Victor Vasarely’s (1906-1997) important legacy to the study of human perception is brought to the forefront and discussed. A large part of his impressive work conveys the appearance of striking three-dimensional shapes and structures in a large-scale pictorial plane. Current perception science explains such effects by invoking brain mechanisms for the processing of monocular (2D) depth cues. Here in this study, we illustrate and explain the local effects of 2D color and contrast cues on the perceptual organization in terms of figure-ground assignments, i.e. which local surfaces are likely to be seen as “nearer” or “bigger” in the image plane. Paired configurations are embedded in a larger, structurally ambivalent pictorial context inspired by some of Vasarely’s creations. The figure-ground effects these configurations produce reveal a significant correlation between perceptual solutions for “nearer” and “bigger” when no other monocular depth cues are given in the image. In consistency with previous findings on similar, albeit simpler visual displays, a specific color may compete with luminance contrast in resolving the planar ambiguity of a complex pattern context. Vasarely intuitively understood, and successfully exploited, this kind of subtle context effect in his art, well before empirical investigations had set out to study and explain their genesis in terms of information processing by the visual brain.

Programmed cell death protein 1 (PD-1) is a biomarker on the surface of cells that has a role in promoting self-tolerance by suppressing the inflammatory activity of T cells. In this work, one peptide of PD-1 was used as the template in molecular imprinting. The magnetic peptide-imprinted poly(ethylene-co-vinyl alcohol) composite nanoparticles (MPIP NPs) were characterized by dynamic light scattering (DLS), high-performance liquid chromatography (HPLC), Brunauer-Emmett-Teller (BET) analysis and superconducting quantum interference device (SQUID) analysis. Natural killer-92 (NK-92) cells were added to these composite nanoparticles and then incubated with human hepatoma (HepG2) cells. The viability and apoptosis pathway of HepG2 were then studied using cell counting kit-8 (CCK8) and the quantitative real-time polymerase chain reaction (qRT-PCR), respectively. These nanoparticles were found significantly enhance the activity of natural killer cells toward HepG2 cells by increasing expression of NK-kB, caspase 8 and especially caspase 3.

When using computer-aided translation systems in a typical, professional translation workflow, there are several stages at which there is room for improvement. The SCATE (Smart Computer-Aided Translation Environment) project investigated several of these aspects, both from a human-computer interaction point of view, as well as from a purely technological side. This paper describes the SCATE research with respect to improved fuzzy matching, parallel treebanks, the integration of translation memories with machine translation, quality estimation, terminology extraction from comparable texts, the use of speech recognition in the translation process, and human computer interaction and interface design for the professional translation environment. For each of these topics, we describe the experiments we performed and the conclusions drawn, providing an overview of the highlights of the entire SCATE project.

Abstract Introduction: Visual perceptual skills are essential for independent participation in self-care tasks, educational, work and leisure time activities. The effect of HIV on the visual perceptual skills is not well understood among children in low resource settings like Zimbabwe. Methods: A cross sectional comparative study was done with 30 children living with HIV and 30 children living without HIV residing in Harare urban area. The TVPS-3 was used to assess their visual perceptual skills. SPSS version 22, STATISTICA 13 and Microsoft 2016 were used for data analysis. Results: Both groups of children had mean percentile ranks below 50 on their TVPS-3 scores. Children without HIV generally performed better than those with HIV but the difference was not statistically significant in most cases. Through univariate analysis, only performance on Spatial Relations significantly differed between the two groups. Both groups had lowest scores in Basic visual perceptual skills. Age and school grade were the independent predictors of the children’s performances in the study. Conclusion: There is need for Occupational therapy services in public primary schools and in the pediatric Opportunistic Infections clinics in hospitals to be part of the health team which caters for children with visual perceptual challenges.

To cope with a projected global population increase from 7.2 bn to 9.6 bn by 2050, many more cities must be built. Although there are great benefits to modern urban living, there also great costs, such as the seemingly unstoppable rise in Type 2 diabetes, obesity, coronary issues and various cancers. The new towns should be designed to contain or constrain the epidemic of those ‘Western Lifestyle Diseases’ that currently plagues today’s cities. But how might this be achieved? It is suggested here that a greater understanding of human evolution combined with the potency of the ‘Palaeolithic genome’ holds the key to our future urban wellbeing. Consequently, a new paradigm is suggested that underpins positive forward thinking on townplanning and city lifestyles to create healthier urban environments. This builds directly on the ‘Evolutionary Determinants of Health’ programme initiated at University College London (UCL). A four-stage model is proposed that integrates and develops both evolutionary-concordant personal and institutional health behaviours with appropriately reconfigured town-planning and building regulations. When integrated, these strands could deliver a healthier urban culture within greened, active townscapes by proactively constraining or eliminating some of the key underlying causes of the so-called ‘Western Lifestyle Diseases’.

Here we report the preparation and characterization of a novel biomimetic toothpaste containing morphogenetically active amorphous polyphosphate (polyP) microparticles enriched with retinyl acetate (“a-polyP/RA-MP”). The spherical microparticles (average size, 550±120 nm), prepared by co-precipitating sodium-polyP with calcium chloride and supplemented with retinyl acetate, were incorporated into a basis toothpaste at a final concentration of 1% or 10%. The paste containing “a-polyP/RA-MP” significantly increased the growth of human mesenchymal stem cells (MSC), compared to a commercial toothpaste which acts rather inhibitory and the paste without polyP and retinyl acetate. qRT-PCR experiments revealed that the retinoid causes an induction of the expression of the MSC marker genes for osteoblast differentiation encoding collagen type I and alkaline phosphatase. On the other hand, the polyP ingredient, supplied as Zn-polyP microparticles (“Zn-a-polyP-MP”) strongly inhibited the growth of the cariogenic bacterium Streptococcus mutans. We demonstrate that the amorphous polyP-containing toothpaste, enriched with retinyl acetate, efficiently repairs both cracks/fissures and carious lesions in the tooth enamel, and reseals dentinal tubules, already after a 5 d treatment (brushing) of teeth twice daily for 5 min as examined by SEM and quantitative EDX analysis. The stability of the occlusion of dentin cracks even turned out to resist against short high power sonication treatment. Our results demonstrate that the novel toothpaste prepared here, containing amorphous polyP and retinyl acetate, is particularly suitable for prevention/repair of (cariogenic) damages of tooth enamel/dentin and for treatment of dental hypersensitivity.

Access to medical care is a global issue. Technology-aided approaches have been applied in addressing this. Interventions have however not focused on medical diagnosis as a fully automated procedure and available applications employ mainly text-based inputs rather than conversation in natural language. We explored the utility of ontology-based chatbot technology for the design of intelligent agents for medical diagnosis through a systematic review of the most recent related literature. English articles published in 2011-2016 returned 233 hits which yielded 11 relevant articles after a 3-stage screening. Findings showed that the creation of expert systems had been the focus of many the studies which utilize the physician-system-patient framework with system training based mostly on expert knowledge for designing web- or mobile phone-based applications that serve assistive purposes. Findings further indicated gaps in the design and evaluation of more effective systems deployable as standalone applications, for example, on an embodied robotic system. The need for technology supporting the physical examination part of diagnosis, connection to data sources on patients’ vitals and medical history are also indicated in addition to the need for more qualitative work on natural language-based interaction. The system should be one that is continuously learning. Future works should also be directed towards the building of more robust knowledge base as well as evaluation of theory-based diagnostic methodological options

Artificial Intelligence (AI) is poised to revolutionize the architectural design and energy management of green buildings, offering significant advancements in sustainability and efficiency. This paper explores the transformative impact of AI on improving energy efficiency and reducing carbon emissions in commercial buildings. By leveraging AI algorithms, architects can optimize building performance through advanced environmental analysis, automation of repetitive tasks, and real-time data-driven decision-making. AI facilitates precise energy consumption forecasting and integration of renewable energy sources, enhancing the overall sustainability of buildings. Our study demonstrates that AI can reduce energy consumption and CO2 emissions by approximately 8% and 19%, respectively, in typical mid-size office buildings by 2050 compared to conventional methods. Further, the combination of AI with energy efficiency policies and low-emission energy production is projected to yield reductions of up to 40% in energy consumption and 90% in CO2 emissions. This paper provides a systematic approach for quantifying AI's benefits across various building types and climate zones, offering valuable insights for decision-makers in the construction industry.

Despite the potential benefits of generative Artificial Intelligence (genAI), concerns about its psy-chological impact on medical students, especially with regard to job displacement, are apparent. This pilot study, conducted in Jordan during July–August 2024, aimed to examine the specific fears, anxieties, mistrust, and ethical concerns medical students could harbor towards genAI. Using a cross-sectional survey design, data were collected from 164 medical students studying in Jordan across various academic years, employing a structured self-administered questionnaire with an internally consistent FAME scale—representing Fear, Anxiety, Mistrust, and Ethics and comprising 12 items, with three items for each construct. The results indicated variable levels of anxiety towards genAI among the participating medical students: 34.1% reported no anxiety about genAI role in their future careers (n = 56), while 41.5% were slightly anxious (n = 61), 22.0% somewhat anxious (n = 36), and 2.4% extremely anxious (n = 4). Among the FAME constructs, Mistrust was the most agreed upon (mean: 12.35±2.78), followed by Ethics construct (mean: 10.86±2.90), Fear (mean: 9.49±3.53), and Anxiety (mean: 8.91±3.68). Sex, academic level, and Grade Point Average (GPA) did not significantly affect the students’ perceptions of genAI. However, there was a notable direct association between the students’ general anxiety about genAI and elevated scores in the Fear, Anxiety, and Ethics constructs of the FAME scale. Prior exposure to genAI and its previous use did not significantly modify the scores of the FAME scale. These findings highlighted the critical need for refined educational strategies to address the integration of genAI in medical training. The results demonstrated a pervasive anxiety, fear, mistrust, and ethical concerns among medical students regarding the deployment of genAI in healthcare, indicating the necessity for curriculum modifi-cations that focus specifically on these areas. Interventions should be tailored to increase genAI familiarity and competency, which would alleviate apprehension and equip future physicians to engage with this inevitable technology effectively. The study also highlighted the importance of incorporating ethical discussions into medical courses to address mistrust and concerns about the human-centered aspects of genAI. Conclusively, the study calls for a proactive evolution of medical education to prepare students for AI-driven healthcare practices shortly to ensure that physicians are well-prepared, confident, and ethically informed in their professional interactions with genAI technologies.

This research addresses the challenge of integrating fairness considerations into optimization problems, focusing on the development of multi-objective optimization techniques that balance traditional efficiency metrics with fairness constraints. In many algorithmic decision-making processes, optimizing for efficiency alone can inadvertently perpetuate or exacerbate biases, leading to inequitable outcomes. This study explores how data analysis and machine learning can be leveraged to identify and mitigate these biases, ensuring that optimization models yield both efficient and fair solutions. The research presents a framework for incorporating fairness constraints into multi-objective optimization, utilizing various fairness metrics such as demographic parity, equal opportunity, and disparate impact. It investigates the application of this framework across different domains, including resource allocation in healthcare systems, loan approvals in finance, and personalized learning platforms in education. By analyzing real-world data sets, the study demonstrates how fairness-aware optimization can lead to more equitable outcomes without significantly compromising efficiency. Empirical results from case studies show that multi-objective optimization with fairness constraints can effectively balance the trade-off between efficiency and equity. The research also discusses the computational challenges and ethical considerations associated with implementing fairness constraints in optimization models. Strategies for addressing these challenges, such as regularization techniques and fairness-aware machine learning algorithms, are evaluated and presented. Findings highlight the importance of incorporating fairness into optimization processes to prevent algorithmic biases and promote social equity. The study concludes with practical recommendations for policymakers, practitioners, and researchers on adopting fairness-aware optimization techniques to ensure that algorithmic decision-making processes are both efficient and just.

The next-generation "Industrial Internet of Things" (IIoT) will support "Machine-to-Machine" (M2M) communications for smart Cyber-Physical-Systems and Industry 4.0, and require guaranteed cyber-security. This paper explores hardware-enforced cyber-security for critical infrastructures. It examines a Quantum-Safe "Software-Defined Deterministic IIoT" (SDD-IIoT), with a new forwarding-plane (sub-layer-3a) for deterministic M2M traffic flows. A "Software-Defined-Networking" (SDN) control-plane controls many "SDD Wide Area Networks" (SDD-WANs), realized with FPGAs. The SDN control-plane provides an "Admission-Control/Access-Control" system for network-bandwidth, using collaborating Artificial Intelligence (AI) rule-based "Zero Trust Architectures" (ZTAs). Hardware-enforced access-control eliminates all congestion, BufferBloat, and DoS/DDoS attacks in the forwarding-plane, reduces buffer-sizes by 100,000+ times, and supports ultra-reliable and uItra-low-latency communications in the SDD-WANs. The SDD-WANs can: (i) Encrypt/Authenticate M2M flows using Quantum-Safe ciphers, to withstand attacks by Quantum Computers; (ii) Implement "Guaranteed Intrusion Detection Systems" in FPGAs, to detect cyber-attacks embedded within billions of IIoT packets/second; (iii) Provide guaranteed immunity to external cyber-attacks against critical infrastructure, and exceptionally-strong immunity to internal cyber-attacks; (iv) Save $US100s of billions annually by exploiting FPGAs; and (v) Enable "Quantum Key Distribution" (QKD) Networks by providing a programmable forwarding-plane with "authenticated classical channels" and full-immunity to DoS/DDoS attacks. Extensive experimental results for an SDD-WAN over the European Union are reported.

Artificial intelligence (AI) and 3D printing (3DP) play critical roles in what is known as the 4th Industrial Revolution by developing data- and machine-intelligence-based integrated production technologies. This shift has led to increasingly complex design requirements and fabrication methods, posing several challenges for implementing design, fabrication process, and architectural quality standardization. This paper systematically reviews AI techniques applied in diverse stages of 3DP production in architecture. The research goals are to (1) offer a comprehensive critical analysis of the body of literature; (2) identify and categorize approaches to integrating AI in the production of 3D-printed structures; (3) identify and discuss challenges and opportunities of AI integration in architectural production of 3DP structures; and (4) identify gap and provide recommendations for future research. The findings indicate that topics related to AI applications are current and trending, receiving increasing attention from researchers in general and particularly those working in machine and deep learning, artificial neural networks, and pattern recognition. However, the potential of the application of AI in architectural production using additive manufacturing still needs to be explored. Considering this, the paper emphasizes the necessity of redefining traditional field boundaries and opening new opportunities in the sector.

Human Pose Estimation (HPE) is a critical technology in computer vision with diverse applications ranging from healthcare to sports analysis. This project presents a method for detecting the 2D stance of multiple persons in an image using a nonparametric representation known as Part Affinity Fields (PAFs). By leveraging the first 10 layers of the VGG-19 convolutional neural network and training on the COCO dataset, our model effectively identifies and associates key points of the human body.The architecture employs a two-branch system that jointly learns part locations and their associations through sequential prediction. This enables the model to maintain real-time performance while achieving high accuracy, regardless of the number of persons in the image. To enhance accessibility, we developed a mobile application using Flutter and TensorFlow Lite, allowing real-time pose estimation via a mobile device’s front camera. The app provides immediate feedback on physical exercises and yoga poses, making it an invaluable tool for fitness enthusiasts and healthcare professionals. Visual outputs such as heatmaps and PAFs confirm the model’s capability to accurately localize and connect key points. Despite potential challenges such as data quality and hyperparameter tuning, the results indicate that our approach is both reliable and practical for real-world deployment. This project not only advances the state-of-the-art in HPE but also opens up possibilities for future enhancements, including integrating 3D pose estimation and applying the technology in augmented and virtual reality applications.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

The human mandible's cancellous bone, which is characterized by its unique porosity and directional sensitivity to external forces, is crucial for sustaining biting stress. Traditional CAD models fail to fully represent bone's anisotropic structure and thus depend on simple isotropic assumptions. For our research, we use the latest versions of nTopology and Creo Parametric software to make biomimetic Voronoi lattice models that accurately reflect the complex geometry and mechanical properties of trabecular bone. The porosity of human cancellous bone is accurately modeled in this work using biomimetic Voronoi lattice models. The porosities range from 70% to 95%, which can be achieved by changing the pore sizes to 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm. Finite element analysis (FEA) was used to examine the displacements, stresses, and strains acting on dental implants with a buttress thread, abutment, retaining screw, and biting load surface. The results show that the Voronoi model accurately depicts the complex anatomy of the trabecular bone in the human jaw, compared to standard solid block models. The ideal pore size for biomimetic Voronoi lattice trabecular bone models is 2 mm, taking into account both the von Mises stress distribution over the dental implant, screw retention, cortical bone, cancellous bone, and micromotions. This pore size displayed balanced performance by successfully matching natural bone's mechanical characteristics. Advanced finite element analysis (FEA) improves biomechanical understanding of how bones and implants interact by creating more accurate models of biological problems and dynamic loading situations. This makes biomechanical engineering better.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

Sirtuins, especially SIRT1, play a significant role in the regulation of inflammatory response, autophagy, and cell response to oxidative stress. Since their discovery, sirtuins have been regarded as anti-aging and longevity-promoting enzymes. Sirtuin-regulated processes seem to take part in most prevalent placental pathologies, such as preeclampsia. Furthermore, more and more research studies indicate that SIRT1 may prevent pre-eclampsia development, or at least alleviate its manifestations. Having taken this into consideration, we have made a review of recent studies on the role of sirtuins, especially SIRT1, in the regulation of processes determining normal or abnormal development and functioning of the placenta.

Here, we propose a prescriptive simulation model of a process operator’s decision-making assisted by artificial intelligence (AI) algorithm in a technical system control loop. We analyze situations fraught with a catastrophic threat that may cause unacceptable damage. Operators’ decision-making is interpreted in terms of a subjectively admissible probability of disaster and subjectively necessary reliability of its assessment. We distinguish four extreme decision-making strategies corresponding to different ratios between the above variables. An experiment simulating a process facility, an AI algorithm and operator's decision-making strategy was held. It showed that depending on the properties of a controlled process (the speed of hazard onset) and the AI algorithm characteristics (Type I and II error rate), each of such strategies or some intermediate strategy may prove to be more beneficial than others. The same approach is applicable to the identification and analysis of sustainability of strategies applied in real-life operating conditions, as well as to the development of a computer simulator to train operators to control hazardous technological processes using AI-generated advice.

Balanced fear supports human rational decision making and useful behavioral responses. In contrast, overwhelming, persistent, and unbalanced fear can paralyze the individual and result in heightened anxiety, lack of cognitive flexibility, fear-based public compliance and serious mental health issues. Psychobiotics research has established that a healthy microbiome is required for balanced fear and mental health protection via control of fear extinction. The recent Covid-19 pandemic featured daily, persistent, fear-of-a single contagion conditioning on a global scale paired with various behavioral mandates (e.g., lockdowns of the healthy, masks, isolation from environmental microbes and each other) that degraded the human microbiome and isolated us from each other and useful environmental microbes. It also ignored the historic role of secondary bacterial pathobionts, in pandemic deaths. This narrative review examines how institutional promotion of fear-of-a single contagion, lack of balanced risk communication, and appalling disregard of our fundamental nature (as majority-microbial human superorganisms) resulted in problems rather than solutions. This review concludes that government-public health-media promotion of pervasive fear and microbiome-degrading behaviors: 1) increased public compliance, 2) reduced cognitive flexibility, and 3) increased risk of mental health conditions. It further argues that microbiome-first public health should be embraced to ensure that human freedom, rather than paralyzing fear, dominates our future.

Ethylene Oxide (EtO) is a colorless, flammable gas at room temperature, produced by the catalytic oxidation of ethylene. EtO is widely used by medical sterilization facilities to clean medical supplies and equipment. Recent epidemiological studies showed that EtO is a more potent carcinogen than previously documented, leading the Environmental Protection Agency (EPA) to update, in December 2016, the inhalation unit risk estimate for EtO. This resulted in the identification of EtO as a potential health concern in several areas across the US, including the state of Utah. The geography surrounding Salt Lake Valley creates a bowl; ideal for collecting air pollution emissions. The region often experiences inversion episodes which inhibit vertical mixing and cause an accumulation of air pollutants, leading to unhealthy pollution levels. Using the EPA's dispersion modeling software, AERMOD, this study estimated EtO concentrations through facility stack and fugitive emissions modeling results. These values were compared with those of canister-based concentrations from ambient air samples taken near a medical device sterilization facility in the Salt Lake Valley. Stainless steel, whole-air passivated canisters were used to collect 24-hour ambient concentration samples of EtO. Eight locations surrounding a Salt Lake Valley medical device sterilization facility and four background sites were chosen to measure the ambient concentrations. Accounting for potential atmospheric impacts on EtO, measurements were sampled in winter 2022 (January-March) and summer 2022 (July-September). The modeled EtO concentrations were adjusted to account for background values associated with the winter or summer data. Then the two methodologies were compared using a Wilcoxon Sign-ranked, paired test. The statistical analysis resulted in six of the eight sample locations surrounding the sterilization facility being significantly different when comparing canister-based measurements of ambient EtO to modeled estimates. Canister-based measurements taken at sites one, three, and four were statistically greater than the modeled estimates, while sites two, five, and seven were statistically less than the modeled estimates. Also, the summer background value calculated was almost 2.5 times greater than the winter. The results do not suggest whether one method is more or less conservative than the other. In conclusion, the five of the closest sites and site seven were statistically different when comparing measured and modeled ambient concentrations of EtO. The comparison results do not clearly indicate if a correction factor could be derived for future human exposure to cancer risk assessment modeling. However, it is reasonable that the closer to the sterilization facility, the more total EtO exposure will be realized.

The extracellular matrix (ECM) is earning an increasingly relevant role in many disease states and the process of aging. Analyzing these disease states is possible with GWAS and PheWAS methodology, and through our analysis, we aimed to explore the relationships between polymorphisms in the compendium of ECM genes (i.e., matrisome genes) in various disease states. A significant contribution on the part of the ECM polymorphisms is evident in many varying types of diseases, particularly those in the core matrisome genes. Our results confirm previous links to connective tissue disorders, but also unearth new and underexplored relationships with neurological, psychiatric, and age-related disease states. Upon analysis of drug indications for gene-disease relationships, we identified numerous targets that may be repurposed for age-related pathology. The identification of ECM polymorphisms and their contribution to disease plays an integral role in future therapeutic developments, drug repurposing, precision medicine, and personalized care.

This paper looks at key elements of global culture that are driving a new paradigm shift in museums causing them to question their raison d'être, their design and physical space, recognizing the need to accommodate visitor interaction and participation, and to reprioritize institutional outcomes and goals reexamining their priorities. As heritage sharing in online spaces reaches across national, political, and social boundaries on platforms and networks, this has been driven by museum engagement with Internet life during the pandemic. Museum relationships and interactions with communities both local and global, continue to challenge core values and precepts, leading to radical changes in how museums define their roles and responsibilities. In this new cultural landscape, museums are responding to human digital identity in a tidal wave of human interactions on the Internet, from social media to online sharing of images and videos. This is revealing shared perspectives on cultural conflict as being tied to freedom of expression of one’s heritage embedded in digital identity.

The analysis of the human movement patterns based on the mobile network data makes it possible to examine a very large population cost-effectively, and led to several discoveries about human dynamics. However, the application of this data source is still not common practice. The goal of this study was to analyze the commuting tendencies of the Budapest Metropolitan Area using mobile network data and propose an automatized alternative to the current, questionnaire-based method. Commuting is predominantly analyzed by the census, but that is performed only once in a decade in Hungary. To analyze commuting, the home and the work locations of the subscribers are determined based on their appearances during and outside the working hours. The home locations were compared to census data at a settlement level. Then, the settlement and district level commuting tendencies were identified and compared to the findings of census-based sociological studies. It has been found that commuting analysis based on mobile network data strongly correlates with the census-based findings, even though home and work locations have been estimated by statistical methods. All the examined aspects, including commuting from sectors of the agglomeration to the districts of Budapest and demographic distribution of the commuters, show that mobile network data can be an automatized, fast, cost-effective, and relatively accurate way of commuting analysis, that could provide a powerful tool to the sociologists interested in commuting.

Reinvigorated public interest in human space exploration has led to the need to address the science and engineering challenges described by NASA's Space Technology Grand Challenges (STGCs) for expanding the human presence in space. Here we define Space Bioprocess Engineering (SBE) as a multi-disciplinary approach to design, realize, and manage a biologically-driven space mission as it relates to addressing the STGCs for advancing technologies to support the nutritional, medical, and incidental material requirements that will sustain astronauts against the harsh conditions of interplanetary transit and habitation offworld. SBE combines synthetic biology and bioprocess engineering under extreme constraints to enable and sustain a biological presence in space. Here we argue that SBE is a critical strategic area enabling long-term human space exploration; specify the metrics and methods that guide SBE technology life-cycle and development; map an approach by which SBE technologies are matured on offworld testing platforms; and suggest a means to train the next generation spacefaring workforce on the SBE advantages and capabilities. In doing so, we outline aspects of the upcoming technical and policy hurdles to support space biomanufacturing and biotechnology. We outline a perspective marriage between space-based performance metrics and the synthetic biology Design-Build-Test-Learn cycle as they relate to advancing the readiness of SBE technologies. We call for a concerted effort to ensure the timely development of SBE to support long-term crewed missions using mission plans that are currently on the horizon.

Abstract: Spatially explicit, fine-grained datasets describing historical urban extents are rarely available prior to the era of operational remote sensing. However, such data are necessary to better understand long-term urbanization and land development processes and for the assessment of coupled nature-human systems, e.g., the dynamics of the wildland-urban interface. Herein, we propose a framework that jointly uses remote sensing derived human settlement data (i.e., the Global Human Settlement Layer, GHSL) and scanned, georeferenced historical maps to automatically generate historical urban extents for the early 20th century. By applying unsupervised color segmentation to the historical maps, spatially constrained to the urban extents derived from the GHSL, our approach generates historical settlement extents for seamless integration with the multi-temporal GHSL. We apply our method to study areas in countries across four continents, and evaluate our approach for two U.S. study sites against historical settlement extents derived from the Historical Settlement Data Compilation for the US, HISDAC-US, achieving Area-under-the-Curve values >0.9. Our results are largely in agreement with model-based urban areas from the HYDE database, and demonstrate that the integration of remote sensing derived observations and historical cartographic data sources opens up new, promising avenues for assessing urbanization, and long-term land cover change in countries where historical maps are available.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

The present paper investigates the effect of poverty on foreign direct investment (FDI) inflows in developing countries. It complements the important extant literature on the effect of FDI inflows on poverty by examining the issue the other way around. The analysis is conducted using a sample of 117 countries over the period 1980-2017, and the two-step system Generalized Methods of Moments (GMM) technique. It has relied on two indicators of poverty, namely poverty headcount ratio and poverty gap. Findings indicate that over the full sample, poverty influences negatively FDI inflows, including through its adverse effect on human capital (that is, both education and health). Unsurprisingly, low-income countries (considered as poorest countries in the full sample) experience a higher negative effect of poverty on FDI inflows than other countries. On another note, participation in international trade matters for the effect of poverty on FDI inflows. In fact, an increase in poverty levels results in lower FDI inflows in countries that experience low workers' productivity, a less developed financial sector, and a low level of infrastructure development. Furthermore, the effect of poverty on FDI inflows does not depend on the prevailing economic growth rate. Finally, the analysis has revealed the existence of a non-linear effect of poverty on FDI inflows for the poverty headcount indicator, but not for the poverty gap indicator. The non-linear effect of poverty headcount on FDI inflows is such that a rise in poverty headcount ratio results in lower FDI inflows, but an additional increase in poverty more than further discourages FDI inflows. The conclusion discusses the implications of these findings.

Biosensors and wearable sensor systems with transmitting capabilities are currently developed and used for the monitoring of health data, exercise activities, and other performance data. Unlike conventional approaches, these devices enable convenient, continuous, and unobtrusive monitoring of a user’s behavioral signals in real time. Examples include signals relative to hand an finger movement/pressure control reflected by individual grip force data. As will be shown here, these directly translate into task, skill and hand-specific (dominant versus non-dominant hand) grip force profiles for different measurement loci in the fingers and palm of the hand. On the basis of thousands of sensor data from multiple sensor locations, individual grip force profiles of an task expert, a trained user and a highly proficient user (expert) performing an image-guided and robot-assisted precision task with the dominant or the non-dominant hand are analyzed in several steps following Tukey’s “detective work” approach. Correlation analyses (Person’s Product Moment) reveal skill-specific differences in individual grip force profiles across multiple sources of variation, functionally mapped to the somatosensory brain networks which ensure grip force control and its evolution with control expertise. Implications for the real-time monitoring of individual grip force profiles and their evolution with training in complex task-user systems are brought forward.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

Interviews from strength and conditioning coaches across all levels of athletic competition identified their two biggest concerns with the current state of wearable technology: (a) the lack of solutions that accurately capture data "from the ground up" and (b) the lack of trust due to inconsistent measurements. The purpose of this research is to investigate the use of liquid metal sensors, specifically Liquid Wire sensors, as a potential solution for accurately capturing ankle complex movements such as plantar flexion, dorsiflexion, inversion, and eversion. Sensor stretch linearity was validated using a Micro-Ohm Meter and a Wheatstone bridge circuit. Sensors made from different substrates were also tested and discovered to be linear at multiple temperatures. An ankle complex model and computing unit for measuring resistance values were developed to determine sensor output based on simulated plantar flexion movement. The sensors were found to have a significant relationship between the positional change and the resistance values for plantar flexion movement. The results of the study ultimately confirm the researchers' hypothesis that liquid metal sensors, and Liquid Wire sensors specifically, can serve as a mitigating substitute for inertial measurement unit (IMU) based solutions that attempt to capture specific joint angles and movements.

The different systems in the nuclear power plants (NPP) are critical and complex which requires a continuous rigorous monitoring for both normal and abnormal conditions. However, due to the nonlinearity of the dynamic behavior of these systems, implementation of artificial intelligence within the NPP components is crucial to enhance the monitoring and the predictability of the key operating parameters trend. On the other hand, lessons learned from large nuclear accident proves that a remote real-time coordination between the different stakeholders involved in the safety of the nuclear reactor is needed. This remote feature can be implemented in the existing power plants by embedding a mobile computing networks within the plant components. This network will send early warning and transmit the NPP data on real-time to different authorities such as the regulatory authority and the decision-making committees, to enhance the interpretability of the nuclear event and deliver a collaborative decision which in return mitigate the risk associated with these events and increase the overall safety of the plant. The integration of AI and mobile computing in NPP would be most of interest in countries where nuclear reactors data are challenged to reach during an accident. For instance, during the meltdown of Chernobyl, the Soviet government covered the accident from the news in an attempt to contain the consequences but there was a spread of radioactive contamination to some other Europe countries. Therefore, in the case of such scenario the implementation of mobile computing and AI would result in different outcomes as the European countries would be notified through the mobile networking and the spread of contamination would be forecasted by the AI algorithms. In this paper, we examine the different modern AI and mobile computing technologies, the different potential application, the associated features and challenges, and future work direction.

This study explores the integration of Artificial Intelligence (AI) and collaborative robotics in industrial surface finishing, focusing on feature detection on object reflective surfaces using neural networks in computationally constrained environments. Central to this investigation is the utilization of cameras considered as sensors that can capture detailed images of reflective surfaces. These images are then analyzed by a custom neural network, demonstrating the feasibility of feature detection with non-powerful computers. The public dataset for recognizing light reflection defects, available in the SPADD repository, supports this approach. Employing open-source tools like Darknet YOLOv3 and Yolo\_mark, this method proves particularly advantageous for small and medium-sized enterprises (SMEs) due to its low cost and maintenance requirements. This research highlights the challenges of AI and collaborative robotics in industrial applications, especially in adapting to varying conditions and the need for continuous training with new data coming from several sensors. Looking ahead, plans are in place to integrate this system with cobot-assisted polishing tasks, using cameras to enhance manufacturing efficiency and quality. This work contributes to the broader understanding of practical applications of AI in industrial automation, surface finishing processes, and the effective use of sensor technology.

One of the most burning topics in cybersecurity in 2023 will undoubtedly be the compliance with the Software Bill of Materials. Since the US president issued the Executive Order 14028 on Improving the Nation’s Cybersecurity, software developers have prepared and bills are transmitted to vendors, customers, and users, but they don’t know what to do with the reports they are getting. In addition, since software developers have identified the values of the Software Bill of Materials, they have been using the reports extensively. This article presents an estimate of 270 million requests per month, just from form one popular tool to one vulnerability index. This number is expected to double every year and a half. This simple estimate explains the urgency for automating the process. We propose solutions based on artificial intelligence and machine learning, and we base our tools on the existing FAIR principles (Findable, Accessible, Interoperable, and Reusable). This methodology is supported with a case study research and Grounded theory, for categorising data into axis, and for verifying the values of the tools with experts in the field. We showcase how to create, and share Vulnerability Exploitability eXchange data, and automate the Software Bill of Materials compliance process with AI models and a unified computational framework combining solutions for the following problems: (1) the data utilisation problem, (2) the automation and scaling problem, (3) the naming problem, (4) the alignment problem, (5) the pedigree, and provenance problem, and many other problems that are on the top of mind for many security engineers at present. The uptake of these findings will depend on collaborations with government and industry, and on the availability and the ease of use of automated tools.

In this paper, we present a novel approach for managing the file system in Linux using a voice assistant. Our system allows users to perform file system operations such as creating directories, renaming files, and deleting files by issuing voice commands. We develop a voice assistant using Python libraries and integrate it with the file system in Linux. The voice assistant is capable of understanding natural language and executing commands based on the user's voice inputs. We conduct experiments to evaluate the performance of the system and demonstrate that our approach is effective and efficient in managing the file system using voice commands. Our system can enhance the accessibility and usability of the file system in Linux for individuals with disabilities or those who prefer a hands-free approach to file management.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising chemotherapeutic agent because of its selective apoptotic action on cancer cells. However, resistance to TRAIL-induced apoptosis remains a challenge in many cancers. The gintonin-enriched Panax ginseng extract fraction (GEF) has diverse pharmacological benefits. We explored the combined efficacy of GEF and TRAIL in inducing apoptosis in human renal cell carcinoma (RCC) cells. The effect of GEF treatment on viability, clonogenic potential, wound healing, and TRAIL-induced apoptotic signaling of RCC cells was studied in vitro. Our investigation revealed that GEF pre-treatment sensitized RCC cells to TRAIL-induced apoptosis, as evidenced by DNA fragmentation and cell proliferation, colony formation, and migration inhibition. This sensitization was linked to the upregulation of death receptors 4 and 5 and alterations in apoptotic protein expression; notably, decreased expression of Mu-2-related death-inducing gene, a novel anti-apoptotic protein. Our findings underscore the necessity of caspase activation for GEF/TRAIL-induced apoptosis using the pan-caspase inhibitor Z-VAD-FMK. It demonstrates that GEF sensitizes human RCC cells to TRAIL-induced apoptosis by upregulating DR4/5 and modulating apoptotic protein expression. These findings suggest a promising strategy for overcoming TRAIL resistance in cancer therapy and highlight the potential of GEF as a valuable adjunct to TRAIL-based treatments.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer’s disease (AD) patients leads to Aβ accumulation and formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is reduction of free Aβ level by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) of HSA to improve its affinity for Aβ. Here we develop this approach by bioinformatic search for the clinically approved AD-related LMWLs of HSA, followed by classification of the candidates according to the predicted location of their binding sites on HSA surface, ranking of the candidates, and selective experimental validation of their impact on HSA affinity for Aβ. The top 100 candidate LMWLs were classified into the five clusters. The specific representatives of the different clusters exhibit dramatically different behavior, with 3- to 13-fold changes in equilibrium dissociation constants for the HSA-Aβ40 interaction: prednisone favors HSA-Aβ interaction, mefenamic acid shows the opposite effect, while levothyroxine exhibits the bidirectional effects. Overall, the LMWLs of HSA chosen here provide a basis for drug repurposing for AD prevention, and for search for the medications promoting AD progression.

The precise molecular basis of anti-tumor immunity is not yet fully understood, although commensal Bifidobacterium (c-BIF) is expected to be one of the key players in cancer control via antigenic mimicry. We investigated the sequence similarity between c-BIF and cytotoxic T lymphocyte (CTL) epitope peptides against human tumor-associated antigens to better understand the molecular basis of antigenic mimicry. We used two different similarity analyses for this purpose, a linear sequence analysis and a similarity analysis of T cell receptor (TCR)-mediated recognition of CTL epitope peptides on antigen-presenting cells. The linear sequence analysis revealed 3,900 positive numbers of similarity sites between them with 126 mean per peptide and 107 median per peptide, while the TCR-mediated recognition analysis revealed 5,018 positive numbers with a mean of 162 and median of 132 per peptide. These results demonstrated the existence of durable and abundant sequence similarities between c-BIF and CTL epitope peptides, suggesting that the former play a pivotal in inducing cellular and humoral immunity against the latter in the absence of cancer cells via antigenic mimicry.

In this paper, we critically examine the burgeoning role of advanced computational methodologies in deciphering the complex tapestry of farm animal behaviors and emotions. Leveraging digital imaging and artificial intelligence, we unearth nuanced behavioral patterns and micro-expressions, offering predictive insights into animal emotional states. Sound vocalization analysis, often overlooked, emerges as a pivotal tool, decoding intricate communicative nuances and emotional undertones. Cognitive tests, including mirror and bias assessments, challenge long-standing perceptions, revealing surprising depths of animal self-awareness and cognitive sophistication. However, the paper also underscores the imperative of integrating these tools with a profound understanding of animal psyche, ensuring technology serves as an enhancer, not a replacement, of traditional observational methods. This research not only highlights the transformative potential of cognitive computing in animal welfare but also calls for a judicious application, ensuring technology augments, not undermines, the intrinsic value of human-animal interactions and understanding.

We have previously developed several successful decellularization strategies yielding porcine cardiac extracellular matrices (pcECMs), which exhibit tissue-specific bioactivity and bioinductive capacity when cultured with various pluri- and multipotent stem cells. Here, we studied the tissue-specific effects of the pcECM on seeded human mesenchymal stem cells (hMSCs) phenotype using reverse transcribed quantitative polymerase chain reaction (RT-qPCR) arrays for cardio-vascular related genes. We further corroborated interesting findings at the protein level (flow cytometry and immunological stains) as well as bioinformatically using several mRNA sequencing and protein databases of normal and pathologic adult tissue expression, as well as during human embryonic organogenesis. We discovered that upon seeding of human mesenchymal stem cells (hMSCs) on the pcECM they displayed partial MET toward endothelial phenotypes (CD31+) and morphologies, which were preceded by an early spike (~day 3 onward after seeding) in HAND2 expression at both the mRNA and protein levels compared to plate controls. CRISPR-Cas9 knockout (KO) of HAND2 and its associated antisense long non-coding RNA (HAND2-AS1) regulatory region resulted in proliferation arrest, hypertrophy, and senescent-like morphology. Bioinformatic analyses revealed that HAND2 and HAND2-AS1 are highly correlated in expression, are expressed in many different tissue types albeit at distinct yet tightly regulated expression levels. Deviation (down or up regulation) from these basal tissue expression levels are associated with a long list of pathologies. We thus suggest that HAND2 expression levels may finetune cell plasticity possibly affecting senescence and mesenchymal-to-epithelial transition states, through yet unknown mechanisms. Targeting this pathway may represent a promising new therapeutic approach for a wide range of diseases, including cancer, degenerative disorders, and aging. Nevertheless, further investigations are required to better understand the molecular players involved, potential inducers and inhibitors of this pathway, and eventually potential therapeutic applications.

The less virulent human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 cause mild, self-limiting respiratory tract infections, while the more virulent SARS-CoV-1, MERS-CoV, and SARS-CoV-2 have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoVs infections, may provide insight into this disparate severity of the disease. We, therefore, generated full-length E protein models for SARS-CoV-1, -2, MERS-CoV, HCoV-229E, and HCoV-NL63 and docked C-terminal peptides of each model to the PDZ domain of the human PALS1 protein. The PDZ-binding motif (PBM) of the SARS-CoV-1, -2, and MERS-CoV models adopted a more flexible, extended coil while the HCoV-229E and HCoV-NL63 models adopted a less flexible alpha helix. All the E peptides docked to PALS1 occupied the same binding site and the more virulent hCoV E peptides generally interacted more stably with PALS1 than the less virulent ones. We propose that the increased flexibility of the PBM in more virulent hCoVs may permit more stable binding to various host proteins, thereby possibly contributing to more severe disease. This is the first paper to model full-length 3D structures for both more virulent and less virulent hCoVs E proteins, providing novel insights for possible drug and/or vaccine development.

Chatbots are intelligent conversational computer systems designed to mimic human conversation to enable automated online guidance and support. The increased benefits of chatbots led to their wide adoption by many industries in order to provide virtual assistance to customers. Chatbots utilise methods and algorithms from two Artificial Intelligence domains: Natural Language Processing and Machine Learning. However, there are many challenges and limitations in their application. In this survey we review recent advances on chatbots, where Artificial Intelligence and Natural Language processing are used. We highlight the main challenges and limitations of current work and make recommendations for future research investigation

Bone tissue engineering has developed significantly in recent years as the increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

There is little understanding of patients' experiences and perceptions with satisfaction by health professionals such as medical and dental clinicians. Furthermore, patient satisfaction is not well understood. The objective of this article is to better understand patients' satisfaction with their medical and dental care. The methods of the current article are based on a narrative review of the literature strategy. Patient satisfaction's multidimensional nature has been established since the perceived reasons for satisfaction varied widely among patients. Many aspects of the treatment influence participant satisfaction at different stages of the intervention's process. An improved understanding of the basis for managing patients' expectations with information reiteratively and efficiently may ultimately reduce patients' potential for negative feelings toward the medical and dental treatment experience. The consumerist method may misrepresent the concept of satisfaction in health service.

In this paper we review dynamics and roughness of bonds in proteins on example of albumin, that is important from the physiological point of view. We have performed computer simulations of albumin chain. Statistics were collected by performing many simulations realizations for each experimental setting. We concentrate on hydrogen bonds, cation-π and π- π interactions and NP contacts. Histograms of hydrogen bonds length are positively skewed in contrary to histograms of interactions and HP contacts that are negatively skewed. Scaling exponents of power spectra of energies of bonds / interactions /contacts are in range -0.2 to -0.5 and significantly differ between various hydrogen bonds or interactions. Varying scaling of such spectra can be used to classify between distinct bonds or contacts. Concerning particular amino-acids, largest amount of HBO H20 bonds are between Glutamate (GLU) amino-acids and water particle, while large amount of HBO bonds are formed with Lysine (LYS). For HP contacts the mayor role plays Phenylalanine (PHE) and Leucine (LEU) amino-acids. From decay curves HBO H2O bonds decays in fastest rate, while HBO bonds and HP contacts at slowest rate. We present as well decay curves of bonds formed by particular amino-acids, that gives interesting results.

Tuberculosis cause of death worldwide and the leading cause from a single infectious agent, ranking above Human immunodeficiency virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). The aim of this study is to ascertain the trend of tuberculosis prevalence and the effect of HIV prevalence onl Tuberculosis case in some West African countries from 2000 to 2016 using count panel data regression models. The data used annual HIV and Tuberculosis cases spanning from 2000 to 2016 extracted from online publication of World health Organization (WHO). Panel Poisson regression model and Negative binomial regression model for fixed and random effects were used to analyzed the count data, the result revealed a positive trend in TB cases while increased in HIV cases leads to increase in TB cases in West African countries. Among the competing models used in this study, Panel Negative Binomial Regression Model with fixed effect emerged the best model with log likelihood value of -1336.554. This study recommended that Government and NGOs need more strategies to fight against HIV menace in West Africa as this will in turn reduced TB cases in West Africa.

In Sub-Saharan African Countries such as Nigeria with high prevalence rate, Child HIV/AIDs acquired through Mother-to-Child transmission (MTCT) can be largely prevented by using a well-established prevention programme and scheme. This study examined factors that can enhanced Prevention of Mother-to-Child transmission (PMTCT) in Nasarawa State. To achieve this, structured questionnaire were used to collect data from one hundred and sixteen (116) women attending two (2) primary facilities and two (2) secondary facilities in the State. This study utilized methods of Poisson Regression, Negative Binomial Regression and Logistic Regression Analyses. Results revealed that women with at least a secondary school education, women with husband in military and women with perceived confidentiality of their HIV status significantly enhanced PMTCT of HIV in Nasarawa State while significant proportion of the women attest to the fact that drugs are available in the facilities (p-value=0.0000<0.05) . Other factors include mother income level, willingness to continue with PMTCT programme and women in support group can also enhanced PMTCT though they are not significant. This study recommends that the factors identified should be explored by NGOs, Ministry of Health and, Support groups and other relevant agencies since they have the capacity to enhanced PMTCT of HIV in Nasarawa State, Nigeria.

This pioneering study explores the geospatial and temporal patterns of natural and human-induced disasters from 1900 to 2024, providing essential insights into their global distribution and impacts. Utilizing the comprehensive international EM-DAT database, our analysis reveals significant trends and disparities in disaster occurrences and their widespread consequences. Results showed a dramatic escalation in both natural and man-made (technological) disasters over the decades, with notable surges in the 1991-2000 and 2001-2010 periods. A total of 25,836 disasters were recorded worldwide, of which 69.41% were natural disasters (16,567) and 30.59% were man-made (technological) disasters (9,269). The most significant increase in natural disasters occurred from 1961-1970, while man-made (technological) disasters surged substantially from 1981-1990. Seasonal trends reveal that floods peak in January and July, while storms are most frequent in June and October. Droughts and floods are the most devastating in terms of human lives, while storms and earthquakes cause the highest economic losses. The most substantial economic losses were reported during the 2001-2010 period, driven by catastrophic natural disasters in Asia and North America. Our research highlights Asia as the most disaster-prone continent, accounting for 41.75% of global events, with natural disasters making up 61.89% of these events. Oceania, despite experiencing fewer total disasters, shows a remarkable 91.51% of these as natural disasters. Africa is notable for its high incidence of man-made (technological) disasters, which constitute 43.79% of the continent's disaster events. Europe, representing 11.96% of total disasters, exhibits a balanced distribution but tends towards natural disasters at 64.54%. Examining specific countries, China, India, and the United States emerged as the most frequently affected by both natural and man-made (technological) disasters. The impact of these disasters has been immense, with economic losses reaching their highest during the decade of 2010-2020, largely due to natural disasters. The human toll has been equally significant, with Asia recording the most fatalities and Africa the most injuries. Particularly, the decade from 2001 to 2010 experienced the greatest economic losses, primarily driven by natural disasters in Asia and North America. These insights highlight the urgent need for tailored disaster risk management strategies that address the distinct challenges and impacts in various regions. By understanding historical disaster patterns, policymakers and stakeholders can better anticipate and manage future risks, ultimately safeguarding lives and economies.

Experiential learning, defined as the result, source, or context of knowledge obtained from direct experience, is increasingly bolstered by technology and human-computer interaction (HCI) principles and protocols. This article will describe how technology-based human-computer interaction (HCI) has been used in experiments to enhance direct knowledge experience. In this paper, immersive technologies (such as Virtual Reality, Augmented Reality, and haptics) will be described based on cognitive learning theory, empirical research and practical experience gained from implementing cutting-edge technology and maximizing HCI principles in constructive learning. Additionally, this article will describe how AI can be used to create individualized learning environments according to a student's needs in the future. While cost, technical issues and specialised trainings are the obstacle to deliver personalized learning experiences especially to economically disadvantaged students, technological change opportunities are projected, and these technologies will take educational outcomes to the next level.

This research introduces an Intelligent Robotic Arm with Adaptive Collision Avoidance, employing real-time current fluctuation analysis for human-proximity detection. Precision and versatility in motors and actuators are given top priority in the robotic arm setup. Motor power lines are continually monitored by integrated high-precision current sensors, and a real-time data processing system separates natural fluctuations from those caused by outside influences. When a human comes into contact with the surface of the robotic arm, the system excels at detecting their closeness by identifying unique patternsin the variations of current. This sets off an adaptive collision avoidance system, which quickly flips the main power supply’s kill switch to bring the vehicle to an emergency stop. A crucial component is adaptability, as the system dynamically modifies sensitivity in response to environmental condi- tions. Comparative studies show that this approach performs better than conventional static sensing techniques. Experiments under control confirm the great precision, accuracy, and low false positive rate. The use of a failsafe technique improves system integrity by preventing false alarms and enabling recovery after an emergency

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained through an extensive review of the literature, and additionally included target genes identified by the COVID-19 Host Genetic Initiative, as well as the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with severe COVID-19 outcome.

(1) Background: Double-strand breaks (DSBs) in a single nucleus are usually measured using the sperm chromatin structure assay (SCSA), sperm chromatin dispersion (SCD) test, and comet assay (CA). We developed mono-dimensional single-cell pulsed-field gel electrophoresis (1D-SCPFGE) and angle-modulated two-dimensional single-cell pulsed-field gel electrophoresis (2D-SCPFGE) to observe DNA fragmentation in separated motile sperm. (2) Methods: We set up comparative standards, calibration curves, the required sensitivity, and eligibility criteria for test sperm to validate their measurement principles. (3) Results: We revealed that the conventional methods overlooked the interference of nucleoproteins in their measurements. In-gel proteolysis improves the measurement accuracies of 1D- and 2D-SCPFGE. We recommend using naked DNA for comparative standards and test specimens. Moreover, we have observed several dysfunctions that may induce DNA damage in the separated motile sperm. Overall, our discussion highlights the need to revisit the conventional univariable analyses based on the SCSA, SCD test, and CA. (4) Conclusions: Human infertility is a complex syndrome, and the aim of quality control in intracytoplasmic sperm injection is to identify the underlying dysfunctions remaining in the separated motile sperm that render them ineligible for injection. Well-designed, multivariable analyses with special consideration to confounding factors are necessary in future cohort studies.

The pathophysiology of Nonketotic Hyperglycinemia (NKH), a rare neuro-metabolic disorder associated with severe brain malformations and life-threatening neurological manifestations, remains incompletely understood. Therefore, a valid human neuronal model is essential. We aimed to investigate the impact of GLDC gene variants, which cause NKH, on cellular fitness during the differentiation process of human induced pluripotent stem cells (iPSCs) into iPSC-derived astrocytes and to identify sustainable mechanisms capable of overcoming GLDC deficiency. We developed the GLDC27-FiPS4F-1 line and performed metabolomic, mRNA abundance and protein analyses. The study showed that although GLDC27-FiPS4F-1 maintained the parental genetic profile, it underwent a metabolic switch to an altered serine-glycine-one-carbon metabolism with a coordinated cell growth and cell cycle proliferation response. We then differentiated the iPSCs into neural progenitor cells (NPCs) and astrocyte-lineage cells. Analysis showed that GLDC-deficient NPCs had shifted towards a more heterogeneous astrocyte lineage with increased expression of the radial glial markers GFAP and GLAST and the neuronal markers MAP2 and NeuN. In addition, we detected changes in other genes related to serine and glycine metabolism and transport, all consistent with the need to maintain glycine at physiological levels. These findings improve our understanding of the pathology and offer new perspectives for therapeutic options.

Cathepsin B (CatB) is thought to be essential for the induction of Porphyromonas gingivalis lipopolysaccharide (Pg LPS)-induced Alzheimer’s disease- like pathologies in mice, including interleukin-1β (IL-1β) production and cognitive decline. However, little is known about the role of CatB in Pg virulence factor-induced IL-1β production by microglia. We first subjected IL-1β-luciferase reporter BV-2 microglia to inhibitors of Toll-like receptors (TLRs), IκB kinase, and the NLRP3 inflammasome following stimulation with Pg LPS and outer membrane vesicles (OMVs). To clarify the involvement of CatB, we used several known CatB inhibitors, including CA-074Me, ZRLR, and human β-defensin 3 (hBD3). IL-1β production in BV-2 microglia induced by Pg LPS and OMVs was significantly inhibited by the TLR2 inhibitor C29 and the IκB kinase inhibitor wedelolactonne, but not by the NLRPs inhibitor MCC950. Both hBD3 and CA-074Me significantly inhibited Pg LPS-induced IL-1β production in BV-2 microglia. Although CA-074Me also suppressed OMV-induced IL-1β production, hBD3 did not inhibit it. Furthermore, both hBD3 and CA-074Me significantly blocked Pg LPS-induced nuclear NF-κB p65 translocation and IκBα degradation. In contrast, hBD3 and CA-074Me did not block OMV-induced nuclear NF-κB p65 translocation or IκBα degradation. Furthermore, neither ZRLR, a specific CatB inhibitor, nor shRNA-mediated knockdown of CatB expression had any effect on Pg virulence factor-induced IL-1β production. Interestingly, phagocytosis of OMVs by BV-2 microglia induced IL-1β production. Finally, the structural models generated by AlphaFold indicated that hBD3 can bind to the substrate-binding pocket of CatB, and possibly CatL as well. These results suggest that Pg LPS induces CatB/CatL-dependent synthesis and processing of pro-IL-1β without activation of the NLRP3 inflammasome. In contrast, OMVs promote the synthesis and processing of pro-IL-1β through CatB/CatL-independent phagocytic mechanisms. Thus, hBD3 can improve the IL-1β-associated vicious inflammatory cycle induced by microglia through inhibition of CatB/CatL.

The fresh bulbs of Stenomesson miniatum, a plant belonging to Amaryllidaceae family with a poorly investigated phytochemical profile, were traditionally employed by Andean healers to treat tumors and abscesses. The aims of this study were to characterize the alkaloid extract from the bulbs of S. miniatum and test its cytotoxic and antibacterial potential. The alkaloid extract was characterized by dereplication using various techniques (CPC, NMR, UPLC-HRMS) and referring to in-home or online databases for spectroscopic data matching. Cytotoxic activities were evaluated on A431 human epidermoid carcinoma cells through a metabolic assay, and on Jurkat human acute T-leukemia cells through a cell-impermeant fluorescent nuclear probe. Antibacterial assays were carried out against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes by using a standardized microdilution broth method 96-well plate. Eleven known Amaryllidaceae alkaloids were identified together with another compound determined as being an extraction artefact. The alkaloid extract showed good cytotoxic activity against both the tumor cell lines, reaching an IC50 of 3.3 µg/mL against A431 cells and of 10.9 µg/mL against Jurkat cells. The analysis of the fractions allowed the activity to be attributed to the presence of pretazettine and haemathamine. Conversely, no antibacterial activities were recorded for any of the samples.

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.

The research is focusing on analyzing the concentrations of particulate matter (PM) next to a highly congested road section, with 39,900 as a maximum number of vehicles per 24 h, in the vicinity of Timisoara, Romania. Concentrations have been measured in multiple episodes using two different measurement methods, gravimetric and dynamic light scattering, showing a disperse range of PM concentrations. Presence of metal particles in the samples have been analyzed using an electron microscope. Additionally, impact on human health is described by evaluating results for inhalable, thoracic, and alveolar sized particles.

The complex adaptive systems (CAS) research study investigates into the theoretical link of a sustained economic growth as a critical pathway to lift people out of poverty and improve their quality of life. The results show a left-skewed global behavior of an economy-driven human development of 189 countries with 20% or 27 countries obtaining low human development; 80% or 162 countries obtaining medium to very high human development of which 21.16% or 39 countries with medium HDI, 53 or 28.04% or 53 countries with high HDI, and 31.22% or 59 countries with very high HDI. Using the Log (GDP) for visual transformation, closer investigation into the scatterplot diagram reveals that there are also bimodal patterns where countries in the high amplitude and low amplitude groups obtained different human development outcomes despite less or more on economic growth variances mirror on the government policy priorities resulting in four differentiating conditions. Very few countries experience virtuous cycles where both growth and human development are successful; few countries with vicious cycles where both are weak; and many countries with lopsided conditions where the economy is strong but human development is weak, or conversely ones where human development is strong but the economy is weak. The global pattern of economy and human development illustrated by an upward sinusoid or sine wave refutes the conventional linear approach. Uniquely and most importantly, the sinusoidal wave illustrates a decreasing amplitude and decreasing periods as countries manifest apparently complex behaviors that emerge as a result of often nonlinear spatio-temporal interactions among a large number of component systems at different levels of organizations and governments leading to an emergence of a behavior characterizing of a complex adaptive system.

The innovation driven Industry 5.0, in agreement with Industry 4.0, leads to consider human in a prominence position as the center of manufacturing field. This pushes towards the hybridization of manufacturing plants promoting a fully collaboration between human and robot. Furthermore, the new paradigm of "human centred design" and "anthropocentric design" allows enabling a synergistic combination of human and robot skills. However, properly collaborative workplaces are currently very few. Industry is still not confident, and systems integrators hesitate to venture into Human-Robot Collaboration (HRC). Despite the effort in collaborative robotics, a general solution to overcome the current limitations in designing of collaborative workplaces still misses. In the current work, a Knowledge-Based Approach (KBA) is adopted to face collaborative workplace designing problem. The framework resulting from the KBA allows developing a modelling paradigm that enable to define a streamlined approach for the layout designing of a collaborative workplace. Finally, a what-if analysis and a ANOVA analysis are performed to generate and evaluate a set of scenarios related to a collaborative workplace for quality inspection of welded parts. Facing the high complexity and multidisciplinary of HRC can be conveyed to develop a general design approach aimed at overcoming the difficulties that limit the spread of HRC in the manufacturing field.

The research work examined the trend of HIV/AIDS, Tuberculosis, and Hepatitis diseases in Plateau state. Annual data from 2003 to 2018 was collected from the department of biostatistics at Plateau State Specialist Hospital (PSSH), Jos. The methods of analysis used are the Poisson Autoregressive Model (PAR(1)) and the Poisson Exponentially Weighted Moving Average Model (PEWMA). The results revealed a significant annual decrease of 23.9% and 4% in Tuberculosis and HIV/AIDS respectively. Furthermore, the results showed a significant annual increase of 46% in Hepatitis. The PEWMA model used revealed that TB increased by 0.02% when there is an increase in HIV but not significant, while Hepatitis significantly aggravates TB by at least 0.24%. Also, there is a significant rise in HIV by 0.85% when TB increases but Hepatitis has no such effect on HIV. Lastly, PEWMA model indicated a rise of 0.5% in Hepatitis cases when there is an increase in TB, but a surge in HIV has no such effect on Hepatitis cases in Jos. The study recommended that fight against TB should be intensified since TB cases significantly affect both HIV and Hepatitis in Jos, Nigeria.

Software project estimating (SPE) is a powerful but necessary step in the production of projects for software. Software project estimating includes several components, estimating software time, software resources, software costs, and software effort estimation (SEE). SEE seeks to estimate the number of "hours-person" and "months-person" of work required for developing or managing a software program. During the initial phase of the development of software, future efforts are impossible to predict. To estimate effort, many deep learning (DL) and machine learning (ML) models were previously created. For estimate, single-model techniques and ensemble methods were investigated in this research. Ensemble methods involve a combination of multiple separate models. Bagging, boosting, and voting were the ensemble methods looked into for estimation. Datasets considered for estimation were COCOMO81, COCOMONasa I, COCOMONasa II, Albrecht, Maxwell, China, Desharnais, Desharnais_1_1, Kitchenham, Boehm, and Belady. The evaluation criteria used MAE, RAE, RMSE, RRSE, and CC. The result from previous studies is that the total size of the set of data utilized is small in predicting the effort, as the largest size of the set of data used is the China dataset containing only 499 projects. So, in this study, the dataset has been merged to increase the total size of the set of data and increase the accuracy of prediction. The results indicated that the suggested merged dataset increased effort estimation accuracy.

The integration of Artificial Intelligence (AI) in dairy farm management through biometric facial recognition for cows is a significant stride in livestock management. This review critically evaluates the evolution, applications, and challenges of AI-driven biometric facial recognition in dairy farming. It emphasizes the role of this technology in enhancing individual monitoring of dairy cows, providing accurate health, behavior, and productivity tracking. Originally derived from human facial recognition systems, this approach utilizes distinctive bovine facial features for essential, non-invasive, real-time monitoring in large-scale operations. The progression of AI from elementary pattern recognition to advanced Convolutional Neural Networks (CNNs) and deep learning models marks a shift toward data-driven farming. This study addresses key challenges such as environmental variability, data collection hurdles, ethical concerns, and technological limitations. It also contrasts various AI models, spotlighting their unique strengths and practical utility in dairy farming scenarios. Despite these challenges, facial recognition technology holds promise for improving farm efficiency, animal welfare, and sustainable practices, highlighting the need for continuous research and development. The review concludes by advocating for future research focused on environmental adaptability, ethical AI application, cross-breed compatibility, and integration with other farming technologies. Ultimately, it underscores AI's transformative potential in modernizing dairy farming towards a more data-oriented, responsible agricultural future.

Some of the barriers preventing Virtual Reality (VR) from being widely adopted are the cost and unfamiliarity of VR systems. Here we propose that in many cases the specialized controllers shipped with most VR head-mounted displays can be replaced by a regular smartphone, cutting the cost of the system, and allowing users to interact in VR using a device they are already familiar with. To achieve this, we developed SmartVR Pointer, an approach that uses smartphones as a replacement for the specialized controllers for two essential operations in VR: selection and navigation by teleporting. In SmartVR Pointer a camera mounted on the head-mounted display (HMD) is tilted downwards so that it points to where the user will naturally be holding their phone in front of them. SmartVR Pointer supports three selection modalities: tracker-based,gaze-based, and combined/hybrid. In the tracker-based SmartVR pointer selection we use image-based tracking to track a QR code displayed on the phone screen and them map the phone’s position to a pointer shown within the field of view of the camera in the Virtual Environment. In the gaze-based selection modality the user places the pointer using their gaze and taps on the phone for selection. The combined technique is a hybrid between head-gaze-based interaction in VR and smartphone-based Augmented Reality. It allows the user to control a VR pointer that behaves like a mouse pointer by moving their smartphone to select objects within the virtual environment, and to interact with the selected objects using the smartphone’s touch screen. The touchscreen is used for selection and dragging. SmartVR Pointer is simple and requires no calibration and no complex hardware assembly or disassembly. We demonstrate successful interactive applications of SmartVR Pointer in a VR environment with a demo where the user navigates in the virtual environment using teleportation points on the floor and then solves a Tetris-style key-and-lock challenge.

Our skin epidermis constitutes the most important innate defense barrier against all pathogens. Therefore, even if skin lesions are common due to infections, scarring, genetic disorders, and other diseases, skin integrity is crucial for maintaining body homeostasis. Marine collagen peptides (MCPs) and Glycosaminoglycans (GAGs) have been described as potential wound healing (WH) agents. Recently, through an ex vivo clinical approach, we have demonstrated the nutricosmetic potential of fish cartilage hydrolysate (FCH), which presents a combination of collagen peptides and GAGs. Here, we coupled a clinical approach with in vitro experiments on human dermal fibroblasts (HDFs) and applied a Data Independent Acquisition - Parallel Accumulation Serial Fragmentation (diaPASEF) proteomic analysis, to assess the potential benefit of FCH in WH and its mode of action. Our results show that human serum enriched with circulating metabolites resulting from FCH ingestion, improved wound closure in scratch assays. In support, some proteins with anti-inflammatory and immunomodulatory properties or prone to promote hydration and extracellular matrix (ECM) stability showed increased expression in HDFs, after exposure to FCH-enriched serum. These findings suggest that FCH appears as a promising nutrient for WH and skin regeneration.

Human T-cell leukemia virus type-1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATL). HTLV-1 carriers have a life-long asymptomatic balance between infected cells and host antiviral immunity, but 5–10% of carriers lose this balance and develop ATL. Coinfection with Strongyloides also promotes ATL development, suggesting that the immunological status of infected individuals is a determinant of viral pathogenicity. As CD4+ T cells play a central role in host immunity, deregulation of their function and differentiation by HTLV-1 promotes the immune evasion of infected T cells. During ATL development, the accumulation of genetic and epigenetic alterations in key host immunity-related genes further disturbs immunological conditions. Various therapeutic approaches have been developed to treat these abnormalities. Allogeneic hematopoietic stem cell transplantation is currently the only treatment with the potential to cure ATL; however, the patient's immune state may also contribute to its outcome. Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, also depends on immune functions, such as antibody-dependent cytotoxicity. In this review, we comprehensively summarize the immunological pathogenesis of HTLV-1 infection in ATL and integrate clinical findings to determine the factors to be considered for developing treatment strategies for ATL.

Integrating voice assistant technology can potentially enhance accessibility and user interaction in web-based platforms for geospatial data visualisation and processing. This paper presents an open-source development incorporating a voice virtual assistant into the BStreams web application platform, designed specifically for visualising geospatial data. The study aimed to mitigate the observed limitations of virtual assistants in understanding the semantics and context of user commands in the geospatial domain. A discourse framework specialised for geospatial data was developed using a structured prototype methodology. In addition, a survey assisted in identifying commonly used English terminologies for geospatial data interaction. The questionnaire results were subsequently assessed using the ChatGPT natural language processing model. The application used open-source frameworks, including Web Speech API, Leaflet, Mapbox geocoding, and JavaScript. This investigation indicates that voice virtual assistants can potentially enhance human-computer interaction for geospatial data visualisation and processing. However, challenges related to natural language understanding, accents, and domain knowledge were raised. The paper advocates for further research to refine the integration of voice technology in this domain.

This paper responds to the research question, “can urban farming help Nepali cities become more sustainable”? Especially after the Covid-19 pandemic, urban residents have begun to realize that food transported from long distances could not always be reliable. Urban farming can help produce fresh food locally and avoid long-distance transportation, and refrigeration. This practice also helps reduce greenhouse gases through plant carbon use efficiency (CUE). Urban farming not only helps city-dwellers towards achieving self-reliance in food production but also in vegetation carbon dynamics (VCD) while supporting the circular economy. Urban farming consists of edible landscapes, which can also be an aesthetic public space. As urban lands command higher prices than agricultural land, urban farming usually happens on residential yards, roofs, balconies, community gardens, and dedicated areas in public parks. Rainwater harvesting, and redirecting can help irrigate urban farms which can be part of rain gardens. The national census of 2021 (CBS 2022, p5) identifies that 66 percent of Nepal’s population live in urban areas. However, the World Bank (2018), shows that only 21 of Nepal’s population was projected to live in urban areas in 2021. It is not debatable that the urbanization process in Nepal is on the rise. Thus, urban agriculture can play an important role to supplement the residents’ food needs. Many cities in Nepal have already successfully adapted to urban farming where residents grow food on their building site, balconies, and rooftop often growing plants on pots, vases, and other types of containers. The UN-Habitat, with the support of European Union and local agencies, has published a rooftop farming training manual (2014) showing the feasibility of urban farming in Nepal.The paper discusses how Public Private Partnership (PPP) can promote urban agriculture and make the process more effective and attractive to urban farming households. It also analyzes how a PPP approach also facilitates the use of better technology, advisory support, and use of research extension activities. This paper draws on literature review, secondary data (e.g., from National Census Nepal 2021) and authors’ professional experiences related to best practices in the areas to analyze the benefits and challenges related to urban farming in Arizona, USA. The paper will provide recommendations for Nepali cities to maximize the benefit provided by urban farming. It is expected to be useful to Nepali policy makers, and government agencies, and nonprofit organizations which promote sustainability, and organic farming.

COVID-19 and long COVID-19 vulnerabilities may be caused indirectly by albumin binding deficiency (ABD) which can be corrected by the correct administration of human serum albumin (HSA). The liver is the primary site of nutrient regulation and fluid volume maintenance, control of both is by changes to albumin concentration. In healthy subjects the HSA lymphatic nutrient pump (HSALNP) ensures continual pumping of nutrients from the liver are appropriately distributed to organs. Nutrients are delivered to cells according to the availability of binding to HSA. The HSALNP therefore maintains the correct nutrients and colloidal pressure balance in all tissues independently. In unhealthy tissues, following COVID-19 infection, the passage of HSA/nutrients through the interstitial spaces and lymph will be impeded. Fluid therapy into the periphery leads to dilution of essential nutrients attached to the protein-carriers such as albumin. The levels of albumin being charged by the liver with nutrients is critical in maintaining immune stability by maintaining nutrient support and colloidal pressure of cellular structures. The site of HSA binding by the liver is of great importance and direct infusion of albumin into the Hepatic Portal Vein is the most appropriate method of maintaining colloid pressure and cellular nutrient levels.

Avian mutations in vaccine strains obtained from embryonated eggs could impair vaccine effec-tiveness. We performed a systematic review and meta-analysis of the adjusted relative vaccine effectiveness (arVE) of seed cell-cultured influenza vaccines (ccIV) compared to egg-based influ-enza vaccines (eIV) in preventing laboratory-confirmed influenza related outcomes (IRO) or IRO by clinical codes, in subjects 18 and over. We completed the literature search in January 2021; ap-plied exclusion criteria, evaluated risk of bias of the evidence, and performed heterogeneity, pub-lication bias, qualitative, quantitative and sensitivity analyses. All estimates were computed us-ing a random approach. International Prospective Register of Systematic Reviews, CRD42021228290. We identified 12 publications that reported 26 adjusted arVE results. Five publications reported 13 laboratory confirmed arVE and seven reported 13 code-ascertained arVE. Nine publications with 22 results were at low risk of bias. Heterogeneity was explained by season and risk of bias. We found a significant 11% (8 to 14%) adjusted arVE favoring ccIV in preventing any IRO in the 2017-2018 influenza season. The arVE was 3% (-01 to 7%) in the 2018-2019 influenza season. We found moderate evidence of a significant advantage of the ccIV in preventing IRO, compared to eIV, in a well-matched A(H3N2) predominant season.

Engineered nanomaterials (ENMs) are of significant relevance due to their unique properties, which have been exploited for widespread applications. Cerium oxide nanoparticles (CeO2-NPs) are one of most exploited ENM in the industry due to their excellent catalytic and multi-enzyme mimetic properties. Thus, toxicological effects of these ENMs should be further studied. Acute and subchronic toxicity of CeO2-NPs were assessed. First an in vitro multi-dose short-term (24h) toxicological assessment was performed in three different cell lines: A549 and Calu3, representing the lung tissue, and 3T3 as an interstitial tissue model. After that, a sub-chronic toxicity assessment (90 days) of these NPs was carried out on a realistic and well stablished reconstituted primary human airway epithelial model (MucilAir™), cultured at the Air-Liquid Interface (ALI), to study long-term effects of these particles. Results showed minor toxicity of CeO2-NPs in acute exposures. However, in subchronic exposures, cytotoxic and inflammatory responses were observed in the human airway epithelial model after 60 days of exposure to CeO2-NPs. These results suggest that acute toxicity approaches may underestimate the toxicological effect of some ENM, highlighting the need of subchronic toxicological studies in order to accurately assess the toxicity of ENM and their cumulative effects in the organism.

The knowledge of what separates us genetically from our less-evolved relatives is crucial for gaining new biomedical insights about the human-chimpanzee relatedness for the use of appropriate stand-in towards the development of new treatments and diagnostic aids for various ailments. Although the genomes of humans and chimpanzees share 99% similarity, significant differences exist between the two species in their non-coding intronic regions. However, no work has been carried out in the aspects of target prediction concerning the ‘predicted homology’ in their microRNA sequences. Non-coding miRNAs which are post-transcriptional regulators of development, differentiation, growth, and metabolism, harboring the intronic regions may be crucial for expanding the horizons of our understanding. In this study, we proposed to perform the target prediction for the human-chimp miRNA homologs in the PHEX gene of the human X chromosome using various computational tools and databases. We identified a total of 1296 human miRNAs, 46, 957 gene targets, and 30, 563 targets of human and homologous chimp miRNAs respectively. Furthermore, we analysed gene interacting networks to identify the top interacting targets in both the species. Finally, we interpreted the biological importance of top-interacting miRNAs and their targets. The results demonstrated varying levels of multiplicity and cooperativity between the predicted miRNAs and target genes in the two genera. Such miRNAs may be responsible for the dysregulation of gene expression in several signaling pathways.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

Pteridine reductase 1 is a trypanosomatid multifunctional enzyme that provides a mechanism for escape of Dihydrofolate reductase (DHFR) inhibition. This is because PTR1 can reduce pterins and folates. Trypanosomes require folates and pterins for survival and are unable to synthesize them de novo. Currently there are no anti-folate based Human African Trypanosomiasis (HAT) chemotherapeutics in use. Thus, successful dual inhibition of TbDHFR and TbPTR1 has implications in the exploitation of anti-folates. We carried out molecular docking of a ligand library of 5742 compounds against TbPTR1 and identified 18 compounds showing promising binding modes. The protein-ligand complexes were subjected to Molecular dynamics to characterize their molecular interactions and energetics followed by in vitro testing. In this study, we identified five potential TbPTR1 inhibitors that showed low micromolar Trypanosome growth inhibition in in vitro experiments with no significant human cell cytotoxicity. Compounds RUBi004, RUBi007, RUBi014, and RUBi018 displayed moderate to strong antagonism when used in combination with the known TbDHFR inhibitor, WR99210. This gave an indication that the compounds might inhibit both TbPTR1 and TbDHFR. RUBi016 showed an additive effect in the isobologram assay. Our results provide a basis for scaffold optimization for further studies in the development of HAT antifolates.

In order for robots to attain more general-purpose utility, grasping is a necessary skill to master. Such general-purpose robots may use their perception abilities in order to visually identify grasps for a given object. A grasp describes how a robotic end-effector can be arranged on top of an object to securely grab it between the robotic gripper and successfully lift it without slippage. Traditionally, grasp detection requires expert human knowledge to analytically form the task-specific algorithm, but this is an arduous and time-consuming approach. During the last five years, deep learning methods have enabled significant advancements in robotic vision, natural language processing, and automated driving applications. The successful results of these methods have driven robotics researchers to explore the application of deep learning methods in task generalised robotic applications. This paper reviews the current state-of-the-art in regards to the application of deep learning methods to generalised robotic grasping and discusses how each element of the deep learning approach has improved the overall performance of robotic grasp detection. A number of the most promising approaches are evaluated and the most successful for grasp detection is identified as the one-shot detection method. The availability of suitable volumes of appropriate training data is identified as a major obstacle for effective utilisation of the deep learning approaches, and the use of transfer learning techniques is identified as a potential mechanism to address this. Finally, current trends in the field and future potential research directions are discussed.

Background: Open AI developed ChatGPT, a language model based on the GPT architecture, designed for text-based communication. Trained on diverse internet texts, ChatGPT generates contextually appropriate responses using machine learning. It understands input through analysis and context interpretation, generating coherent and contextually relevant responses. Interaction is possible through messaging platforms. Materials and Methods: In November 2023, we utilized ChatGPT 3.5, the default version at that time, to answer questions from the Italian National Residency Program Admission Tests (SSMs) of 2021, 2022, and 2023. The questions cover clinical, diagnostic, analytical, therapeutic, and epidemiological scenarios, sometimes accompanied by images. The study compared ChatGPT's answers to the official corrections on the Italian Ministry of University and Research (MUR) website. The scoring method used for evaluation was 1 point for correct answers, 0 points for unanswered questions, and -0.25 points for incorrect answers, reflecting the SSM test scoring system. Results: In summary, ChatGPT was tested with a total of 420 questions, 140 for each test. It achieved an overall accuracy of 80.48%, providing correct answers for 338 questions and incorrect answers for 82 questions. When faced with questions containing both text and images, it answered 55% correctly and 45% incorrectly. The model's performance varied over time, with an 82.14% accuracy rate in 2021 and 2022 (115 correct out of 140) and a 77.14% accuracy rate in 2023 (108 correct out of 140). Applying thisscoring method to the SSM test, ChatGPT would have scored 105 points in 2021 and 2022, and 100 points in 2023. Conclusions: ChatGPT has exhibited above-average performance in the last three SSM tests, highlighting its robust capability to interpret clinical scenarios and offer precise diagnostic and therapeutic guidance. Despite this, some limitations persist, notably the software's inability to interpret non-textual information.

Background: Humoral memory and specific antibodies levels depend on kind of the antigen and individual immunofactors., The presence of IgM antibodies or fourfold rise in specific IgG level, are generally accepted as diagnostic in serology of acute viral infection. This basic model is not adequate for herpesvirome especially after hematopoietic stem cell transplantation (HSCT) due to continuous, usually multifocal antigenic stimulation, various donor serostatus, immunosuppresion and individual immunoreconstitution. Methods: A  case-control study was conducted for identifying cases of Human herpesviruses (HHV) active infection (from 300 diagnosed immunocompromised patients) and evaluating historically associated humoral factors to look at outcomes. We enrolled only patients’ data with meticulous differential diagnosis to exclude other causes, thereby observe pathways and temporal relationships, not statistical ones, usually collected in cohorts. Despite the small number such data collection and analysis avoids a number of biases and indicates cause and effect.Results. In the observational study retrospective analysis of data from 300 patients with clinical diagnosis of herpes simplex (HSV) and varicella zoster virus(VZV) reactivation showed a number of biases. In two well differentiated cases (confirmed by Tzanck test) with various disease and conditioning evolution of immunoparameters showed interesting pathway. Exponential decrease of specific IgG after HSCT precedes virus replication with cytopathic effect (shingles, VZV-encephalitis and HSV-induced mucositis). Minima (smallest IgG levels) before herpes virus reactivation were 234,23 mIU/ml and 94 RU/ml for VZV and HSV, respectively. This coincides with low CD4 titer, but without other infectious process. Other immune response parameters such as Treg, cytotoxic T cells, complement and total IgG level were quite the same as before the transplant procedure. Interestingly, the second wave of immunoreconstitution with anamnestic antibody response was not always observed. It coincided with prolonged herpes viral infection. Patient with lymphocyte depletion in conditioning showed earlier second wave of immunoreconstitution (6th vs 14th month) Conclusions: Typical for infancy kinetics of IgG level is unique after HSCT (the decline phase is first). Host-microbiome factors (i.e. HHV1-3 -serostatus) should be taken into account to predict risk of non-relapse mortality and survival after HSCT. The levels of specific antibodies help to predict the prognosis and improve the management. The lack of differentiation, assessor and confusing bias are the main obstacles in statistical HHV1-3 research. Such time-lapse case studies may be first to build evidence of a pathway and association between immunoparameters and HHV disease.

This study centered on examining 60 different antibiotics by assessing their primary toxicity parameters through the pkCSM database. The parameters included Max. Tolerated Dose (Human) (log mg/kg/day), Oral Rat Acute Toxicity (LD50) (mol/kg), Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day), and Minnow Toxicity (LC50) (log mM). The results highlight four potential antibiotics—cefotaxime, ceftriaxone, imipenem, and meropenem—that exhibited lower toxicity effects compared to other compounds. These findings imply a relatively favorable safety profile for these antibiotics concerning the specified toxicity parameters. However, it is crucial to interpret these outcomes within the context of the specific clinical application and to consider additional factors for a comprehensive safety assessment. It's essential to acknowledge that evaluating toxicity is intricate, and the determination of what is considered "less toxic" can rely on specific criteria and the context of use. Furthermore, individual responses to antibiotics may vary, and the selection of an antibiotic should be based on diverse factors, including the specific infection being treated, the patient's health, and potential side effects.

This research investigates the potential application of generative language models, especially ChatGPT, in aviation safety analysis as a means to enhance the efficiency of safety analyses and accelerate the time it takes to process incident reports. In particular, ChatGPT was leveraged to generate incident synopses from narratives, which were subsequently compared with ground truth synopses from the Aviation Safety Reporting System (ASRS) dataset. The comparison was facilitated by using embeddings from Large Language Models (LLMs), with aeroBERT demonstrating the highest similarity due to its aerospace-specific fine-tuning. A positive correlation was observed between synopsis length and their cosine similarity. In a subsequent phase, human factor issues involved in incidents as identified by ChatGPT were compared to human factor issues identified by safety analysts. A concurrence rate of 61% was found, with ChatGPT demonstrating a cautious approach towards attributing human factor issues. Finally, the model was used to attribute incidents to relevant parties. As no dedicated ground truth column existed for this task, a manual evaluation was conducted. ChatGPT attributed the majority of incidents to the Flight Crew, ATC, Ground Personnel, and Maintenance. This study opens new avenues for leveraging AI in aviation safety analysis.

Mobile phones have become an integral part of our lives in the last two decades, leaving a digital trace of our activities and communication. This study aims to develop a data processing framework to evaluate human mobility and socioeconomic status based on call detail records. The methodology proposed first calculates radius of gyration and entropy for each user, then estimates the socioeconomic status by the price and age of the subscribers' phones. Finally, an unsupervised machine learning algorithm was used to group the cells into clusters based on their mobility and socioeconomic metrics. The research showed differences between Buda and Pest during a large scale social event using mobile phone ages and prices. Additionally, the clustering results revealed homogenous groups of cells around Budapest, with similar mobility and socioeconomic metrics. The main conclusion is that mobile network data combined with mobile phone properties offer a useful tool for characterising urban mobility and socioeconomic status.

ABSTRACT. The immunotherapies, as a modern therapeutic approach, get an attention because of theirs’ promise to treat a large number of different medical disorders. Immunomodulation effects of low titres (10 HA/ml) of NDV (Newcastle Disease Virus) ZG1999HDS or La Sota were tested on TLT (Human macrophage cell line) bound to PBMC (Peripheral Blood Mononuclear Cells). During the immunomodulation, the amount of NO, H2O2, lysozym and induced antibacterial activity against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) and against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) were analysed. In addition, the cytokine secretion, IL-1α, IL-2, IL-4, GM-CSF, TNF-α, IFN-α and IFN-α were evaluated. Firstly, the TLT cells are activated through the NDV ZG1999HDS or La Sota binding, followed by the NO “burst” and H2O2 and lysozyme level increase. Secondly, after the binding to the TLT cells and interaction with the PBMCs, the decrease of GM-CSF, and an increase of TNF – α and IFN – γ were found. Simultaneously, the decrease of pro – inflammatory cytokine IFN-α and the differentially increase of IL-1α, IL-2 and IL-4 were recorded. During the induction of the antibacterial response, against Gram - positive bacteria (Staphylococcus aureus, MRSA, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus mutants) the effect was one third higher with NDV ZG1999HDS compared to La Sota. Antibacterial response against Gram - negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Acinetobacter baumanii) was not so clear. In general, NDV ZG1999HDS or La Sota activated TLT cells, further bound to PBMC; the ZG1999HDS is stronger immunomodulator than La Sota.

The biology of sexual orientations has intrigued people for generations. Many models have been providing insights to that topic, but there are still unanswered questions. In humans, sexual orientation has a learned component. Humans have to learn cues by which they identify the sex of their mates, and cues of the emotional messages that those mates broadcast. Many of those cues depend on arbitrary societal conventions. The cues are learned automatically and subconsciously during childhood, based on non-sexual experiences. When sexual orientation emerges at puberty, the youngsters cannot tell how and when they have acquired it. A model that deals with those phenomena is presented. A basic tenet of the model is that a sexual orientation is determined by the innate wirings of the brain. The model describes how the brain learns cues for identifying the sex of the mate, and cues for identifying emotional messages that the mate broadcasts. The learning mechanism is conditioning. The unconditioned stimulus is human voice. The unconditioned responses are the triggers of the physical and emotional manifestations of sexual activity. The model suggests that innate connections from auditory detectors of men’s and women’s voice onto brain centers that trigger sexual activities, such as the hypothalamus, determine the sexual orientation that emerges at puberty. Innate connections from those auditory centers to emotional centers, such as the amygdala, determine the learned emotional cues. It is also proposed that during evolution, the roles of the chemosensory system in identifying mates were taken over by the auditory system.

This article presents and discusses analytical data on the scientific publication record from 1910 to 2020 on two topics: "climate" and "climate change/global warming/climate emergency". The goal is to visualize how the publication record on these two topics has evolved over time, from different classification perspectives (year, country, source and organization). Three hypotheses are tested using data collected from Web of Science and various graphical representations of the data. It is found that research output related to the Earth’s contemporary changing climate overtook that of general climate research in 2011, and the publication ratio has been expanding in the last decade. There are significant differences in the publication countries and sources between the two topics, and conversely less significant differences in terms of organizations publishing these works. Differentiation factors that affect the level of research output and engagement on the climate challenge include: island versus landlocked nations, specialized versus general scientific journals, academic versus institutional organizations. The future of the publication records is discussed, such as the emergence of new terms to refer to the climate challenge, such as “climate emergency”.

The Model-View-Controller (MVC) architecture, a cornerstone of modern software engineering, offers a robust framework for developing dynamic user interfaces. This paper conducts a broad analysis of MVC’s deployment across various sectors, emphasizing its critical role in technological advancement and market integration. By examining implementation strategies in web development, mobile applications, and enterprise solutions, the study illustrates how MVC enhances application manageability, promotes efficient code reuse, and facilitates parallel development. The paper explores the adoption of MVC principles within major technologies such as Java, .NET, and JavaScript frameworks, underlining its widespread acceptance. Additionally, the analysis covers the preferential use of MVC frameworks within diverse market sectors including technology enterprises, educational institutions, e-commerce, and financial services, which leverage MVC for superior data management and user experience. Emerging trends such as the shift towards the Model-View-ViewModel (MVVM) architecture and the integration of MVC with artificial intelligence and machine learning technologies are also discussed. This comprehensive review not only reaffirms MVC’s enduring relevance but also its adaptive evolution in response to emerging technological demands and market needs.

One in 12 babies is born with a rare genetic disease. Sadly, most cases are undetected until later age, missing time for early treatment and opportunity to prevent complications. Humanity has entered a new era where Big Data collected by governments, including 2D and 3D facial scans, are available. Many rare genetic diseases can be identified by artificial intelligence (AI) analysis of the facial photo. Phenotyping AI utilizations facilitate comprehensive and accurate genetic evaluations. AI processing of this Big Data to identify rare genetic diseases could bring unimaginable benefits to healthcare, although this would be a questionable step in terms of citizen privacy and could lead to future "Orwellian" ramifications with government abuse. Going forward, a balance must be found between protecting the privacy of citizens and the enticing use of AI for their health risks and cost savings through prevention. The unimaginable potential of AI early diagnostics from facial photos also raises various ethical and legal concerns. This paper presents concept, protentional methods and legal and other limitations within EU legal framework in contrast with potential benefits. This paper is focused on AI utilization to early diagnostic of rare genetic diseases. Shift of paradigm in the screening for rare genetic diseases in population with AI face analysis is expected to have a significant impact. The potential of AI algorithms utilizations similar to face2gene app in general population or systematically on Big governmental datasets recording facial traits changes in time can have significant impact on public health but at the same time give raise to profound concern as violation of one’s privacy.

Digital technologies have changed the way supply chain operations are structured. In this article, we conduct systematic syntheses of literature on the impact of new technologies on supply chains and the related cyber risks. A taxonomic/cladistic approach is used for the evaluations of progress in the area of supply chain integration in the Industrial Internet of Things and Industry 4.0, with a specific focus on the mitigation of cyber risks. An analytical framework is presented, based on a critical assessment with respect to issues related to new types of cyber risk and the integration of supply chains with new technologies. This paper identifies a dynamic and self-adapting supply chain system supported with Artificial Intelligence and Machine Learning (AI/ML) and real-time intelligence for predictive cyber risk analytics. The system is integrated into a cognition engine that enables predictive cyber risk analytics with real-time intelligence from IoT networks at the edge. This enhances capacities and assist in the creation of a comprehensive understanding of the opportunities and threats that arise when edge computing nodes are deployed, and when AI/ML technologies are migrated to the periphery of IoT networks.

Congenital breast asymmetry represents a particular challenge to the classical techniques of plastic surgery due to a young group of patients. This study compares traditional breast augmentation using silicone implants to the more innovative lipograft technique regarding long-term results. To achieve this, we not only captured subjective parameters like satisfaction with outcome and symmetry, but also objective parameters such as breast volume and anthropometric measurements. Objective examination was performed manually and by using the Vectra® H2 photogrammetry scanning system. Patients who underwent implant augmentation and lipograft both showed no significant differences in patient´s satisfaction with surgical outcome (p = 0.55) and symmetry (p = 0.69). Furthermore, a breast symmetry of 93 % in both groups was reported. Likewise, no statistically significant volume difference between left and right breast was observed in both groups (p<0.41). However, on average, lipograft patients needed 1.3 procedures more until the desired result was achieved. In contrast, patients treated with implant-based breast augmentation usually need several implant changes during their life. In conclusion, both methods should be considered for patients with congenital breast asymmetry.

Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications, formed by reducing sugars and carbonyl products of their degradation. Resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied in respect of glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in dramatic suppression of primary seed metabolism, although secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.

Abstract5′,8-Cyclo-2′-deoxyadenosine (cdA), in the 5′R and 5′Sdiastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA. So far, it was unknown whether the diastereomeric cdA lesions could induce specific PARP1 binding. Here we provide the first evidence of PARP1 to selectively recognize the diastereomeric lesions 5′S-cdA and 5′R-cdA in vitro as compared to deoxyadenosine in model DNA substrates (23-mers) by using circular dichroism,fluorescence spectroscopy, immunoblotting analysis and gel mobility shift assay. Several features of the recognition of the damaged and undamaged oligonucleotides by PARP1were characterized. Remarkably, PARP1 efficiently binds to both cdA lesions in the double stranded (ds)-oligonucleotides. In particular, PARP1 proved to bind 5′S-cdAwith a higher affinity constant for the 5'S lesion in a model of ds DNA than 5′R-cdA, showing different recognition patterns, also compared with undamaged dA. This new finding highlights the ability of PARP1 to recognize and differentiate the distorted DNA backbone in a biomimetic system caused by different diastereomeric forms of a cdA lesion.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

Dry eye disease (DED) is a multifactorial disorder in which tear fluid homeostasis is lost, resulting in increased tear film osmolarity and ocular surface irritation. In Asia, the short tear film breakup time type-DED is common, and stabilization of the tear film is the first goal of treatment. Treatment of DED begins with eye drops. Until now, artificial tears and steroid eye drops have been the main treatment for DED. However, artificial tears require frequent administration of eye drops and thus pose adherence problems, while steroids have problems with side effects (cataracts, increased intraocular pressure). This review evaluates the new generation of DED therapies in Asia based on what is known about them and demonstrates that they are more effective for DED than traditional therapies such as artificial tears and steroids. Based on these considerations, it is proposed that the optimal treatment for DED in Asia is the initial application of mucin secretion enhancing eye drops (long-acting diquafosol) and oral supplements, and if additional treatment is needed, cyclosporine eye drops and the adjunctive therapies presented in this review are added.

This paper is referred to a top frontline research in life science, showing that in spite of the large variation of the physiological architecture and behavioral forms of the living systems, the fundamental structure of their informational system is basically the same, allowing the body growth/development by micro to macro-structuration processes, maintaining the same informational configuration and functions like the basic unit of life – the eukaryotic cell. Starting and based on the determination of the special/specific info-operability in living structures and the role of information in structuration and their functionality, there are discussed the informational functions of the eukaryotic/prokaryotic cells, the simplest units of life and is elaborated and presented the Informational Model of the Living Structures, showing that these structures operate on the basis of two main informational systems: one of them defined as the Programmed Informational System, composed by three components, assuring respectively the info-generation, maintenance and the proliferation/reproduction, and another one defined as the Operative Informational System, necessary for the continuous communication with the environment for adaptation, consisting in four main components referred to memory, decision, sentience and info-connection/info-selection. The revealed properties are compared with the Informational System of the Human Body, as a prototype of a living system on the top of the evolutionary scale, showing/demonstrating the compatibility of structuration and functions on the entire scale, from prokaryotic/eukaryotic unit cells to multicellular organisms – plants, animals and human, by means of a continuous adaptation process, which always follows the same line of micro to macro-structuration process based on the same Info-organization and functionality. These models are new and revolutionary in the information and life sciences

The urgency to develop vaccines against Covid-19 is putting pressure on the long and expensive development timelines which are normally required for development of lifesaving vaccines. There is a unique opportunity to take advantage of new technologies, smart and flexible design of clinical trials, and evolving regulatory science to speed up vaccine development against Covid-19 and transform vaccine development altogether.

The development of nucleic acid sequencing technology and the unprecedented availability of metadata has evidenced that 45% of human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically needed. Aberrant regulation of TEs, and of human retroviral endogenous sequences (HERVs) in particular, associates with several neurologic and autoimmune diseases, including the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) frequently comorbid with fibromyalgia (FM). However, no study has yet addressed whether abnormal expression of these sequences correlates with FM. The work presented here shows, for the first time, that in fact HERVs of the H, K and W types are overexpressed in the cells of the immune system of FM patients with or without comorbid ME/CFS. The patients with increased HERV expression (N=14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. In support of our proposal that TE activation is a contributor to FM, we find that the tRNA pools are decreased in comparison to matched healthy participants (N=14). The findings reported here could explain the flu-like symptoms FM patients present with in the absence of concomitant infections. Future work towards identifying specific genomic loci differentially affected in FM and ME/CFS is granted.

Among the many Lysosomal Storage Disorders (LSDs) that would benefit from the establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem cell transplantation (HSCT) may also hold promise whenever the disorder is diagnosed soon enough, both approaches have their own drawbacks. Here we present our results on the establishment and characterization of two MPS II pa-tient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population is isolated from LSD patient samples obtained from the oral cavity. Taking into account our results on the molecular and biochemical characterization of those cells and our first insights on their subcellular MPS phenotype, we consider these cells will be a valuable tool for both pathophysiological assessments and drugs screenings. Ultimately, we believe patient-derived dental pulp stem cells (DPSC) may represent a feasible alternative to induced pluripotent stem cells (iPSC) in many labs with standard cell culture con-ditions and limited (human and economic) resources.

A recent study published in Nature Medicine (Mautner et al., Nat Med 2023 Nov 2. doi: 10.1038/s41591-023-02632-w. Epub ahead of print) reported findings regarding a four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients, aimed at comparing the therapeutic effectiveness of orthobiologic interventions against corticosteroid injections for the treatment of knee osteoarthritis (OA). The study concluded that, one-year post-treatment, all orthobiologic therapies examined were equivalent in effectiveness to each other and to corticosteroid injections. While we commend the scope and methodological rigor of the trial, the publication could be enhanced by a more comprehensive presentation of data to support the conclusions drawn. Particularly, the omission of baseline data for primary outcomes, the missing context to evaluate absolute values, the lack of discussion regarding interindividual variability, and the unexpectedly favorable results for corticosteroids that contrast the established literature, are areas that merit additional examination and insight. Here we aim to highlight these points for consideration, and advocate for the release of supplementary data to facilitate a comprehensive understanding and utilization of this rich dataset.

Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.

This paper presents a novel integration of Systems Engineering (SE) methodologies and Industry 4.0 (I4.0) technologies in the design of robotic systems, with a focus on enhancing underwater robotic missions. Using the conceptual design of an underwater exploration vehicle as a case study, we demonstrate how SE can systematically incorporate I4.0 tools to improve mission performance and meet stakeholder expectations. The study begins with an overview of the SE approach, emphasizing the conceptual design stage, aligning with the application and case study of design theories. We then explore various I4.0 technologies, highlighting their functional benefits rather than technical specifics, addressing design methods for Industry 4.0. Remotely Operated Vehicles (ROVs) are examined in terms of classification, components, and tasks, showcasing their evolution driven by technological advancements, thus tackling the complexity and design of complex systems. The core of our study involves defining stakeholder expectations, using quality function deployment for requirements definition, and performing a functional and logical decomposition of the ROV system. Our approach underscores the importance of understanding and integrating new technologies functionally, aligning with the transition towards Industry/Society 5.0. This work not only illustrates the synergy between SE and I4.0 but also offers a structured methodology for advancing the design and functionality of complex systems, setting a blueprint for future developments in this field.

Recombinant human collagen peptide (RCP) is a recombinantly created xeno-free biomaterial enriched in RGD (arginine-glycine-aspartic acid) sequences, with good processability that is being investigated for regenerative medicine applications. Recently, the biocompatibility and osteogenic ability of β-TCP/RCP (RCP granules combined with β-tricalcium phosphate (TCP) submicron particles) were demonstrated. In the present study, β-TCP/RCP was implanted into experimental periodontal tissue defects (three-walled bone defect) created in beagle dogs to investigate tissue responses and subsequent regenerative effects. Micro computed tomography image analysis at 8 weeks postoperatively showed that the amount of new bone after β-TCP/RCP graft was significantly greater (2.2 fold, P&lt;0.05) than that of the control (no graft) group. Histological findings showed that the transplanted β-TCP/RCP induced active bone-like tissue formation including TRAP-positive and OCN-positive cells as well as bioabsorbability. Ankylosis did not occur, and periostin-positive periodontal ligament-like tissue formation was observed. Histological measurements revealed that β-TCP/RCP implantation formed 1.7-fold more bone-like tissue and 2.1-fold more periodontal ligament-like tissue than the control, and significantly suppressed gingival recession and epithelial downgrowth (P&lt;0.05). These results suggest that β-TCP/RCP is effective as a periodontal tissue regenerative material.

Camptothecin (CPT) is a potent anticancer drug, and its putative oral administration is envisioned although difficult due to physiological barriers that must be overcome. A comprehensive biophysical analysis of CPT interaction with biointerface models can be used to predict some pharmacokinetic issues after oral administration of this or other drugs. To that end, different models were used to mimic the phospholipid composition of normal, cancer, and blood-brain barrier endothelial cell membranes. The logD values obtained indicate that the drug is well distributed across membranes. CPT-membrane interaction studies also confirm the drug’s location at the membrane cooperative and interfacial regions. The drug can also permeate membranes at more ordered phases by altering phospholipid packing. The similar logD values obtained in membrane models mimicking cancer or normal cells imply that CPT has limited selectivity to its target. Furthermore, CPT binds strongly to serum albumin, leaving only 8.05% of free drug available to be distributed to the tissues. The strong interaction with plasma proteins, allied to the large distribution (VDSS=5.75 ± 0.932 L·Kg-1) and tendency to bioaccumulate in off-target tissues, were predicted to be pharmacokinetic issues of CPT, implying the need to develop drug delivery systems to improve its biodistribution.