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.

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”.

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.

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.

In the wake of rapid advancements in artificial intelligence (AI) and sensor technologies, a new horizon of possibilities has emerged across diverse sectors. Livestock farming, a domain often sidelined in conventional AI discussions, stands at the cusp of this transformative wave. This paper delves into the profound potential of AI and sensor innovations in reshaping animal welfare in livestock farming, with a pronounced emphasis on a human-centric paradigm. Central to our discourse is the symbiotic interplay between cutting-edge technology and human expertise. While AI and sensor mechanisms offer real-time, comprehensive, and objective insights into animal welfare, it's the farmer's intrinsic knowledge of their livestock and environment that should steer these technological strides. We champion the notion of technology as an enhancer of farmers' innate capabilities, not a substitute. Our manuscript sheds light on: Objective Animal Welfare Indicators: An exhaustive exploration of health, behavioral, and physiological metrics, underscoring AI's prowess in delivering precise, timely, and objective evaluations. Farmer-Centric Approach: A focus on the pivotal role of farmers in the adept adoption and judicious utilization of AI and sensor technologies, coupled with discussions on crafting intuitive, pragmatic, and cost-effective solutions tailored to farmers' distinct needs. Ethical and Social Implications: A discerning scrutiny of the digital metamorphosis in farming, encompassing facets like animal privacy, data safeguarding, responsible AI deployment, and potential technological access disparities. Future Pathways: Advocacy for principled technology design, unambiguous responsible use guidelines, and fair technology access, all echoing the fundamental principles of human-centric computing and analytics. In essence, our paper furnishes pioneering insights at the crossroads of farming, animal welfare, technology, and ethics. It presents a rejuvenated perspective, bridging the chasm between technological advancements and their human beneficiaries, resonating seamlessly with the ethos of the Human-Centric Intelligent Systems journal. This comprehensive analysis thus marks a significant stride in the burgeoning domain of human-centric intelligent systems, especially within the digital livestock farming landscape, fostering a harmonious coexistence of technology, animals, and humans.

The innate and adaptive immune systems collaborate to detect SARS-CoV-2 infection, minimize the viral spread, and kill infected cells, ultimately leading to the resolution of the infection. The adaptive immune system develops a memory of previous encounters with the virus, providing enhanced responses when rechallenged by the same pathogen. Such immunological memory is the basis of vaccine function. Here, we review the current knowledge on the immune response to SARS-CoV-2 infection and vaccination, focusing on the pivotal role of T cells in establishing protective immunity against the virus. After providing an overview of the immune response to SARS-CoV-2 infection, we describe the main features of SARS-CoV-2-specific CD4+ and CD8+ T cells, including cross-reactive T cells, generated in patients with different degrees of COVID-19 severity, and of Spike-specific CD4+ and CD8+ T cells induced by vaccines. Finally, we discuss T cell responses to SARS-CoV-2 variants and hybrid immunity and conclude by highlighting possible strategies to improve the efficacy of COVID-19 vaccination.

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.

HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing HLA-E monomeric heavy chain (HC) (Open Conformers, OCs). Two of the mAbs (TFL-006 and TFL-007) bound to the HC’s coated on a solid matrix. The binding was inhibited by a peptide 117AYDGKDY123, present in all alleles of the six HLA-I isoforms but masked by 2-microglobulin -m) in intact HLA-I trimers (Closed Conformers, CCs). Identical HLA-I polyreactivity is observed in IVIg administered to lower anti-HLA antibodies (Abs) in HLA-sensitized patients, but the mechanism is unknown. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might mimic the immunomodulatory functions of IVIg. We tested the relative binding affinity of the mAbs and IVIg for both OCs- and CCs and compared their effects on (a) the phytohemagglutinin (PHA)-activation T-cells, (b) the production of anti-HLA-II antibody (Ab) by B-memory cells, and anti-HLA-I Ab by immortalized B-cells, and (c) the upregulation of CD4+, CD25+, and Fox P3+ T-regs. The mAbs bound only to OCs, whereas IVIg is bound to both CCs and OCs. The mAbs suppressed blastogenesis and proliferation of PHA-activated T-cells, anti-HLA Ab production by B-cells and expanded the T-regs, better than IVIg. We conclude that a humanized version of the TFL-mAbs could be an ideal therapeutic IVIg-mimetic.

Recent improvements in deepfake creation have made deepfake videos more realistic. Moreover, open-source software has made deepfake creation more accessible, which reduces the barrier to entry for deepfake creation. This could pose a threat to the people’s privacy. There is a potential danger if the deepfake creation techniques are used by people with an ulterior motive to produce deepfake videos of world leaders to disrupt the order of countries and the world. Therefore, research into the automatic detection of deepfaked media is essential for public security. In this work, we propose a deepfake detection method using upper body language analysis. Specifically, a many-to-one LSTM network was designed and trained as a classification model for deepfake detection. Different models were trained by varying the hyperparameters to build a final model with benchmark accuracy. We achieved 94.39% accuracy on the deepfake test set. The experimental results showed that upper body language can effectively detect deepfakes.

The unresolved territories are privileged places for the proliferation of degradation phenomena that affect the environment and human well-being. The impacts of their critical conditions go beyond the limits of the damaged urban fragments, involving the built environment, society, economy, culture and conditioning quality of life. This paper proposes a methodological approach to landscape design supported by an evaluation framework to orient strategic design planning with specific attention to unresolved territories consistent with circular economy perspective. The circular city principles are applied to spatial planning of landscape, by operationalising Ecosystem Services, Landscape Services, and Ecosystem Disservices, as interpretative categories for multi-dimensional regenerative strategies. Starting from the theoretical framework, the objective of the analysis is to implement an approach to the regenerative design of landscapes of waste, defined wastescapes. The industrial area of East Naples is the case study where an incremental evaluative approach has been defined to design scenarios to provide services and values, aimed to drive the conversion in a regenerativescape. A multi-criteria analysis through PROMETHEE-GAIA method has been implemented to compare the base case scenario with two incremental new scenarios and identify situated sustainable priorities.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

Background: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population. Methods: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed. Results: HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p&lt;0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women. Conclusion: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

In this article, we introduce a new approach to human movement by defining the movement as a static object or a super object in one two-dimensional image. This method can allow researchers to label and describe the total movement as an object isolated from a reference video. This ap-proach allows us to perform various tasks, including finding similar movements in a video, measuring, and comparing movements, generating new similar movements, and defining chore-ography by controlling specific parameters in the human body skeleton. As a result of the pre-sented approach, we can eliminate the need to label images manually, disregard the problem of finding the beginning and the end of a movement, overcome synchronization issues between movements, and perform any deep learning network-based operation that processes super objects in images in general. As part of this article, we will demonstrate two application use cases: one il-lustrates how to verify and score a requested movement. In contrast, the other illustrates how to generate similar movements in the human skeleton space by addressing the challenge of supply-ing sufficient training data for deep learning applications (DL). A Variational Auto Encoder (VAE) simulator and an EfficientNet-B7 classifier architecture embedded within a Siamese twin neural network are presented in this paper in order to demonstrate two use cases. These use cases demonstrated the versatility of our innovative concept in measuring, categorizing, inferring hu-man behavior, and generating gestures for other researchers.

The Environmental interactions contributed to the processes of settlement and development of the first settlers at southern Peru 15,000 BC. The determination of this process is based on paleoclimatic studies at southern Peru and ethnoarchaeological evidence. The determination of this process is based on paleoclimatic studies of southern Peru and ethnoarchaeological evidence; establishing as a result of this analysis the hypothesis of environmental interaction and territorial occupation of the first hunter-gatherer populations until their consolidation, dominating the geographical space from Tacna. The Disruptive disaster events and their effects on climate during the Peruvian Paleolithic resulted in the origin of local societies that shaped the Tiawanaku societies of the early horizon at Southern Peru and Northern Chile.

In order to counter the impending shortage of skilled professionals in the aging societies of our time in many western countries such as Germany, solutions for business and society are urgently needed. Here, artificial intelligence (AI) can play an important role in mitigating the problem with the help of diverse applications. At the same time, it is important to consider both the needs of the respective employee1 and the company to ensure that the use of AI has a positive impact on the organization and finds social acceptance. In this article, we describe the newly developed OSQE model (Optimize, Secure, Qualify, Expand), which for the first time outlines an AI cycle against the shortage of skilled professionals in a holistic approach that focuses equally on people and companies. This can serve organizations as a guide for strategy development, decision-making for and implementation of AI-supported measures in an entire cycle of an employee's affiliation with a company. The model takes three driving forces into account: companies, professionals, and AI applications. In the model, the measures to be implemented are prioritized with ascending numbering based on what would be most urgent for a company to implement. All measures relate to areas of action that place people at the center and can be assigned to the classic cycle of belonging of an employee in the company. In this regard, the opportunities that AI offers to professionals and companies are highlighted.

The COVID-19 pandemic drew public attention back to the living conditions related to housing, access to green areas in close neighbourhood and nearby recreation. Several studies confirm that visiting green spaces improved the health and wellbeing in times of crisis. This representative study for the metropolitan area of Vienna, Austria’s capital, confirms the high relevance of contact with nature, particularly for citizens to cope with the negative consequences and perceived stress, anxiety, nervousness and many other negative symptoms experienced during the health crisis. It highlights the importance of nearby smaller but also medium to large scale green areas in cities for health and wellbeing of the population. Moreover, it specifically adds novel insights on age effects in use and perception of urban green spaces during COVID-19 pandemic. The online panel survey (n=1012) was conducted in summer 2021. In order to obtain a representative sample reflective of the population’s characteristics, a (stratified) random sample was selected by applying the quota method. The objective was to obtain a sample which represented gender, age and regional distribution of the population of the City of Vienna as well as the immediately surrounding local communities. Interestingly, particularly young people spent more time outside in green areas during the pandemic, discovered novel spaces for the first time and stated a high relevance of contact with nature for their wellbeing. Elderly people above sixty five, on the contrary, stayed more frequently at home. Significant differences are visible between the age groups also with regard to negative symptoms experienced in case of restricted access to green areas due to strict pandemic measures such as lockdowns and quarantine. All age groups, however, similarly acknowledged the importance of green areas for their physical, mental and emotional health in general during the pandemic.

The human ankle is a complex joint, most commonly represented as talocrural and subtalar axes. It is difficult to locate and take in vivo measurements of the ankle joint. There are no instruments for patients lying on a bed or the floor; that can be used in outdoor or remote sites. We have developed a "Turmell-meter" to address these issues. We started with the study of ankle anatomy and anthropometry, then we used the product of exponentials’ formula to visualize the movements. Furthermore, we built a prototype using human proportions and statistics. For pose estimation, we used a trilateration method by applying tetrahedral geometry. Additionally, we computed the axis direction by fitting 3D circles, plotting the manifold and chart as an ankle joint model. We presented the results of simulations, a prototype comprising 45 parts, specifically designed draw-wire sensors, and electronics. Finally, we tested the device by capturing positions and fitting them into the bi-axial ankle model as a Riemannian manifold. The Turmell-meter is intended to be a hardware platform for human ankle joint axis estimation, it is adjustable and has an easy setup. The proposed model has the properties of a chart in a geometric manifold, we provided the details

Retinal apoptosis plays a critical role in the progression of diabetic retinopathy (DR), a common diabetic complication. Currently, the tight control of blood glucose levels is the standard approach to prevent or delay the progression of DR. However, prevalence of DR among diabetic patients remains high. Focusing on natural nutrients or herbal medicines that can prevent or delay the onset of diabetic complications, we administered an ethanol extract of the aerial portion of Osteomeles Schwerinae (OSSCE), a Chinese herbal medicine, over a period of 17 weeks to spontaneously diabetic Torii (SDT) rats. OSSCE was found to ameliorate retinal apoptosis through the regulation of advanced glycation end products (AGEs) accumulation, oxidative stress, and mitochondrial function via inhibition of NF-κB activity, in turn through the downregulation of PKCδ, P47phox, and ERK1/2. We further demonstrated in 25 mM glucose-treated human retinal microvascular endothelial cells (HRMECs) that hyperoside (3-O-galactoside-quercetin), quercitrin (3-O-rhamnoside-quercetin), and 2''-O-acetylvitexin (8-C-(2''-O-acetyl-glucoside)-apigenin) were the active components of OSSCE that mediated its pharmacological action. Our results provide evidence that OSSCE is a powerful agent that may directly mediate a delay in development or disease improvement in patients of DR.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein which leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed.

Background: Over the past two decades, the Copenhagen Psychosocial Questionnaire (COPSOQ) has been established as a valid instrument to measure psychosocial stress at work. Currently, the COPSOQ international network is responsible for monitoring and improving COPSOQ. In 2019, a new questionnaire was published, and the Greek version is now being validated. Methods: The measurement qualities of the Greek COPSOQ III have been explored in accordance with the usual requirements of a validation study as defined by DIN EN ISO 10075-3. A sample of observations from 2,189 participants surveyed with the COPSOQ in Greece was used to validate the current version with appropriate statistical analyses. Exploratory factor analysis was used to assess the statistical relationships for many scales. Results: With its 108 items and 40 scales, the Greek COPSOQ III includes all psychosocial work factors that have been internationally validated and remain compatible with approximately 72% of the COPSOQ III German version content. In addition to the primary results, congruence with widely used theoretical approaches such as the demand-control (−support) model (DCM) or the job demands-resources model (JDR) is generally satisfactory. In summary, our validation study for the Greek COPSOQ III version showed adequate reliability and validity, which is in line with the findings of the COPSOQ III questionnaire from other European countries, and it is also compatible with the validation of the German COPSOQ III (Lincke, 2021). Our regression analysis revealed that 34 psychosocial work factors (34 “context” scales) could adequately predict the scores of the satisfactory and health scales (6 “outcome” scales). The analysis also revealed the top five (5) predictors (context variables) for each of the six (6) “effect” scales (outcome variables). Conclusions: With the launch of COPSOQ III in Greece, current and new workplace psychosocial aspects could be explored. COPSOQ III (GR) is a beneficial instrument for enterprise research and risk assessment.

Air pollution has been a major environmental issue worldwide from the last few decades. It is a man-made issue that has a serious harmful impact on the environment and the health of humans. There are different sources of emission, but industrial processes and motor vehicles contribute to a chief part of air pollution. It has acute as well as chronic effects on the health of humans and affects different organs. It is thought the main environmental risk factor in the incidence and progression of several diseases such as lung cancer, asthma, Alzheimer's and Parkinson's diseases. Long-term exposure to air pollution has different toxicological impacts on humans such as respiratory and cardiovascular diseases, neuropsychiatric complications, eye irritation and skin diseases. As per the study by the World Health Organization (WHO), nitrogen oxides (NOx), carbon monoxide (CO), ozone (O₃), sulfur dioxide (SO₂), volatile organic compounds (VOCs) and heavy metals are the major air contaminants. These pollutants are different in their properties, composition and time of disintegration. The aim of this study is to review the different sources, types, impacts, challenges and mitigation of air pollution in detail.

Smart Living, an increasingly prominent concept, entails incorporating sophisticated technologies in homes and urban environments to elevate the quality of life for citizens. A critical success factor for Smart Living services and applications, from energy management to healthcare and transportation, is the efficacy of human action recognition (HAR). HAR, rooted in computer vision, seeks to identify human actions and activities using visual data and various sensor modalities. This paper extensively reviews the literature on HAR in Smart Living services and applications, amalgamating key contributions and challenges while providing insights into future research directions. The review delves into the essential aspects of Smart Living, the state of the art in HAR, and the potential societal implications of this technology. Moreover, the paper meticulously examines the primary application sectors in Smart Living that stand to gain from HAR, such as smart homes, smart healthcare, and smart cities. By underscoring the significance of the four dimensions of Context Awareness, Data Availability, Personalization, and Privacy in HAR, this paper serves as a valuable resource for researchers and practitioners striving to advance Smart Living services and applications.

Smart living, a concept that has gained increasing attention in recent years, revolves around integrating advanced technologies in homes and cities to enhance the quality of life for citizens. Sensing and human action recognition are crucial aspects of this concept. Smart living applications span various domains, such as energy consumption, healthcare, transportation, and education, which greatly benefit from effective human action recognition. This field, originating from computer vision, seeks to recognize human actions and activities using not only visual data but also many other sensor modalities. This paper comprehensively reviews the literature on human action recognition in smart living environments, synthesizing the main contributions, challenges, and future research directions. This review selects five key domains: Sensing Technology, Multimodality, Real-time Processing, Interoperability, and Resource-Constrained Processing, as they encompass the critical aspects required for successfully deploying human action recognition in smart living. These domains highlight the essential role that sensing and human action recognition play in successfully developing and implementing smart living solutions. This paper serves as a valuable resource for researchers and practitioners seeking to explore further and advance the field of human action recognition in smart living.

Measures in the SARS-CoV-2 pandemic were based on rough ideas regarding transmission routes of pathogens. Quantified models of physical transmission routes are mostly lacking, a gap to be filled. Vaccines and medicines, important, are not studied here. We first survey main routes, from primary production in the alveoli and intestines to emissions, environmental routes, to exposure and alveolar infection. Next, specific routes are modelled, mostly at a preliminary state, open to systematic improvement. Starting from a standardized emitter, modelling results show extreme differences in potential exposure, in a range covering up to 4 orders of magnitude. The outcomes are pathogen-specific, already different between SARS-CoV-2 and influenza. Extreme exposures may result in smaller spaces; with lower ventilation rates; with a high density of emitting persons per m3; who stay there for several hours; and visitors staying more than a few minutes. In spaces where a build-up of concentrations is low, exposures are low, lowest in open air situations. A main conclusion for the next pandemic is that a quantified model can give strong guidance on where measures are primarily due. For SARS-CoV-2, ventilation can be improved short-term. Longer-term, effective ventilation rules and adaptation of buildings may reduce high exposures substantially.

The Ayers Rock of Australia which is known for its charming colors at different time is actually the Celestial Body Ring of the planet Earth that implies the great Celestial Body Love happened on Earth long long ago. The Tasmania island of Australia which is known for the World Heart is actually in the state of face to face with the main island of Australia, which implies the image spokesperson for the inner core (the heart) of the planet Earth. In other words, with the outline of the main island of Australia, the basic key information of the inner core of the planet Earth could be easily obtained by deducing logically, just like the similarity between the fists and heart of human body. Similar to the mechanism of the blood circulation dominated by the heart of human body, it is dominated and motivated by the inner core of the Earth which forms the circulation of mantle magma between the crust and the inner core, and what leads to the formation of expanding and active area on the equatorial and middle-lower latitude area and the silent and convergent area on the North and South Pole central area. Therefore, the mantle magma whirlpools under the crust on the North and South Pole are supposed to exist logically. The walking sideways of the crabs just implies the celestial body language of the motive trend of the main island of Australia based on their similar outline.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

In this paper, we thoroughly explore the complex realm of cryptography, examining its historical, cultural, and metaphorical aspects. We delve into the roots of cryptography, tracing back to its Ancient Greek origins where it meant the study of secure and hidden writing. We also reveal the historical significance of cryptography in times of war and conflict, showcasing how it has been a vital tool for encoding messages and maintaining confidentiality. Furthermore, we uncover the surprising connection between cryptography and love, highlighting moments from history, such as the encrypted letters between Marie Antoinette and Axel von Fersen during the French Revolution, which showcase the human desire to communicate and connect even during times of turmoil. This paper delves into the cultural and metaphorical representations of cryptography, with a specific focus on the iconic characters Alice and Bob and how they are reinterpreted in different cultural contexts. The paper draws parallels between the complexities of the intertwining of logical, emotional, technical, and personal narratives in cryptographic discourse, offering insights into the lasting legacy of cryptographic metaphors in explaining complex concepts and emphasising the universal human desire for secure and intimate connections.

The United Nations Convention on the Rights of Persons with Disabilities (hereafter CRPD) has provided a radical imperative for the reform of mental health and capacity legislation around the world. The interpretation of the CRPD has been controversial, ranging from complete abolition of detention, forcible treatment and substitute decision making, to acceptance that elements of these measures need to be retained but based on non-discriminatory criteria, additional safe-guards and a comprehensive shift towards supported decision-making. While the potential ef-fects of the CRPD on mental health social work and social work generally are considerable given their shared commitment towards social justice, to date there has been no review of research evi-dence exploring their relationship. In addressing this knowledge gap, this study held a prelimi-nary discussion with practitioners and academics at the European Association of Social Work Mental Health Special Interest Group in Amsterdam 2022, followed by a scoping literature re-view on the question: What impact, if any, has the CRPD had on social work practice? The review produced four main findings: impact on legislation; positive impact on practice; limited impact on practice; and impact on social work education and research. In sum, while there were some positive indications of social work and mental health social work practice being influenced by the CRPD, these were scant. Barriers to change included tendencies among some social workers to practise substitute decision-making, in part related to resourcing and policy contexts, and under-standings of disability aligned to individualised/medical rather than social perspectives. The results indicate that legal reform on its own is insufficient to impact social work practice, and that realising the potential of the CRPD will necessitate good quality training, as well as improv-ing social workers’ knowledge of the human rights of people with mental impairment.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

There is a lot of pressures from organizations to continually redesign the business processes and the technology infrastructure to support the organization, but to also help organizations manage competing stakeholder needs, changing objectives and behaviour, and so on. A key part of this is making sure that all their activities in the different components of the business are interconnected and that they are moving in the same direction. Enterprise Architecture (EA) is an effective way of dealing with the challenge of designing business activities and supporting IT. This paper will summarize the organization of EA and look more closely at some major components of EA: governance architecture, business architecture, information architecture and technical architecture and consider the overlap and constructive interaction involved. Enterprise Architecture can be best understood through business process redesign. So, it is useful to briefly review the leading frameworks for business process redesign, including COBIT from ISACA, LEAN from the Toyota Group, TOGAF from the Object-Management Group, and the Capgemini Integrated Architecture Framework (IAF). All these frameworks allow us to more successful transformation, to return to the central idea of this paper.

Traffic Inspection (TI) work in this article is positioned as a specific module of road traffic with its primary function oriented towards monitoring and controlling safe traffic and the execution of significant events within a particular geographic area. Exploratory research on the significance of event execution in simple, complicated and complex traffic flow and process situations is related to the activities of monitoring and controlling functional states and performance of categorical variables, which include objects and locations of road infrastructure, communication infrastructure and networks of traffic inspection resources. It is emphasized that the words “work” and “traffic” have the semantic status as synonyms (in one world language), which is explained in the design of the Agent-based model of the complexity of content and contextual structure of TI work at the singular and plural level with 12 points of interest (POI) in the thematic research. An Event Execution Log (EEL) was created for on-site data collection with eight variables, seven of which are independent (event type, activities, objects, locations, host, duration-period and periodicity of the event) and one dependent (significance of the event) variable. The structured data set includes 10,994 input-output vectors in 970 categories collected in the EEL created by 32 human agents (traffic inspectors) over a 30-day period. An algorithmic presentation of the methodological research procedure for preprocessing and final data processing in the ensemble of machine learning models for classification and selection of TI tasks is given. Data cleaning was performed on the available dataset to increase data consistency for further processing. Vector elimination was carried out based on the Location variable, such that the total number of vectors equals the number of unique categories of this variable, which is 636. The main result of this research is the Classification modeling of the significance of events in TI work based on machine learning techniques and the Stacking ensemble. The created machine learning models for event significance classification modeling have high accuracy values. To evaluate the performance metrics of the Stacking ensemble of models, the confusion matrix, Precision, Recall, ND F1-score are used.