results suggest that further interventions are needed in Hungary and that differentiated, professionalised health promotion is needed for young people with disabilities. The researchers propose to extend the research to adolescents with disabilities living in the Visegrad countries, on the basis of which a methodology for injury-specific health promotion could be developed, including through interna-tional interprofessional cooperation.

The endometrium, the inner mucosal lining of the uterus, undergoes complex molecular and cellular changes across the menstrual cycle in preparation for embryo implantation. Transcrip-tome-wide analyses have mainly been utilized to study the endometrial receptivity, the prerequisite for successful implantation, with most of the studies, so far, comparing the endometrial transcriptomes between (i) secretory versus proliferative endometrium or (ii) mid-secretory versus early-secretory endometrium. In the current study, we provide the complete transcriptome description of the endometrium across the entire menstrual cycle and, for the first time, comprehensively characterize the proliferative phase of the endometrium. Our temporal transcriptome analysis includes five time points: mid-proliferative, late-proliferative (peri-ovulatory phase), early-secretory, mid-secretory, and late-secretory phases. Thus, we exhaustively unveil the transitions between the consecutive proliferative and secretory phases, highlighting their unique gene expression profiles and possible distinct biological functions. Transcriptome analysis reveals many differentially expressed genes (DEGs) across the menstrual cycle, most of which are phase-specific. As an example of the coordinated gene activity, the expression profile of his-tone-encoding genes within the HIST cluster on chromosome 6 showed an increase in cluster activity during the late-proliferative and a decline during the mid-secretory phase. Moreover, numerous DEGs are shared among all phases. In conclusion, in the current study, we delineate the endometrial proliferative phase-centered view of transcriptome dynamics across the menstrual cycle. Data analysis highlights significant transcriptomic and functional changes occurring during the late-proliferative phase – an essential transition point from the proliferative to the secretory phase. Future studies should explore how the biology of the late-proliferative phase endometrium impacts the achievement of mid-secretory endometrial receptivity or contributes to molecular aberrations leading to embryo implantation failure.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

Studies of mast cell biology is dependent on relevant and validated in vitro models. We here present detailed information concerning the phenotype of both freshly isolated human skin mast cells (MCs), and of in vitro cultures of these cells that was obtained by analyzing their total transcriptome. Transcript levels of MC-related granule proteins and transcription factors were found to be remarkably stable over a 3-week culture period. Relatively modest changes were also seen for important cell surface receptors including the high affinity receptor for IgE, FCER1A, the low affinity receptor for IgG, FCGR2A, and the receptor for stem cell factor, KIT. FCGR2A was the only Fc receptor for IgG expressed by these cells. Comparisons of the present transcriptome against previously reported transcriptomes of mouse peritoneal MCs and mouse bone marrow derived MCs (BMMCs) revealed both similarities and major differences. Strikingly, cathepsin G was the most highly expressed granule protease in human skin MCs, in contrast to the almost total absent of this protease in both mouse MCs. Transcript levels for the majority of cell surface receptors were also very low compared to the granule proteases in both mouse and human MCs, with a difference of almost two orders of magnitude. An almost total absence of T cell granzymes was observed in human skin MCs, indicating that granzymes have no or only a minor role in human MC biology. Ex vivo skin MCs expressed high levels of selective immediate early genes and transcripts of heat-shock proteins. In validation experiments, we determined that this expression was an inherent property of the cells and not the result of the isolation process. Three to four weeks in culture results in an induction of cell growth related genes accompanying their expansion by 6-10-fold, which increases the number of cells for in vitro experiments. Collectively, we show that cultured human skin MCs resemble their ex vivo equivalents in many respects and are a more relevant in vitro model compared to mouse BMMCs for studies of MC biology, in particular human MC biology.

In vineyards, Botryosphaeria dieback (BD) occurs in young and old plants. In the field, the prevalence and severity of the disease increase proportionally with the age of the vineyards. Among the pathogens that cause (BD), Diplodia seriata is the most prevalent species in Chile and other countries with a Mediterranean climate. To date, no information is available on the sus-ceptibility of adult wood to infection by this pathogen since most of the pathogenicity tests have been carried out on 1- or 2-year-old shoots or detached canes. Therefore, a pathogenicity test was carried out on plants under field conditions, with inoculations in plants, on one-year-old shoots, and 2- and 10-year-old wood in grapevine cv. Cabernet Sauvignon. A pathogenicity test was carried out with two isolates of D. seriata selected in an assay in detached canes that were 2-year-old. The results on plants showed that D. seriata was significantly more aggressive on 10-year-old than on one- or two-year-old tissue. These results were compared with the lesions ob-tained from two-year-old canes. The results of this work are consistent with the damage ob-served in the field, highlight the importance of identifying each pathogenic species that causes (BD) and contribute to the knowledge of the epidemiology of this disease in Mediterranean cli-mates.

Over the past few decades, aircraft Ground Handling Operations (GHO) have been investigated by numerous researchers. Some aspects of GHO have been more focused on than others due to their importance in the GH processes. For instance, GHO performance has been tackled from different perspectives while workers and vehicles allocation suffer from the lack of research in the area. This paper is a literary review of the research that has been conducted in different areas of GHO. It sheds light on GHO performance, resource allocation and scheduling, operations scheduling, vehicle routing, and workers and vehicles allocation.

The proposed method deals with the problem of data privacy and sharing when processing personal mobility tracking data. Previous methods concentrate on producing highly detailed data on short-term and restricted areas, e.g. for autonomous driving scenarios. Another possibility consists of city-wide scales and beyond, that are used to predict general traffic flows. The presented approach takes the tracked mobility behavior of individuals to create coherent new mobility data that reflects the long-term mobility behavior of the person, guaranteeing location persistency and sound embedding within the point-of-interest structure of the observed area. After an analysis and clustering step with the original data, the area is distributed into a geospatial grid structure (H3 is used here), and the neighborhood relationships between the grids are interpreted as a graph. A feed-forward-autoencoder and a graph encoding-decoding network generate a latent space representation of the area. The original clustered data is associated with their respective H3 grids. With a greedy algorithm approach and concerning privacy strategies, new combinations of grids are top-level patterns for individual mobility behavior. Concrete locations are found and connected within the grids based on the original data. The described method is then applied to a study with 1000 participants from the city of Munich in Germany, and the results are described, showing the application of the approach in generating synthetic data, enabling further research on individual mobility behavior and patterns. The result is a sharable dataset on the same abstraction level as the input data, which makes it interesting, particularly for machine learning applications.

Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, and cell-matrix adhesion. Here, we use vimentin knock out cells (Vim KO) to assess how vimentin impacts cell spreading, morphology, and myofibroblast transformation of human corneal fibro-blasts. Overall, loss of vimentin did not significantly impact corneal fibroblast spreading, as indicated by Vim KO morphology and mechanical activity (traction force). However, we found that Vim KO cells had reduced elongation in response to PDGF as compared to controls. Furthermore, absence of vimentin did not completely block TGFβ induced myofibroblast transformation, since αSMA protein expression was detected in Vim KO cells. Nonetheless, the degree of transformation and amount of αSMA protein was reduced as compared to control cells. Proteomics showed that Vim KO cells cultured in TGFβ had a similar pattern of protein expression as controls. One exception included periostin, an ECM protein associated with wound healing and fibrosis in other cell types, which was highly expressed only in Vim KO cells. We also demonstrate for the first time that LRRC15, a protein previously associated with myofibroblast transformation of cancer-associated fibroblasts, is also expressed by corneal myofibroblasts. Overall, our data shows that vimentin has a limited, yet measurable impact on corneal fibroblast spreading and myofibroblast transformation. We also identified novel proteins that may regulate corneal myofibroblast transformation in the presence and/or absence of vimentin.

AbstractThe emergence of AI-powered deepfakes, manipulatively realistic synthetic media, raises unprecedented challenges for human information processing and decision-making. This paper explores the cognitive and emotional consequences of exposure to deepfakes, delving into how these digitally fabricated experiences can reshape perception, trust, and social interactions. By reviewing existing research and outlining potential methodological approaches, this paper aims to establish a framework for investigating the multifaceted impact of deepfakes on the human brain.BackgroundThe digital age has ushered in an era of unprecedented information abundance and accessibility. Yet, this abundance breeds vulnerability, particularly with the emergence of AI-powered deepfakes. These hyper-realistic synthetic media creations present a potent threat to the fundamental trust and integrity of information sources. Deepfakes have infiltrated various domains, from entertainment and social media to politics and journalism, blurring the lines between truth and fabrication. Consequently, understanding the cognitive and emotional consequences of encountering deepfakes becomes crucial for navigating this increasingly deceptive landscape.ObjectivesThis research aims to: Investigate how exposure to deepfakes impacts various cognitive functions, including perception, attention, memory, and decision-making. Elucidate the emotional responses elicited by deepfakes and their underlying neural mechanisms. Evaluate the role of individual differences, such as susceptibility to deception and emotional sensitivity, in mediating the impact of deepfakes. Develop a comprehensive framework for understanding the multifaceted influence of deepfakes on the human brain. Results (anticipated)This research is expected to yield insights into: The specific cognitive and emotional processes altered by deepfakes, providing evidence for potential mechanisms of deception and manipulation. The neural circuitry involved in detecting and responding to deepfakes, leading to the development of more effective detection methods. The influence of individual differences (e.g., age, cognitive style) on susceptibility to deepfakes, informing targeted interventions and educational efforts.ConclusionBy deciphering the impact of deepfakes on the human brain, this research will offer valuable tools for mitigating the harmful consequences of misinformation and promoting responsible use of this powerful technology. Ultimately, understanding how deepfakes manipulate our cognitive and emotional landscape is not merely a scientific pursuit, but a critical step towards ensuring a future where truth prevails in the digital world.

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. However, emerging research from detailed studies of comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language suggest that language and social cognition are two deeply interrelated capacities of the human species. For instance, recent developmental studies on the acquisition of language in infants and young children, draw attention to the important crucial benefits associated with several different aspects of social stimulation for youngsters, including the quantity and quality of linguistic input, dyadic infant/child-to-parent verbal and non-verbal social interactions, and other important social cues integral for facilitating language learning and social bonding. Studies of the adult human brain further suggest a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting the function of these regions may link language with social cognition and social bonding. In effect, the social brain and social complexity hypotheses may jointly help to explain how neurotypical children and adults learn language, why autistic adults and children exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other animals with significant computational abilities do not acquire the capacity for language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain, while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain.

SRC homology 3 (SH3) domains are critical interaction modules that orchestrate the assembly of protein complexes involved in diverse biological processes. They facilitate transient protein-protein interactions by selectively interacting with proline-rich motifs (PRMs). A database search revealed 298 SH3 domains in 221 human proteins. Multiple sequence alignment of human SH3 domains is useful for phylogenetic analysis and determination of their selectivity towards PRM-containing peptides (PRPs). However, a more precise functional classification of SH3 domains is achieved by constructing a phylogenetic tree only from PRM-binding residues and using existing SH3-PRP structures and biochemical data to determine the specificity within each of the 10 families for particular PRPs. In addition, the C-terminal proline-rich domain of the RAS activator SOS1 covers 13 of the 14 recognized proline-rich consensus sequence motifs, encompassing differential PRP pattern selectivity among all SH3 families. To evaluate binding capabilities and affinities, we conducted fluorescence dot blot and polarization experiments using 25 representative SH3 domains and various PRPs derived from SOS1. Our analysis has identified 45 interacting pairs with binding affinities ranging from 0.2 to 125 micromolar out of 300 tested and potential new interactors of SOS1. Furthermore, it establishes a framework to bridge the gap between SH3 and PRP interactions and provides predictive insights into potential interactions of SH3 domains with PRMs based on sequence specifications. This novel framework has the potential to enhance the understanding of protein networks mediated by SH3-PRM interactions and be utilized as a general approach for other domain-peptide interactions.

When the skin is afflicted by disease such as cancer, these essential functions are disrupted, putting the entire person at risk. While the American Cancer Society lists 6 major cancer types, the National Institute of Arthritis and Musculoskeletal and Skin Diseases identifies 13 significant benign skin disorders, reflecting the diversity of skin conditions in dermatology. This topical review aims to provide an overview of the pathophysiology of these major skin cancers and disorders and summarize conventional diagnostic methods and current treatment approaches.

The endogenous miRNAs of breast milk are the products of more than 1,000 nonprotein-coding genes, giving rise to mature small regulatory molecules of 19–25 nucleotides. They are incorporated in macromolecular complexes, loaded on Argonaut proteins, sequestrated in exosomes, lipid complexes, or present in exfoliated cells of epithelial, endothelial, or immune origins. Their expression is dependent on the stage of lactation, however their detection depends on progress in RNA sequencing and the reappraisal of small RNAs definition. Some miRNAs from plants are detected in breast milk, opening the possibility of stimulation of immune cells of the allergic repertoire. Each miRNA harbors a seeding sequence, which targets mRNAs, gene promoters, or long noncoding RNAs. Their activities depend on their bioavailability. Efficient doses of miRNAs are estimated at roughly 100 molecules in the cytoplasm of target cells from in vitro and in vivo experiments. Each miRNA is included in networks of stimulation/inhibition/sequestration driving the expression of cellular phenotypes. Three types of stress applied during lactation to manipulate miRNA supply, have been explored on the rodent offspring: foster mother, cafeteria diet, early weaning. The review present the main mature miRNAs described across current mothers’ cohorts, their bioavailability in experimental models, and the studies assessing the potentials of miR-26 or miR-320 miRNA families to alter offspring phenotype.

Calcium (Ca2+) ions act as second messenger, regulating several cell functions. Mitochondria are critical organelles for the regulation of intracellular Ca2+. Mitochondrial calcium (mtCa2+) uptake is ensured by the presence in the inner mitochondrial membrane (IMM) of the mitochondrial calcium uniporter (MCU) complex, a macromolecular structure composed of pore-forming and regulatory subunits. MtCa2+ uptake plays a crucial role in the regulation of oxidative metabolism and cell death. Many evidences demonstrate that dysregulation of mtCa2+ homeostasis can have serious pathological outcomes. In this review, we briefly discuss the molecular structure and the function of the MCU complex and then we focus our attention on human diseases in which a dysfunction in mtCa2+ has been showed.

Groundwater use for domestic and agricultural purposes is every day in rural communities. However, groundwater quality in those communities is still being determined due to the lack of water quality monitoring programs. The purpose of this study was to evaluate groundwater quality in rural communities using physiochemical parameters. Eight communities using communal boreholes were selected. Water samples were analysed for temperature, pH, electrical conductivity, total dissolved solids (TDS), ammonia, nitrate, and nitrite as Nitrogen. The pH means ranged from 6.6 to 8.1, whereas high TDS levels of 1390 mg/L and 1470 mg/L were observed in two boreholes. Three boreholes had higher electrical conductivity. Two boreholes had elevated nitrate levels of 15 and 21.5 mg/L. The high nitrate level correlates with the pH, EC, and TDS values. Our results suggest that high nitrate levels measured in communities’ boreholes pose ill health to the community, especially children, infants, and elders. Prenatal exposure to high nitrate has been found to have acute health effects in infants. Therefore, there is a need for further longitudinal studies on health risks among vulnerable groups in these communities.

The German Constitutional Court’s climate verdict provides a re-interpretation of liberal- democratic core concepts and is highly relevant for liberal constitutional law in general – including EU and international law. The verdict accepts human rights as intertemporal and globally applicable; it applies the precautionary principle to these rights and frees them from the misleading causality debate. However, the court fails to address the most important violations of human rights, and it categorised climate policy as a greater threat to freedom than climate change. And the court does not make it clear that the Paris 1.5-degree limit implies a radically smaller carbon budget. Furthermore, little attention has so far been paid to the fact that the ruling implies an obligation for more EU climate protection, especially since most emissions are regulated supranationally. To be effective, the EU emissions trading system demands a reform, which should go well beyond the existing EU proposals to enable societal transformation to sustainability.

Embryoid bodies (EBs) are multicellular three-dimensional (3D) aggregates generated from induced pluripotent stem cells (iPSCs) in suspension and serve as useful biological sources for many downstream applications. Imaging of live EBs has been hampered mainly due to the inherent limitations of the imaging techniques applied to date. This study aimed to image human iPSC (hiPSC) derived EBs to obtain their 3D volume, determining size, morphology, and cell viability from day 7 to 14 using Light Sheet Fluorescence Microscopy (LSFM). Furthermore, chromosomal stability was assessed using Multicolor fluorescence in situ hybridization (M-FISH) from day 8 to 14. EB volume increased from day 7 to 13 which, decreased at day 14. From day 7 to 11, the EBs mainly appeared spherical and morphed into an ellipsoidal shape by day 13. All EBs showed varied external morphologies and larger cavities at day 14. The EB karyotype was diploid 46XY at day 8 and exhibited a low level of aneuploidy from day 10 to 14. This study shows that an increase in cell death affects the morphology and chromosomal stability in EBs derived from hiPSC. We demonstrate that the combination of LSFM and M-FISH helps characterize EBs that will assist future stem cell therapies.

Scientific theories on the functioning and dysfunction of the human brain require a good understanding of both its development — before and after birth, and through maturation to adulthood — and its evolution from the ancestral primate brain. Adopting a complex-systems approach, here we propose that the apparent uniqueness of humans’ cognitive capacities might best be understood as emerging from multiple nested “virtuous cycles.” In particular, we propose that the intimate link that exists between oxygen metabolic loops, cortical expansion, and ultimately cognitive and social demands is a key driver of genetic developmental programs for the human brain. Overall, our proposed evolutionary model makes explicit mechanistic links between metabolism, molecular and cellular brain heterogeneity, and behaviour that may in time provide a clearer understanding of brain developmental trajectories and their disorders.

Malnutrition, unhealthy diets, and lifestyle changes have become major risk factors for non-communicable diseases while ad-versely impacting economic growth and sustainable development. Anthocyanins, a group of flavonoids that are rich in fruits and vegetables, contribute positively to human health. This review focuses on genetic variation harnessed through crossbreeding and biotechnology-led approaches for developing anthocyanins-rich fruit and vegetable crops. Significant progress has been made in identifying genes involved in anthocyanin biosynthesis in various crops. Thus, the use of genetics has led to the development and release of anthocyanin-rich crop cultivars in Europe and USA. Such a trend is emerging in the developing world. The purple pota-to “Kufri Neelkanth” has been released for cultivation in northern India, and a few colored grain wheat lines, developed through crossbreeding, are being tested for their productivity and adaptation. Although tomato is deficient in anthocyanins, some of its wild relatives are known to accumulate anthocyanins in their sub-epidermal fruit tissue. In Europe, anthocyanin-rich tomato cul-tivar ‘Sun Black’ developed via the introgression of Aft and atv genes has been released. The development of anthocyanin-rich food crops without any significant yield penalty has been due to the use of genetic engineering involving specific transcription factors or gene editing. The anthocyanin-rich food ingredients have the potential of being more nutritious than those devoid of anthocyanins. The inclusion of anthocyanins as a target characteristic in breeding programs can ensure the development of culti-vars to meet the nutritional needs for human consumption, particularly in the developing world.

Since the 1970s, the application of microprocessor in industrial machinery and the development of computer systems have transformed the manufacturing landscape. The rapid integration and automation of production systems have outpaced the development of suitable human design criteria, creating a deepening gap where human factor was seen as an important source of errors and disruptions. Today the situation seems different: the scientific and public debate about the concept of Industry 4.0 has raised the awareness about the central role humans have to play in manufacturing systems, to the design of which they must be considered from the very beginning. The future of industrial systems, as represented by Industry 4.0, will rely on the convergence of several research fields such as Intelligent Manufacturing Systems (IMS), Cyber-Physical Systems (CPS), Internet of things (IoT), but also socio-technical fields such as social approaches within technical systems. This article deals with different Human dimensions associated with CPS and IoT and focuses on their conceptual evolution of automatization to improve the sociability of such automated production systems and consequently puts again the human in the loop. Hereby, our aim is to take stock of current research trends, and to show the importance of integrating human operators as a part of a socio-technical system based autonomous and intelligent products or resources. As results, different models of sociability as way to integrate human into the broad sense and/or the development of future automated production systems, were identified from the literature and analysed.

Possible alterations of maternal immune function due to psychological stress may reflect immunoactive factor levels in breast milk. This study aimed to assess the association between maternal distress and breast milk levels of secretory IgA (SIgA), IgM, IgG, and lactoferrin (LF). We hypothesized this association is moderated by maternal social support achieved from others during lactation. The study group included 103 lactating mothers and their healthy 5-months-old infants. Maternal distress was determined based on the State Anxiety Inventory and the level of salivary cortisol. Social support was assessed using Berlin Social Support Scales. Breast milk samples were collected to test for SIgA, IgM, IgG, and LF using the ELISA method. Milk immunoactive factors were regressed against maternal anxiety, social support, salivary cortisol, and infant gestational age using the general regression model. Maternal anxiety was negatively associated with milk levels of LF (β=-0.22, p<0.05) and SIgA (β=-0.29, p<0.01), while social support was positively associated with milk IgG (β=0.25, p<0.05). Neither anxiety nor social support was related to milk IgM. No association was found between the level of maternal salivary cortisol and immunoactive factors in milk. Our results suggest that maternal psychological well-being and social support may affect milk immune properties.

Space missions have always assumed that the risk of spacecraft malfunction far outweighs the risk of human system failure. This assumption breaks down for longer duration exploration missions and exposes vulnerabilities in space medical system. Space agencies can no longer buy down the majority of human system risk through the crew member selection process and emergency re-supply or evacuation. No mature medical solutions exist to close the risk gap. With recent advances in biotechnology, there is promise in augmenting a space pharmacy with a biologically-based space foundry for on-demand manufacturing of high-value medical products. Here we review the challenges and opportunities of molecular pharming, the production of pharmaceuticals in plants, as the basis of a space medical foundry to close the risk gap in current space medical systems. Plants have long been considered an important life support object in space and can now also be viewed as programmable factories in space. Advances in molecular pharming-based space foundries will have widespread application in promoting simple and accessible pharmaceutical manufacturing on Earth.

The mass concentration of particulate matter (PM) has been systematically used in epidemiological studies as exposure indicator, to relate airborne concentrations with a wide variety of human health effects, which can be hardly explained by using this single parameter. In fact, PM is a “particle cocktail” that includes a complex mixture of compounds with a wide range of sizes, chemical compositions and emission sources. Current research hypothesizes that many of the adverse health effects are derived from oxidative stress in biological systems caused by the deposition of PM into the lungs. This emerging hypothesis is called the oxidative stress paradigm. In this commentary article we analize how this new paradigm could help to answer the as-of-yet unanswered questions related to the mechanism of action of PM pollution on human health. Acellular oxidative potential (OP) assays have been emerged as a promising approach to quantify the PM potential to induce oxidative stress and to relate it with the chemical composition and size distribution of PM. Recent researches have shown that the OP is related to the presence of metals, organic carbon, polyaromatic hydrocarbons and quinones. However, the association between PM and particle-induced toxicity is still largely unknown. Therefore, additional research is needed to identify the specific PM characteristic(s), such as its specific size, emission source or chemical content, which contribute the most to its redox activity. Thus, the OP measurements provide information that allows us to evaluate and integrate the toxic potential of PM in a unique parameter, whose relationships with emission sources, size distribution and/or chemical composition should be faced in the near future.

Maternal milk, from well-nourished and healthy mothers, is a source of several bioactive compounds and balanced nutrients required for proper growth and development of the infant. Hence it is regarded as the optimal form of nourishment. Human milk fat from human milk is the most crucial component and is a necessity for the growing infant. However, in certain cases, the breast milk may fulfill the nutritional needs or the breast-feeding of the infant is not feasible; infant formulae are then considered as the best alternative as nutritional support. It becomes essential for the infant formula to behave and provide nutritive support in the same way as human milk. In order to achieve so, the most crucial components of all should also be prepared precisely, i.e., the analogue of human milk fat. This analogue, which mimics the actual human milk fat, can be then used as a prime ingredient while designing the infant formula. Significant research and several advances have been made in preparing the infant formula enriched with adequate fat content, and more studies are still being conducted in order to achieve a more sound product in the most economical and simplest way possible.

With the evolution of computing technology in many application like human robot interaction, human computer interaction and health-care system, 3D human body models and their dynamic motions has gained popularity. Human performance accompanies human body shapes and their relative motions. Research on human activity recognition is structured around how the complex movement of a human body is identified and analyzed. Vision based action recognition from video is such kind of tasks where actions are inferred by observing the complete set of action sequence performed by human. Many techniques have been revised over the recent decades in order to develop a robust as well as effective framework for action recognition. In this survey, we summarize recent advances in human action recognition, namely the machine learning approach, deep learning approach and evaluation of these approaches.

Background: The SARS-CoV-2 virus is a new highly pathogen virus that can suppress cell immune response (Poly ADPR process, and interferon releasing in infected cell) by viral macrodomain and create fatal pneumonia. Cytokine storm phenomenon which can create consequence of SARS COV-2 by increase of the performance of human TRPM2, is a dangerous condition for human and its body organ such as kidney, heart, and liver. it seems like prevention of beginning of these events is necessary. Material and methods: in this study drug and drug like database was used for inhibition of the viral macrodomain and human TRPM2 that can initiate of the viral cell cycle infection and human cytokine storm respectively. Ligand base drug designed, pharmacophore modeling, docking and molecular dynamic simulation was performed Results: among up to billion compounds, 20 compounds were screened by infinisee program. Then 7 compounds were selected by pharmacophore modeling. between 7 compounds, 5 compound was removed because of high similarity to ADPR and possibility of toxic effect for human RNA and DNA polymerase. One compound was losartan and selected for docking and molecular dynamic simulation. Conclusion: losartan earned a proper dock score and binding affinity to create the complexes with TRPM2 and macrodomain. Molecular dynamic simulation has shown losartan had an adequate binding free energy for human trpm2 and viral macrodomain. The inhibitory effect of losartan on these protein has shown and it could interfere in several points (PARP, PARG- macrodomain and TRPM2) and decreases oxidative stress, apoptosis, cytokine storm in COVID-19.

It is proposed that both human creativity and human consciousness are (unintended) consequences of the human brain’s extraordinary energy efficiency. The topics of creativity and consciousness are treated separately, though have a common sub-structure. It is argued that creativity arises from a synergy between two cognitive modes of the human brain (which broadly coincide with Kahneman’s Systems 1 and 2). In the first, available energy is spread across a relatively large network of neurons. As such, the amount of energy per active neuron is so small that the operation of such neurons is susceptible to thermal (ultimately quantum decoherent) noise. In the second, available energy is focussed on a small enough subset of neurons to guarantee a deterministic operation. An illustration of how this synergy can lead to creativity with implications for computing in silicon are discussed. Starting with a discussion of the concept of free will, the notion of consciousness is defined in terms of an awareness of what are perceived to be nearby counterfactual worlds in state space. It is argued that such awareness arises from an interplay between our memories on the one hand, and quantum physical mechanisms (where, unlike in classical physics, nearby counterfactual worlds play an indispensable dynamical role) in the ion channels of neural networks. As with the brain’s susceptibility to noise, it is argued that in situations where quantum physics plays a role in the brain, it does so for reasons of energy efficiency. As an illustration of this definition of consciousness, a novel proposal is outlined as to why quantum entanglement appears so counter-intuitive.

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its copy number alteration (CNA) and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2 and 12p13.31 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

Human milk composition is dynamic and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) followed by multivariate data analyses as a tool to analyze peptide profiling of mammalian, human and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS and data were exported for statistical elaborations. Mass spectra for each milk closely clustered together, whereas different milk samples resulted well separated. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although specifically characterized and well correlated each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and low cost consuming, suggesting that the MALDI-TOF MS pipelines may result useful for milk adulteration assessment but also for the characterization of banked milk specimens in paediatric clinical settings.

Hubei, Hunan and Henan Provinces are located in Central China, a region with extensive transport networks and trade. Bursaphelenchus xylophilus, the causative agent of pine wilt disease, is spreads mainly through human activities. In order to further understand the genetic structure of PWN in Central China, we studied the genetic information of PWN populations in this region and compared the genetic relationship with strains from Guangdong and Jiangsu provinces. We found that the HB (Hubei) 15, HEN (Henan) 20, HN (Hunan) 07, HN08 and HN10 had significantly more SNPs and homozygotes than other strains from Central China, and their most frequent mutant genotypes also differed from other strains. The clustering results indicated that HB15, HEN 20, HN07, HN08 and HN10 were genetically distinct from other strains and closely related to Guangdong strains. We also observed significant genetic variation among strains in Henan province, suggesting that some of them might have different transmission sources than those from Hubei and Hunan provinces. The results provide a basis for tracing the origin and spread of PWD in China.

This paper introduces an intelligent model that combines military expertise with the latest ad-vancements in machine learning (ML) and Geographic Information Systems (GIS) to support humanitarian demining decision-making processes. The model is based on direct input and val-idation from field decision-makers for their practical applicability and effectiveness. With a survey polling the inputs of demining experts, 95% of the responses came with an affirmation of the potential of the model to reduce threats and increase operational efficiency. It includes mili-tary-specific factors that factor in the proximity to strategic locations as well as environmental variables like vegetation cover and terrain resolution. With Gradient Boosting algorithms such as XGBoost and LightGBM, the accuracy rate is almost 97%. Such precision levels further enhance threat assessment, better allocation of resources, and around a 30% reduction in the cost and time of conducting demining operations, signifying a strong synergy of human expertise with algo-rithmic precision for maximal safety and effectiveness in demining

This paper exposes the initial part of a larger research on the impact of the automotive on human health and the quality of life and environment. After a brief introduction on the need for responsible and sustainable approaches and few questions on the subject, some considerations and statistical data are presented, based on a study of the literature on the impact of road traffic and vehicles noise and vibration on people's comfort and health and their quality of life. The research results show, based on official statistics, the significant harmful impact of noise and vibration from motor vehicles and road transport on people's health and quality of life, especially in urban areas during the day. Also, the significant increase in the number of electric and hybrid vehicles from one year to another, a reality and a necessity nowadays, and the awareness that electric vehicles are not perfectly quiet and comfortable, open new research opportunities and require the development of new standards, materials, tools, equipment and test methods in the field of NVH, in a sustained synergistic approach from all stakeholders, to meet the needs and demands of today's consumers, and to comply with existing regulations and standards on environmental protection and sustainable development.

Different types of disasters, whether natural or human character, lead to the significant loss of human lives. In the latter case, the quick action of identification of corpses and human remains is mandatory. There are a variety of protocols to identify victims, however, genetics is one of the tools that allow an exact identification of the victim. However, several factors may interfere with this identification, from the biological samples’ degradation not allowing the analysis of nuclear information, to failure to dispose of biological samples from family members. Access to certain family members could be a determinant of the proper choice of genetic markers that allow the identification of the victim, or his/her inclusion in a given genetic maternal or paternal lineage. With the new advances in the genetic field, it is expected to allow soon the identification of victims from disasters only with his/her biological postmortem samples, being possible to draw a robot portrait and its most likely physical characteristics. In all cases, genetics is the only modern tool with universal character and can be used in essentially all biological samples, giving and identification of more or less accurate statistical character, depending on whether nuclear or lineage markers are used.

As a fundamental, overall, and strategic issue facing human society, human migration is a key factor affecting the development of countries and cities given constantly changing population numbers. The fuzziness of the spatiotemporal attributes of human migration limits the pool of open-source data for human migration prediction, leading to a relative lag in human migration prediction algorithm research. This study expands the definition of human migration research, reviews the progress of research into human migration prediction, and classifies and compares human migration algorithms based on open-source data. It also explores the critical uncertainty factors restricting the development of human migration prediction. Given the effect of human migration prediction, in combination with artificial intelligence and big data technology, the paper concludes with specific suggestions and countermeasures aimed at enhancing human migration prediction research results to serve economic and social development and national strategy.

A growing number of studies focus on methods to estimate and analyze the functional connectome of the human brain. Graph theoretical measures are commonly employed to interpret and synthesize complex network-related information. While resting state functional MRI (rsfMRI) is often employed in this context, is known to exhibit poor reproducibility, a key factor which is commonly neglected in typical cohort studies using connectomics-related measures as biomarkers. We aimed to fill this gap by analyzing and comparing inter- and intra- subject variability of connectivity matrices as well as graph-theoretical measures in a large (n=1003) database of young healthy subjects which underwent four consecutive rsfMRI sessions. We analyzed both directed (Granger Causality and Transfer Entropy) and undirected (Pearson Correlation and Partial Correlation) time-series association measures and related global and local graph-theoretical measures. While matrix weights exhibit a higher reproducibility in undirected as opposed to directed methods, this difference disappears when looking at global graph metrics and, in turn, exhibits strong regional dependence in local graphs metrics. Our results warrant caution in the interpretation of connectivity studies, and serve as a benchmark for future investigations by providing quantitative estimates for the inter- and intra- subject variabilities in both directed and undirected connectomic measures.

Bacteriophages, viruses that are widespread throughout the world, are highly specific for bacteria, usually of a single species and often of a particular strain. After being discovered and isolated 100 years ago, their use, called phage therapy, was instituted in medicine two years later and quickly used around the world to treat various bacterial infections. In the West, phage therapy was overshadowed in the second half of the 20th century by antibiotic therapy, which was then thought to be the definitive solution. But because of the increase in bacterial resistance to antibiotics, the idea of using bacteriophages in medicine has been reawakened. The innumerable observations reported over the years in the literature constitute an invaluable experience. We and some of our colleagues have, in the last decade treated some patients compassionately. With the available documentation and our own experience we discuss the potential indications and limitations of phage therapy. The observation of the increasing number of therapeutic failures in the announced perspective of a post-antibiotic era, we believe, that the introduction of bacteriophages into the therapeutic arsenal seems conceivable today to two preconditions: that their production as biologic drug meets current regulatory standards and that the benefit-risk assessment was conducted in a modern setting. Phage therapy could be applied as a substitution or supplement to antibiotic therapy under multiple circumstances in different modes, precise indications and limits.

Alterations in the composition and diversity, metabolism, and products of the microbiome, and of the gut microbiome (GM), have been shown to be closely associated with the onset and progression of many human diseases, including cancer (i.e. hematological neoplasms). Acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy. Affected cases present typical alterations of GM, followed by inflammation, which contribute to its progression, response to therapy, as well as possible relapses. Recent evidence also reports that GM influences the development and functions of the newborn's hematopoietic system through the process of developmental programming during fetal life, as well as its susceptibility to the onset of onco-hematological pathologies, namely ALL. Furthermore, in children with ALL, GM has been found to vary in composition, variety, and functions during the clinical stages of ALL, and such variation may influence and predict the complications and prognosis of ALL after chemotherapy treatment or stem cell hematopoietic transplant. Here, we suggest some therapeutic strategies, which can be applied at two levels of intervention to recover the microbiome, and consequently prevent/delay ALL or arrest its progression.

Gut colonization by multidrug resistant organisms(MDROs) is a risk factor for bloodstream infections(BSI) in the early phase of Hematopoietic Stem Cell Transplantation(HSCT). We evaluated, in an exploratory study, the impact of Lactobacillus plantarum on modulation of the gut microbiome in HSCT patients colonized by MDROs. Participants were allocated to an intervention group(IG=22) who received capsules of L. plantarum(5x109 CFU) twice a day until the onset of neutropenia and a control group(CG=20). The V4 region of the 16S bacterial rRNA gene in 93 stool samples from a subset of 33 patients was sequenced(IG=20 and CG=13). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) (PICRUSt2) program was used for prediction of metagenome functions. L. plantarum had an average 86%(±11%) drug-target engagement at 43(±29) days of consumption and it was safe, tolerable and associated with an increase in the abundance of the Lactobacillales(p=0.004). A significant increase of Lactococcus and reduction of Turicibacter(p<0.05) were identified on the second-week of L. plantarum use. Although Enterococcus abundance had a greater rise in the CG (p=0,07), there were no significant differences concerning the gram-negative MDROs. No serious adverse effects was reported in the IG. . We observed greater non-significant pyruvate fermentation to propanoate I (p=0.193) relative abundance in the IG comparing with CG. L. plantarum use was safe and tolerable by HSCT patients. Although it may have impact on Enterococcus abundance and reduction of Turicibacter, it has not showed impact on Gram-Negative MDRO abundance in MDRO gram-negative colonized HSCT patients.

Gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between response to the anti-PD-1 therapy and the baseline gut microbiome in the Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy and 10 healthy subjects were recruited. Response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis, and metataxonomics of the microbiota. The Bacteroidota to Firmicutes ratio was higher, and the richness was decreased in the responders. The abundance of Prevotella copri and Bacteroides uniformis was related to the response, whereas non-responder gut microbiota was enriched with Faecalibacterium prausnitzii and Desulfovibrio intestinalis, and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption, but also gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota alongside diet were found associated with response to the therapy in the Polish population of melanoma patients.

Atherosclerosis, a complex metabolic-immune disease characterized by a chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis while atherosclerosis with its inflammatory microenvironment can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review we want to summarize the state-of-the-art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology with a positive impact on precision cardiology and cardioncology.

Purpose: The objective of this paper is to explore the association between insufficient lycopene intake and risk of periodontitis among older adults. Methods: Data analysis was conducted using data from the National Health and Nutritional Examination Survey 2009-2014. Overall, 1227 adults aged 65- to 79-years-old were investigated. Results: Overall, 48.7% of older adults in this study were classified with different levels of periodontitis and 49.1% of individuals with a form of periodontitis had insufficient dietary lycopene intake. Sufficient lycopene intake was found to be associated with a lower likelihood of severe periodontitis (OR: .33; 95% CI: 0.17-.65; p=0.002). Non-Hispanic Black (NHB) older adults were more likely to develop severe forms of periodontal disease in comparison to Non-Hispanic White (NHW) older adults (OR: 2.82, 95% CI: 1.46-5.45, p=0.003). Gender was also found to play a role in periodontitis status, with women being less likely to have severe periodontitis status, compared to men (OR: 0.27; 95% CI: 0.14-0.55; p=0.0007,). However, only NHW females were less likely to have severe periodontitis compared to NHW males (OR: 0.26; 95% CI: 0.12-0.56; p= 0.001). Conclusion: Dietary intake of lycopene associated with periodontitis disease for individuals over the age of 65; those who consume a sufficient amount of lycopene are less likely to develop severe periodontitis. In general, more men suffered from periodontitis in comparison to women. Such association also has been found between NHB with severe periodontitis. In addition, reduced risk of moderate periodontitis is associated with sufficient lycopene intake is explored in NHW, future targeted interventions using lycopene in dietary intake as a preventative measure to delay or prevent the onset of periodontal disease needs to be race and gender specific.

In this paper we explore the known connection among sustainability, resilience, and well-being within the framework of active inference. Initially, we revisit how the notions of well-being and resilience intersect within active inference before defining sustainability. We adopt a holistic concept of sustainability denoting the enduring capacity to meet needs over time without depleting crucial resources. It extends beyond material wealth to encompass community networks, labor, and knowledge. Using the Free Energy Principle, we can emphasize the role of fostering resource renewal, harmonious system-entity exchanges, and practices that encourage self-organization and resilience as pathways to achieving sustainability, both in an agent and in collectives. We start by connecting Active Inference with well-being, building on exsiting work. We then attempt to link resilience with sustainability, asserting that resilience alone is insufficient for sustainable outcomes. While crucial for absorbing shocks and stresses, resilience must be intrinsically linked with sustainability to ensure that adaptive capacities do not merely perpetuate existing vulnerabilities. Rather, it should facilitate transformative processes that address the root causes of unsustainability. Sustainability, therefore, must manifest across extended timescales and all system strata, from individual components to the broader system, to uphold ecological integrity, economic stability, and social well-being. We explain how sustainability manifests at the level of an agent, and then at the level of collectives and systems. To model and quantify the interdependencies between resources and their impact on overall system sustainability, we introduce the application of network theory and dynamical systems theory. We emphasize the optimization of precision or learning rates through the active inference framework, advocating for an approach that fosters the elastic and plastic resilience necessary for long-term sustainability and abundance.

The paper provides a comprehensive review of the recent advancements and methodologies in Human-Robot Collaboration (HRC) applied to the manufacturing assembly process. In modern manufacturing, the assembly process involves intricate and time-consuming operations, often necessitating flexible manual interventions. However, the cost and stability issues associated with manual labor highlight the need for collaborative solutions integrating humans and robots. HRC, as a viable solution, involves the joint effort of humans and robots in manufacturing tasks, presenting advantages in terms of precision, reproducibility, and cycle time. This review categorizes and discusses methodologies such as task allocation, reinforcement learning, and Cyber-Physical Systems (CPS)-based planning approaches that facilitate HRC in the assembly process. It also explores experiments and future trends to address challenges and enhance efficiency in manufacturing assembly through intelligent collaboration between humans and robots. The objective of this research is to provide insights and directions for further research in HRC to optimize manufacturing processes. By analyzing the existing state-of-the-art and presenting future prospects, this paper aims to guide researchers and practitioners toward more effective implementations of HRC in manufacturing assembly, ultimately leading to improved operational efficiency and productivity.

Therapeutic phages are primarily chosen based on their in vitro bacteriolytic activity. Although anti-phage antibodies are known to inhibit phage infection, the influence of other immune system components is less well known. An important anti-bacterial and anti-viral innate immune system that may interact with phages is the complement system, a cascade of proteases that recognizes and targets invading microorganisms. In this study, we aimed to study the effects of serum components such as complement on the infectivity of different phages targeting Pseudomonas aeruginosa. We used a fluorescence-based assay to monitor the killing of P. aeruginosa by phages of different morphotypes in presence of human serum. Our results reveal that several myophages are inhibited by serum in a concentration-dependent way, while the activity of four podophages and one siphophage tested in this study is not affected by serum. By using specific nanobodies blocking different components of the complement cascade, we show that activation of the classical complement pathway is a driver of phage inhibition. To determine the mechanism of inhibition, we produced bioorthogonally labeled fluorescent phages to study their binding by means of microscopy and flow cytometry. We show that phage adsorption is hampered in presence of active complement. Our results indicate that interactions with complement may affect in vivo activity of therapeutically administered phages. A better understanding of this phenomenon is essential to optimize the design and application of therapeutic phage cocktails.

Human Action Recognition is widely used in multiple fields to recognize activities and extract spatial and temporal information. This paper focuses on analyzing various methods as well as provides extensive knowledge of the foundational concepts of the HAR. A dataset is also very crucial for any research study so we discussed the popular dataset and its features in this paper.

Among the five human senses, light, sound, and force perceived by eye, ear, and skin, respectively are physical actions, and therefore can be easily measured and expressed as objective, univocal, and simple digital data with physical quantity. However, taste and odor molecules perceived by tongue and nose are chemical actions, it has been difficult to express them as objective and univocal digital data, since no reference chemicals can be defined. Therefore, while the recording, saving, transmitting to remote locations, and replaying human visual, auditory, and tactile information as digital data in digital devices has been realized (this series of data flow is defined as DX (digital transformation) in this review), the DX of human taste and odor information is not yet in the realization stage. Particularly, since there are at least 400,000 types of odor molecules and an infinite number of complex odors that are mixtures of these molecules, it has been considered extremely difficult to realize "human olfactory DX" by converting all odors perceived by the human olfaction into digital data. In this review, we discuss the current status and future prospects of the development of "human olfactory DX," which we believe can be realized by utilizing odor sensors that employ the olfactory receptors (ORs) that support human olfaction as sensing molecules (i.e., human OR sensor).

Human serum albumin (HSA) is the ultimate, homeostatic determinant of fluid volume (FV) in all compartments of the body. The ability to change the pressure and flow of nutrient medium to cellular structures selectively has clinical significance in almost all areas of clinical medicine. We have shown that present fluid therapy (FT) using either colloid or saline dilutes nutrients. HSA binds and delivers nutrients, a lack of HSA binding causes Albumin Binding Disease (ABD) changing both colloidal pressure and nutrients leading to symptoms of sepsis. A reduction in HSA binding can be through lack of HSA or external ligands taking up binding sites on HSA. Many diseases cause ABD when immunoglobulins, infectious particles and by products bind to HSA including COVID-19 and other bacterial diseases like streptococcus as well as metabolic and cardiac disease due to incorrect pressure and nutrients. To raise HSA binding potential and remove vulnerabilities to these diseases we propose raising HSA. We show how present methods of fluid therapy (FT) are inefficient in that control of both pressure and nutrients forms initial equilibrium in the liver. HSA production and binding to nutrients is maintained at a level by the pressure in hepatocytes with the pancreatic and adrenal hormones moderating. Glucose and Ke-tone production are critical in the management of HSA binding and control of blood, colloidal pressure, and health of cells. Ketones provide a distinct mechanism of liver to lungs-heart metabolism during hypoglycaemia and activity. This known chain of nutrition becomes critical during disease like acute respiratory distress syndrome (ARDS) when ketones may be overproduced. HSA must therefore be infused into the liver to raise HSA levels safely. We investigated the control of HSA as a product of the actions of pressure in hepatocytes and changes in pancreatic and adrenal hormones. We found that in addition to pressure during glucose abundancy HSA is re-leased with ketones on administration of insulin and consider that this mechanism retains HSA moderation. HSA can therefore be increased by increasing insulin in the presence of glucose in the correct amounts. We suggest a protocol to increase FV, blood, lymph volume by infusion of HSA, insulin, and glucose direct to the liver so that the level of HSA stabilises. We suggest this will raise all other nutrients in the new FV, blood, lymph culminating in the creation of new blood cells. We propose that in a clinical situation maintaining this protocol will alleviate the symptoms of ABD and decrease the likelihood of serious illness and death.

Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.

Ramsey’s theory (RAM) from combinatorics and network theory goes looking for regularities and repeated patterns inside structures equipped with nodes and edges. RAM represents the outcome of a dual methodological commitment: by one side a top-down approach evaluates the possible arrangement of specific subgraphs when the number of graph’s vertices is already known, by another side a bottom-up approach calculates the possible number of graph’s vertices when the arrangement of specific subgraphs is already known. Since natural neural networks are often represented in terms of graphs, we suggest to utilize RAM for the analytical and computational assessment of a peculiar structure supplied with neuronal vertices and axonal edges, i.e., the human brain connectome. We discuss how a RAM approach in neuroscientific issues might be able to locate and trace unexplored motifs shared between different cortical and subcortical subareas. Furthermore, we will describe how notable RAM outcomes, such as the Ramsey’s theorem and the Ramsey’s number, could contribute to uncover still unknown anatomical connexions endowed in neuronal networks and unexpected functional interactions among grey zones of the human brain.

The impact that new technologies have on all aspects of our lives, work, and businesses is significant and growing over time. Blockchain and artificial intelligence, among other innovative technologies, are having a profound effect on practically all business functions, including most human resources (HR) tasks. The HR sector is currently facing a variety of challenges as HR departments invest many hours in vetting candidates' applications and authenticating records to decrease the chances of imperfect recruiting. Nowadays, more technologically based processes are utilised for talent search, selection and management, as well as for accumulating, retaining, and integrating new talents into a company. These HR practices are far more effective compared to traditional methods but can also be more expensive if the transactional costs are considered. This paper consists of two parts. Following an introduction, the first part discusses the trust and confidentiality that can be attained, while the second part examines security, fraud prevention and the productivity gained from using blockchain technology in HR activities. Finally, there is a concluding section, discussing the implications of blockchain technology for firms who choose to employ it.

Not only are humans responsible for the anthropogenic causes of currently observed climate change, but we are also responsible for our responses to climate change. How we choose to respond provides important insights into our ability to collectively act in the face of threats with the unique characteristics of climate change. This communication attempts to provide an overview of some the difficulties in forging new policy directions along our coastlines in an era of climate change. It is meant as a referential framing for the research presented in this special issue. As this communication is being written, the world is gripped by a global pandemic caused by a variant of the coronavirus. There are important corollaries between the underlying characteristics of the coronavirus and the causes and effects of climate change. Seeing how the global citizenry is responding to the current epidemic provides some insight into the difficulties in fostering collective action towards climate change. As with the pandemic, the issue is not really one of understanding the problem, but rather the varying human responses to the problem. We can expect the same difficulties as we continue to confront the ever-growing problem of climate change.

In the last decade, the objectives outlined by the needs of personal robotics have led to the rise of new biologically-inspired techniques for arm motion planning. This paper presents a literature review of the most recent research on the generation of human-like arm movements in humanoid and manipulation robotic systems. Search methods and inclusion criteria are described. The studies are analysed taking into consideration the sources of publication, the experimental settings, the type of movements, the technical approach, and the human motor principles that have been used to inspire and assess human-likeness. Results show that there is a strong focus on the generation of single-arm reaching movements and biomimetic-based methods. However, there has been poor attention to manipulation, obstacle-avoidance mechanisms, and dual-arm motion generation. For these reasons, human-like arm motion generation may not fully respect human behavioural and neurological key features and may result restricted to specific tasks of human-robot interaction. Limitations and challenges are discussed to provide meaningful directions for future investigations.

As the world grapples with a pandemic with various and expanding epicenters, a flurry of medical and scientific activity has gained speed and momentum in a race to halt COVID-19. A controversial topic has been the connection between COVID-19 and the Renin-Angiotensin system (RAS). COVID-19, like Sars before it, enters by way of the Angiotensin Converting Enzyme 2 (ACE2). ACE2 is ubiquitously expressed in many tissues in the body serving as the doorway by which the virus can enter and spread causing inflammatory havoc. Demographic evidence coming out of China and other locations make it clear that the elderly and those suffering cardiovascular complications such as hypertension etc are most at risk. The connection to RAS and the demographic nature of the data coming out has led many to advance hypothesis, recommendations and even therapies based on existing RAS inhibitors and other components of the renin-Angiotensin system. It is pertinent to review the literature in the context of our understanding of the renin-angiotesnin system to allow better judgements to be made as well as lines of research initiated advancing a quick resolution to COVID-19. Covid-19 appears invincible as if dipped in the river Styx, but even Achilles had a vulnerable heel. Understanding the homeostatic balance that the coronavirus disrupts, we can discover the arrow in corona’s heel.

In this paper we have discussed the importance of human resource management in project management. As a concept human resource management emerged in 1980 [9]. It is very important to utilize resources effectively in any organization. Like triple constrains (cost, quality, scope) human resources are also considered as one of the most important factor for the success of any project. Management of human resources involve hiring experienced workers, giving appropriate training, acknowledgement about the significance of the project and the effective use of techniques and tools in order to get the project done productively with in time and budget. It becomes the responsibility of the project manager to effectively manage human resources as it is more challenging than managing other technical resources. In this paper we have also discussed the challenges that an organization faced during the management of the resources and use of some strategic human practices in order to overcome these challenges.

Identifying human actions in complex scenes is widely considered as a challenging research problem due to the unpredictable behaviors and variation of appearances and postures. For extracting variations in motion and postures, trajectories provide meaningful way. However, simple trajectories are normally represented by vector of spatial coordinates. In order to identify human actions, we must exploit structural relationship between different trajectories. In this paper, we propose a method that divides the video into N number of segments and then for each segment we extract trajectories. We then compute trajectory descriptor for each segment which capture the structural relationship among different trajectories in the video segment. For trajectory descriptor, we project all extracted trajectories on the canvas. This will result in texture image which can store the relative motion and structural relationship among the trajectories. We then train Convolution Neural Network (CNN) to capture and learn the representation from dense trajectories. . Experimental results shows that our proposed method out performs state of the art methods by 90.01% on benchmark data set.

Bartonella spp. bacteria can be found around the globe and are the causative agents of multiple human diseases. The most well-known infection is called cat-scratch disease, which causes mild lymphadenopathy and fever. As our knowledge of these bacteria grows, new presentations of disease have been recognized with serious manifestations. Not only has more severe disease been associated with these bacteria, but Bartonella species have also been discovered in a wide range of mammals and the pathogens’ DNA can be found in multiple vectors. This review will focus on some common mammalian reservoirs as well as the suspected vectors in relation to disease transmission and prevalence. Understanding the complex interactions between these bacteria, their vectors, and reservoirs as well as the breadth of infection by Bartonella around the world will help toassess the impact of Bartonellosis on public health.

The speech entailed in human voice comprises essentially para-linguistic information used in many voice-recognition applications. Gender voice-recognition is considered one of the pivotal parts to be detected from a given voice, a task that involves certain complications. In order to distinguish gender from a voice signal, a set of techniques have been employed to determine relevant features to be utilized for building a model from a training set. This model is useful for determining the gender (i.e, male or female) from a voice signal. The contributions are involved in two folds: (i) providing analysis information about well-known voice signal features using a prominent dataset, (ii) studying various machine learning models of different theoretical families to classify the voice gender, and (iii) using three prominent feature selection algorithms to find promisingly optimal features for improving classification models. Experimental results show the importance of sub-features over others, which are vital for enhancing the efficiency of classification models performance. Experimentation reveals that the best recall value is equal to 99.97%; 99.7% of two models of Deep Learning (DL) and Support Vector Machine (SVM) and with feature selection the best recall value is 100% for SVM techniques.

Blood perfusion quantification is important vital parameters in different diagnostic procedure, using infrared thermography imaging; it is reliable to use this technique as non-contact, non-invasive blood flow measurement method. Therefore, we developed a measurement protocol for blood flow over the arm's anterior surface. By using the superficial brachial and radial veins to be monitored under the impact of cold-excitation of (2 °C to 5 °C), the blood perfusion signal was detected using thermal imager of long-wave infrared spectral range (LWIR, 7μm - 14 μm). The simulation of Penne's bioheat transfer equation was performed to be compared with results obtained from the infrared thermography. Furthermore, the proposed blood flow monitoring using external adjusting of the excitation temperature, by using (cold-compress, or cold air-stream) applied to the region under testing. The signal detected resembles to the hemodynamic pulse of the superficial veins, in the definition of systolic and diastolic phases of the cardiac cycle. Moreover, statistical analysis applied to the BFIRT signals from 24 subjects to estimate the skin's mean temperature after recovery from the thermal excitation.

This study investigates the cytotoxicity profile of superparamagnetic Fe3O4-Ag decorated nanoparticles against human fibroblasts (HFF-1) and breast cancer cells (MCF-7). The nanoparticles underwent comprehensive characterization employing scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, X-ray photoelectron spectroscopy (XPS), and magnetic assays including hysteresis curves and zero-field-cooled (ZFC) plots. Notably, the nanoparticles exhibited superparamagnetic behavior as evidenced by magnetic studies. Remarkably, cytotoxicity assays demonstrated that both HFF-1 and MCF-7 cells maintained nearly 100% viability upon nanoparticle exposure. These results underscore the outstanding biocompatibility of Fe3O4/Ag decorated nanoparticles, suggesting their potential utility in biomedical applications such as drug delivery and magnetic targeting without inducing significant cytotoxic effects. This investigation advances our understanding of the behavior of nanostructured materials in biological settings and highlights their promising prospects in biomedicine.

Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigation for new therapeutic approaches is necessary. Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription-quantitative polymerase chain reaction technologies. Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 6.97 μg/mL and 4.89 μg/mL, respectively. IMBZC did not alter cell growth of normal cells HEK293. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyzes revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. In conclusion, the study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC.

This study presents a research plan that utilizes data obtained from wearable devices to identify human activities and gain insights into human behavior. We developed a model capable of classifying activities similar to human behavior and evaluated the effectiveness and generalization capabilities of this model. The data underwent initial preprocessing, including standardization and normalization. Additionally, recognizing the inherent similarities between human activity behaviors, we introduced a multi-layer classifier model. The first layer is a random forest model based on stepwise regression, which may encounter reduced accuracy for similar activities. The second layer employs a Support Vector Machine (SVM) model based on Kernel Fisher Discriminant Analysis (KFDA). KFDA is used to reduce the dimensionality of data points with potential confusion, followed by SVM for classification. The model was experimentally evaluated and applied to four benchmark datasets: UCI DSA, UCI HAR, WISDM, and IM-WSHA. The experimental results demonstrate that our approach achieved recognition accuracies of 99.71%, 98.71%, 99.12%, and 97.6% on these datasets, indicating excellent recognition performance. Furthermore, to assess the model's generalization ability, we performed K-fold cross-validation on the random forest model and utilized ROC curves for the SVM classifier. The results indicate that our multi-layer classifier model exhibits robust generalization capabilities.

Curcumin, a natural polyphenolic compound isolated from the plant Curcuma longa, is known to induce autophagy in various cancer cells, including lung cancer. In the present study, we also confirmed by LC3 immunofluorescence and immunoblotting analyses that curcumin triggers autophagy in human lung adenocarcinoma A549 cell line. In parallel with autophagy induction, gene expression of human GD3 synthase (hST8Sia I) responsible for ganglioside GD3 synthesis was markedly elevated in response to curcumin in A549 cells. To investigate transcriptional activation of hST8Sia I associated with autophagy formation in curcumin-treated A549 cells, functional characterization of the 5’-flanking region of the hST8Sia I gene was carried out using luciferase reporter assay system. Deletion analysis demonstrated that the -1146 to -646 region, which includes putative c-Ets-1, CREB, AP-1 and NF-κB binding sites, functions as the curcumin-responsive promoter of hST8Sia I in A549 cells. Site-directed mutagenesis and chromatin immunoprecipitation assay demonstrated that the NF-κB binding site at -731 to -722 was indispensable for the curcumin-induced hST8Sia I gene expression in A549 cells. Moreover, the transcriptional activation of hST8Sia I by curcumin A549 cells was strongly inhibited by compound C, an inhibitor of AMP-activated protein kinase (AMPK). These results suggest that curcumin controls hST8Sia I gene expression via AMPK signal pathway in A549 cells.

Children’s beneficial relationships with animals are well known. Companion animals, particularly dogs have become an integral part of family life and children’s material culture. Aside the proven physiological benefits there is little research about what children say about their relationships with animals and how they describe them. In this paper we bring together both horse-human and dog-human interactions, finding common ground for understanding the complexity of human development, well-being and flourishing. Dogs in schools are fast becoming a trend in helping support and enhance children’s learning as well as their social and emotional well-being. Studies have shown that the very presence of a dog can increase children’s concentration, executive function and behavior. Also, equine therapy is gaining momentum and empirical studies are showing noteworthy benefits to children and young people. However, the lack of children’s voices means that the mechanisms for these benefits are somewhat unknown and unclear. In seeking to explore this, the authors utilize a visual, sensory and diffractive ethnographic approach to illuminate and illustrate, experiment and re-enact, how the children relate, share spaces and multiple subjectivities with their classroom canine, “Ted” and companion horse “Henry”. ”Henry” is part of a programme in which youngsters care for and engage in activities with horses.

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk‐reducing salpingo‐oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT alleviated menopausal symptoms in BRCA2 carriers and women who were physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in those with a history of cancer. MBSR, on the other hand, was associated with increased intensity of most menopausal symptoms. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level while their need for extensive measures to optimize their psychological wellbeing is ongoing. Adverse effects of MBSR, which are captured in the present study imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in those women.

There is a growing body of research exploring Complementary and Alternative Medicine (CAM) for the overall population; however, few studies have examined the effectiveness and applications of CAM practices in the paediatric population. According to the World Health Organization (WHO), parent's prevalence using CAM in their dependents is estimated to be as high as 80%. This literature review identified broad, heterogeneous, and inconclusive evidence regarding CAM applications and effectiveness caused mainly by variances in sociodemographic factors and national healthcare systems differences. Additionally, a lack of consensus and polarised positions among mainstream professionals regarding the CAM mechanism of action, applications, and effectiveness were identified. This narrative review shows debatable results for most CAM therapies and their applications. However, some evidence suggests that acupuncture, Yoga, Tai Chi, and massage might benefit users' physical and mental health. Additionally, meditation's available evidence indicates that it might be only helpful in the enhancement of mental health, whereas Reiki only displays an effect on patients' perceptions of comfort. Lastly, herbal medicine was observed to have non-specific evidence to support its claim, given the diverse nature and complexity of herbal compounds and procedures. This comprehensive narrative review might offer health professionals a reference to guide their health practices towards a personalised approach, taking into account the patient's values and beliefs, both important aspects of integrated, evidence-based practice, aiming to improve the quality of the offered health services and patients' satisfaction.

Harnessing the Remarkable Bio-Remediation Potential of Vernonia spp. for the Sustainable Restoration of Hydrocarbon-Polluted Clay Soil in Ogoni Land, Nigeria This study explores the potential of utilizing Vernonia spp. for eco-friendly bio-remediation of hydrocarbon-polluted clay soil in Ogoni Land, Nigeria. The aim is to find a sustainable and effective solution that promotes the restoration of the polluted soil while minimizing the use of external additives. The process of bio-remediation can occur naturally, through natural attenuation or intrinsic bio-remediation. However, it has been observed that in certain cases, the addition of fertilizers, oxygen, or organic matter is required to enhance the effectiveness of bio-remediation. In this research, we focus on the bio-remediation potential of Vernonia spp., a native plant species known for its strong phytoremediation abilities. By harnessing the remarkable bio-remediation properties of Vernonia spp., we seek to restore the hydrocarbon-polluted clay soil in Ogoni Land in an environmentally friendly and sustainable manner. Our methodology involves conducting greenhouse experiments to assess the bio-remediation efficiency of Vernonia spp. in different soil conditions. We will analyze the soil's physical and chemical properties, as well as the degradation of hydrocarbons over time. The experimental results will provide valuable insights into the effectiveness of Vernonia spp. in removing hydrocarbon pollutants from clay soil. Through this study, we aim to develop a cost-effective and sustainable approach to restore hydrocarbon-polluted clay soil in Ogoni Land. By leveraging the natural bio-remediation potential of Vernonia spp., we can potentially reduce the reliance on external additives, thus minimizing the environmental impact associated with traditional remediation methods. The research article explores methods to promote the growth of pollution-eating microbes in order to enhance bio-remediation. Bio-remediation refers to the use of naturally occurring organisms to break down harmful substances into less toxic or non-toxic forms. In situ bio-remediation involves treating the contaminated material directly at the site, while ex-situ bio-remediation involves removing the contaminated material for treatment elsewhere. This study specifically investigates ex-situ bio-remediation techniques for hydrocarbon-contaminated clay soil. The researchers found that the application of room dry and wet blended bitter leaf showed promising results in the bio-remediation of hydrocarbons in the clay soil. Using Vernonia galamensis, a concentration as high as 0.55 ug/ml was achieved, while Vernonia amygdalina yielded a concentration as high as 0.67 ug/ml when applied at 35g and 40g respectively, based on the wet blended approach. These findings highlight the effectiveness of wet blended Vernonia species in the bio-remediation process.During the remediation process of the clay soil, the pH levels showed a trend of increasing from acidic to normal to alkaline. This can be attributed to the remediation of excessive metals present in the soil. After 40 days, the pH of the clay soil reached 6.97 when treated with 40 grams of Vernonia galamensis, and 7.00 when treated with 40 grams of Vernonia amygdalina. Interestingly, while the remediation efficiency of HC (hydrocarbon) decreased with increasing mass of Vernonia galamensis, the remediation efficiency of HC increased when using Vernonia amygdalina. These observations highlight the varying effects of different Vernonia species on hydrocarbon remediation.The highest remediation values were observed when using Vernonia galamensis at 35g and Vernonia amygdalina at 40g. These particular amounts of these Vernonia species demonstrated effective remediation of the targeted pollutants. However, in comparison to other metals, the remediation effects were relatively lower for zinc (Zn), with only approximately 0.25 ug/ml being remediated. This suggests that the remediation potential of the Vernonia species may vary depending on the specific contaminant.The higher remediation effects observed for Zn metal in the soil can be attributed to the wet blended preparation method of the Vernonia species. In contrast, the room dried Vernonia species exhibited the lowest performance in remediating the soil, with approximately 0.17 ug/ml and 0.10 ug/ml remediation for galamensis and amygdalina, respectively. Both Vernonia leaf extracts achieved a remediation of 0.5 ug/ml for chromium. The sun dried and room dried methods also showed considerable remediation potential, with values above 0.4 ug/ml. The level of significance for the model was attained at 0.05, and the r2 value was appreciable. These findings indicate the effectiveness of different preparation methods and Vernonia species in soil remediation

This paper proposes a concise literature review aimed at identifying the current body of knowledge on the adoption of Social Networks in Crisis Management. The major input is a structured research question based on the initial reading around the topic. Before the recent pan-demic, most literature has focused on local crises, with a relatively low number of exceptions. Additionally, self-organizing system are spontaneous established between people who are af-fected by a crisis. Among the identified challenges, there is the need to integrate official commu-nication by emergency agencies with citizen-generated contents in a contest of credibility and trustworthiness. In certain cases, it has been reported a lack of specific competence, knowledge, and expertise, as well as a lack of sufficient policies and guidelines in the use of Social Networks. Those challenges need to be framed by considering the classic difficulties to provide timely and accurate information, to deal with fake news, unverified or misleading information, and infor-mation overload. Bridging major gaps though advanced analytics and AI-based technology is expected to provide a key contribution to establish and safely enable in practice an effective and efficient communication, to contrast dissonant mental models, which are often fostered by Social Networks, and to enable a shared situational awareness.

Human adipose stem cell-derived extracellular vesicles (hASC-EVs) are key mediators of paracrine signaling with promising therapeutic applications. Although hASC-EVs are derived from human cells and are less immunogenic, their immunogenicity cannot be completely excluded. Here, we evaluate the immune responses of ICR and C57BL/6 mice to high doses of hASC-EVs for 10 days after injection. Lymphocyte subpopulations are analyzed using flow cytometry at 0.5, 1, 3 and 24 h post injection. In the spleen and blood of C57BL/6 mice, neutrophils sharply increased at 0.5 h and decreased at 3 h following hASC-EV treatment. We observe increased proportions of monocytes, macrophages, and natural killer cells at 3 h but returned to similar level of vehicle control at 24 h post injection in the spleen and blood of ICR mice. Although the in vivo experiments reveal different immune responses to hASC-EV treatment in C57BL/6 and ICR strains, no major changes occur in human peripheral blood mononuclear cell composition after applying hASC-EVs in vitro. In conclusion, unlike those in mice, immune responses to hASC-EVs in humans are not detectable, indicating a minimal risk of fatal side-effects from hASC-EV-based therapies.

Pericyte and their tunnelling nanotubes (P-TNTs) have been described as involved in the early phases of angiogenesis in the human normal developing brain and glioblastoma, being a common feature of combined endothelium/pericyte vessel sprouts. Based on the few data available so far about this ‘alternative’ pericyte-TNT-driven mode of angiogenesis, whose precise function in vessel growth through vascular cells communication, has still to be determined, this study aims to cast light on the regulative molecules involved in this process, governed by intimate pericyte-endothelial interactions. After considering the existence of the sprout guiding pericyte and P-TNT, as shown by pioneering ultrastructural studies as well as by more recent observations with NG2/CD146 pericyte markers and basal lamina molecules, a step-by-step profile of the process has been suggested and an investigation undertaken on ‘unconventional’, pro-angiogenic ligand/receptor systems, that may have a role aside from the canonical pathways. In this context, a possible candidate worthy of investigation is the c-KIT receptor, a member of the tyrosine kinase family of proteins, which also includes the well-known VEGFR and PDGFR. According to the obtained results showing a primary localization of c-KIT on endothelial cells and pointing out a differential distribution of the receptor on normal vs glioblastoma vessels, it seems conceivable to propose the stem cell factor/c-KIT signaling as a key factor in pericyte-TNT-driven angiogenesis, advancing this alternative mode of angiogenesis and the c- KIT pathway as possible targets for devising effective antiangiogenic therapeutic strategies.

Rutin has been reported as a potential anti-cancer agent for several decades. This study evaluated the effects of rutin on the proliferation, metastasis, and angiogenesis of MDA-MB-231 and MCF-7 breast cancer cell lines. Increasing concentrations of rutin significantly stimulated the proliferation of MDA-MB-231 and MCF-7 cells compared to controls. Wound scratch assay demonstrated that rutin had an inducing effect on the migration of the cells. In MDA-MB-231 and MCF-7 cells, rutin upregulated MKI67, VIM, CDH2, FN1, and VEGFA and downregulated CDH1 and THBS1 genes. It also increased N-cadherin and VEGFA and decreased E-cadherin and thrombospondin 1 protein expression. Our data indicated that rutin could stimulate proliferation, migration, and pro-angiogenic activity in two different breast cancer cell lines. This phytoestrogen induced invasion and migration of both cell lines by a mechanism involving the EMT process. This suggests that rutin may act as a breast cancer-promoting phytoestrogen.

In today’s world face detection is the most important task. Due to the chromosomes disorder sometimes a human face suffers from different abnormalities. For example, one eye is bigger than the other, cliff face, different chin-length, variation of nose length, length or width of lips are different, etc. For computer vision currently this is a challenging task to detect normal and abnormal face and facial parts from an input image. In this research paper a method is proposed that can detect normal or abnormal faces from a frontal input image. This method used Fast Fourier Transformation (FFT) and Discrete Cosine Transformation of frequency domain and spatial domain analysis to detect those faces.

Lymph nodes are secondary lymphoid organs that appear as bean-like nodules usually <1 cm in size, and they are localized throughout the body. Many antigen-presenting cells such as dendritic cells and macrophages reside in lymph nodes, where they mediate host defense responses against pathogens such as viruses and bacteria. In cancers, antigen-presenting cells induce cytotoxic T lymphocytes (CTLs) to react to cancer cell–derived antigens. Macrophages located in the lymph node sinus are of particular interest in relation to anti-cancer immune responses because many studies using both human specimens and animal models have suggested that lymph node macrophages play a key role in activating anti-cancer CTLs. The regulation of lymph node macrophages therefore represents a potentially promising novel approach in anti-cancer therapy.

It has recently been discovered that mere cell contact by human cytomegalovirus (CMV) particles leads to profound modulation of cellular gene expression. Reduced monocyte human leukocyte antigen (HLA-DR) expression is a novel biomarker of severity and outcome in many diseases. Modulation of CD14 protein by CMV was shown in vitro, but little is known about the phenomenon in vivo (during active cytomegalovirus disease). Therefore, we investigated monocyte CD14 and HLA-DR expression in CMV infected patients in relation to logarithmic phase of infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. After CD45/SSC gating monocyte CD14 and HLA-DR expression were determined by double-color flow-cytometry. Significant monocytosis and poor correlation between CMV replication and CD14+HLA-DR(-) cells prompted CD14 investigation. During logarithmic phase of CMV infection increased count and percentage of CD14low monocytes were observed which correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, most of CD14low monocytes are HLA-DR+. The increase of CD14low monocytes is also observed under the influence of high dose of glucocorticoids (20 mg of dexamethasone). The reduction in CD14 induced by CMV and dexamethasone indicates that the monocyte balance is disturbed between the classical and non-classical phenotype. A high percentage of CD14lowHLA-DR+ probably gives rise to adaptive and a decrease of innate immune response. In light of the logarithmic increase of viral load (with exponent between 3,23 and 5,77), high monocytosis above 1200 / µl is a hallmark of CMV replication.

Background: Cardiomyopathy is commonly observed disease that may occurs due to mutations in either susceptible genes or modifier gene. People with broad age group are affected either attributable to spontaneous or inherited mutations of these genes. Various gene mutations are reported so far but only few of them were studied in detail. Methods: In the current study, we evaluated epidemiological variables like age, sex, familial status, parental consanguinity. We also described specific clinical symptoms associated with the cardiomyopathy condition in Indian population. Results: Our studies on mutation screening of phospholamban gene revealed two transitions (4880 C/T, 4887 T/G) in 5’ flanking region which might cause inherited dilated cardiomyopathy with refractory congestive heart failure are We further deliberated the gene polymorphism of renin angiotensin system gene angiotensin-1-converting enzyme as an associated marker/ modifier in cardiomyopathy patients and their family members. Conclusions: Information on epidemiological, clinical statistics, phospholamban gene mutation analysis and angiotensin-1-converting enzyme gene polymorphism is essential to guide the successful execution for future therapies and benefits us to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

Mercury contamination in the Amazon is a significant public health concern arising from both natural sources and intensive mining activities in the region. This metal is used to separate Au from sediments, forming an amalgam that facilitates the extraction of precious metals. Accordingly, this study aimed to address the following question: What is the impact of mining on mercury contamination in the animal and human populations of the Amazon? The overall objective of this study was to conduct a systematic review of the existing literature to identify gaps in geographic coverage and assess the impact of Hg contamination on human and animal populations in the Amazon region. Our hypothesis was that higher mercury concentrations in tissue samples would be found closer to the mining areas. We employed the PECO and PRISMA-ScR protocols to collect articles published between 2017 and 2023, selected based on criteria representing projected points on a map within the biogeographic boundaries of the Amazon. Mercury concentrations increase with trophic levels, reaching high values of 3.7 µg/g in the muscles of predatory fish and 34.9 µg/g in human hair. The average level of mercury in humans exceeds 6 µg/g, surpassing tolerance levels. Although mining regions show high concentrations of Hg, the highest incidence was observed among populations with fish-based diets. Research on fish is crucial for assessing the risk to human health, given that fish are the main source of protein in the region.

Forensic anthropologists play a key role in skeletal trauma analysis and commonly use macroscopic features to distinguish between trauma types. However, this approach can be challenging, particularly in cases of highly comminuted or incompletely recovered fractures. Histological analysis of microscopic fracture characteristics in fractured bones may thus help provide additional information on trauma type and bone fracture biomechanics in general. This study analysed the extent of microcrack damage to osteons in long bones with blunt force trauma (BFT) and gunshot trauma (GST), from both traumatic death cases and post-mortem experimental fractures. We identified four types of osteonal damage (OD). In traumatic death cases, OD affecting the inside of the osteon and compromising the Haversian canal (type 1) was found to be indicative of BFT. Moreover, OD affecting the cement line (type 3) and interstitial lamellae (type 4) was more common in the GST samples. OD affecting the inside of the osteon without compromising the Haversian canal (type 2) was not found to be indicative of either trauma type. In cases of experimental fractures, our study revealed that post-mortem fractures in dry bone samples featured the highest amount of OD, particularly of type 4. This study also found that the experimentally produced GST featured similar OD pattern to GST death cases. These findings support our hypothesis that there are distinct osteonal damage patterns in human long bones with BFT and GST, which are of relevant value for trauma analysis in forensic anthropology.

Human Pose Estimation (HPE) is a technique in computer vision and AI for detecting and tracking human body parts and poses from images or videos. Widely used in augmented reality, animation, fitness applications, and surveillance, HPE methods using monocular cameras are highly versatile due to their applicability in standard video and CCTV footage. These methods have evolved from 2D to 3D pose estimation. However, current 3D HPE methods trained on laboratory-based motion capture data encounter challenges such as limited training data, depth perception ambiguity, left/right switching, and issues with occlusions when applied in real-world environments. This study compares two representative 3D HPE methods by assessing their strengths and weaknesses with real-world videos. Then, we propose data processing techniques to eliminate and correct anomalies like left/right inversion and false detections of joint positions in daily life motions. Finally, we obtain joint angle trajectories using an optimization method based on a 3D humanoid simulator, taking as input the joint coordinate data corrected by applying the proposed human joint data processing technique. The efficacy of the proposed 3D HPE method is verified by applying it to three-dimensional freehand gymnastics exercises and comparing the joint angle trajectories during the motion.

We review our theory of interdependence applied to autonomous human-machine teams, with which we have made several generalizations based on theory that have led to new discoveries, compared to social science which is struggling to break free of its validation crisis, but also has no generalizations to new discoveries with human teams, let alone to human-machine teams. In this invited article, based around the stability of a team, of our discoveries, we review the uncertainty between a team's structure and its performance, our first finding. We generalize that finding to deception, vulnerability, innovation and fittedness. From there, our next generalization is to the quantum likeness of interdependence and quantum mechanics; we move on to Shannon holes, knowledge, and conclude with the value of debate and the need for boundaries to contain debate, to reduce interference, and to protect states of interdependence. After the introduction, we extend our model in Section 2 to energy and time, and we close with a brief review of innovation and future plans.

The retrospective noninterventional study investigated the kinetic energy of video images of 18 fertilized eggs (7 were normal and 11 were abnormal) recorded by a time-lapse device leading up to the beginning of the first cleavage. The norm values of cytoplasmic particles were measured by the optical flow method. Three phases profile for normal cases were found regarding the kinetic energy that were 2.199×10⁻²⁴±2.076×10⁻²⁴, 2.369×10⁻²⁴±1.255×10⁻²⁴, and 1.078×10⁻²⁴±4.720×10⁻²⁵ (J) for the phases 1, 2, and 3, respectively. In phase 2, the energies were 2.369 × 10⁻²⁴ ± 1.255 × 10⁻²⁴ and 4.694 × 10⁻²⁴ ± 2.996 × 10⁻²⁴ (J) (mean ± SD, P = 0.0372), and the time required was 8.114 ± 2.937 and 6.018 ± 5.685 (H) (P = 0.0413) for the normal and abnormal cases, respectively. The kinetic energy change was considered a condition for applying the free energy principle that states that, for any self-organized system to be in equilibrium in its environment, it must minimize its informational free energy. The kinetic energy while interpreting it in terms of the free energy principle suggesting clinical usefulness would further our understanding of the phenomenon of fertilized egg development with respect to the birth of human life.

Diffuse intrinsic pontine glioma (DIPG), affecting children aged 4-7 years, is a rare, aggressive tumor that originates in the pons and then spreads to nearby tissue. DIPG is the leading cause of death for pediatric brain tumors due to its infiltrative nature and inoperability. Radiotherapy has only a palliative effect in stabilizing symptoms. In silico and preclinical studies identified ONC201, as a cytotoxic agent against some human cancer cell lines, including DIPG ones. Single crystal X-ray analysis of the complex of the human mitochondrial caseinolytic serine protease type C (hClpP) and ONC201 (PDB ID: 6DL7) allowed to identify hClpP as its main target. Hyperactivation of hClpP causes damage to mitochondrial oxidative phosphorylation and cell death. In some DIPG patients, receiving ONC201, an acquired resistance was observed. In this context, a wide program was initiated to discover original scaffolds for new hClpP activators to treat ONC201-non-responding patients. Harmaline, a small molecule belonging to the chemical class of β -carboline, was identified through Fingerprints for Ligands and Proteins (FLAP), a structure-based Virtual Screening approach. Molecular dynamics simulations and a deep in vitro investigation showed interesting information on the interaction and activation of hClpP by harmaline.

Advances in biomimetic triboelectric nanogenerators (TENGs) have significant implications for electronic skin (e-skin) and human-machine interaction (HMI). Emphasizing the need to mimic complex functionalities of natural systems, particularly human skin, TENGs leverage triboelectricity and electrostatic induction to bridge the gap in traditional electronic devices' responsiveness and adaptability. The exploration begins with an overview of TENGs' operational principles and modes, transitioning into structural and material biomimicry inspired by plant and animal models, proteins, fibers, and hydrogels. Key applications in tactile sensing, motion sensing, and intelligent control within e-skins and HMI systems are highlighted, showcasing TENGs' potential in revolutionizing wearable technologies and robotic systems. This review also addresses the challenges in performance enhancement, scalability, and system integration of TENGs. It points to future research directions, including optimizing energy conversion efficiency, discovering new materials, and employing micro-nanostructuring techniques for enhanced triboelectric charges and energy conversion. The scalability and cost-effectiveness of TENG production, pivotal for mainstream application, are discussed along with the need for versatile integration with various electronic systems. The review underlines the significance of making bioinspired TENGs more accessible and applicable in everyday technology, focusing on compatibility, user comfort, and durability. Conclusively, it underscores the role of bioinspired TENGs in advancing wearable technology and interactive systems, indicating a bright future for these innovations in practical applications.

Angiotensin-converting enzyme (ACE)1, ACE2, and renin are components of the renin-angiotensin system (RAS), which regulates blood pressure. ACE2 also serves as a receptor for SARS-CoV-2 and together with the transmembrane serine protease 2 (TMPRSS-2), mediates viral cell-endocytosis. As the placenta expresses all these factors, it acts as a target for SARS-CoV-2 and also as a source of blood pressure modulators. An ACE1/ACE2 ratio imbalance can lead to RAS dysregulation and a bad prognosis in COVID-19 patients. Calcitriol, the vitamin D active metabolite, negatively regulates RAS, reduces inflammation, and enhances antiviral immunity, thereby playing a protective role against COVID-19 severity. Placental calcitriol has been inversely correlated with maternal blood pressure; however, its regulatory role in RAS components and SARS-CoV-2 receptors within the fetomaternal unit has been barely explored. Therefore, we investigated the effects of calcitriol on placental RAS components. Calcitriol downregulated ACE1, ACE2, TMPRSS-2, and renin gene expression in cultured syncytiotrophoblasts and the extravillous trophoblast cell line HTR-8/SVneo. The ACE1/ACE2 ratio was also downregulated by calcitriol. Similar results were obtained in syncytiotrophoblasts treated with calcidiol, the precursor of calcitriol. Altogether, these results support that vitamin D is essential in restricting SARS-CoV-2 placental infection while helping to regulate maternal blood pressure during pregnancy.

The level of air pollution by nano and microparticles raises rapidly. One of the methods of human exposure to nanoparticles is through inhalation. Indoor environments contain airborne plastic particles, primarily from synthetic textiles, leading to unintended inhalation or occupational exposure. In outdoor environments, exposure could happen through breathing in contaminated aerosols from ocean waves or airborne fertilizer particles from dried wastewater treatments. Airborne particles affect human health in various ways and they also act directly on the epithelium and its mucus layer after deposition in the mouth and respiratory system. Exposure via ingestion to microplastics present in the various environmental compartments may occur either directly or indirectly via the food chain or drinking water. The aim of the study was to determine the influence of plastic microparticles on the rheology of mucus and saliva, and thus on their functioning. The artificial mucus and saliva, as and plastic nanoparticles (namely PS – polystyrene and PE - polyethylene) were used in experiments. The rheological properties of saliva and mucus were determined with the use of an oscillatory rheometer, at various temperatures (namely 36.6 C and 40 C, what corresponds to the case of healthy and ill human) The results were compared with those obtained for pure saliva and mucus. The influence of the presence of the particles on the parameters of the constituitive viscosity equations was studied. The presence of plastic micro- and nanoparticles in the saliva and mucus may interfere with their physiological functions.

The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. It has been shown that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on way to an endemic form, however the threat of the virus is more for susceptible (older people and immunocompromised) people. The human body has more bacterial cells than its own, thus making us more bacterial than humans. As a consequence, the bacteriomes in the human body heavily influence human health and disease. The bacteriomes in the body and the immune system seem to be in constant association during bacterial and viral infections. In this review, we identify various bacterial spp. in major bacteriomes (oral, nasal, lung, and gut) of the body in healthy humans and compare them with dysbiotic bacteriomes of COVID-19 patients. We try to identify key bacterial spp. that have a positive effect on the functionality of the immune system and human health. These select bacterial spp. could be used as potential probiotics to counter or prevent COVID-19 infections. In addition, we try to identify key metabolites produced by probiotic bacterial spp. that could have potential anti-viral effects against SARS-CoV-2. These metabolites could be subject to future therapeutic trials to determine their anti-viral efficacy.

In this review, we present several extracellular proteases, enzymes, membrane permeases, and transporters as essential accessories proteins for nutrient assimilation, conservation, and transportation as determined by nutrient repletion or depletion. As an obligate aerobic pathogen, it is crucial for invading Cryptococcus (C.) neoformans to negotiate its adaptation to human internal organs like the brain and spinal cord, where the oxygen level is low compared to peripheral organs. Besides, essential metals like copper and iron are important cofactors to functional proteins; however, these metals are not usually freely available to invading human pathogens. Again, the phagolysosome low pH with glucose paucity, internal temperature, immune response, and complex extracellular matrixes are challenging environments that must be circumvented by C. neoformans in the systemic tissues for survival, adaptation, and infection in humans. We review extensive works on several extracellular proteases, enzymes, membrane permeases and transporters orchestrated by different transcription factors and present these proteins as weapons needed to outwit systemic resistance to invading pathogens. Lastly, we examine the extracellular secretory vesicles of C. neoformans as “an exosomal virulence bag” that harbours urease, laccase, phosphatase, and capsular components as additional secretory weapons for tissue invasion and persistence.

Background: Diffuse glioma is a malignant human brain cancer that is hard to overcome. This represents a high risk of mortality. The current challenge is limited to the control of tumor progression and survival improvement. Immunotherapy consists of stimulating the immune system in order to eliminate the non-self-elements that damage the human body, including cancer cells. However, in human glioma, the current immunotherapeutic targets did not show significant benefit. In this study, we aimed at evaluating the expression and potential role of a new immunosuppressive molecule, TIGIT in glioma patients. Methods: A cohort of 667 patients from the TCGA database along with a cohort of 53 Moroccan patients, were analyzed in order to assess the role of TIGIT in human glioma progression and to estimate whether blocking this immune checkpoint molecule would be of a potential therapeutic benefit. Real time RT-PCR from fresh human biopsies and RNAseq data analysis were performed in this study. Results: Our results showed that high expression of TIGIT had prognostic value with some known clinical glioma risk factors such as sex, age and IDH mutation status. High expression of TIGIT was positively associated with advanced grades of glioma. Interestingly, elevated rates of TIGIT were significantly associated to elevated levels of other inhibitory immune checkpoint molecules (PD-1, VISTA and Tim-3) in human glioma patients, also TIGIT showed strong association with Treg cell-secreted cytokines (TGF-beta and IL-10), indicating the high potential involvement of TIGIT in immunosuppression in human glioma. Moreover, we reported that high TIGIT expressing CD8 T-cells displayed more surface inhibitory molecules and, elevated levels of Treg cells and FoxP3 were linked to higher rates of TIGIT, supporting the likely involvement of TIGIT in the suppression of the intra-tumoral immune cells. Finally, high expression of TIGIT was significantly linked to advanced histological subtypes of glioma and was associated with poor overall survival in human glioma. Conclusion: TIGIT blockade might be of valuable therapeutic benefit in patients with advanced glioma.

Background: When we talk about zoonoses, it is undeniable that we have a human and animal population that has been isolated in studies over time. Besides human and animal health, zoonoses also impact the economy and society. Therefore, the integration of the analysis in this area is essential to optimize resources in public health decisions. We have new challenges in public health that we need to overcome in a more comprehensive method such as One Health. For better measures in public health, the dual burden of zoonoses seems a logical way to determine the integral impact of such diseases in society and thus take better measures to prevent and reduce the impact of these diseases. Methods: We follow the guidelines for “Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). We search human and animal zoonoses on Embase, Ovid Medline, Scopus, Web of Science, and Google Scholar, from an unrestricted period until November 2021. For the search, we consider the Disability Adjusted Life Years (DALYs) for the human zoonotic burden and the animal zoonotic burden in monetary terms. A librarian collaborates to optimize the search string for the databases, and two reviewers screen eligible articles (first by title, then by abstracts, and finally, by full-text assessment.) For the analysis, we aim to convert the burden of zoonoses of all selected studies into the zoonotic Disability Adjusted Life Years (zDALYs) – including the human and animal components. Discussion: The study results will provide information on published studies that have accounted for the dual burden of zoonoses (both human and animal health aspects.) In addition, the synthesis of the available literature will address the knowledge gap in this area in order to know to what extent it is possible to convert the burden of human zoonoses to the animal burden of zoonoses and integrate them into a more comprehensive approach (dual burden of zoonoses.)

Placental hypervascularization has been reported in pregnancy-related pathologies such as gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate receptor) in human placental endothelial cells and hypothesized that succinate-SUCNR1 axis might play a role in the placental hypervascularization reported in GDM. We measured significantly higher succinate levels in placental tissue lysates from women with GDM relative to matched controls. In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential link between succinate-SUCNR1 axis and placental angiogenesis. In our in-vitro experiments, succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs) such as proliferation, migration and spheroid sprouting. These results were further validated in fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation. VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet, knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the migratory ability and wound healing in response to succinate. In conclusion, our data underline SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced placental angiogenesis in GDM.

Most hair relaxers or straighteners used for Afro-textured hair have a pH above 11. This pH, according to international occupational health and safety guidelines, is corrosive to the skin. Further, relaxers are associated with a 3-6 times increased risk of alopecia. The skin also gets into contact with these hair straightening products during application resulting in skin irritation. Using animals as test subjects to determine these products' potential risk and safety margin is standard practice; however, with the European Union (EU) ban on animal testing, the testing method needs to be replaced by newer in vitro laboratory technologies. This study used previously and newly established in vitro cell-based technologies and human-skin derived cells as laboratory models to evaluate relaxer-induced cytotoxicity. These technologies include endpoint (MTT, CCK-8 and flow cytometry) and real-time assays (real-time cell analysis (RTCA) and extracellular flux analysis). Cellular toxicity was evident following treatment of keratinocytes and fibroblasts with acceptable concentrations of thioglycolic acid (TGA, HSCH2COOH), ammonium bisulphite (NH4HSO3), lithium hydroxide (LiOH) and sodium hydroxide (NaOH) based relaxers. Real-time assays showed significant reductions (P<0.001) in cell index and ATP production following treatment of keratinocytes with as little as one-tenth of the acceptable concentrations. Increased apoptosis (47.9%, 58.0%, 76.7% and 80.3%) also occurred in cells after treatment with TGA, NH4HSO3, NaOH and LiOH, respectively. In conclusion, this study demonstrated that using skin cells in conjunction with advanced cell-based technologies could serve as alternatives to laboratory animals for accessing the toxicity margin of hair relaxers, straighteners and other cosmetics.