Solid waste has become a tenacious issue worldwide. It has been increasing exponentially due to urbanization and the increase in the population. Since the twentieth-century technological revolution, there have been significant changes in the composition of solid waste. It poses significant challenges for waste management systems worldwide. Waste management is the process of handling waste right from its creation to its final disposal, including transport, collection, treatment, and monitoring. The present solid waste management (SWM) system is affected by unfavorable institutional, economic, technical, legislative, and operational constraints. Poor waste management is affecting ecosystems and human health, damaging our finite natural resources, impeding human economic progress, and harming people's quality of life. Now, researchers are concerned about the environment's degradation, a decline in quality of life, and risks related to waste management grow as the volume of solid waste. So, they are focusing on sustainable waste management practices which will be crucial for creating a cleaner and healthier environment for future generations. This chapter focuses on the concept of solid waste, its types, management, and its effect on the health of humans and the environment.

The way in which a person walks, known as human gait, is a significant indicator of overall health and well-being. Abnormalities in gait can indicate the presence of metabolic disorders, such as diabetes or obesity. However, detecting these disorders can be challenging using traditional methods, which often involve subjective assessments or invasive procedures. In this study, a novel methodology known as Criticality Analysis (CA) was proposed for the detection and monitoring of human gait in people with metabolic disorders taking part in an intervention to increase activity and reduce weight. The CA approach utilised inertial measurement unit gait data, alongside clinical health measures. This allows for the control of nonlinear growth in the system, resulting in lower dimensional, nonlinear, free-scale, stable, controlled, and organised trajectories. These trajectories were then analysed using a Support Vector Machine (SVM) algorithm, which is well-suited for this task due to its ability to handle nonlinear and dynamic data. The combination of the CA approach and the SVM algorithm demonstrated high accuracy and non-invasiveness in detecting metabolic disorders, yielding an average accuracy within the range of 78.2% to 90%. Additionally, the classification technique accuracy, at a group level was observed to reduce during period of the intervention (e.g., from week 2 to week 3) alongside changes in fitness and health, which indicates the potential of using the approach to measure and monitor biological systems. As such, this novel methodology has the potential to be a valuable tool for healthcare professionals in detecting and monitoring metabolic disorders, as well as other unknown diseases associated with the human biological system.

This study explores the relationship between mental and physical therapeutic through three dimensions: man-environment relationships; a sense of place and symbolic landscapes. The study used a combination of qualitative and quantitative research methods. Local residents living in the coastal area of Xinglin Bay are the research objects. Quantitative data analysis revealed that the frequency of residents' visits was an important variable affecting their physical and treatment perceptions. In addition, the significance is higher for females than for males. The text analysis shows that the environment, especially the ecological restoration of water quality and migratory birds, is of great significance to the identity of local residents. Daily activities contribute to a sense of place and are what make the coast a place of therapeutic landscape function.

In the 21st century, museums have come to realize that the human skeletons they display might have problematic origins. The older anthropological skeletal collections typically originate from anatomical dissection of the executed and the very poor, or from scavenged graves of indigenous people. Such collections are currently being re-evaluated in many countries, and reburying or repatriating museum skeletons have become viable options. A particularly difficult question is what to do with human remains of unknown origins. Here, we present and discuss one such case, where a human skeleton of unclear origin in the 1930’s was brought to a local museum in Bollnäs, Sweden, under likely unethical circumstances. Most of the bones have now been lost, except for the skull, the sacrum and one lumbar vertebra, which in 2007 were transferred to the Museum of Ethnography in Stockholm. The skull was there put on display as the “Bollnäs skull”, and was presented to the public to illustrate the dilemmas involved in handling human remains in the post-colonial era. The original gift letter from 1934 stated that the skeleton came from San Nicolas Island outside the California coast, but this letter contained numerous instances of incorrect information and was therefore deemed not trustworthy. However, our critical examination of the skull and its background information indicates that San Nicolas Island is a plausible origin, and we suggest that a bioarchaeological comparison should be made between the skull and living descendants of the San Nicolas Island population, and/or with archaeological human skeletons excavated from the island.

Human pluripotent stem cells (PSCs), which include both embryonic and induced pluripotent stem cells, are widely used in fundamental and applied biomedical research. They have been instrumental for better understanding development and cell differentiation processes, disease origin and progression, and can aid in the discovery of new drugs. PSCs also hold great potential in regenerative medicine to treat or diminish the effects of certain debilitating diseases, such as degenerative disorders. However, some concerns have recently been raised over their safety for the use in regenerative medicine. One of the major concerns is the fact that PSCs are prone to errors in passing the correct number of chromosomes to daughter cells, resulting in aneuploid cells. Aneuploidy, characterised by an imbalance in chromosome number, elicits the upregulation of different stress pathways that are deleterious to cell homeostasis, impair proper embryo development and can potentiate cancer development. In this review we will summarise known molecular mechanisms recently revealed to impair mitotic fidelity in human PSCs and the consequences of the decreased mitotic fidelity of these cells. We will finish with speculative views on how the physiological characteristics of PSCs can affect the mitotic machinery and how their suboptimal mitotic fidelity may be circumvented.

Cruor, the main component responsible for the red color of blood in mammals, contains 90% hemoglobin, a protein that is considered a rich source of bioactive peptides. The aim of the present study is to evaluate the potential of human hemoglobin as a source of bioactive peptides, compared to bovine hemoglobin, which has been widely studied in recent years. More specifically, the study focused on neokyotorphin, a natural antimicrobial peptide and meat preservative, which corresponds to the α137-141 fragment of bovine hemoglobin produced by enzymatic hydrolysis. Firstly, the results of the in-silico analysis showed that the two types of hemoglobin have a high similarity for the α and β chains (identities of 88% and 91%, respectively). Secondly, both types of hemoglobin were subjected to similar enzymatic hydrolysis conditions, which showed that the hydrolysis of human hemoglobin followed the same reaction mechanism as the hydrolysis of bovine hemoglobin, the 'Zipper' mechanism. The hydrolysis conditions (23°C, pH 3.5) made it possible to obtain α137-141 in significant quantities to allow for significant valorization from an industrial point of view. The hydrolyses were able to take place at high initial substrate concentrations, allowing for faster and more efficient processing of the co-product in the same amount of time, with over 65% of this production achieved in just 30 min. Increasing the substrate concentration (from 1% to 10% (w/v)) resulted in a proportional increase in α137-141 production. Regardless of the concentrations tested, the kinetic pattern remained similar. Finally, the results of the mass spectrometry analysis revealed the presence of several bioactive peptides in cattle and humans. Although some were known before, new bioactive peptides were discovered in human hemoglobin, such as four antibacterial peptides (α37-46 PTTKTYFPHF; α36-45 FPTTKTYFPH; α137-141 TSKYR; α133-141 STVLTSKYR), four opioid peptides (α137-141 TSKYR; β31-40 LVVYPWTQRF; β31-37 LVVYPWT), an ACE inhibitor (β129-135 KVVAGVA), an anticancer agent (β33-39 VVYPWTQ) and an antioxidant (α137-141 TSKYR). These peptides have never been found in human hemoglobin before, according to our knowledge. These results highlight the potential of human hemoglobin as a source of bioactive peptides useful for the food or pharmaceutical industry.

Beta-carotene is a fat-soluble antioxidant commonly found in foods such as fruits, vegetables, and palm oil. Despite various liquid chromatography methods are proposed to detect and measure the sera carotenoid level, a long retention time to elute this marker is needed. This study attempted to develop a rapid reverse phase method in eluding beta-carotene in human sera. The researchers managed to elute the antioxidant in 2.2 minutes by applying a combination of a C8 column, mobile phase comprising of acetonitrile mixed with methanol in 70:30 proportion, and an ultra-high performance liquid chromatography system. The outputs had a good calibration curve (R²=0.959) and low coefficient of variation (0.2%), suggesting this protocol is reliable. A column with a lower carbon chain such as C8 allows the beta-carotene molecule to flow through the column faster. Besides, selecting solvents with high elution strength coupled with an ultra-high performance liquid chromatography system which equipped with high pressure can force the beta-carotene through the column in a shorter duration compared to previous reported methods. Therefore, it is recommended to adopt this protocol in epidemiological studies where beta-carotene is screened as a dietary biomarker associated with disease of interest by using human sera in the population level.

Kinases play an important role in regulating various intracellular signaling pathways that control cell proliferation, differentiation, survival and other cellular processes and their deregulation causes more than 400 diseases. Consequently, macrocyclization can be considered a noteworthy approach to develop new therapeutic agents for human diseases. Macrocyclization has emerged as an effective drug discovery strategy over the past decade to improve target selectivity and potency of small molecules. Small compounds with linear structures upon macrocyclization can lead to changes in their physicochemical and biological properties by firmly reducing conformational flexibility. A number of distinct protein kinases exhibit similar binding sites. Comparison of protein binding site provides crucial insights for the drug discovery and development. Binding site similarities are helpful to understand polypharmacology, identifying potential off-targets and repurposing of known drugs. In this review, we focused on comparing binding sites of those kinases for which macrocyclic inhibitors are available/studied so far. Furthermore, we calculated the volume of binding site pocket for each targeted kinase and then compared it with the binding site pocket of the kinase for which only acyclic inhibitors were designed till date. Our review and analysis of several explored kinases might be useful to target new protein kinases for macrocyclic drug discovery.

Existing methods for 3D human pose estimation mainly divide the task into two stages. The first stage identifies the 2D coordinates of the human joints in the input image, namely the 2D human joint coordinates. The second stage uses the results from the first stage as input to recover the depth information of human joints from the 2D human joint coordinates to achieve 3D human pose estimation. However, the recognition accuracy of the two-stage method relies heavily on the results of the first stage and includes too many redundant processing steps, which reduces the inference efficiency of the network. To address these issues, we propose the EDD, a fully End-to-end 3D human pose estimation method based on transformer architecture with Dual Decoders. By learning multiple human poses, the model can directly infer all 3D human poses in the image using a pose decoder, and then further optimize the recognition result using a joint decoder based on the kinematic relations between joints. With the attention mechanism, this method can adaptively focus on the most relevant features to the target joint, effectively overcoming the feature misalignment problem in the human pose estimation task and greatly improving the model performance. Any complex post-processing step, such as non-maximum suppression, is eliminated, further improving the efficiency of the model. The results show that the method achieves an accuracy of 87.4% on the MuPoTS-3D dataset, significantly improving the accuracy of end-to-end 3D human pose estimation methods.

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

Nuclear vacuoles are specific structures present on the head of the human sperm of fertile and non-fertile men. Human sperm head vacuoles have been previously studied using motile sperm organelle morphology examination (MSOME) and their origin related to ab-normal morphology, abnormal chromatin condensation and DNA fragmentation. How-ever, other evidences argued that human sperm vacuoles are physiological structures and consequently, to date, the nature and origin of the nuclear vacuoles remains to be elucidat-ed. Here, we aim to define the incidence, position, morphology, and molecular content of the human sperm vacuoles using transmission electron microscopy (TEM) and immuno-cytochemistry techniques. Results showed that ~50% of the analyzed human sperm cells (n = 1908; 17 normozoospermic human donors) contained vacuoles mainly located (80%) in the anterior head region. A significant positive correlation was also found between the sperm vacuole and nucleus areas. Furthermore, it was confirmed that nuclear vacuoles were invaginations of nuclear envelope containing cytoskeletal proteins and a cytoplas-mic enzyme, discarding a nuclear or acrosomal origin. According to our findings, these human sperm head vacuoles are cellular structures which take the origin from nuclear invaginations and contain perinuclear theca (PT) components, allowing to define a new term of ‘nuclear invaginations’ rather than ‘nuclear vacuoles.

Plaque psoriasis is a common, long-lasting illness that affects the immune system and causes significant negative impacts on a patient's physical health, well-being, and ability to work effectively. Deucravacitinib (DEU) is the first oral medication used in the treatment of plaque psoriasis, a chronic skin condition that causes red, scaly patches on the skin. DEU is a type of medication called an oral Janus kinase (JAK) inhibitor, which works by blocking specific enzymes that play a role in the inflammation and immune response associated with psoriasis. Therefore, a quick, easy, novel, reliable, sensitive, and straightforward Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) approach was used to analyse DEU in plasma samples. The LC-MS/MS method for the determination of DEU in human plasma was based on using trimethoprim as an internal standard (IS). The separation of DEU and IS was carried out via liquid-liquid extraction (LLE). The isolated substances were then subjected to the chromatographic system using the ACE-C18 column (4.6x100 mm, 5 µm). The mobile phase employed consisted of methanol and a solution of 2 mM ammonium formate (80:20 v/v, respectively). The flow rate used was set at 0.9 mL min-1. The creative strategy was performed by running an ABSCIEX API 4000 mass spectrometer with an electron spray ionization source in Multiple Reaction Monitoring (MRM) modes. The ion transitions m/z 426.3  358.2 was used for DEU quantitation, while the ion transitions m/z 291.1  261.1 was used for trimethoprim quantitation. The accuracy, precision, linearity, recovery, and selectivity of DEU were deemed acceptable when validated for a concentration range between 0.500 to 601.050 ng/mL, utilizing a weighting factor of 1/x2.

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

In this discussion paper, I give an account for non-experts of, arguably, quantum dynamics in the brain, underlying the modeling of affective behavior of humanoid robots in the making. Outreach to the larger audience inevitably leads to abbreviations and simplifications; nonetheless, I try to offer the backgrounds of why it is important to study the virtual aspects of ‘people’ we meet online, what dimensions play a role in assessing such creatures, what humanities, psychology, communication, and computer science provide to help us understand how we become attached to non-existent others. As its capstone for the time being, an approach derived from physics is discussed for a robot to handle emotional ambiguity and vagueness of its user. Two computational models, Silicon and Quantum Coppélia, are discussed for their potential and limitations in explaining human affective behavior while dealing with mediated characters.

Bovine tuberculosis (BTB) is endemic in Ethiopian cattle. BTB is caused by Mycobacterium bovis (M. bovis) and has economic and public health significance. which has significant impact on the health of livestock and human. It has been significantly a cause for great economic loss in animal production. Associated risk factors contributed to the prevalence of the disease in cattle and its transmission. Moreover, the majority of cattle owners lack awareness about the disease and its public health significance. The presence of multiple hosts including wild animals, inefficient diagnostic techniques, absence of defined national controls and eradication programs could impede the control of bovine TB. Awareness rising about the disease, its transmission andzoonotic implication however, in Ethiopia Bovine Tuberculosis in Human-Livestock-Wildlife Interface is not well studied in the country and there were no studies concerning the burden of the disease between human ,animal and wild life which is of great importance for reduction and control measures. This paper aims to review the potential health and economic impact of bovine tuberculosis control in order to safeguard human and animal population in Ethiopia

Forests are increasingly becoming fragmented and declining due to natural causes and human-induced activities. The latter creates an imbalance which put the survival of vulnerable species such as those of avifauna at risk. Honeyeaters are group of birds common in Fiji, with certain species strictly confined to specific habitats. This study is an attempt to compare the abundance and foraging behaviours of three sympatric honeyeaters namely Kikau wattled honeyeater, Orange-breasted myzomela and Giant honeyeater at two contradicted sites (USP campus and Colo-i-Suva Forest Reserve). The survey was carried out using point count method along three different transect routes of approximately 2 Km on each study sites . A higher species diversity and abundance was observed in Colo-i-Suva Forest Reserve than in USP campus. Kikau wattled honeyeater are more populated at USP campus due to adequate nectar-producing plants. Whereas both Orange-breasted myzomela (highly adaptable bird species) and Giant honeyeater (forest specifics) are frequent in Colo-i-Suva Forest Reserve. All exhibited a wider range of foraging techniques across forest vertical strata and plant species, except for Giant honeyeater (not observed). The statistical analysis showed that there is a significant difference (p < 0.05) in abundance as well as between the number of honeyeater species in both sites across the forest vertical strata. However, there is no significant difference in the foraging behaviour and the number of honeyeaters found foraging on diverse plant species (p > 0.05).

Despite more than hundred years of research since Sir Sherrington’s studies on reflexes, his questions are still somehow unanswered. On what anatomical stage do the play of spinal reflex interaction take place? What are the physiological properties of this anatomical substrate? In this paper, we address these questions in light of the most advanced theory of motor control and the anatomical discoveries on the fascia that are changing how we think about control of action and perception. There are two sides of the problem: the neurological (reflex) connections that are at the base of movement, and the anatomical substrate that regulates and coordinates the movement. We recently advanced a hypothesis on how these two elements are connected and how they interplay. Here we further explain the concept of the somatic equilibrium point – SEP – and its central role in movement control and coordination. It is our belief that the concept of SEP explains how the neuro-mechanical control of movement is organized at peripheral level. At this level, intrafusal and extrafusal muscle fibres are combined in myofascial units, organized in anatomical directions. Myofascial units are closed systems whose behaviour can be affected by neural (voluntary) control or changes in external forces. SEPs represent the intrinsic equilibrium of the myofascial units, and are connected through the continuum of the fascia so that mechanical transfer of tension from segment to segment pre-adjust muscle fibers length and hence their excitation level. This is how coordination between segments is achieved. Finally, we suggest SEPs create the neurological representation of the referent configuration for action, and configurations are linked to the architecture of the fascial system.

Overimitation, the copying of causally irrelevant or non-functional actions, is well-known from humans but completely absent in other primates. Recent studies from our lab have provided evidence for overimitation in canines. Previously, we found that half of tested pet dogs copied their human caregiver's irrelevant action, while only few did so when the action was demonstrated by an unfamiliar experimenter. Therefore, we hypothesized that dogs show overimitation as a result of socio-motivational grounds. To test this more specifically, here we investigated how the relationship with the caregiver influenced the eagerness to overimitate. Given the high variability in the tendency to overimitate their caregiver, we hypothesized that not only familiarity, but also relationship quality influences whether dogs faithfully copy their caregiver. For this purpose, we measured on the one hand the overimitation tendency (with the same test as in the two studies before) and on the other hand the relationship quality between the dogs and their caregivers. Although not significant, results revealed that dogs who overimitated seemed to show more referential and affiliative behaviours towards the owner (like gazing, synchronization and greeting) than dogs who showed less or no copying of the irrelevant action. Possible reasons for these findings are discussed.

Human Rhinovirus (HRV) is the most common cause of upper respiratory infections and exacerbations of asthma. In this work, we selected 14 peptides (6 from HRV A and 8 from HRV C) encompassing potential CD4 T cell epitopes. Peptides were selected for being highly conserved in HRV A and C serotypes and predicted to bind to multiple HLA II molecules. We found positive T cell recall responses by IFNγ-ELISPOT assays to 8 peptides, validating 7 of them (3 from HRV A and 4 from HRV C) as CD4 T cell epitopes through intracellular cytokine staining assays. Additionally, we verified their promiscuous binding to multiple HLA II molecules by quantitative binding assays. According to their experimental HLA II binding profile, the combination of all these 7 epitopes could be presented and recognized by > 95 % of the world population. We actually determined IFNγ responses to a pool encompassing these CD4 T cell epitopes by intracellular cytokine staining, finding positive responses in 29 out of 30 donors. The CD4 T cell epitopes identified in this study could be key to monitor HRV infections and to develop peptide-based vaccines against most HRV A and C serotypes.

Chemical simulants have long been used in human trials of mass decontamination to determine the efficacy of decontamination interventions against more toxic agents. Until now, reliance has mostly been on individual chemicals as surrogates to specific agents (e.g. methyl salicylate for sulphur mustard). A literature review was conducted to identify chemicals that had been previously tested on human volunteers and that represent diverse physicochemical characteristics in order to create a repository for chemical simulants. Of the 171 unique chemicals identified 78 were discounted for the risk they could pose to human volunteers, 39 were deemed suitable for use and a further 54 were considered to be possible simulants but would require further research. Suitable simulants included both solid and liquid chemicals spanning a wide range of physicochemical properties including molecular weight, octanol/ water partition coefficient, vapour pressure and solubility. This review has identified an array of potential simulants suitable for use in human volunteer decontamination studies and is of relevance to future studies on systemic absorption and surface decontamination.

The Italian Peninsula, a natural pier across the Mediterranean Sea, witnessed intricate population events since the very beginning of human occupation in Europe. In the last few years, an increasing number of modern and ancient genomes from the area has been published by the international research community. This genomic perspective started unveiling the relevance of Italy to understand the post-Last Glacial Maximum (LGM) re-peopling of Europe, the earlier phase of the Neolithic westward migrations, and its linking role between Eastern and Western Mediterranean areas after the Iron Age. However many open questions are still waiting for more data to be addressed in full. With this review, we summarize the current knowledge emerging from the available ancient Italian individuals and, by re-analysing them all at once, we try to shed light on the avenues future research in the area should cover. In particular, open questions concern i) the fate of pre-Villabruna Europeans and to what extent their genomic components were absorbed by the post-LGM hunter-gatherers; ii) the role of Sicily and Sardinia before LGM; iii) to what degree the documented genetic structure within the Early Neolithic settlers can be described as two separate migrations; iv) what are the population events behind the marked presence of an Iranian Neolithic-like component in Bronze Age and Iron Age Italian and Southern European samples.

Background: Tele-rehabilitation has grown significantly in the past years, especially in 2020 when it has been a crucial tool for supporting patients during the COVID-19 pandemic. Within the context of tele-rehabilitation, serious games have a significant role. However, realizing software for serious games capable of responding to the variety of user needs is resource demanding. Methods: we present Proteo, a modular framework for developing serious games from scratch, but with the ability of providing a high-level interface for game customization by therapists and researchers. We also present two serious game implementation examples with analysis of end user’s and therapists/researchers’ satisfaction. Results: by involving a group of 11 specialized therapists and 9 end users we analyzed the Proteo user’s satisfaction. We found that therapists and end users scored high level of involvement, and the therapists scored also high level of suitability. More in depth, both groups showed significant differences between positive and negative feeling, with positive feeling scoring higher than negative ones. Finally, concerning Users’ level of suitability the condition of successfulness of the system, ability to control, clarity and helpfulness were reported as high while the difficulty of the system and the difficulty of the task were reported as low. Conclusions: the proposed framework is a step forward in providing a comprehensive open-source, modular framework, to develop serious games for tele-rehabilitation. Proteo is distributed with a MIT license and available to researchers on GitHub and has been well accepted by the users we involved in the evaluation tests.

Every year, General Practitioners (GPs) see over 13 million patients for dermatological concerns making dermatology the highest referring speciality. Artificial Intelligence (AI) systems could improve system efficiency by supporting clinicians in making appropriate referrals, but they are, like human clinicians, imperfect and there may be a trade-off between sensitivity and specificity that is likely to result in false negatives. In this paper, a study is presented to explore two areas. Firstly, the aptitude of GPs to trust appropriately (or not trust) the outputs of a fictitious AI-based decision support tool when assessing skin lesions. Secondly, to identify which individual characteristics could make GPs less prone to adhere to erroneous diagnostics results and to refrain from passive adherence to AI. Findings suggest that when the AI is correct, there is a positive effect on GPs’ performance and confidence suggesting the potential to reduce referrals for benign lesions. However, when an inexperienced GP is presented with a false-negative result, they may passively deviate from their initial clinical judgement to accept the wrong diagnosis provided. AI systems will have a false-negative rate and, when adopting new technologies, this needs to be acknowledged and fed into risk-benefit discussions and considerations around additional safety measures.

Human metapneumovirus (HMPV) is an important cause of upper and lower respiratory tract disease in individuals of all ages. It is estimated that most individuals will be infected by HMPV by the age of 5 years old. Despite this burden of disease, there remains caveats in our knowledge of virus global genetic diversity due to a lack of HMPV sequencing, particularly at whole genome scale. The purpose of this study was to create a simple and robust approach for HMPV whole genome sequencing to be used for genomic epidemiological studies. To design our assay, all available HMPV full length genome sequences were downloaded from the NCBI GenBank database and used to design four primer sets to amplify long, overlapping amplicons spanning the viral genome and, importantly, specific to all known HMPV subtypes. These amplicons were then pooled and sequenced on an Illumina iSeq; however the approach is suitable to other common NGS platforms. We demonstrate the utility of this method using a representative subset of clinical samples and examine these sequences using a phylogenetic approach. Here we present an amplicon-based method for the whole genome sequencing of HMPV from clinical extracts that can be used to better inform genomic studies of HMPV epidemiology and evolution.

This paper presents a framework for the motion planning and control of redundant manipulators with the added task of collision avoidance. The algorithms that were previously studied and tested by the authors for planar cases are here extended to full mobility redundant manipulators operating in a three-dimensional workspace. The control strategy consists of a combination of off-line path planning algorithms with on-line motion control. The path planning algorithm is used to generate trajectories able to avoid fixed obstacles, detected before the robot starts to move; it is based on the potential fields method combined with a smoothing interpolation that exploits Bézier curves. The on-line motion control is designed to compensate for the motion of the obstacles and to avoid collisions along the kinematic chain of the manipulator; it is realized by means of a velocity control law based on the null space method for redundancy control. A term of the control law takes into account the speed of the obstacles as well as their position. In order to test the algorithms, a set of simulations are presented: the robot KUKA LBR iiwa is controlled in different cases, where fixed or dynamic obstacles interfere with its motion. Simulations are also used to estimate the required computational effort in order to verify the transferability to a real system.

In January 2020, the World Health Organization declared a public health emergency and announced a new coronavirus disease (COVID-19), which would later go on to be declared as a pandemic, changing the global sphere and placing the economies of almost all countries under heavy stress. The airline industry, that had just begun recovering after facing crises one after another in the last two decades, from early 2000 due to 9/11, to the global financial crisis later, is now oce again facing an enormous challenge of closed borders and greater lockdowns due to the pandemic. Borders are closed, with very few planes are in the air, while the rest are grounded. The purpose of this paper is to give a conceptual understanding of the current pandemic situation and its consequences on the airline industry. The paper takes a unique perspective of human resource management (HRM) that is rarely used in the airline industry.

The main purpose of this research is to analyze the perception of climate change impacts on human health in Bangladesh through data from nationality representative surveys conducted in some district of Bangladesh. In Bangladesh there have a few research has been conducted on public perceptions about the impact of climate change on human health. A structured questionnaire method was conducted, and data collected from 615 respondents. The findings of this study reveal that out of 615 respondents, 76.0% of the respondents replied positively while remaining 24.0%, almost one-fourth of total respondents, indicated that they have not heard the term climate change before. Knowledgeable in climate change, 92.5% of respondents agreed that climate change has an impact on human health while only 7.5% respondents disagreed with this statement. 90.5% of respondents argued that they are agreed with the opinion that climate change is a serious threat to human health.

The way in which the human being learns certain complex contents has always been a focus of interest and a challenge for researchers. Given the fact that children's cognitive abilities do not fully develop until a certain age, this topic is particularly important in the young children's learning scope as they do not correctly and easily learn some content of abstract nature, such as contents in math class. This work presents the results of the use of an application called "Mathematics Learning System with Augmented Reality based on Kinect" (SAM-RAK by its acronym in Spanish), which was designed to cover basic topics of mathematics in the Basic General Education level (EGB by its acronym in Span-ish) in Ecuador. The research was carried out under an experimental quantitative approach with 30 children (18 girls and 12 boys), who study in third grade of EGB level, from 2 different educational in-stitutions in Riobamba city. In order to obtain the results that evaluate the developed application, a pre-test and a post-test were applied, which were contrasted with the student’s t-test for paired samples. The statistical evidence suggests that the proposed computer system had a positive effect on children's performance, when it was used as a support tool in the classroom. The system was more effective in low performance children compared to those of high performance. It was also proved that children were motivated and showed positive attitudes when using the proposed System.

Organophosphate pesticides (also known OPPs) have for many years been the choice candidate globally for pest control. OPPs have for over 80 years, been used in gardens, fields and greenhouses as crop protection agents, and even in homes as insecticides and mosquito abatement. Thus, year after year and with the repeated application of organophosphate agents, many problems have appeared as a result of excessive use of pesticides. The adverse effects of pesticides are well documented in human health, environment, pesticide residue in crops, soil and water contaminated by these pesticides. Therefore, it is necessary to shed more light on the risks associated with the irresponsible usage of organophosphate pesticides.

The microbiota of human breast milk (HBM) contributes to infant gut colonization; however, whether bacterial extracellular vesicles (EVs) are present in HBM or might contribute to this process remains unknown. In the present study, we characterized the HBM microbiota of healthy Korean mothers and measured the key bacteria likely affecting infant gut colonization by analyzing both the microbiota and bacterial EVs. A total of 22 HBM samples were collected from lactating mothers. The DNA of bacteria and bacteria-derived EVs was extracted from each sample. Gene analysis was performed using Illumina MiSeq. Firmicutes accounted for the largest portion among the phyla, followed by Proteobacteria, Bacteroides, and Actinobacteria in both bacteria and bacterial EV samples. At the genus level, Streptococcus (25.1%) and Staphylococcus (10.7%) were predominant in bacterial samples, whereas Bacteroides (9.1%), Acinetobacter (6.9%), and Lactobacillaceae(f) (5.5%) were prevalent in bacterial EV samples. Several genera including Bifidobacterium were significantly positively correlated between the two samples. Our findings reveal the diverse bacterial communities in HBM of healthy lactating mothers and suggest the presence of key bacteria with metabolic activity in HBM and that EVs derived from these bacteria may contribute to the vertical transfer of gut microbiota from mother to infant.

Human resources are the major input of health systems therefore the equitable distribution of human resources in health care remain critical in making progress towards the goal of universal health coverage and thus to sustainable development. The purpose of this study is to evaluate the health care human resources distribution across regions of Poland between 2010 and 2017 and estimate the level of equity. This research by applying to Polish conditions will allow to fill in the gap in existing literature. Data was derived from the Knowledge Database Health and Health Care of Statistic Poland and Polish Statistical Yearbook. In purpose to examine the distribution of health resources against population size and geographic size in Poland, the Gini coefficient calculated based on the Lorenz Curve was engaged. This study has several major findings. The amount of most types of human resources – as apart from internist, obstetrics and gynecology, occupational medicine - when expressed as number of them per 10,000 population or 1 square km increased in 2017 compared to 2010. Moreover, for most types of health care human resources the level of access slightly changed during analysied period as Gini coefficients decreased. However, the geographical distribution of all types of human resources is less equitable then in case of population distribution. The most troublesome is relatively lower equity in case of oncologist, family medicine and occupational medicine and cardiologist in both population and geographical distribution. Thus this research provides some implications for policy and practice. As the main reason to establish National Health Fund (which meant the centralization of the system) in Poland was to to eliminate regional differences in access to health care, thus this research confirms that still some more corrective actions, in this field, should be undertaken.

The use of fluoride (F^-) for decreasing the prevalence and incidence of tooth decay was the greatest worldwide preventive public health measure of the 20th century. There have been controversial reports about the benefits of the use of F^-, because in small amounts it helps prevent dental caries, but in high concentrations it can be potentially toxic and harmful to dental and systemic health. Since the mid-20th century, F^- has been studied by toxicologists, looking at its deleterious effects in human populations. During the last decade, the interest on the undesirable effects has resurfaced because of the knowledge that it interacts with the cellular system, even in low doses, with a very small safety margin. Acute ingestion of toxic amounts of fluoride can cause corrosive gastric mucosa injury. Also respiratory effects such as bleeding, pulmonary edema, tracheostomy and shortness of breath, have been observed in individuals who inhale hydrogen fluoride. Some researchers had shown that F^- is an oxidizing agent and a well-known reversible enzymatic inhibitor that interferes with the enzyme activity of at least 80 proteins, can altered the intracellular redox equilibrium, lipid peroxidation, as well as, alteration in the gene expression and apoptosis induction. The primary purpose of this review is to examine findings of the action of inorganic F^-, and an overview of hard and soft tissue disturbances, known as fluorosis. The goal of this review is to enhance understanding of the mechanisms by which F^- affects cells with an emphasis on human tissue-specific events.

This paper sets out to reconsider the Hohfeldian framework of rights in celebration of the centenary anniversary of Hohfeld's death. It begins by conceptualising each of the Hohfeldian incidents or rights before outlining the molecular or complex structure of rights to ‘things’. I adopt a broad use of the term of ‘right’ and apply it to Legal, Moral, Equitable and Human conceptions and constructions. It sets out an argument in favour of a further definitional model - in addition to Hohfeld’s scheme of opposites and correlatives – which focuses on the function of these conceptual rights. Finally, it will consider the broader implications of how rights are held and the relationships which these rights govern. Ultimately, this paper seeks to demonstrate the benefit, and indeed necessity, of the Hohfeldian model in any discussion of rights. Without it ‘rights talk’ is debased and impoverished.

This study investigated the presence of human Norovirus (HuNoV) by genotype in 1,486 groundwater samples, collected from 843 groundwater wells suspected of contamination during 2007-2016, in Republic of Korea. We identified and genotyped 186 HuNoV sequences in 178 HuNoV-positive samples using the RIVM-NoroNet norovirus genotyping tool (NGT) and phylogenetic tree analysis based on RIVM-NoroNet reference sequences. HuNoV GII was more prevalent than GI. The major genotypes detected were HuNoV GII.4 (43.0%), GII.22 (15.6%), GI.5 (10.2%) and GI.1 (8.6%); 14 genotypes accounted for < 5.0%. Increasing HuNoV GII.17 has displayed a worldwide trend, including in Europe and Asia since 2010, and it was the dominant HuNoV genotype during 2013-2014 in Korea. However, HuNoV GII.4 was the major genotype detected in groundwater in Korea in 2015-2016, and it is becoming increasingly prevalent similar to HuNoV GII.17.

We assume that the current mathematical knowledge K is a finite set of statements from both formal and constructive mathematics, which is time-dependent and publicly available. Any theorem of any mathematician from past or present belongs to K. The set K exists only theoretically. Ignoring K and its subsets, sets exist formally in ZFC theory although their properties can be time-dependent (when they depend on K) or informal. In every branch of mathematics, the set of all knowable truths is the set of all theorems. This set exists independently of K. Algorithms always terminate. We explain the distinction between algorithms whose existence is provable in ZFC and constructively defined algorithms which are currently known. By using this distinction, we obtain non-trivial statements on decidable sets X⊆N that belong to constructive and informal mathematics and refer to the current mathematical knowledge on X. This and the next sentence justify the article title. For any empirical science, we can identify the current knowledge with that science because truths from the empirical sciences are not necessary truths but working models of truth about particular real phenomena.

Different dopamine receptor (DR) subtypes are involved in pathophysiological conditions such as Parkinson´s Disease (PD), schizophrenia and depression. While many DR-targeting drugs have been approved by the FDA, only a very small number is truly selective for one of the DR subtypes. Additionally, most of them show promiscuous activity at related G-protein coupled receptors, thus suffering from diverse side-effect profiles. Multiple studies have shown that combined in silico / in vitro approaches are a valuable contribution to drug discovery processes. They can also be applied to divulge the mechanisms behind ligand selectivity. In this study, novel DR ligands were investigated in vitro to assess binding affinities at different DR subtypes. Thus, nine D2R/D3R-selective ligands (micro- to nanomolar binding affinities, D3R-selective profile) were successfully identified. The most promising ligand exerted nanomolar D3R activity (KI = 2.3 nM) with 263.7-fold D2R/D3R selectivity. Subsequently, ligand selectivity was rationalized in silico based on ligand interaction with a secondary binding pocket, supporting selectivity data determined in vitro. The developed workflow and identified ligands could aid in the further understanding of structural motifs responsible for DR subtype selectivity, thus, benefitting drug development in D2R/D3R-associated pathologies like PD.

This paper discussed the concept of quality assurance (QA) in higher education and its implications to higher education institutions (HEIs) and the possible challenges. The study evaluated literature concerning QA in Zambia and elsewhere. The findings of the study show that QA is implemented through external and internal mechanisms such as accreditation, registration, institutional auditing, and the use of external examiners, self-evaluation, and peer reviews. The QA implications to HEIs in Zambia are that there is a need for accreditation of academic programmes with the Higher Education Authority (HEA) by HEIs. Further, HEIs should establish QA units to spearhead quality issues, reactive, and introduce the use of external examiners to ensure quality. The challenges identified in the implementation of QA in HEIs include inadequate funding, infrastructure, shortage of qualified academic staff, and lack of standalone QA units in some HEIs. In this regard, it has been recommended among other things, government improve funding in public HEIs, construct infrastructure, HEIs establish QA units, and recruit and retain qualified academic staff to ensure the quality of education.

OpenAI has managed to turn 100 million heads in two months towards their new Language model tool (LM) ChatGPT. The third generation Generative Pretrained Transformer (GPT-3) has the capacity to tackle simple to complex and sophisticated problems, while providing reasoning behind its generated answers. ChatGPT can be used to increase productivity and improve efficiency and face challenging problems. Programming mobile applications is a challenging task that requires professional software engineers, skills and abilities to be developed. The following paper takes a case study approach to assess how novice app developers can use ChatGPT to generate Java scripts that will be used in Android studio to create a functional application. The results after, many iterations and ongoing conversations with ChatGPT managed to create an application for the anticipated function. Important insights have been drawn from the case study that could set the ground for any novice user seeking to create applications using Java scripting and Android Studio.

Emerging organic contaminants (EOCs) of anthropogenic origins are ubiquitous in environmental compartments, including aquatic systems. Thus, EOCs have attracted considerable research and public attention due to their potential human and ecological health risks. However, compared to other aquatic environments such as wastewater systems, comprehensive reviews focussing on the occurrence and human health risks of EOCs in drinking water systems are still lacking. Therefore, to address this knowledge gap, the current review posits that drinking water systems harbour a cocktail of toxic EOCs, which pose public health risks via multiple exposure routes. In the present review, global evidence is examined to track EOCs along the source-pathway-receptor-impact-mitigation (SPRIM) continuum. Evidence shows that, various groups of EOCs, including pharmaceuticals and personal care products, solvents, plasticizers, endocrine disrupting compounds, gasoline additives, per- and polyfluoroalkyl substances (PFAS), food colourants, artificial sweeteners, and musks and fragrances, have been detected in drinking water systems. The anthropogenic sources of EOCs detected in drinking water systems, including wastewater systems and industrial emissions, are summarized. Further, the behaviour and fate of EOCs in the drinking water systems, including removal processes are discussed. Once in drinking water systems, human exposure to EOCs may occur via ingestion of contaminated drinking water and cooked foods, and possibly dermal contact and inhalation. The high-risk environments, and risk factors and behaviours predisposing humans to EOC exposure are discussed. Evidence on the human health risks of the various EOCs and a critique of the data are presented. Notably, besides inferential data, quantitative epidemiological evidence directly relating the occurrence of EOCs in drinking water systems to specific adverse human health outcomes is still scarce. Lastly, future research directions, including the need for quantitative public health risk assessment, and the application of emerging detection tools are discussed.

Human pluripotent stem cells (hPSCs) have widespread potential biomedical applications. There is a need for large-scale in vitro production of hPSCs, and optimal culture methods are vital in achieving this. Physiological oxygen (2% O2) improves key hPSCs attributes, including genomic integrity, viability, and clonogenicity, however, its impact on hPSC metabolism remains un-clear. Here, Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) was used to detect and quantify metabolic Volatile Organic Compounds (VOCs) in the headspace of hPSCs and their differentiated progeny. hPSCs were cultured in either 2% O2 or 21% O2. Media was collected from cell cultures and transferred into glass bottles for SIFT-MS measurement. The VOCs acetaldehyde and dimethyl sulfide (DMS)/ethanethiol were significantly increased in undifferentiated hPSCs compared to their differentiating counterparts, and these observations were more apparent in 2% O2. Pluripotent marker expression was consistent across both O2 concentrations tested. Transcript levels of ADH4, ADH5, and CYP2E1, encoding enzymes involved in converting ethanol to acetaldehyde, were upregulated in 2% O2, and chemical inhibition of ADH and CYP2E1 decreased acetaldehyde levels in hPSCs. Acetaldehyde and DMS/ethanethiol may be indicators of altered metabolism pathways in physiological oxygen culture conditions. The identification of non-destructive biomarkers for hPSC characterization has the potential to facilitate large-scale in vitro manufacture for future biomedical application.

The loop and knot securities of 2 braided and 2 monofilament sutures of four diameters (3.0, 2.0, 0, 1) were evaluated with a tensiometer for four 4-throw knots known to be secure with a 2.0 polyfilament suture. Loop security of monocryl 1 is low, being 14.7 + 3.0 Newton (N) for a 3-throw half-knot (H3) and 15.4 + 2.4 N and 28.3+ 10 N for 2 (SSs) and 4-throw (SSsSsSs) symmetrical sliding half-hitches. This is lower than 18, 24, and 46 N for similar knots with vicryl. Polyfilament sutures have excellent knot security for all diameters. Occasionally, some slide to open with slightly lower knot security, especially for larger diameters, although not clinically problematic. Knot se-curity of monofilament sutures was unpredictable for all 4 knots, especially for larger diameters, resulting in many clinically insecure knots. A secure monofilament knot requires a 6-throw knot with 2 symmetrical sliding half-hitches or 2 symmetrical half-knots secured with 4 asymmetric blocking half-hitches. In conclusion, with polyfilament sutures, 4 or 5-throw half-knot or half-hitch sequences result in secure knots. For monofilament sutures, loop and knot security is much less, half-knot combinations should be avoided, and secure knots require 6-throw knots with 4 asym-metric half hitches. This conclusion is valid for gynecologic laparoscopic and open surgery, and for surgery in general.

Ribotoxin-like proteins (RL-Ps) are specific ribonucleases found in mushrooms that are able to cleave a single phosphodiester bond located in the Sarcin-Ricin Loop (SRL) of the large rRNA. The cleaved SRL interacts differently with some ribosomal proteins (P-stalk). This action blocks protein synthesis because the damaged ribosomes are unable to interact with elongation factors. Here, the amino acid sequence of eryngitin 3 and 4, RL-Ps isolated from Pleurotus eryngii fruiting bodies, was determined to: i) obtain structural information on this specific ribonuclease family from edible mushrooms; and ii) explore the structural determinants which justify their different biological and antipathogenic activities. Indeed, eryngitin 3 (exhibited higher toxicity with respect to eryngitin 4 against tumoral cell lines and model fungi. Structurally, eryngitin 3 and 4 consist of 132 amino acids, most of them identical and exhibit a single free cysteinyl residue. The amino acidic differences between the two toxins are: i) an additional phenylalanyl residue at the N-terminus of eryngitin 3, not retrieved in eryngitin 4; and ii) an additional arginyl residue at C-terminus of eryngitin 4, not retrieved in eryngitin 3. The 3D-models of eryngitins show slight differences at the N- and C-terminal regions. In particular, the positive electrostatic surface at C-terminal of eryngitin 4 is due to the additional arginyl residue not retrieved in eryngitin 3. This additional positive charge could interfere with the binding to the SRL (substrate) or with some ribosomal proteins (P-stalk structure), during substrate recognition.

The inherent value and use of hydrocarbon from waste plastics and solvents can be extended through open-loop chemical recycling as this process converts plastic to range of non-plastic materials. This process is enhanced by first creating plastic-solvent-combinations from multiple sources which are then streamlined through single process stream. We report on the relevant mechanics for streamlining industrially relevant polymers such as polystyrene (PS), polypropylene (PP), high-density polyethylene (HDPE) and acrylonitrile butadiene styrene (ABS) into chemical slurries mixed with various organic solvents such as toluene, xylene and cyclohexane. The miscibility of the polymer feedstock within the solvent was evaluated using the Relative Energy Difference method, and the dissolution process was evaluated using the “Molecular theories in a continuum framework” model. These models were used to design a batch process yielding 1 tonne/h slurry by setting appropriate assumptions including constant viscosity of solvents, disentanglement-controlled dissolution mechanism and linear increase of the dissolved polymer’s mass fraction over time. Solvent selection was found to be the most critical parameter for the dissolution process. The characteristics of the ideal solvent are high affinity to the desired polymer and low viscosity. This work serves as a universal technical guideline for open-loop chemical recycling of plastics avoiding the growth of waste plastic in a circular economy framework.

A variety of techniques have been utilized in metal additive manufacturing (AM) for melt pool size management, including modeling and feed-forward approaches. In a few cases, closed-loop control has been demonstrated. In this research, closed-loop melt pool size control for large-scale, laser-wire based Directed Energy Deposition is demonstrated with a novel modification: site-specific changes to the controller set-point were commanded at trigger points, the locations of which were generated by the projection of a secondary geometry onto the primary 3D-printed component geometry. The present work shows that, through this technique, it is possible to print a specific geometry that occurs beyond the actual toolpath of the print head. This is denoted as an extra-toolpath geometry and is fundamentally different from other methods of generating component features in metal AM. A proof-of-principle experiment is presented in which a complex oak leaf geometry was embossed on an otherwise ordinary double-bead wall made from Ti-6Al-4V. The process is introduced and characterized primarily from a controls perspective with reports on the performance of the control system, the melt pool size response, and the resulting geometry. The implications of this capability, which extend beyond localized control of bead geometry to the potential mitigations of defects and functional grading of component properties, are discussed.

We discuss what we believe could be an improvement in future discussions of the ever-changing brain. We do so by distinguishing different types of brain variability and outlining methods suitable to analyse them. We argue that, when studying brain and behaviour data, classical methods such as regression analysis and more advanced approaches both aim to decompose the total variance into sensible variance components. In parallel, we argue that a distinction needs to be made between innate and acquired brain variability. For varying high-dimensional brain data, we present methods useful to extract their low-dimensional representations. Finally, to trace potential causes and predict plausible consequences of brain variability, we discuss how to combine statistical principles and neurobiological insights to make associative, explanatory, predictive, and causal enquires; but cautions are needed to raise association- or prediction-based neurobiological findings to causal claims.

The main foundations of the standard $\Lambda $CDM model of cosmology are that: 1) The redshifts of the galaxies are due to the expansion of the Universe plus peculiar motions; 2) The cosmic microwave background radiation and its anisotropies derive from the high energy primordial Universe when matter and radiation became decoupled; 3) The abundance pattern of the light elements is explained in terms of primordial nucleosynthesis; and 4) The formation and evolution of galaxies can be explained only in terms of gravitation within a inflation+dark matter+dark energy scenario. Numerous tests have been carried out on these ideas and, although the standard model works pretty well in fitting many observations, there are also many data that present apparent caveats to be understood with it. In this paper, I offer a review of these tests and problems, as well as some examples of alternative models.

Infections due to Candida spp., they are a threat to global health, with high rates of morbidity and mortality due to their drug resistance, especially in immunocompromised people. Thus, the search for new alternatives is urgent today. In recent years, combined therapy with compounds of natural origin has been proposed as an alternative. Considering the biological potential of isoespintanol (ISO) and continuing with its study, the objective of this research was to assess the effect of ISO in combination with the antifungals, fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP), against clinical isolates of C. tropicalis and evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84), in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. Evaluation of the mice by direct vision showed no behavioral changes or variation in weight during treatment; furthermore, the analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process and histopathological studies of lung, liver and kidney showed no signs of toxicity caused by ISO; this was consistent with the analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated. Our results place ISO as a monoterpene of interest in the search for compounds with pharmacological potential.

This survey provides a comprehensive overview of in-context learning (ICL) in large language models (LLMs), a phenomenon where models can adapt to new tasks without parameter updates by leveraging task-relevant information within the input context. We explore the definition and mechanisms of ICL, investigate the factors contributing to its emergence, and discuss strategies for optimizing and effectively utilizing ICL in various applications. Through a systematic review of recent literature, we first clarify what ICL is, distinguishing it from traditional fine-tuning approaches and highlighting its unique characteristics. We then delve into the underlying causes of ICL, examining theories ranging from implicit meta-learning during pre-training to the emergence of task vectors in LLMs. The survey also covers various approaches to enhance ICL performance, including prompt engineering techniques, demonstration selection strategies, and methods for improving generalization across diverse tasks. Additionally, we discuss the limitations and challenges of ICL, such as its sensitivity to demonstration ordering and potential biases. By synthesizing findings from numerous studies, we aim to provide researchers and practitioners with a clear understanding of the current state of ICL research, its practical implications, and promising directions for future investigation. This survey serves as a valuable resource for those seeking to leverage ICL capabilities in LLMs and contributes to the ongoing discourse on the remarkable adaptability of these models.

The domain of Information and Communication Technology (ICT) education has garnered significant consideration in recent times. However, several challenges are inherent to this area of study, including monetary expense, temporal factors, pedagogical environment, teacher training programs, incentive, syllabus design, and health-related concerns. This paper presents an analysis of the difficulties encountered in the realm of ICT education in Japan, taking into account ten different perspectives.

Artificial Intelligence (AI) experienced significant advancements in recent years, and its impact is already recognized across various industries. Yet, the rise of AI has led to a growing concern about its impact on meeting the Sustainable Development Goals (SDGs). The aim of this paper was to evaluate contributions and the potential impact of AI to sustainable development in the society domain. Furthermore, the study analyzed GPT-3 responses, as one of the largest language models developed by OpenAI, descriptively. We conducted a set of queries on the SDGs to gather infor-mation on GPT-3`s perceptions of AI impact on sustainable development. Analysis of GPT-3’s contribution potential towards the SDGs showcased its broad range of capabilities for contributing to the SDGs in areas such as education, health, and communication. The study findings provide valuable insights into the contributions of AI to sustainable development in the society domain and highlight the importance of proper regulations to promote the responsible use of AI for sustainable development. We plan subsequent research for effects on ecologic and economic domains of SDGs. We highlighted the potential for improvement in neural language processing skills of GPT-3 by avoiding imitating weak human writing styles with more mistakes in longer texts.

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

In the ambitiously evolving construction industry of Kuwait, characterized by its vision 2035 and rapid technological integration, there exists a pressing need for advanced analytical frameworks. This research paper introduces a groundbreaking deep learning approach utilising an autoencoder neural network to analyse the complexities of the Kuwait Construction Market and identify data irregularities. The construction sector’s significant investment influx and project expansion make it an ideal candidate for deploying sophisticated analytical techniques to detect anomalous patterns indicating inefficiencies or unveiling potential opportunities. Our approach leverages the capabilities of autoencoder architectures to delve into and understand the prevalent patterns in market behaviours. This meticulous analysis allows for the detection of deviations that may lead to operational or financial consequences. We elucidate the mathematical foundations of autoencoders, highlighting their proficiency in managing the complex, multidimensional data typical of the construction industry. Through training on an extensive dataset—comprising variables like market sizes, investment distributions, and project completions—our model demonstrates its ability to pinpoint subtle yet significant anomalies. The outcomes of this study enhance our understanding of deep learning’s pivotal role in construction and building management. Additionally, our findings proactively sketch the future market trajectory and facilitate anomaly detection, thereby contributing substantially to the academic discussion on integrating machine learning into construction management. This research offers valuable insights for professionals within Kuwait, aiming to harness deep learning techniques to boost operational efficiency and strategic foresight in the construction sector.

In the rapidly advancing field of Artificial Intelligence (AI), this study presents a critical evaluation of the resilience and cybersecurity efficacy of leading AI models, including ChatGPT-4, Bard, Claude, and Microsoft Copilot. Central to this research is the use of innovative adversarial prompts designed to rigorously test the content moderation capabilities of these AI systems. The study introduces new types of adversarial tests and the Response Quality Score (RQS), a metric specifically developed to assess the nuances of AI responses. Additionally, the research spotlights FreedomGPT, an AI tool engineered to optimize the alignment between user intent and AI interpretation. The empirical results from this investigation are pivotal for assessing the current robustness and security of AI models. They highlight the necessity for ongoing development and meticulous testing to bolster AI defenses against an array of adversarial challenges. Importantly, the study also delves into the ethical and societal implications associated with employing advanced 'jailbreak' techniques in AI testing. The findings are significant for understanding AI vulnerabilities and formulating strategies to enhance the reliability and ethical soundness of AI technologies, paving the way for safer and more secure AI applications.

Contrast agents developed for X-ray computed tomography (CT) offer extremely valuable tools and techniques in diagnostics via contrast enhancements. Heavy metal-based nanoparticles (NPs) can provide high contrast in CT images. These result from a high density of heavy metal atoms with high X-ray attenuation coefficients that exceed that of iodine (I), which is currently used in hydrophilic organic CT contrast agents. Nontoxicity and colloidal stability are vital characteristics in designing heavy metal-based NPs as CT contrast agents. In addition, the particle size must be small for in vivo renal excretion. In vitro phantom imaging studies can provide X-ray attenuation efficiency, which is a critical parameter for CT contrast agents, and the imaging performance of CT contrast agents can be demonstrated via in vivo experiments. This review focuses on in vitro and in vivo studies of various heavy metal-based NPs (metal: Au, Pt, Pd, Ag, Ce, Gd, Dy, Ho, Yb, Ta, W, and Bi) and provides an outlook on their use as high-performance CT contrast agents.

Paratuberculosis (PTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP) that affects a wide variety of domestic and wild animals. It is considered as one of the diseases with the highest economic impact in the ruminant industry. Despite many efforts and intensive research, PTB control is still controversially discussed and diagnostic and immunoprophylactic tools lack great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Here, we review the potential and limitations of different experimental approaches currently used in PTB research, focusing on laboratory animals and cell based models. The aim of this review is to offer a vision of the models that have been used and what has been achieved or discovered with each one so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.

Recently, in a previous study, we have experimentally shown the existence of an optimal injected steam mass flow rate, per unit length, ϕopt, which produces the maximal recovery of con- densate in a preformed steam chamber with an elliptical cross section of horizontal semi-major axis. Mutatis mutandis, in this work we present experimental studies in preformed steam chambers, one elliptical and the other circular. In both cases, we also have found the existence of unique optimal values. These configurations try to recreate the steam condensation, at a given time lapse, as it would occur during the growth stage of the steam-assisted gravity drainage (SAGD) process, a method used in the recovery of heavy and extra-heavy oil from homogeneous reservoirs. Finding the optimal mass flow rates in actual recovery process could become useful in the design of optimized SAGD processes.

This paper takes the VR animation display of the Ming Xiao Mausoleum General stone statue life as an example to study the advantages of VR animation in the display of material heritage. Combined with literature and pictures, the digital restoration of the Ming Xiao Mausoleum stone statue is carried out in MAYA and Z brush, and the construction of the scene and the output of the final effect are realized in UE4.

Seedling emergence is crucial for the establishment and growth of crops and is influenced by topsoil temperature and moisture. Mulching has been widely used to promote seedling emergence in areas with a cold spring. This study was conducted to determine and simulate the effects of transparent plastic film mulch on surface soil moisture, temperature, and seedling emergence of spring maize in Northwest China. Four treatments were used: no mulching (CK), full plastic film mulch (PMF), and partial plastic film mulch, 60 cm in width (PM60, 40 cm uncovered between rows of mulch) or 30 cm in width (PM30, 20 cm uncovered between rows of mulch). The effects of soil water conservation and temperature enhancement gradually decreased as the plastic film width decreased, but there was little difference between PMF and PM60 treatments. Soil-water-modified growing degree days (WGDD) described the beneficial effects of soil moisture and temperature with respect to seedling emergence under mulching conditions. Plastic film mulching markedly accelerated seedling emergence and increased final seedling emergence rate because mulching can shorten the autotrophy duration and maintain surface soil moisture, which leads to increased germination. The effects of seedling emergence improvement decreased as the plastic film width decreased. The relationship between WGDD and cumulative relative seedling emergence (CRE) was adequately described by a Gompertz function.

Traditional methodologies for measuring combat effectiveness rely on various contribution factors, where the main challenge lies in the complexity and subjectivity of these factors. Using frontline variation to measure combat effectiveness circumvents the limitations of many previous methods regarding complexity and subjectivity. Employing this methodology, we have quantitatively measured the combat effectiveness of both parties in the Russo-Ukrainian War across various temporal scales. Utilizing the time series data derived from our measurements, we constructed Daily, Weekly, Monthly, and Annual Candlestick Charts to illustrate the variation trends in combat effectiveness between the two sides across different temporal scales. This comprehensive approach facilitated a nuanced and all-encompassing analysis of the conflict, capturing the intricate dynamics of individual military engagements and the broader strategic operations' context. This case underscores the distinctive utility of our method in quantifying combat effectiveness, offering detailed and strategically significant insights.

ESG (Environmental, Social, and Governance) responsibility fulfillment increasingly affects enterprise valuation. Although researchers debate about the precise effects, the prevailing view suggests a linear relationship between ESG performance and enterprise value. This study introduces a novel ESG responsibility performance metric through the Regulated Intermediary Model to delve into this relationship within the Chinese context. Our findings reveal an inverted U-shaped relationship between ESG performance and enterprise value, with financing constraints having a significant moderating effect. These findings remain robust after employing instrumental variables to mitigate potential endogeneity. Heterogeneity analysis demonstrates that this inverted U-shaped relationship is particularly pronounced in non-polluting and non-state-owned enterprises. Moreover, a comparison between equity and debt financing mechanisms underscores that improved ESG performance is associated with lower cost of equity financing, thereby enhancing enterprise value. Financial institutions are encouraged to leverage innovative financial instruments to diversify enterprise financing channels and alleviate financing constraints of enterprises that fulfill their ESG responsibilities.

It is proved that there exist two odd prime numbers, p_i and p_j , such that p_i + p_j = 2r + 2(r ⩾ 2), where p_n denote the n-th odd prime number, 1 ⩽ i, j ⩽ n. By the theory of generating functions, we prove that there exist two positive integers, h_i and h_j , such that h_i + h_j = r(r ⩾ 2), where h_n = (p_n − 1)/2，(p_n ⩾ 3).Then we complete the proof.

Through long-term Rayleigh lidar observations during 2010-2022, atmospheric gravity wave (AGW) activities in the middle atmosphere (30–65 km) are statistically investigated at Haikou (110.3°E, 19.9°N) in China. In total, 827 quasi-monochromatic AGW events are identified from the lidar dataset, and the vertical wavelength, observed wave period, and vertical propagation direction of dominant waves are extracted for each AGW event by analyzing the power spectra of wave-induced temperature perturbations. It is revealed that 81.7% of all AGW events were associated with upward-propagating waves, and the proportion of upward-propagating AGWs reached a maximum in autumn and a minimum in winter. The most common vertical wavelengths and wave periods were 6–11 km and 4–10 hours, respectively. In particular, 68 AGW events associated with simultaneous upward and downward propagating waves were observed by lidar, corresponding to 8.2% of the events. The occurrence of such special AGW phenomena is qualitatively discussed, and multiple formation mechanisms may exist. Comparisons are made with previously reported lidar observation results, and the statistical features of AGW activity in the low-latitude middle atmosphere may vary over a relatively wide range depending on the location and altitude. However, a majority of AGWs propagate upward in the middle atmosphere.

This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this therapy to other malignancies and broader patient populations. However, several limitations remain, including those associated with the time-consuming and highly personalized manufacturing of autologous CAR-Ts. Technologies to establish “off-the-shelf” allogeneic CAR-Ts with low alloreactivity are currently being developed, with a strong focus on gene editing technologies. Although these technologies have many advantages, they have also strong limitations including double-strand breaks in the DNA with associated multiple safety risks as well as the lack of modulation. As an alternative, non-gene editing technologies provide an interesting approach to support the development of allogeneic CAR-Ts in the future, with possibilities of fine-tuning gene expression and easy development. Here we will review the different ways allogeneic CAR-Ts can be manufactured and discuss which technologies are currently used. The biggest hurdles for successful therapy of allogeneic CAR-Ts will be summarized and finally an overview of the current clinical evidence for allogeneic CAR-Ts in comparison to its autologous counterpart will be given.

Time series ground deformation monitoring and reservoir parameter inversion are crucial for the dynamic assessment of oilfield resources and sustainable exploitation in an oilfield. As one of the regions with the richest oil reserves in China, the oilfield areas in the western Qaidam Basin are selected as a typical study area. Firstly, we used SAR images collected by the Sentinel-1A satellite from January 2021 to December 2022 and applied the Multidimensional Small Baseline Subset (MSBAS) method to obtain vertical and east-west deformation measurements. On this basis, a nonlinear Bayesian inversion method was applied to model the shallow reservoir in a series of complex deformation areas, based on a single-source model and a multi-source model, respectively. As a result, the ground deformation monitoring results obtained by long time series InSAR clearly reflect the uneven ground deformation caused by the oil extraction and water injection operation process. There is slight subsidence in the Huatugou oilfield, while significant uplift deformation occurred in the Ganchaigou oilfield and the Youshashan oilfield, with a maximum uplift rate of 48 mm/year. Further analysis indicates that the introduction of the 2D deformation field helps to improve the robustness of oilfield reservoir parameter inversion. Moreover, the dual-source model is more suitable than the single-source model for inverting complex deformation reservoir parameters. This study not only fills the blank of InSAR deformation monitoring for the oilfields in the western Qaidam Basin but also provides a theoretical reference for model and method selection of reservoir parameter inversion in other oilfields.

The paper presents a method for estimating the inertia tensor components of a spacecraft that has expired its active life using measurement data of the Earth's magnetic field induction vector components. The implementation of this estimation method is supposed to be carried out when cleaning up space debris in the form of a clapped-out spacecraft with the help of a space tug. It is assumed that a three-component magnetometer and a transmitting device are attached on space debris. With the help of this measuring system, the parameters for the rotational motion of space debris are estimated. Then the known controlled action from the space tug is transferred to the space debris. Next, measurements for the rotational motion parameters are carried out once again. Based on the available measurement data and parameters of the controlled action, the space debris inertia tensor components are estimated. It is assumed that the measurements of the Earth's magnetic field induction vector components are made in a coordinate system which axes are parallel to the corresponding axes of the main body axis system. Such an estimation makes it possible to effectively solve the problem of cleaning up space debris, to calculate the costs of the space tug working body and the parameters of the space debris removal orbit. Examples of numerical simulation using the measurement data of the Earth's magnetic field induction vector components on the Aist-2D small spacecraft are given. The results of the work can be used in the development and implementation of missions to clean up space debris in the form of clapped-out spacecraft.

First described in 1760 by the anatomist Morgagni, CoA is a congenital heart defect characterized by narrowing the aorta, typically distal to the left subclavian artery. It accounts for approximately 5-8% of all congenital heart diseases, with an incidence estimated at 4 per 10,000 live births. In 1944, the Swedish surgeon Clarence Crafoord achieved the first successful surgical CoA repair by performing an aortic end-to-end anastomosis on two patients aged 12 and 27 years old. Presently, the most prevalent techniques for surgical repair, particularly in infants and neonates with isolated coarctation, involve resection with end-to-end anastomosis (EEA) and the modified Crafoord technique (extended resection with end-to-end anastomosis (EEEA)). Subclavian flap aortoplasty (SCAP) is an alternative surgical option for CoA repair in patients under two years of age. In cases where the stenosis extends beyond resection and end-to-end anastomosis feasibility, patch aortoplasty (PP) employing a prosthetic patch can augment the stenotic region, especially for older patients. Despite advances in pediatric cardiology and cardiac surgery, recoarctation remains a significant concern after surgical or interventional repair. This comprehensive review aims to provide a thorough analysis of coarctation management, covering the pioneering techniques introduced by Crafoord using head-to-tail anastomosis and now extending to the contemporary era marked by percutaneous interventions as well as the recoarctation rate associated with each type.

The purpose was to reflect on the sustainability of artisanal and informal mining in the Peruvian Andean zone by 2022. The type of research was basic, non-experimental design, ex post facto scope. The sample consisted of: statistics on crime prevention due to socio-environmental conflicts from the National Prosecutor's Office and the Ombudsman's Office, reports of interventions targeted at artisanal and informal miners. The procedure focused on gathering secondary information for a documentary review analysis that is based on proven and disseminated past facts. Artisanal and informal mining is strengthened in the Peruvian Andean zone by incidence and force: 1) the social license and agreements by community assembly, 2) the flexibility in compliance with the formalization, preventive and environmental protection laws, 3) the 50% increase in socio-environmental conflict due to mining activity, 4) a 25% progressive increase in the production costs of agricultural and livestock activities. The direct consequences on environmental sustainability are: 1) the delimited reconversion of the change in agricultural land use in a third of the communal territories in basin headwaters; 2) displacement of environmentally friendly economic activity by 20% in basin headwaters; 3) the impossibility of modification or intervention in water surfaces, bofedales by communal agreements.

Cancers of the head and ne¬ck and their treatment can cause disfigurement and loss of functioning, with a profound negative impact on the person’s self-image and psychosocial wellbeing. This can lead to experiences of shame and stigma, which are important targets for psychosocial interventions. Accurate measurement and identification of these problems enables clinicians to offer appropriate interventions and monitor patients’ progress. This study aimed to validate the Canadian version of the Shame and Stigma Scale (SSS) among French and English speaking head and neck cancer patients. Data from 258 patients from two major Canadian hospitals was analysed. The existing 4-factor structure of the SSS was supported, with the following subscales: Shame with Appearance, Sense of Stigma, Regret, and Social/Speech Concerns. The Canadian SSS showed adequate convergent and divergent validity and test-retest reliability. Rasch analysis suggested scale improvement by removing two misfitting item and two items with differential functioning between French and English speaking patients. The final 16-item scale version had adequate fit to the Rasch model. The SSS provides more accurate measures for people with high levels of shame and stigma, and thus has utility in identifying patients with more severe symptoms who may be in need of psychosocial interventions.

The link of fracture analysis of large ships is an essential part of the structural safety of ships. However, the finite element analysis of large structure according to the traditional method not only has high requirements on the computer, but also the influence of the mesh encryption at special locations makes further requirements on the accuracy of the ship. In this paper, based on the extended finite element method (XFEM) and the multi-point constraint method (MPC), the dynamic crack expansion process of the rectangular plate containing cracks under the multi-scale model is comparatively studied by using ABAQUS simulation software Finally, the applicability of the method is verified by applying the multi-scale model of ship nodes. The results show that the computational effort of the multi-scale model is significantly reduced with the same accuracy and allowable error, which proves the accuracy and efficiency of the method.

High-performance anodes are contributed to nanostructure of transition metal oxides for rechargeable Li-ion batteries (LIBs). In this work, we report the fabrication of high-performance anode materials for lithium-ion batteries, MnO2 nanotube directly grown into fabrics of carbon nanofibers, the MnO2/Carbon nanofibers (CNFs) were investigated by X-ray diffraction, scanning and transmission electron microscopies. When tested as the anode material in LIBs, the MnO2/CNFs exhibit superior performance and excellent long cycling performance with a reversible capacity of 835 mA h g-1 at 0.1 A g-1 after the 133 th cycle, a high initial specific capacity of 1094 mA h g-1 at a current density of 0.1 A g-1. The MnO2/CNFs demonstrates notable specific capacities, specifically, with a coulombic efficiency of 99.5 %, both stability and capacity are conspicuously above literature data. These impressive results indicate that MnO2/CNFs has great potential for high-energy and high-power energy storage applications.

The purpose of this article is to demonstrate the ability of bibliometric data from the Lens platform to identify relevant bibliometric/scientometric issues based on the construction of a network of key terms co-occurrence and their clustering. The advantages of using the Lens platform for bibliometric analysis are briefly demonstrated. Key terms were selected on the basis of n-grams and noun phrases. VOSviewer, Scimago Graphica, and Sifaka text mining application were used as analytical tools. Analysis of the Lens metadata on bibliometrics/scientometrics showed their predominant use in the political, social, and medical fields of research.

Psycho-social factors are key factors to the powerlessness of infant mothers who breastfeed. As the theory of planned behavior (TPB) is widely used to investigate the correlation between psycho-social factors and breastfeeding behavior, this study aims to examine the utility of TPB constructs to predict breastfeeding behavior and understand TPB-based psycho-social factors’ effectiveness on breastfeeding behavior. A narrative review consulting Web of Science, Scopus, Ebsco, PubMed, and PsycInfo in English and Chinese has been conducted, with the inclusion of twenty studies published between January 2000 and May 2022. It is reported that psycho-social factors based on TPB for breastfeeding such as affective attitude, instrumental attitude, subjective norm, perceived behavioral control (including self-efficacy), moral norm, breastfeeding knowledge, and self-identity can effectively explain the breastfeeding behavior. Future research should improve the theoretical model of TPB-based breastfeeding and implement more localized prediction and intervention studies on breastfeeding.

In this article, by focusing on the two main protagonists, Mitya Karamazov and Pavel Smerdyakov, we would like to analyze the murder of Fyodor Karamazov, which is the crucial event in the novel The Brothers Karamazov. We have conducted analysis of these two characters from the perspective of literature studies, psychology and psychiatry. Although we agree with Freud’s opinion (1) that it is not important who killed the father, but who wanted to kill him, we hope that our findings will allow us to formulate conclusions that will be helpful in new interpretations of this masterpiece.

With the depletion of shallow surface resources, the future mining work will develop towards the deep surface, and the objective conditions such as the mining environment will be more complex and dangerous than now, and the requirements for personnel and equipment will be higher and higher. The efficient exploitation of deep space cannot be separated from such mobile and flexible production and transportation equipment as scraper. In the new era, intelligence is the development trend of the LHD, and path tracking control technology is the key to the intelligent LHD, and it is also an urgent problem to be solved for its unmanned driving. This paper describes the realization of the automatic operation function of articulated LHD from two aspects of mathematical model and trajectory tracking control method, and focuses on the research of the path tracking control scheme in the field of unmanned driving, that is, LQR controller. On this basis, the parameters of the LQR controller are optimized by combining different intelligent cluster algorithms to find the optimal solution of the LQR controller.

The research results presented in the article were carried out during the realization of the project, the aim of which is to develop a method of drying cellulose insulation in power transformers with the use of synthetic ester. This method uses a very high water absorption of the ester. During the drying of transformers, the ester is systematically contaminated with mineral oil, which gradually loses its ability to absorb water. Information on the oil concentration in the mixture is needed in two cases: at the stage of making a decision on the treatment of the mixture and during its treatment. The article presents the results of investigations of two methods: 1) based on the measurement of the mixture density, and 2) based on the measurement of the capacitance of the capacitor immersed in the mixture. The conducted research shows that the method of measuring the density of the mixture gives an uncertainty of 2.6 p. %, while the method of measuring the capacitance of a capacitor gives an uncertainty of 2.2 p. %. A significant advantage of the method of measuring the capacitance is the possibility of using it online to control the ester treatment process.

In this paper, we study singularities of the spherical indicatrix and evolute of spacelike ruled surface with spacelike ruling. Finally, we give an example to illustrate our results.

In this paper, we study the symmetry between the supersingular prime number according to smallest sphenic number. With this symmetry, we show that the elements of sporadic group generates all prime numbers with the order by a simple application.

Overcoming terrain obstacles presents a major problem for people with disabilities or with limited mobility who are dependent on wheelchairs. An engineering solution designed to facilitate the use of wheelchairs are assisted propulsion systems. The objective of the research described in this article is to analyse the impact of the hybrid manual-electric wheelchair propulsion system on the kinematics of the anthropotechnical system when climbing hills. The tests were carried out on a wheelchair ramp with an incline degree of 4°, using a prototype wheelchair with a hybrid manual-electric propulsion system in accordance with the patent application P.427855. The test subjects were three people whose task was to propel the wheelchair in two assistance modes supporting manual propulsion. The first mode is hill climbing assistance, while the second one is assistance with propulsion torque in the propulsive phase. During the tests, a number of kinematic parameters of the wheelchair were monitored. An in-depth analysis was performed for the amplitude of speed during a hill climb and the number of propulsive cycles performed on a hill. The tests performed showed that when propelling the wheelchair only using the hand rims, the subject needed an average of 13 pushes on the uphill slope, and their speed amplitude was 1.8 km/h with an average speed of 1.73 km/h. The climbing assistance mode reduced the speed amplitude to 0.76 km/h, while the torque assisted mode in the propulsive phase reduced the number of cycles required to climb the hill from 13 to 6. The tests were carried out at various values of assistance and assistance amplification coefficient, and the most optimally selected parameters of this coefficient were presented in the results. The tests proved that electric propulsion assistance has a beneficial and significant impact on the kinematics of manual wheelchair propulsion when compared to a classic manual propulsion system when overcoming hills. In addition, assistance and assistance amplification coefficient were proved to be correlated to operating conditions and the user's individual characteristics.

Battlefield miracle stories are not rare. This paper suggests a typology of battlefield miracles. From this perspective it asks what sort of miracles can we expect to see in battle and when can we expect to see them? After presenting the main points of discussion regarding miracles, it proposes a range of categories for military miracles (miracles as acts that violate nature versus miracles as everyday acts; those involving the divine versus occurrences not requiring the presence of a heavenly emissary; acts of benevolence versus acts with no such intent; having a clear purpose versus acts where there is disagreement regarding interpretation). After discussing these categories, the articles uses Operation Cast Lead (December 2008–January 2009) as a case study to test the typology suggested above. Since this field is underdeveloped, this paper sets out to initiate a conversation on battlefield miracles, with hope that future studies will build upon it.

Preventing malnutrition and dehydration in older care home residents is complex, with both conditions remaining prevalent, despite numerous guidelines spanning several decades. This policy-mapping scoping review used snowballing search methods to locate publicly-available policies, reports and best practice guidelines relating to hydration and nutrition in UK residential care homes, to describe the existing knowledge base and pinpoint gaps in practice, interpretation and further investigation. Findings were synthesised narratively to identify solutions. Strategies for improvements to nutritional and hydration care include: development of age and population-specific nutrient and fluid intake guidelines; statutory regulation, contractual obligations for commissioners, appropriate menu-planning, implementation and auditing of care, acknowledgment of residents’ eating and drinking experiences, effective screening, monitoring and treatment and staff training. The considerable body of existing knowledge is failing to influence practice, relating to translational issues of implementing knowledge into care at the point of delivery, and this is where future research and actions should focus.

The value of landscape, as part of collective heritage, can be acquired by GIS due to the multilayer approach of the spatial configuration. Proficiency in geospatial technologies in order to collect, process, analyze, interpret, visualize and communicate geographic information is being increased by undergraduate and graduate students, but in particular by those who are training to become geography teachers at secondary education. This training can be carried out through personalized learning and distance learning methodology. Personalized GIS education aims to integrate students and enhance their understanding of landscape. Some teaching experiences are shown whereby opportunities offered by WebGIS will be described, through quantitative tools and techniques that will allow this modality of learning and improve its effectiveness. Results of this research show that students, through geospatial technologies, learn landscape as a diversity of elements but also the complexity of physical and human factors involved. Several conclusions will be highlighted: i) the contribution of geospatial training to education for sustainable development; ii) spatial analysis as a mean of skills acquisition about measures for landscape conservation; iii) expanding and applying acquired knowledge to other geographic spaces and different landscapes.

In this paper new upper limits on the parameters of the Continuous Spontaneous Localization (CSL) collapse model are extracted. To this end the X-ray emission data collected by the IGEX collaboration are analyzed and compared with the spectrum of the spontaneous photon emission process predicted by collapse models. This study allows to obtain the most stringent limits within a relevant range of the CSL model parameters, with respect to any other method. The collapse rate $\lambda$ and the correlation length $r_C$ are mapped, thus allowing to exclude a broad range of the parameter space.

The main goal of our scientific study is to determine the particular characteristics of the endo-scopic image of the otorhinolaryngologic pathology of nasopharynx, which is called chronic rhinosinusitis in association with gastroesophageal acid reflux disease. Background/Objectives: to identify a specific features in the endoscopic picture of chronic rhinosinusitis associated with acid gastroesophageal reflux disease symptoms. Methods: there were selected 521 adult patients, from this sample as a main group we have selected only 95 patients with the highest scores on the Reflux Symptom Index (RSI) (>20) and Reflux Symptom Score-12 (RSS-12) (>130) questionnaires. As a control group we have selected 41 adult patients only with chronic rhinosinusitis and 10 healthy patients. Results: there were significant changes in the nasopharyngeal mucosa. In-creased vascularity of the nasopharyngeal mucosa was noted in 91 patients (95,7%). Hypertrophy of the nasopharyngeal mucosa was found in 83 patients (87,4%). In 77 (81,1%) patients, mucus was found in the nasopharynx with different characteristics of color and consistency, and no mucus or other secretions were found in the middle nasal passages in these patients. In 62 pa-tients (65,3%) asymmetric hypertrophy of the mucosa of the oropharynx was noted. Conclusions: the presence of specific features of the endoscopic picture of the nose and nasopharynx of pa-tients with chronic rhinosinusitis associated with gastroesophageal disease symptoms and pro-posed a method for assessing the degree of influence of gastroesophageal reflux disease on the mucosal layer of the nose and nasopharynx. The possible influence of symptoms of gas-tro-oesophageal reflux disease on the course and severity of clinical manifestations of exacerba-tions of chronic rhinosinusitis needs further investigation.

Background: The manifestations, severity, and mortality of COVID-19 are considered to be associated with the changes in various hematological parameters and in immunity. Associations of immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status with cardiac function and hematological and biochemical parameters in apparently health subjects are poorly understood. Methods: The present cross-sectional study included 307 healthy volunteers (24-69 years of age; 44.8±8.6 years; 80.4% men) and was initiated in 2019 before the COVID-19 pandemic. COVID-19 episodes were confirmed by detection of IgG-SARS against SARS-CoV-2 S1 RBD to reveal 70 IgG-SARS-positive and 237 negative participants. Numerous ultrasound characteristics were assessed by echocardiography, and 15 hematological and biochemical parameters were assayed in the blood. Descriptive and comparative analysis was based on the IgG-SARS status of the participants. Results: The left ventricular mass index, mitral ratio of peak early to late diastolic filling velocity or flow velocity across the mitral valve, and deceleration time of early mitral inflow were decreased (P<0.05) in IgG-SARS-positive participants versus those in IgG-SARS-negative participants according to multivariate logistic regression analysis. Erythrocyte sedimentation rate and platelet count were slightly increased, and blood hemoglobin was decreased in IgG-SARS-positive participants compared with those in IgG-SARS-negative participants. Conclusions: LV filling, inflammation, blood coagulation, and hemoglobin appear to be influenced by COVID-19 infection in healthy participants. These observations contribute to the development of a population recovery strategy after the episodes of COVID-19.

The article analyzes the problems connected with ensuring the coordinated operation of slipway drives that arise during the launch of a ship. The dynamic model of load of the electric drive of the ship's cart is obtained taking into account the peculiarities of the construction of the ship-lifting complex, which allows to analyze the influence of external factors and random influences during the entire process of launching the ship. A linearized mathematical model of the dynamics of a complex vessel movement in the process of descent in the space of states is developed, which allows to identify the mode of operation of the multi-drive system, taking into account its structure. The analysis of efficiency of application of recurrent methods of identification (stochastic approximation and least squares) of the parameters of the linearized model in the space of states is carried out. A decision support system has been developed in the automated system of operational control by the module for estimating the situation and the control synthesis to ensure a coherent motion of a complex ship-carts object in a two-phase environment.

Backward electromagnetic waves are extraordinary waves with contra-directed phase velocity and energy flux. Unusual properties of the coherent nonlinear optical coupling of the phase-matched ordinary and backward electromagnetic waves with contra-directed energy fluxes are described which enable greatly-enhanced frequency and propagation direction conversion, parametrical amplification, as well as control of shape of the light pulses. Extraordinary transient processes that emerge in such metamaterials in pulsed regimes are described. The results of the numerical simulation of particular plasmonic metamaterials with hyperbolic dispersion are presented, which prove the possibility to match phases of such coupled guided ordinary and backward electromagnetic waves. Particular properties of the outlined processes in the proposed metamaterial are demonstrated through numerical simulations. Potential applications include ultra-miniature amplifiers, frequency changing reflectors, modulators, pulse shapers, and remotely actuated sensors.

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.

Peptide-based inhibitors represent a promising approach for the treatment of HIV-1, offering a range of potential advantages including specificity, low toxicity, and the ability to target various stages of the viral lifecycle. This review outlines the current state of research on peptide-based anti-HIV therapies, highlighting key advancements and identifying future research directions. Over the past few years, there has been significant progress in developing synthetic peptide-based drugs that target various stages of the viral life cycle, including entry and replication. These approaches aim to create effective anti-HIV therapies. Additionally, peptides have proven valuable in the development of anti-HIV vaccines. In the quest for effective HIV vaccines, discovering potent antigens and designing suitable vaccine strategies are crucial for overcoming challenges such as low immunogenicity, safety concerns, and increased viral load. Innovative strategies for vaccine development through peptide research are, therefore, a key focus area for achieving effective HIV prevention. This review aims to explore the strategies for designing peptides with anti-HIV activity and to highlight their role in advancing both therapeutic and preventive measures against HIV.

Wild-grown edible mushrooms are important in world diet, which are also efficient metal accumulators. Yunnan, southwest China is the main producing region with typically high geochemical metals. Environmental factors, bioaccumulation, distribution and human health risk of metals were examined in paired soil and Tricholoma matsutake (n=54). T. matsutake grows on acidified soils (pH=3.95–6.56) and metals showed strong heterogeneity with Fe, Mn, Zn and Cu ranged at 16–201, 0.046–8.58 g kg–1 and 22.6–215, 3.7–155 mg kg–1. High soil Fe content led to its great accumulation in T. matsutake (0.24–18.8 g kg–1). However, though soil Mn content was great higher than Zn and Cu, their concentrations in T. matsutake were comparable (21.1–487 vs. 38.7–329 and 24.9–217 mg kg–1). This suggested that T. matsutake prefers to accumulate Zn and Cu than Mn, and supported by bioaccumulation factor (BAF=0.32–17.1 vs. 0.006–1.69). Fe was mainly stored in stipe, while Mn, Zn and Cu were in cap, with translocation factor (TF) was 0.58 vs. 1.28–1.94. Therefore, stipe Fe showed the highest health risk index (HRI) at 1.28–26.9, followed by cap Cu (1.01–2.33), while 98–100% of Mn and Zn were risk-free. The higher concentration and greater risk of Fe was attributed to the significant effect of soil Fe content (R=0.34) and soil pH (R=–0.57). This study suggested that Fe as an essential mineral may exert toxic effects via T. matsutake consumption from geochemical high background areas.

Activating the cytosolic innate immune sensor cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway via natural and synthetic agonists holds great potential for priming robust antitumor immunity. However, the effectiveness of STING agonists is often impeded by the insufficient tumor accumulation, poor cellular entry, and rapid clearance, thus leading to difficulty of their clinic translation. Herein, we apply the human serum albumin as the single-molecule nanoreactor to encapsulate SR-717 (SH-NPs) for enhanced targeting delivery efficiency and biological potency. SH-NPs with rational size distribution exhibited superior serum stability, considerable cellular uptake and abundant tumor accumulation, thus increasing the STING signaling including phosphorylation of STING-associated proteins (TBK1, IRF3), and cytokines secretion inside tumor region. Subsequently, SH-NPs remarkably reshape the immunosuppressive tumor microenvironment into an immunogenic one that boosts antitumor T-cell immunity and improves the therapeutic efficacy of checkpoint blockade against murine tumors. We also validate SH-NPs in freshly isolated human renal tumor tissues to highlight their clinic translation capability. These findings pave the way towards targeted STING agonist delivery for reinvigorated immunotherapy of intractable cancers.

The proliferation of wearable technology enables the generation of vast amounts of sensor data, offering significant opportunities for advancements in health monitoring, activity recognition, and personalized medicine. However, the complexity and volume of this data present substantial challenges in data modeling and analysis, which have been tamed with approaches spanning time series modeling to deep learning techniques. The latest frontier in this domain is the adoption of Large Language Models (LLMs), such as GPT-4 and Llama, for data analysis, modeling, understanding, and generation of human behavior through the lens of wearable sensor data. This survey explores current trends and challenges in applying LLMs for sensor-based human activity recognition and behavior modeling. We discuss the nature of wearable sensors data, the capabilities and limitations of LLMs to model them and their integration with traditional machine learning techniques. We also identify key challenges, including data quality, computational requirements, interpretability, and privacy concerns. By examining case studies and successful applications, we highlight the potential of LLMs in enhancing the analysis and interpretation of wearable sensors data. Finally, we propose future directions for research, emphasizing the need for improved preprocessing techniques, more efficient and scalable models, and interdisciplinary collaboration. This survey aims to provide a comprehensive overview of the intersection between wearable sensors data and LLMs, offering insights into the current state and future prospects of this emerging field.

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatic and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many of the ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the diagnostic and prognostic value of these ncORF as well as their carcinogenic role in cancer progression and underestimated potential as therapeutic targets.

Flavonoids are important natural compounds characterized by their extensive biological activities. Citrus flavonoids form a significant segment within the broader flavonoid category. Naringenin, an integral part of this series, is recognized for its powerful anti-inflammatory and antioxidant properties. In addition, considering the lack of existing research on naringenin's potential effectiveness and intracellular mechanisms of action in skin-related applications, especially as a cosmetic ingredient, this study aimed to explore naringenin's role in reducing the fundamental generation of reactive oxygen species. This was achieved by examining its inhibitory effects on the expression levels of NADPH oxidase and iNOS, ultimately leading to a reduction in NO production. This research examined the anti-inflammatory and antioxidant capacities of naringenin by employing a cellular senescence model of LPS-induced HDFs. The evaluation of naringenin's efficacy was validated through several investigative procedures, including the NF-κB luciferase assay, ELISA assay, and qRT-PCR. To verify the anti-inflammatory effectiveness of naringenin, the study measured the responsive elements of NF-κB using a luciferase reporter assay. This assessment revealed that naringenin could decrease the concentration of genes activated by NF-κB. Moreover, the study found that naringenin inhibited the transcriptional expression of known NF-κB regulated inflammatory cytokines, including IL-1β, IL-6, and IL-8. In addition, results from the qRT-PCR analysis indicated a reduction in iNOS expression facilitated by naringenin. Based on the data gathered and analyzed in this study, it can be conclusively inferred that naringenin possesses promising potential as a cosmetic ingredient, offering both anti-inflammatory and antioxidant benefits.

The Shule River Basin (SRB) is a typical arid area in northwest China with a fragile ecology. Un-derstanding vegetation dynamics and its response to climate change and human activities provides essential information for ecological and environmental resource management. This study extracted fractional vegetation coverage (FVC) data from 2000 to 2019 using the Google Earth Engine plat-form and Landsat satellite images, employing trend analysis and other methods to examine spati-otemporal changes in vegetation in the SRB. Additionally, partial correlation and residual analysis were utilized to explore the response of FVC to climate change and human activities. The main results were as follows: (1) The regional average FVC in the SRB showed a significant upward trend from 2000 to 2019, increasing by 1.3 × 10−3 y–1. The area within 1 km of roads experienced a higher increase of 3 × 10−3 y–1, while the roadless areas experienced a lower increase of 1.1 × 10−3 y–1. Road construction from 2004 to 2006 significantly reduced the FVC within 200 meters of the roads. FVC spatial heterogeneity in the SRB is significant. (2) Partial correlation analysis shows that FVC has a strong positive correlation with precipitation and surface water area, with correlation coefficients of 0.575 and 0.744, respectively. There is a weak negative correlation between FVC and land surface temperature (LST). FVC changes are more influenced by precipitation than by LST. (3) Compared to climate factors, human activities have a greater impact on vegetation dynamics in the SRB. The contributions of climate change to vegetation recovery are increasing. (4) The area changes of dif-ferent land types are closely related to climate factors and human activities, reflecting their impact on vegetation. These results provide valuable information for ecosystem restoration and environ-mental protection in the SRB.

Marine industries are dependent on the ocean and often have a direct impact on the marine environment. Although previous studies have talked about pollution from marine industries, it is not known to what extent and to what extent these behaviors affect the ocean. Therefore, this study examines the impacts of major marine industries on the marine environment, using China as an example. The Ministry of Ecology and Environment of the People's Republic of China categorizes the quality of seawater into Class I, Class II, Class III, Class IV, and Inferior Class IV in descending order according to the quality from good to poor. In this study, water quality of Class I and Class II are defined as good quality seawater, Class III as average quality, Class IV and Class IV as poor quality, and the proportion of the area of seawater with different water quality to the total area of the sea area symbolizes the overall quality of the marine environment. We use panel data from 11 provinces and cities along the coast of mainland China from 2006 to 2020, estimated by the full feasible generalized least squares (FGLS) method, to study the impacts of the development of coastal tourism, marine transportation, marine shipbuilding, marine salt, mariculture, and marine fishing on the marine environment. The empirical results show that, in descending order of the degree of influence, the marine industries that cause a decrease in the area of good quality seawater are coastal tourism, mariculture and shipbuilding, and the marine industries that cause an increase in the area of poor quality seawater are marine transportation and shipbuilding, while the marine salt industry has no obvious influence on the marine environment, and the development of the marine fishing industry indirectly contributes to the improvement of the marine environment.

Retiring coal power plants can reduce air pollution and health damages. However, the spatial distribution of those impacts remains unclear due to complex power system adjustments and pollution chemistry and transport. Focusing on coal retirements in Pennsylvania (PA), we analyze six counterfactual scenarios for 2019 that differ in retirement targets (e.g., reducing 50% of coal-based installed capacity vs. generation) and priorities (e.g., closing plants with higher cost, closer to Environmental Justice Areas, or with higher CO₂ emissions). Using a power system model of the PJM Interconnection, we find that coal retirements in PA shift power generation across PA and the Rest of PJM region leading to scenario-varying changes in the plant-level release of several air pollutants. Due to air pollution chemistry and transport and socio-demographics, these changes in turn give rise to a reduction of 10 to 182 PM_2.5-attributable deaths in PJM across the six scenarios, with most reductions occurring in PA. Scenarios that reduce more coal power generation yield greater aggregate health benefits due to air quality improvements in PA and adjacent downwind regions. In addition, vulnerable populations—in both PA and Rest of PJM—benefit most in scenarios that prioritize plant closures in PA near Environmental Justice Areas. These results demonstrate the importance of considering cross-regional linkages and socio-demographics in designing equitable retirement strategies.

Nicotinamide mononucleotide (NMN), a key NAD+ precursor, exhibits distinct metabolic characteristics and potential health benefits. Recent investigations underscore the pivotal role of gut bacteria and specialized uptake mechanisms in NMN metabolism. While human trials demonstrate NMN's safety and promising health outcomes, challenges persist. Variability in results is likely influenced by lifestyle, health conditions, and individual genetic and gut microbiota differences. Understanding how these factors affect NMN metabolism is crucial for personalized approaches and maximizing NMN's potential. Advances in delivery systems show promise for enhancing NMN bioavailability, but further understanding of optimal NAD+ levels and reliable measures of NMN's effects is necessary. This comprehensive approach is key to optimizing NMN's impact on human health and longevity.

A new trend in cow's milk has emerged in the market called type A1 and A2 milk. These products have piqued the interest of both consumers and researchers. Recent studies suggest that A2 milk may have potential health benefits, which is why researchers are investigating this product further. It is interesting to note that the A1 and A2 milk types have area-specific characteristics compared to breed-specific characteristics. Extensive research has focused on milk derivatives obtained from cow’s milk, primarily through in vitro and animal studies. However, few clinical studies have been conducted in humans, and the results have been unsatisfactory. New molecular techniques for identifying A1 and A2 milk may help researchers to develop new studies that can clarify certain controversies surrounding A1 milk. It is essential to exercise extreme caution when interpreting the updated literature. It has the potential to spread panic worldwide and have negative economic implications. Therefore, this study aims to investigate the new aspects of A1 and A2 milk in different research areas and clarify some aspects regarding these two types of milk.

Apoptotic cells possess immunomodulatory effects that can be utilized to treat imbalanced immune conditions. Information on the preclinical safety of such treatment is sparse. In this study, the safety of apoptotic cells (Allocetra-OTS) was assessed in a GLP toxicological study on Sprague Dawley rats. Three doses of Allocetra-OTS or vehicle were administered intravenously (IV) for 3 consecutive days. Animals in the Main study were sacrificed on day 4, while animals from the Recovery groups were kept for 14 or 28 days. Allocetra-OTS was well tolerated, and no adverse effects were observed in body weight, clinical signs, food consumption or ophthalmologic observation. Thus, the No Observed Adverse Effect Level (NOAEL) dose was determined as the highest dose administered. An observed elevation in immune cells was suspected to be due to Allocetra-OTS; similarly to other clinical chemistry parameters, however, it was resolved in the Recovery phases. Splenomegaly and a dose-related Extramedullary Hematopoiesis (EMH) in the red pulp were observed, with no adverse events, and were considered to be a normal and expected reaction following IV administration of cell-based therapies. In conclusion, under the conditions of this study Allocetra-OTS was concluded to be safe, further supporting its potential candidacy for clinical studies

In this study, the effect of NaOCl (10–200 ppm of Cl2) on the inactivation of human norovirus (HuNV) GII.4 and hepatitis A virus (HAV) in groundwater was investigated using PMA/RT­qPCR. Initially, 4.00 log copies/μL of HuNV GII.4 or 5.50 log copies/μL of HAV were artificially inoculated in ground water. The titers of HuNV GII.4 and HAV decreased significantly (p < 0.05) with increasing Cl2 concentrations. Ground water was treated with 10, 30, 50, 100, 150, and 200 ppm of Cl2, and the viable HuNV GII.4 was significantly (p < 0.05) reduced to 3.28 (0.21 log reduction), 3.18 (0.31 log reduction), 3.01 (0.48 log reduction), 2.75 (0.74 log reduction), 2.54 (0.95 log reduction), and 2.34 (1.15 log reduction) log copies/μL, respectively. The viable HAV was also significantly (p < 0.05) reduced to 4.99 (0.23 log reduction), 4.76 (0.46 log reduction), 4.55 (0.67 log reduction), 4.21 (1.01 log reduction), 3.89 (1.33 log reduction), and 3.64 (1.58 log reduction) log copies/μL, respectively. The decimal reduction time (D-value) (1-log reduction) of HuNV GII.4 and HAV infectivity in ground water was predicted as 116.7 and 98.9 ppm of Cl2, respectively using the first-order kinetics model (HuNV GII.4 ; y = - 0.0054x + 3.3585, R2= 0.97, HAV ; y = - 0.0091x + 5.0470, R2= 0.97). The result specifically suggests that 150–200 ppm Cl2 can potentially be used for the inactivation of > 1 log copies/μL HuNV GII.4 and HAV in ground water.