Mast cells (MC) are resident tissue cells found primarily at the interphase between tissues and environment. These evolutionary old cells store large amounts of proteases within cytoplasmic granules, and one of the most abundant of these proteases is the tryptase. To look deeper into the question their in vivo targets, we have analyzed the activity of the human MC tryptase on 69 different human cytokines and chemokines, and the activity of the mouse tryptase (mMCP-6) on 56 mouse cytokines and chemokines. These enzymes were found to be remarkably restrictive in their cleavage of these potential targets. Only five were efficiently cleaved by the human tryptase: TSLP, IL-21, MCP3, MIP-3b and eotaxin. This strict specificity indicates a regulatory function of these proteases and not primarily as unspecific degrading enzymes. We recently showed that the human MC chymase also had a relatively strict specificity, indicating that both of these proteases have regulatory functions. One of the most interesting such regulatory functions may involve controlling excessive TH2 mediated inflammation by cleaving several of the most important TH2-promoting inflammatory cytokines, including IL-18, IL-33, TSLP, IL-15 and IL-21 indicating a potent negative feedback loop on TH2 immunity.

Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show that the expression of the SARS-CoV E protein is associated with the hyperinflammatory response that could culminate in acute respiratory distress syndrome (ARDS), a potentially fatal complication. This immune-mediated damage is largely caused by a cytokine storm, which is induced by significantly elevated levels of inflammatory cytokines interleukin (IL)-1beta and IL-6, which are partly mediated by the expression of the SARS-CoV E protein. The interaction between the SARS-CoV E protein and the host protein, syntenin, as well as the viroporin function of SARS-CoV E, are linked to this cytokine dysregulation. This review aims to compare the clinical presentation of virulent hCoVs with a specific focus on the cause of the immunopathology. The review also proposes that inhibition of IL-1beta and IL-6 in severe cases can improve patient outcome.

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

Autonomous systems and intelligent machines are involved in almost all areas of human activity and they are now more and more present in our everyday life. The reason for this extensive use certainly resides in all the benefits these machines offer to the users. In experimental settings, numerous studies have demonstrated the positive effects that the introduction of autonomous systems have on human decision-making and performance. However, studies have shown in addition that the introduction of these systems can have important negative effects as well. Considering that autonomous systems are now introduced in sensitive domains like the military or medicine, we need more than ever a comprehensive understanding of the effects they cause on human performance and decision-making, and particularly in tasks and contexts with a social or moral dimension. The aim of this narrative review is threefold. First, we will provide an overview of the main effects on a human agent’s decision-making and performance produced by the introduction of autonomous systems. Second, we will review the conditions identified as underlying factors of these effects, and see how current models of human – autonomous systems interaction integrate those conditions. Third, we will conclude this review by highlighting new directions for future investigations.

Cervical cancer is the fourth most common malignancy in women worldwide, although it is preventable with prophylactic HPV vaccination. HPV transmission-dynamic models can predict the potential for global elimination of cervical cancer. The random network model is a new approach that allows individuals to be followed, and to implement a given vaccination policy according to their clinical records. We developed an HPV transmission dynamics model on a lifetime sexual partners network based on individual contacts, also accounting for the sexual behavior of men who have sex with men (MSM). We analyzed the decline in the prevalence of HPV infection in a scenario of 75% and 90% coverage for both sexes. An important herd immunity effect for men and women was observed in the heterosexual network, even with 75% coverage. However, HPV in-fections are persistent in the MSM population, with sustained circulation of the virus among un-vaccinated individuals. Coverage around 75% of both sexes would be necessary to eradicate HPV-related conditions in women within five decades. Nevertheless, the variation in the decline in infection in the long term between vaccination coverage of 75% and 90% is relatively small, suggesting that reaching coverage of around 70-75% in the heterosexual network may be enough to confer high protection. Nevertheless, HPV eradication maybe achieved if men’s coverage is strictly controlled. This accurate representation of HPV transmission demonstrates the need to maintain high HPV vaccination coverage, especially in men, for whom the cost-effectiveness of vaccination is questioned.

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.

Gesture-based recognition is one of the most intuitive methods for inputting information and is not subject to cumbersome operations. Recognition is performed on human's consecutive motion without reference to retrial or alternation by user. We propose a gesture recognition model with a mechanism for correcting recognition errors that operates interactively and is practical. We applied the model to a setting involving a manual grading task in order to verify its effectiveness. Our system, named GERMIC, consists of two major modules, namely, handwritten recognition and interactive correction. Recognition is materialized with image feature extraction and convolutional neural network. A mechanism for interactive correction is called on-demand by a user-based trigger. GERMIC monitors, track, and stores information on the user's grading task and generates output based on the recognition information collected. In contrast to conventional grading done manually, GERMIC significantly shortens the total time for completing the task by 24.7% and demonstrates the effectiveness of the model with interactive correction in two real world user environments.

Globally, saline lakes occupying 23% by area 44% by volume among all the lakes might desiccate by 2025 due to agricultural diversion, illegal encroachment, pollution, and invasive species. India’s largest saline lake, Sambhar is currently shrinking at the rate of 4.23% due to illegal saltpan en-croachment. This research article aims to identify the trend of migratory birds and monthly wetland status. Birds survey was conducted for 2019, 2020 and 2021 and combined with literature data of 1994, 2003, and 2013 for visiting trend, feeding habit, migratory and resident ratio, and ecological diversity index analysis. Normalized Difference Water Index was scripted in Google Earth Engine. Results state that it has been suitable for 97 species. Highest NDWI values for the was whole study period was 0.71 in 2021 and lowest 0.008 in 2019 which is highly fluctuating. The decreasing trend of migratory birds coupled with decreasing water level indicates the dubious status for its existence. If the causal factors are not checked, it might completely desiccate by 2059 as per its future prediction. Certain steps are suggested that might help conservation. Least, the cost of restoration might exceed the revenue generation.

Studies on human mobility have a long history with increasingly strong connections to multi-disciplines across social science, environmental science, information and technology, computer science, engineering, and health science. However, what is lacking in the current research is a summary of studies on human mobility to identify the evolutional pathway and future research directions. To address this gap, we conduct a systematic review of human mobility-related studies published from 1990 to 2020. Drawing on the selected publications retrieved from the Web of Science, we conduct a bibliometric analysis and network visualisation by CiteSpace and VOSviewer on publication years and numbers, authors and their countries and afflictions, citations, topics, abstracts, keyword, and journals. Our findings show that human mobility-related studies have become increasingly interdisciplinary and multi-dimensional, enhanced by the involvement of multi-source big data, the development of technologies, the innovation of modelling approaches, and the novel applications in various areas. We also summarise four future research directions proposed by top cited authors and mobility studies, in terms of data sources, modelling methods, applications, and technologies. We advocate in-depth research on human mobility to address real-world problems and contribute to social good as promising future orientations through integrating multi-source big data and advanced modelling methods facilitated by artificial intelligence, and machine and deep learning.

Background: In March 2020, a COVID-19 outbreak associated with the Falles Festival in Borriana, Spain, led to significant infections. Methods: In June 2022, we conducted a cross-sectional follow-up study of 473 socially engaged adults aged 18 to 64, examining the cumulative experience after SARS-CoV-2 infection and vaccination responses. Data included demographic details, lifestyle habits, medical history, infection records, and vaccinations from a population-based vaccine registry. Blood samples were analyzed for SARS-CoV-2 antibodies and cellular immunity. We employed a doubly robust inverse weighted probability analysis to estimate the booster vaccine dose's impact on long COVID prevalence and symptom count. Results: 28.1% of participants met the WHO criteria for long COVID, with older individuals showing higher rates. Not complying with long COVID criteria associated with factors including O blood group, higher occupational status, physical activity, three vaccine doses, strong SARS-CoV-2-S-reactive IFNγ‐producing‐CD8+ response, and infection during the Omicron period. Conversely, increased age, high or low social activity, underlying health conditions, a severe initial COVID episode, and reinfection associated with higher long COVID likelihood. A booster dose, compared to one or two doses, reduced long COVID risk by 74% (95% CI: 56.4% to 91.7%) and symptom count by 55.2% (95% CI: 31.6% to 78.7%). Conclusion: Long COVID was prevalent in a significant portion of those who contracted COVID-19, underscoring the need for sustained follow-up and therapeutic strategies. Vaccinations, notably the booster dose, had a substantial beneficial effect on long-term infection outcomes, affirming the vaccination’s role in mitigating SARS-CoV-2 infection consequences.

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

Cervical cancer (CC) is the most common cancer in women worldwide and is almost always associated with repeated infections by human papillomavirus (HPV). Screening by traditional tests combined with biomarker identification techniques for low- or high-grade injuries, are becoming increasingly important in diagnosis and prognosis, avoiding countless deaths. This article explores existing literature on the main serum biomarkers and the identification of biomarkers associated with the oncogenesis of HPV expression in the identification of pre-cancerous lesions and of CC for an effective treatment, with reduction of recurrence, as well as we explain strategies for the development of biomarkers based on DNA, proteins and other markers. We also describe how markers of chromosomal instability host DNA, promoting hypo- or hypermethylation of DNA, as well as polymorphisms and epigenetic events in the p53 gene. Finally, we discuss changes in gene expression using cDNA microarray techniques and changes in the expression of proteins and markers identified through mass spectrometry.

There is a strong anticipated future for human pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The transcriptomics analysis revealed that 86% of the genes were expressed at similar levels in hiPS-HEP as in human primary hepatocytes (hphep). Adult characteristics of the hiPS-HEP were confirmed by the presence of important hepatocyte features, e.g. Albumin secretion and expression of major drug metabolizing genes. Normal energy metabolism is crucial for modeling metabolic diseases, and both transcriptomics data and functional assays showed that hiPS-HEP were similar to hphep regarding uptake of glucose, LDL and fatty acids. Importantly, the inflammatory state of the hiPS-HEP was low under standard conditions, but in response to lipid accumulation and ER stress the inflammation marker TNFα was upregulated. Furthermore, hiPS-HEP could be co-cultured with primary hepatic stellate cells both in 2D and in 3D spheroids, paving the way for using these co-cultures for modeling NASH. Taken together, hiPS-HEP have the potential to serve as an in vitro model for metabolic diseases. Furthermore, differently expressed genes identified in this study can serve as targets for future improvements of the hiPS-HEP.

This study investigated the capability of vocal-identity-cloning Artificial Intelligence (AI) to encode human-specific confident, doubtful, and neutral-intending emotive states. Linear mixed-effects models and machine learning classification with eXtreme Gradient Boosting were employed to examine the underlying acoustic signatures from 2,700 audio clips, comprising of sentences spoken by human speakers and two sets of equivalences (AI-Geography/AI-Trivia, based on the trained text) generated by voice-cloning models designed to clone human speakers’ identities. Compared with neutral-intending voice, human speakers lengthened their vocal tract, raised the fundamental frequency, and increased Chroma constant-Q transform when they intended to be confident; An opposite pattern was shown when they intended to be doubtful. The two sets of AI sounds displayed a similar pattern to human speech, suggesting a shared mechanism for encoding vocal expression across sources. The 1,000 times training-testing classification models reported an in-group advantage for AI sources. The algorithms, trained on AI-Geography/AI-Trivia, resulted in higher accuracies when tested within these AI sources than when tested on human audio. All between-source classifications reported above-chance-level (1/3) accuracies. These findings highlighted that voice-cloning AI, the widely used conversational agent, can learn and generate human-specific vocally-expressed confidence.

Objectives: Our objective was to assess employer preparedness to protect their employees’ health and safety and promote their well-being in the face of potential disasters in a sample of Northeast United States employers. We developed survey instrument and index based on our model of Total Worker Health® (TWH) Employer Preparedness.Methods: We conducted a 40-question on-line survey with the membership of the Northeast Human Resources Association (US). Human resource managers reported their perceptions of their employers’ preparedness in seven domains: planning, human resources policies, hazard reduction, training, staffing, communications, and resources for resilience. Respondents were categorized by size, sector and reach and their responses scored.Results: Seventy-six individuals representing a diverse group of employers responded to the survey. Mean preparedness was “moderate,” with almost an equal number reporting a high level of preparedness as no preparedness. Employers were most prepared for severe weather events and least prepared for acts of violence. There were no significant differences by sector, size, or reach, although the healthcare sector was more prepared than others.Conclusions: There is a range of TWH® Employer Preparedness among Northeast US employers. The survey and model are important tools that can aid employers in the face of growing threats to “business as usual.”

Many causal factors to marine traffic accidents (MTA) influence each other and have associated effects. It is necessary to quantify the correlation path mode of these factors to improve accident prevention measures and their effects. In the application of human factors to the accident mechanisms, the complex structural chains on causes to MTA systems were analyzed combining the Human Failure Analysis and Classification System (HFACS) with theoretical Structural Equation Modeling (SEM). First, the accident causation model was established as a human error analysis classification in sight of MTA, and the constituent elements of the causes of accident was conducted. Second, a hypothetical model of Human factors classification was proposed applying the practice of the structural model. Third, with the data resource from ship accident cases, this hypothetical model was discussed and simulated, and as a result the relationship path dependency mode between the latent independent variable of the accident was quantitatively analyzed based on the observed dependent variable of human behaviors. Application examples show that relationships in HFACS are verified and in line with the path developing mode, and resource management factors have a pronounced influence and a strong relevance to the causal chain of the accidents. Appropriate algorithms for the theoretical model can be used to numerically understand the safety performance of marine traffic systems under different parameters through mathematical analysis. Hierarchical assumptions in the HFACS model are quantitatively verified.

Fucosylated carbohydrates and glycoproteins from human breast milk are essential for the development of the gut microbiota in early life because they are selectively metabolized by bifidobacteria. In this regard, α-L-fucosidases play a key role in this successful bifidobacterial colonization allowing the utilization of these substrates. Although a considerable number of α-L-fucosidases from bifidobacteria have been identified by computational analysis, only a few of them have been characterized. Hitherto, α-L-fucosidases are classified into 3 families, GH29, GH95 and GH151 based on their catalytic structure. However, bifidobacterial α-L-fucosidases belonging to a particular family show significant differences in their sequence. Because this fact could underlie distinct phylogenetic evolves, here extensive similarity searches and comparative analyses of the bifidobacterial α-L-fucosidases identified were carried out with the assistance of previous physicochemical studies available. This work reveals 4 and 2 paralogue bifidobacterial fucosidase groups within GH29 and GH95 families, respectively. Moreover, Bifidobacterium logum subsp. infantis species exhibited the greatest number of phylogenetic lineages in their fucosidases clustered in every family GH29, GH95 and GH151. Since α-L-fucosidases phylogenetically descended from other glycosyl hydrolase families, we hypothesized that could exhibit additional glycosidase activities other than fucosidase, raising the possibility about their application to transfucosylate other substrates than lactose in order to synthesis novel prebiotics.

We aimed to assess awareness, knowledge, and attitudes of healthy pregnant women towards human papillomavirus (HPV), to estimate factors associated with a positive attitude towards HPV immunization and to assess the uptake of the vaccine among their children. A cross-sectional study was conducted at the University Clinic of Gynecology and Obstetrics, Belgrade, Serbia among pregnant women attending their regular gynecological check-ups at the 12th gestational week. Knowledge about HPV and HPV vaccine was assessed using a specifically designed 12-item and 5-item questionnaires. Out of total 265 included women, 79.3% had heard of HPV, and 37.5% knew that HPV vaccine exists. HPV vaccine knowledge score was associated with higher odds for a positive attitude towards vaccination of both female (OR = 4.10, 95% CI 1.50-11.29) and male (OR = 3.71, 95% CI 1.52-9.01) child. The number of children (OR = 1.32, 95% CI 1.04-1.67) and high vaccine knowledge score (OR = 1.64 95% CI 1.13-2.39) were independent predictors associated with willingness to vaccinate child against HPV. The gynecologist was the preferable point of reference for information seeking about the HPV vaccine. Despite relatively high HPV awareness and knowledge among pregnant women in Serbia, about one-third of them are HPV vaccine aware, and are willing to vaccinate their children against HPV.

OBJECTIVES: Most of human papilomavirus (HPV) infections are “cleared” by the immune system, however, in cases of immune system suppression infections could lead to development of malignancies. The aim of this study was to find out the frequency of HR-HPV infection in early period after renal transplantation in Latvian recipients receiving immunosuppressive therapy and to follow the progression of the infection up to one year. METHODS: 43 female renal recipients (median age of 48 IQR= 39-58) and 79 practically healthy female individuals (median age of 48 IQR= 42-57) as a control group were enrolled in this investigation. For the detection of HPV infection patients' samples (blood and vaginal swabs) where collected two weeks after transplantation with following collection of six months and one year. Different polymerase chain reactions for HR-HPV genomic sequences detection and commercial ELISA kit for detection of anti-HPV IgG antibodies were used. RESULTS: In this study we show that frequency rate of HR-HPV infection has increased by the one year after transplantation from early stage of immumosuppressive therapy (from 24% to 36%). Also increase of HR-HPV load was detected over the time, showing the highest median viral load at sixth month after transplantation. CONCLUSIONS: From the obtained data follows that it is very important to carefully monitor patients receiving immunosuppression therapy on progression of HR-HPV. In the case of this viral infection presence, immunosuppressive therapy must be attentively adjusted to avoid the HR-HPV infection rapid progression with the subsequent development of CIN or cervical cancer.

Acinetobacter baumannii is a nosocomial pathogen capable of causing serious infections associated with high rates of morbidity and mortality. Due to its antimicrobial drug resistance profile, A. baumannii is categorized as an urgent priority pathogen by the Centers for Disease Control and Prevention in the United States and priority group 1 critical microorganism by the World Health Organization. Understanding how A. baumannii adapts to different host environments may provide critical insights into strategically targeting this pathogen with novel antimicrobial and biological therapeutics. Exposure to human fluids was previously shown to alter the gene expression profile of a highly drug susceptible A. baumannii strain A118 leading to persistence and survival of this pathogen. Herein, we explore the impact of human pleural fluid (HPF) and human serum albumin (HSA) on the gene expression profile of a highly multi-drug resistant strain of A. baumannii AB5075. Differential expression was observed for ~30 genes, whose products are involved in quorum sensing, quorum quenching, iron acquisition, fatty acid metabolism, biofilm formation, secretion systems and type IV pilus formation. Phenotypic and further transcriptomic analysis using quantitative RT-PCR confirmed RNA-seq data and pointed out a distinctive role of HSA as the molecule involved in A. baumannii response.

Pesticides have a vital contribution to the agricultural industry in Australia. However, pesticide applications may not always selective to its target organism. Exposure to pesticide has been associated with negative impacts to human health. One of the ways to reduce pesticide risk to the population and the environment is through government regulations. To put Australia pesticide regulations into perspective, comparisons were made between Australia and other nation’s pesticides regulations. The EU pesticide regulatory system was chosen for comparison with the Australian’s in the aspect of protecting the population from pesticide exposure. The comparison showed that the assessment to authorize a pesticide in Australia is based on the risk while in the EU, the assessment is based on the hazard of the pesticide. A registered active substance in Australia can be authorized for use indefinitely unless it is nominated for reconsideration while the period of registration of an active substance in the EU lasts for 10 years. In addition, no routine systematic chemical residue surveys are conducted in Australia for food commodities. The results highlight areas for improvement in the Australian pesticide regulatory system from the perspective of controlling undue exposure among the general population.

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

The cyclic regeneration of human endometrium is guaranteed by the proliferative capacity of Endometrial Mesenchymal Stromal Cells (E-MSCs). Due to this, the autologous infusion of E-MSCs has been proposed to support endometrial growth in a wide range of gynecological diseases. We aimed to compare two different endometrial sampling methods, the surgical curettage and the Vacuum Aspiration Biopsy Random Assay, and to validate a novel xeno-free method to culture human E-MSCs. Six E-MSCs cell lines were isolated after a mechanical tissue homogenization and cultured using human platelet lysate. E-MSCs were characterized for the colony formation capacity, proliferative potential and multilineage differentiation. The expression of mesenchymal and stemness markers was tested by FACS analysis and Real-Time PCR, respectively. Chromosomal alterations were evaluated by karyotype analysis, whereas tumorigenic capacity and invasiveness were tested by soft agar assay. Both endometrial sampling techniques allowed to efficiently isolate and expand E-MSCs using a xeno-free method preserving their mesenchymal and stemness phenotype, proliferative potential and multi-lineage differentiation ability during the culture. No chromosomal alterations and invasive/tumorigenic capacity were observed. Herein we report the first evidence of efficient E-MSCs isolation and culture in Good Manufacturing Practice compliance conditions, suggesting Vabra endometrial sampling as alternative to surgical curettage.

Shenzhen is China’s top ten clean air city and the cleanest air megacity. Even so, epidemiologic studies have shown ambient air pollution had significant adverse impacts on human health in this less polluted city. In this study, the concentrations of six criteria air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) from 2014 to 2017 were analyzed and compared to thresholds of both national and international air quality standards. The results showed concentrations of all air pollutants were below target values of current national air quality standard, but levels of particulate matter (PM) and O3 were still much higher than the recommended levels by the World Health Organization. Within national air quality standards, the number of over-limit days was rare with few variations between highly polluted and low pollution areas. The air quality improvement was slowing down recently. Our results suggest annual and daily thresholds for PM are too loose for air quality improvement in Shenzhen. Hence, we call for evaluation and establishment of tougher air quality standard.

The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG, SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded and transfected in vitro with short hairpin Lentivirus targeting NANOG. Gene suppressions were achieved at both transcript and proteome levels. The effect of NANOG knockdown on proliferation after 10 passages and on the cell cycle was evaluated by proliferation assay, colony forming unit (CFU), qRT-PCR and cell cycle analysis by flow-cytometry. Moreover, NANOG involvement in differentiation ability was evaluated. We report that downregulation of NANOG revealed a decrease in the proliferation and differentiation rate, inducing cell cycle arrest by increasing p27/CDKN1B (Cyclin-dependent kinase inhibitor 1B) and p21/CDKN1A(Cyclin-dependent kinase inhibitor 1A) through p53 and regulate DLK1/PREF1. Furthermore, NANOG induced downregulation of DNMT1, a major DNA methyltransferase responsible for maintaining methylation status during DNA replication probably involved in cell cycle regulation. Our study confirms that NANOG regulates the complex transcription network of plasticity of the cells, inducing cell cycle arrest and reducing differentiation potential.

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

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

One of the major problems caused by repeated subcutaneous insulin injections in diabetic patients is insulin amyloidosis. Understanding the molecular mechanism of amyloid fibril formation of insulin and finding effective compounds to its inhibit or eliminate is very important and extensive research has been done on it. In this study, the anti-amyloidogenic and destabilizing effects of the pyrogallol, as a phenolic compound, on human insulin protein were investigated by CR absorbance, ThT and ANS fluorescence, FTIR spectroscopy and atomic force microscopy. According to the obtained results, the formation of amyloid fibrils at pH 2.0 and 50 °C was confirmed by CR, ThT, ANS, FTIR assays. Microscopic images also showed the twisted and long structures of amyloid fibrils. Simultaneous incubation of the protein with pyrogallol at different concentrations reduced the intensities of CR, ThT and ANS in a dose-dependent manner and no trace of fibrillar structures was observed in the microscopic images. FTIR spectroscopy also showed that the position of amide I band in the spectrum of samples containing pyrogallol was shifted. Based on the findings in this study, it can be concluded that pyrogallol can be effective in preventing and suppressing human insulin amyloid fibrils.

The reduction of biodiversity loss is one of the targets of the 2030 Agenda for Sustainable Development. The protection of endangered species is critical for conserving global biodiversity. Asian elephants，as one of the last few mega-herbivores on Earth, are currently threatened by climate changes and anthropogenic modifications. The modelling of their living habitats is of top priority to the conservation of Asian elephant. In this study, we used the maximum entropy model (MaxEnt) to identify the current and potential future habitats of Asian elephants in South and Southeast Asia. We performed analyses for future projections with 17 scenarios by using the present results as baseline. To optimise the modelling results, we delineated the core habitats by using the Core Mapper Tool and compared them with existing protected areas (PAs) through gap analysis. The results showed that the current total area of core habitats is 491,455 km2 in size and will be reduced to 332,544 km2 by 2090 under SSP585 (the shared socioeconomic pathway). The projection analysis under differential scenarios suggested that most of the core habitats in the current protected areas would remain stable and suitable for elephants in the future. However, the remaining 75.17% of the core habitats lay outside the current PAs, and finally we mapped approximately 219,545 km2 of suitable habitats as priority protected areas in the future. Although our model did not perform well in some regions, our analyses and findings still could provide useful references to the planning of protected areas and conservation of Asian elephant.

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr=40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in tumor tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway, and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK, and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker of differentiation in TGCTs.

This study attempts to investigate a method for creating an index from mobility data that not only correlates with the number of people who relocate to a place but also has causal influence on the number of such individuals. By creating an index based on human mobility data, it becomes possible to predict the influence of urban development on future residential movements. In this paper, we propose a method called the travel cost method for multiple places (TCM4MP) by extending the conventional travel cost method (TCM). We assume that the opportunity cost of travel time on non-working days reflects the convenience and amenities of a neighborhood. However, conventional TCM does not assume that the opportunity cost of travel time varies according to the departure place. In this paper, TCM4MP is proposed to estimate the opportunity cost of travel time with respect to the departure place. We consider such estimation to be possible due to the use of massive mobility data. We assume that the opportunity cost of travel time on non-working days reflects the convenience and amenities of the neighborhood. Therefore, we consider that the opportunity cost of travel time has a causal influence on future residential mobility. In this paper, the validity of the proposed method is tested using the smart card data of public transportation in Western Japan. Our proposed method is beneficial for urban planners in estimating the effects of urban development and detecting the shrinkage and growth of a population.

In response to the need to address the safety challenges in the use of artificial intelligence (AI), this research aimed to develop a framework for a safety controlling system (SCS) to address the AI black-box mystery in the healthcare industry. The main objective was to propose safety guidelines for implementing AI black-box models to reduce the risk of potential healthcare-related incidents and accidents. The system was developed by adopting the multi-attribute value model approach (MAVT), which comprises four symmetrical parts: extracting attributes, generating weights for the attributes, developing a rating scale, and finalizing the system. On the basis of the MAVT approach, three layers of attributes were created. The first level contained 6 key dimensions, the second level included 14 attributes, and the third level comprised 78 attributes. The key first level dimensions of the SCS included safety policies, incentives for clinicians, clinician and patient training, communication and interaction, planning of actions, and control of such actions. The proposed system may provide a basis for detecting AI utilization risks, preventing incidents from occurring, and developing emergency plans for AI-related risks. This approach could also guide and control the implementation of AI systems in the healthcare industry.

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

With the advent of Neural Machine Translation, the more the achievement of human-machine parity is claimed at WMT, the more we come to ask ourselves if their evaluation environment can be trusted. In this paper, we argue that the low quality of the source test set of the news track at WMT may lead to an overrated human parity claim. First of all, we report nine types of so-called technical contaminants in the data set, originated from an absence of meticulous inspection after web-crawling. Our empirical findings show that when they are corrected, about 5% of the segments that have previously achieved a human parity claim turn out to be statistically invalid. Such a tendency gets evident when the contaminated sentences are solely concerned. To the best of our knowledge, it is the first attempt to question the “source” side of the test set as a potential cause of the overclaim of human parity. We cast evidence for such phenomenon that according to sentence-level TER scores, those trivial errors change a good part of system translations. We conclude that to overlook it would be a mistake, especially when it comes to an NMT evaluation.

Heat shock proteins (Hsps) are highly conserved molecules that are constitutively expressed and upregulated in response to physiological stress conditions. These immunogenic chaperones can have essential functions in fungi, particularly in dimorphic pathogens. Histoplasma capsulatum and Paracoccidioides species are dimorphic fungi that are the causative agents of histoplasmosis and paracoccidioidomycosis, respectively, which are systemic mycoses with significant rates of morbidity and mortality. Current treatment consists of long-term antifungal agents, and there is an urgent need for new therapeutic approaches with higher efficacy, lower toxicity, better biodistribution and improved selectivity. We engineered an immunoglobulin G1 (IgG1) isotype chimeric mouse-human monoclonal antibody, titled ch-MAb 4E12, from the parental IgG2a MAb 4E12, a monoclonal antibody to H. capsulatum Hsp60 that is protective in experimental histoplasmosis and paracoccidioidomycosis models elicited by H. capsulatum var. capsulatum and Paracoccidioides lutzii, respectively. The ch-MAb 4E12 increased phagolysosomal fusion and enhanced the yeasts uptake by PMA differentiated human THP1 macrophage cells in vitro. At low concentrations, the chimeric antibody significantly reduced the pulmonary and splenic fungal burden compared to an irrelevant antibody or no treatment. These results are the first to show that a chimeric mouse-human antibody can modify infection caused by dimorphic fungi.

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

Background: The course of obesity and type 2 diabetes (T2D) development is highly dependent on adipose tissue (AT) angiogenesis. Moreover, angiogenic microRNAs (miRNAs) play pivotal role in AT functionality. The aim of this study was to analyze the relationship of the human AT miR-221-3p/222-3p cluster and their regulatory network with obesity and T2D. Methods: miR-221-3p/222-3p and their target genes (TG) expression levels were measured in visceral and subcutaneous ATs from patients classified according to their BMI and to their glycemic status with a high degree of insulin resistance (IR) and T2D. In silico analyses of miR-221-3p/222-3p and their TGs were performed to identify relevant signaling pathways. Results: A multivariate analysis, including the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, showed significant differences considering the variables; tissue depot, obesity, IR and T2D altogether as independent variables. In addition, miRNAs and their TGs were differentially expressed according to obesity degree, glycemic status, and AT depot type. Our in silico analysis showed that miR-221-3p/222-3p cluster TGs are mostly involved in angiogenesis, WNT signaling pathway and apoptosis. Conclusion: These findings suggest that the miR-221-3p/222-3p cluster and their related regulatory networks could represent tangible targets for the management of obesity and associated metabolic disorders

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) are environmental pollutants with a great persistence, capacity of bioaccumulation, and well known important toxic effects in humans and animals. Incinerators of hazardous, municipal and medical waste, chlorine bleaching of paper pulp, cement plants, and the traffic of motor vehicles are the most frequent emission sources of these compounds. The diet, followed at a great distance by inhalation, is generally the main way of human exposure to PCDD/Fs. Human biomonitoring is of a great importance to prevent potential adverse effects derived from exposure to chemicals such as PCDD/Fs. In relation to this, blood is among the most used biological monitors. In the current review, we have summarized the recent information (2000-2009) published in the scientific literature (databases: Scopus and PubMed) on the concentrations of PCDD/Fs in blood samples of non-occupationally exposed populations, as well as in some groups of occupationally exposed individuals. We have revised a number of studies conducted in various African American, Asian and European countries, and Australia. Unfortunately, the information is quite limited. No data are available for most countries over the world. Based on the results here reviewed –where available- the current health risks for the general populations do not seem to be of concern. Moreover, taking into account the important reductions observed in the levels of PCDD/Fs in foodstuffs, new decreases in the concentrations of PCDD/Fs in blood -and other biological tissues- are very probable in the immediate years.

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

There are guidelines on lactation following maternal analgo-sedative exposure, but these do not consider the effect of maternal fasting, nor fluid abstention on human milk macronutrient composition. We therefore performed a structured search (PubMed) on ‘human milk composition’ and screened title, abstract and full paper on ‘fasting’ or ‘abstention’ and ‘macronutrient composition’ (lactose, protein, fat, solids, triglycerides, cholesterol). This resulted in 6 papers and one abstract related to religious fasting (n=129 women) and observational studies in lactating women (n=23, healthy volunteers, fasting). These data reflect two different ‘fasting’ patterns: an acute (18-25h) model in 71 (healthy volunteers, Yom Kippur/Ninth of Av) women and a chronic fasting (Ramadan) model in 81 women. Changes were most related to electrolytes and were moderate, with almost no changes in macronutrients during acute fasting. We therefor conclude that neither short term fasting nor fluid abstention (18-25h) affect human milk macronutrient composition, so that women can be reassured when this topic were raised during consulting. Besides the nutritional relevance, this also matters as clinical research samples – especially to estimate analgo-sedative exposure by lactation - are commonly collected after maternal procedural sedation, associated with maternal fasting and physiology-based pharmacokinetic (PBPK) models assume stable human milk composition.

Human African Trypanosomiasis (HAT) commonly known as sleeping sickness, is a neglected tropical vector borne disease caused by trypanosome protozoa. It is transmitted by bites of infected tsetse fly. In this paper we first present the vector-host model which describes the general transmission dynamics of HAT. In the tsetse fly population, the HAT is modelled by three compartments while in the human population, the HAT is modelled by four compartments. The next generation matrix approach is used to derive the basic reproduction number, R₀, and also it is proved that if R₀ ≤ 1 the disease free equilibrium is globally asymptotically stable, which means the disease dies out. The disease persist in the population if the value of R₀ > 1. Furthermore, the optimal control model is determined by using the Pontryagin’s maximum principle with control measures such as education, treatment and insecticides used to optimize the objective function. The model simulations confirm that the use of the three control measures are very efficient and effective to eliminate HAT in Africa.

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

In this review, our goal is to design and test quantum-like algorithms for Artificial Intelligence (AI) in open systems to structure a human-machine team to be able to reach its maximum performance. Unlike the laboratory, in open systems, teams face complexity, uncertainty and conflict. All task domains have complexity levels, some have low, and others high levels. Complexity in this new domain is affected by the environment and the task, which are both affected by uncertainty and conflict. We contrast the individual and interdependence approaches to teams. The traditional and individual approach focuses on building teams and systems by aggregating the best available information for individuals, their thoughts, behaviors and skills. Its concepts are characterized chiefly by one-to-one relations between mind and body, a summation of disembodied individual mental and physical attributes, and degrees of freedom corresponding to the number of members in a team; however, this approach is characterized by the many researchers who have invested in it for almost a century with few effects that can be generalized to human-machine interactions; by the replication crisis of today (e.g., the invalid scales for self-esteem, implicit racism, and honesty); and by its many disembodied concepts. In contrast, our approach is based on the quantum-like nature of interdependence. It allows us to theorize about the bistability of mind and body, but it proposes a measurement problem and a non-factorable nature. Bistability addresses team structure and performance; the measurement problem solves the replication crisis; and the non-factorable aspect of teams reduces the degrees of freedom and the information derivable from teammates to match findings by the National Academies of Science. We begin with a review of the science of teams and a focus on human-machine team research in the laboratory versus the open; justifications for rejecting traditional social science while supporting our approach; a full understand of the complexity of the domain, tasks in the domain, and how teams address both; the mathematics involved; a review of results from our model versus the open field; a discussion of the results; conclusions; and the path forward to successfully advance the science of interdependence and autonomy.

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.

Cariogenic oral biofilms cause a considerable amount of recurrent dental caries around composite restorations every year, resulting in unprosperous oral health status and expensive restorative treatment for many patients. Quaternary ammonium monomers that can be copolymerized with the current dental resin systems have been increasingly explored for modulation of dental plaque biofilm growth over dental composite surfaces. Here, we investigated the effect of bis(2-methacryloyloxyethyl) dimethylammonium bromide (QADM), against human overlying mature oral biofilms grown intra-orally in human participants for 7 and 14 days, for the first time. Seventeen volunteers wore palatal devices containing composite specimens containing 10% by mass of QADM or a control composite without QADM. After 7 and 14 days, the adherent biofilms were collected for determination of bacterial counts via colony-forming unit (CFU) counts. The biofilm viability, chronological changes, and percentage coverage were also determined by live/dead staining. QADM composites caused a significant inhibition of S. mutans biofilm formation for up to seven days. No difference in the CFU values were found for the 14-day period. Our findings suggest that (1) QADM composite was successful in inhibiting 1-3 day biofilms in the oral environment in vivo; (2) QADM significantly reduced the portion of S.mutans group in a time course where patients at high risk of caries would develop initial enamel carious lesions; and (3) stronger antibiofilm activity is required for the control of mature long-term cariogenic biofilms. These results provide a perspective on the value of integrating bioactive restorative materials with traditional caries management approaches into clinical practice. Contact-killing strategies via dental materials aiming to prevent or at least reduce high numbers of cariogenic bacteria seem to be a promising approach in patients at high risk of recurrence of dental caries around composites.

Objective: Lipids are secreted into milk as bilayer-coated structures: milk lipid globules (MLGs). Adipophilin (ADRP) and perilipin 3 (TIP47) are associated with MLGs in human breast milk; however, the role of these proteins in milk lipid secretion is not fully understood. The aim of the study was to investigate levels of ADRP, TIP47 and total lipid content in human breast milk, their mutual correlations and dynamics during lactation. Research Methods & Procedures: Milk samples from 22 healthy lactating women (Caucasian, Central European) were collected at five time points during lactation (1–3, 12–14, 29–30, 88–90 and 178–180 days postpartum). Mass spectrometry-based method was used for quantification of ADRP and TIP47 in the samples. The gravimetric method was used to determine milk total lipid content. Results: We observed distinctive trends in ADRP, TIP47 levels and lipid content in human breast milk during the first 6 months of lactation. We also found a significant association between lipid content and ADRP, lipid content and TIP47, and ADRP and TIP47 concentrations in breast milk at all sampling points. Moreover, we derived an equation for estimating the mean lipid content of milk based on ADRP concentration in human breast milk. Conclusions: A mass spectrometry-based method was developed for quantifying ADRP and TIP47 in human breast milk. Strong mutual correlations were found between ADRP, TIP47 and total lipid content in human breast milk.

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with time. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to boost NAD+ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human) to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support it is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies aimed to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD+ during aging and should provide a foundation for better pharmacological targeting of relevant tissues.

Social distancing is a recommended solution by the World Health Organisation (WHO) to minimise the spread of COVID-19 in public places. The majority of governments and national health authorities have set the 2-meter physical distancing as a mandatory safety measure in shopping centres, schools and other covered areas. In this research, we develop a Deep Neural Network-based Model for automated people detection, tracking, and inter-people distances estimation in the crowd, using common CCTV security cameras. The proposed DNN model along with an inverse perspective mapping technique leads to a very accurate people detection and social distancing monitoring in challenging conditions, including people occlusion, partial visibility, and lighting variations. We also provide an online infection risk assessment scheme by statistical analysis of the Spatio-temporal data from the moving trajectories and the rate of social distancing violations. We identify high-risk zones with the highest possibility of virus spread and infection. This may help authorities to redesign the layout of a public place or to take precaution actions to mitigate high-risk zones. The efficiency of the proposed methodology is evaluated on the Oxford Town Centre dataset, with superior performance in terms of accuracy and speed compared to three state-of-the-art methods.

In recent years in Bangladesh, there has been regular cyclonic event, flooding and erratic pre-monsoons precipitation that has hampered production greatly and forced Bangladesh to import salt from abroad to manage market deficiency. There is much uncertainty about the effects of climate change on the frequency and intensity of small-scale, sudden onset weather phenomena such as heavy rainfall and subsequent loss and damage (L&D). But, several studies indicate that an obvious strong relationship exists between irregular rainfall and associated L&D. Nowadays, severe changing rainfall patterns are observed in Bangladesh, which is rapid-onset in nature, but low exposed in terms of response. The current study explored a ‘double-exposed’ burden combined of both climatic (e.g., uneven rainfall) and non-climatic governance factors (e.g., imperfect trade policy, the absence of risk transfer mechanisms) which are hindering salt production and pushing the country from the aspiration of salt exporting to the net buyer. This chapter mainly assesses the impacts of L&D due to climatic events that are causing overwhelming effects on the well-being of marginal salt farmers at Kutubdia Upazila of Bangladesh. Data were mainly collected through Participatory Vulnerability Analysis (PVA), Key informant interviews (KII), and Sample Surveys (SS). This study would provide insights for improved disaster management policy and an appropriate adaptive measure to address such extreme events as well as to initiate a further study for understanding the nexus of ‘nature and market’ in building resilience among the marginal salt farmers.

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.

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.

This paper presents a multi-year research study conducted at the University of Toledo, aimed at improving human-machine teaming (HMT) methods and technologies. With the incorporation of artificial intelligence (AI) into 21st-century machines, collaboration between humans and machines has become highly complicated for real-time applications. The penetration of intelligent and synthetic assistants (IA/SA) in virtually every field has opened a path for the new area of HMT. When it comes to crucial tasks such as patient treatment and care, defense, and industrial production, the use of non-standardized HMT technologies may pose a risk to human lives as well as up to billions of taxpayer dollars. A thorough literature survey revealed that there are not many established standards or benchmarks for HMT. In this paper, we aim to address the lack of HMT design and development standards. We propose a method to design an HMT based on a generalized architecture. This design includes the development of an intelligent collaborative system and human team. Followed by processes and metrics to test and validate the proposed model, we present a novel human-in-the-loop (HIL) simulation method using two controlled HMT scenarios; first, emergency care provider (ECP) training, and second, patient treatment by an experienced medic. Both scenarios include humans processing visual data and performing actions that represent real-world applications while responding to a Voice-Based Synthetic Assistant (VBSA) as a collaborator that keeps track of actions. As part of these HMT simulation studies, the impact of each parameter related to machines, humans, and HMT (such as errors made by humans and by the VBSA) is presented from the perspective of performance, rules, roles, and operation limitations. In addition, based on the analysis of results from two case studies, we presented guidelines for designing future HMT. Our conclusions indicate that the proposed HIL can be used to perform standardization studies in the pursuit of developing techniques for benchmarking HMT that can be used in critical situations.

Exisitng studies argue life chances are, in part, vertically reproduced. Such a statement is applicable to the Chinese contexts as, but not limited to, parental hukou status, to some extent, determines the life chances their children receive. In this essay, the author would like to introduce human capital theory (HCT) and educational signalling theory (EST), and assess how the applications of each of these two models can enrich the understanding of vertical reproduction of individuals’ social mobility opportunities. The author would also present the limitations of each of these two models when addressing relevant Chinese contexts.

Easter Island (Rapa Nui) deforestation has traditionally been viewed as a single event, synchronous in time and space across the island and caused by Polynesian settlers. However, recent studies have challenged this idea introducing the concept of spatio-temporal heterogeneity and suggesting a role for climate change. This paper presents a continuous paleovegetation record of the last millennium (~960 to ~1710 CE), based on palynological analysis of a peat core from Lake Kao. During this time interval, deforestation was gradual, with three main pulses at ~1070 CE, ~1410 CE and ~1600 CE, likely driven by drought, anthropogenic practices (mostly fire) or the coupling of both. Some forest regeneration trends have been documented after the first and the second deforestation pulses. Forests were totally removed by 1600 CE, coinciding with the full permanent human settlement of the Kao area. Comparison with other continuous palynological records available for the last millennium (Aroi marsh and Lake Raraku), confirms that forest clearing was heterogeneous in time and space, rather than synchronous island-wide.

Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea. Anticancer effect of uvaol, a natural triterpene, has been scarcely studied. The aim of this study was to understand the anticancer mechanism of uvaol in HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Uvaol presented anti-migratory capacity in HepG2, supported by the morphological changes and higher HSP-60 expression. This compound also induced arrest in G0/G1 phase and an increase in apoptosis rate. These results are supported by decreased Bcl-2 expression and down-regulation of AKT/PI3K signaling pathway. A reduction in reactive oxygen species levels in HepG2 cells was observed. Altogether, results showed anti-proliferative and pro-apoptotic effect of uvaol on hepatocellular carcinoma, constituting an interesting challenge in the development of new treatments against this type of cancer.

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.

This study observes, interprets, and analyses the knowledge production in the research field of Human–Robot Interaction (HRI). It intends to foreground the hidden assumptions that are often taken for granted when roboticist design and conduct their research. By doing so, this study demonstrates how these assumptions influence the result of their research. Based on data collected through sociological field observation, this study argues that the current practise in HRI research is highly anthropocentric. In short, the robots are designed to be like human instead of for human. Therefore, the human–robot relationship embodies the existing power relations between human beings. These relations generate inequality, hierarchy, and dominance, which are the opposite of the common imagination of the robotised future among roboticists. For the purpose of enabling the robotised future closer to their ideal, this study suggests that HRI researchers to go beyond the conventional methodology, to allow a human–robot relationship that realises reciprocity.

Background: Endogenous Peptide Inhibitor of CXCR4 (EPI-X4) is a natural antagonist of the CXC chemokine receptor 4 (CXCR4). EPI-X4 is a 16-mer peptide that is released from human serum albumin (HSA) by acidic aspartic proteases such as Cathepsin D and E. Since human serum albumin (HSA) is an important medicinal substance we asked whether different pharmaceutical HSA products contain EPI-X4 which could have been generated during manufacturing and whether HSA can serve as a substrate for cathepsins despite of the presence of stabilizers like caprylate. Methods: Eight pharmaceutical HSA preparations representing all currently used fractionation technologies were analyzed. The previously described specific EPI-X4 ELISA was used for quantification; in vitro EPI-X4 generation by acidification in the presence or absence of cathepsins was followed by quantification with ELISA. Results: None of the pharmaceutical HSA preparations tested contained EPI-X4. Acidification of HSA did not generate EPI-X4. Addition of cathepsins D and E to acidified HSA yielded high concentrations of EPI-X4 in all HSA preparations, indistinguishable between individual products. Conclusion: Medicinal HSA preparations per se do not contain EPI-X4, but will replenish its precursor which can be cleaved to EPI-X4 in vivo, environmental conditions permitting.

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Based on the Organizational Support Theory, this study examines the relationship between human resource management practices and service performance of sharing workers by demonstrating the mediation role of work engagement. We tested this theoretical model using an in-person interview questionnaire survey of 318 downwind drivers. Results showed that: (1) the main effect of human resource management practices of sharing workers on service performance was significant; (2) work engagement played a prominent mediation role between human resource management practices and service performance of sharing workers; (3) the mediation role of employee vigor between the platform incentives and the performance of employee services was significant; (4) employee dedication had an obvious and indirectly positive mediating effect between sharing workers' dimensions of human resource management practice and their service performance; (5) employee absorption on the mediation role between the various dimensions of the sharing human resources management practices (platform support, platform incentives and platform constraints) and employee service performance was significant. This study has important value for the study on human resource management practices in the context of sharing economy, and provides practical enlightenment for employee management of the sharing economy platform.

The effect of proteolytic enzymes including Cathepsin K, a cysteine cathepsin, in onset and progression of cancers in human has been research intensive. Cathepsin K involves in many aspects and stages of cancers including apoptosis, cell proliferation, cancer immunology, inflammatory cell recruitment to tumors and aiding in the process of mobilization of normal healthy cells from their tissue compartments assisting in metastasis and angiogenesis. The objective of this review is to collect together and summarize and analyze the biochemical and physiological pathways of how cathepsin K is involved in onset and progression of cancers with more emphasis on breast and prostate cancers and cathepsin K regulated mechanisms underlying metastasis of such cancers to bones. Information for the review was gathered through published literature from global databases such as Google Scholar, PUBMED and NCBI on different studies on physiological interactions between enzymatic activity of cathepsin K with cancers and metastasis to bones. Analysis of published studies reveal that immunohistochemical studies of breast cancer cells indicate that they overexpress cathepsin K resulting in induction of aberrant mechanisms of cell signaling in breast cancers, creating a higher tendency for their metastasis to bones. Immunohistochemical, immunoprecipitation and fluorgenic assays of several studies done on the association of the same enzymatic activity on prostate cancers shows elevated levels of cathepsin K. Lesions derived from prostate cancer cell masses were observed to undergo increased bone formation and resorption levels. Such resorption levels cause secretion of biological factors promoting tumor expansion. In addition, studies indicate that Cathepsin K was observed to be a key component promoting higher bone resorption levels in patients suffering from cancer. Authors suggest that, to completely understand the association of cathepsin K on cancerous cells and their mechanism in metastasis, distributary patterns of cathepsin K in healthy human tissues needs to be extensively studied initially. It is also suggested that metastasis of breast and prostate cancers to bone could be terminated and overcome by successful production of efficient and precise inhibitory therapeutics targeting the enzymatic activity of Cathepsin K with minimum unintended adverse health effects.

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

Damage to crops from wildlife interference is a common threat to food security among rural communities in or near Game Management Areas (GMAs) in Zambia. This study uses a two-stage econometric model and cross-sectional data from a survey of 2,769 households to determine the impact of land use planning on the probability and extent of wildlife-inflicted crop damage. The results show that crop damage is higher in GMAs as compared to non-GMAs, and that land use planning could be an effective tool to significantly reduce the likelihood of such damage. These findings suggest that there is merit in the current drive to develop and implement land use plans as means to minimize human-wildlife conflict such as crop damage. This is especially critical as Zambian conservation policies do not have an explicit provision for compensation in the event of damage from wildlife.

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.

There is an important role non-human primates (NHP) play in biomedical research. Phylogenetic proximity of any of the NHP species to Homo sapiens assures that much better translatability of research outcomes from model studies involving human diseases can be achieved than from those generated with other pre-clinical systems. Our group and others used during past two decades NHPs in research directed towards viral and autoimmune disorders of the gastrointestinal tract. This review summarizes progress made in the area of enteric viral infections and its applicability to human disease.

The article discusses the issues related to the safety of transport of dangerous goods by road. Research on accidents in transport unambiguously points to the human factor, which is most responsible for causing the accident. Determining the causes of driver unreliability in the hu-man-vehicle-environment system requires thorough research. Unfortunately, in this case, experimental research with human involvement is limited in scope. This leaves modeling and simulation of the behavior of the human factor, i.e., the driver transporting dangerous goods. The human being, due to its complexity, is a challenging element to parameterize. The literature presents various attempts to model human actions. In their work, the authors used heuristic methods, specifically fuzzy set techniques, to build a human factor model. In these models, human actions were specified using a verbal or linguistic description. The specificity of fuzzy sets allows to "naturally" limit the "precision" in describing human behavior. The model was built based on the author's questionnaire and expert research, based on which individual features were selected. Then, the traits were assigned appropriate states. The output parameter of the model is λL - the intensity of human error. The obtained values of the intensity of the accident caused by the driver's error were implemented into the author's method of risk assessment. They constituted one of the factors determining the probability of an accident in the transport of dangerous goods, which allowed to determine the optimal route of transport of these goods characterized by the lowest risk of an undesirable event on the route. The article presents the model's assumptions, structure, and features included in the model, which have the most significant influence on shaping the intensity of human error. The results of the simulation studies showed a diversified effect of the analyzed characteristics on the driver's efficiency.

The PI3K-AKT-mTOR signal transduction pathway regulates a variety of biological processes including cell growth, cell cycle progression and proliferation, cellular metabolism and cytoskeleton reorganization. Fine-tuning of the PI3K pathway signaling output is essential for the maintenance of tissue homeostasis and uncontrolled activation of this cascade leads to a number of human pathologies including cancer. Inactivation of the tumour suppressor phosphatase PTEN and/or activating mutations in the proto-typical lipid kinase PI3K have emerged as some of the most frequent events associated with human cancer and as a result the PI3K pathway has become a highly sought-after target for cancer therapies. In this review we summarize the essential role of the PTEN-PI3K axis in controlling cellular behaviors by modulating activation of key proto-oncogenic molecular nodes and functional targets. Further, we highlight important functional redundancies and peculiarities of these two critical enzymes that over the last few decades have become a central part of the cancer research field and have instructed hundreds of pre-clinical and clinical trials to better cancer treatments.

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

Starting from the fact that the units of local self-government of the Republic of Serbia are not sufficiently oriented towards innovations related to human resources and the environment, the application of quantitative research tradition examines the positioning and understanding of certain procedures and decisions of human resources management regarding the functioning of the environmental protection system, on the one hand, and future strategies for changing the given system, on the other. A series of 105 face-to-face interviews were conducted during the whole of 2016 in 105 of the 191 municipalities in the Republic of Serbia. Examination of the attitudes of the local self-government was carried out using a specially designed closed electronic questionnaire. The results of the multivariate regressions show that the most important predictor of the possible improvement of the environment is the size of the municipality. The remaining variables (e.g., human resources policy, human resources service) did not have significant effects on the ability to improve the environment. In more than half of local self-governments, there was no clearly defined human resources strategy in the field of environmental protection, an environmental protection service, an Environmental Action Plan, as well as an employment plan for waste management in local governments, etc. The research has shown that top managers of local governments agree that the management of human resources in environmental protection represents a significant opportunity to improve the quality of the environment. The results of the research can be used to improve the organization of human resource competence in environmental protection and the quality of a working and sustainable environment in the area of local self-government.

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

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

Technological innovation has led to the development of increasingly efficient and complex industrial plants. To manage this complexity, it is necessary to define an integrated vision of the socio-technological system that includes: technological, human and organizational component. Petrochemicals can be considered one of the most complex socio-technical systems that deserve special attention to high risk management, especially during the emergency conditions. Traditional safety management models only consider static systems, while new resilience engineering models evaluate the performance variability developed between different actions. One of the recent development methods is the Functional Resonance Analysis Method (FRAM) that identifies the pairs between the functions. FRAM unfortunately is a qualitative model, this research integrates this model with the Performance Shaping Factors (PSFs) and with the Bayesian approach to identify the performance variability of the system. The analysis aims to develop a system that improves safety analysis. The proposed model is applied in a case study of an emergency in a petrochemical company.

Vegetation in drylands is sensitive to climatic changes and human activities. Remote sensing and spatial analyses provide us useful tools for monitoring long-term vegetation dynamics over large regional scale. In this study, we analyzed the oasis vegetation cover change of the Tarim Basin using Landsat data sets from six epochs, 1975s, 1990s, 2000s, 2005s, 2010s and 2014. The results show that vegetation cover of oases increases from 34600 km² in 1975s to 101000 km² in 2014, though there was a vegetation coverage decrease from 77600 km² in 2000s to 42680 km² in 2010s. The percentage of annul water consumption has increased from 34% in 1970s to 52% in 2010s in the upper Tarim River, and decreased from 15% in 1970s to 9% in 2010s in the lower Tarim River. The decrease of oases area from 2000s to 2010s probably resulted from the rapid urbanization and large scale land reclamation. Although there is an increasing trend for oases coverage, local degradation of oases especially in the northern part occurred. This may be caused by inadequate water supply of the Tarim River. The results of multiple regression show that human activities contribute 70% of oases area change. Human induced water resources reallocation and heat energy balance is the primary cause of total oasis change.

A new circuit model of the self-powered device for heart rate measurement is presented in this paper. This device consists of piezoelectric energy harvester (PEH), power management circuit (PMC) with energy storage, microcontroller, Photoplethysmography (PPG) sensor, and Wi-Fi module. The PEH is placed under the insole to harvest the pressure energy from human foot-step to generate ac power. In our model, a PEH is represented by sine voltage source, where its parameters were taken from experiments with 20 volunteers. The PMC is simplified by a switch with gain δ placed in series with the main circuit. The model of the main circuit is RC elements in parallel, where C is the capacitance of the storage device, and R is the equivalent parallel resistance of the microcontroller, PPG sensor, and Wi-Fi modules, respectively. The value of R depends on the power and current absorbed by those modules during sleep, deep sleep, sense, and transmit modes which collected from the datasheet. Finally, the proposed circuit model of the self-powered device was built and simulated in SPICE. The simulation results were compared with the laboratory experiment using commercial devices. Based on the results, the proposed model had small gaps compared to the real self-powered devices in terms of average current, voltage, power and efficiency.

Next-generation sequencing (NGS) has actualized human papillomavirus (HPV) virome profiling for in-depth investigation of viral evolution and pathogenesis. However, viral computational analysis remains a bottleneck due to semantic discrepancies between computational tools and curated reference genomes. To address this, we developed and tested automated workflows for HPV taxonomic profiling and visualization using a customized Papillomavirus database in CLC Microbial Genomics Module. HPV genomes from Papilloma Virus Episteme were customized and incorporated into CLC “ready-to-use” workflows for stepwise data processing to include: 1) Taxonomic Analysis, 2) Estimate Alpha/Beta Diversities, and 3) Map Reads to Reference. Low-grade (n = 95) and high-grade (n = 60) Pap smears were tested with ensuing collective runtimes: Taxonomic Analysis (36 min); Alpha/Beta Diversities (5 sec); Map Reads (45 min). Tabular output conversion to visualizations entailed 1-2 keystrokes. Biodiversity analysis between low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) revealed loss of species richness and gain of dominance by HPV-16 in HSIL. Integrating clinically relevant, taxonomized HPV reference genomes within automated workflows proved to be an ultra-fast method of virome profiling. The entire process named “HPV DeepSeq” provides a simple, accurate and practical means of NGS data analysis for a broad range of applications in viral research.

Symmetry in biological and physical systems is a product of self-organization driven by evolutionary processes, or mechanical systems under constraints. Symmetry-based feature extraction or representation by neural networks may unravel the most informative contents in large image databases. Despite significant achievements of artificial intelligence in recognition and classification of regular patterns, the problem of uncertainty remains a major challenge in ambiguous data. In this study, we present an artificial neural network that detects symmetry uncertainty states in human observers. To this end, we exploit a neural network metric in the output of a biologically inspired Self-Organizing Map, the Quantization Error (SOM-QE). Shape pairs with perfect geometric mirror symmetry but a non-homogenous appearance, caused by local variations in hue, saturation, or lightness within and/or across the shapes in a given pair produce, as shown here, longer choice RT for ‘yes’ responses relative to symmetry. These data are consistently mirrored by the variations in the SOM-QE from unsupervised neural network analysis of the same stimulus images. The neural network metric is thus capable of detecting and scaling human symmetry uncertainty in response to patterns. Such capacity is tightly linked to the metric’s proven selectivity to local contrast and color variations in large and highly complex image data.

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

In current efforts to digitize manufacturing and move it into the fourth stage of the industrial revolution, a wide range of integration solutions is being considered to enable manufacturing to adapt to change. In transforming a factory into a self-organized, autonomous factory, companies are currently struggling with rapidly changing requirements and production factors, among other things. This is a particular problem for the human being as an actor within the factory, as the amount of new technologies and protocols increases the training effort. Proprietary interfaces of the control providers, a wide range of different communication protocols, complicate the understanding of the production processes, the evaluation and testability of new use cases and increase the danger of creating silos of knowledge as well as building collaboration barriers. As a solution to these problems, we propose an open software platform and define a way to model use case driven domain specific asset representation (DSA) that focuses on the human being and his needs for representing the factory in a way that it meets his requirements for the current production needs. We therefore conducted research on google scholar on human factors in industry 4.0 and used technologies as well as already existing platforms and their architecture.

Aedes aegypti is the primary mosquito vector of several human arboviruses including dengue virus (DENV). Vector control is the principal intervention to decrease the transmission of these viruses. The characterization of molecules involved in the mosquito physiological responses to blood-feeding may help to identify novel targets useful in the design of effective control strategies. In this study, we evaluated the in vivo effect of feeding adult female mosquitoes with human blood containing either heat-inactivated (IB), normal serum (NB), and RNA-seq based transcript expression was compared against sugar-fed (SF) mosquitoes. In the in vitro experiments, we treated Aag2 cells with a recombinant version of the complement proteins (hC3 or hC5a) and compared transcript expression to untreated control cells after 24h. The transcript expression analysis revealed that human complement proteins modulate approximately 2,300 transcripts involved in multiple biological functions, including the immune system. We also found 161 up-regulated and 168 down-regulated transcripts differentially expressed when hC3 and hC5a were compared against the control untreated cells. We conclude that active human complement induces significant changes in the transcriptome of Ae. aegypti mosquitoes, which can influence the infective capacity of pathogens ingested during blood meals.

The aim of the present study is to investigate themes related to visitors’ perceptions of captive wildlife in particular, attitudes towards non-human primates (henceforth, primates). This research took place in free-roaming, multi-species primate sanctuary, Monkeyland (South Africa), where 400 visitors were interviewed using an anonymous survey both before and after attending a guided tour. The answers were divided into different categories, in order to standardize the motivations behind tourists’ choices. The results of the survey demonstrated that most visitors agree that a primate would not be a good companion animal. Visitors’ desire to touch primates was found to be positively correlated with desire for companion primates and inversely associated with visitor age. In response to: “would you like to touch a monkey?”, the majority of tourists who expressed this desire seemed aware that such interactions are not appropriate, with concern for animal welfare and human health. Of the various primate species present in the sanctuary, visitors preferred the ring-tailed lemur (Lemur catta) and, generally speaking, expressed appreciation for primates’ “cuteness”. Our results indicate a general awareness by the visitors on the importance of animal welfare in the human interactions with captive wildlife, in agreement with the “hands-off” policy of Monkeyland primate sanctuary. We discuss the findings from a general to zooanthropological point of view, proposing some reflections on the attitudes of visitors toward non-human primates.

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulate disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified 3 MTBC lineages of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (N=149 and N=127). We found a significant interaction between a SNP in PPIAP2 and the Uganda lineage (combined p=4x10-8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host-pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human-MTBC coevolution is likely to explain patterns of disease severity.

Human Parechoviruses, officially known as Parechovirus A (PeV-A), is associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of PeV-A in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to determine the presence of PeV-A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients in Panama. Two hundred samples of pediatric patients with a negative diagnosis for the main respiratory viruses, rotavirus and neurological viruses such as herpesvirus, enterovirus and cytomegalovirus, collected between 2014 and 2015, were analyzed by real-time RT-PCR. Eight positive PeV-A infections were detected, 2 in respiratory samples, 5 in stool samples and one detected in cerebrospinal fluid. This is the fisrt report of PeV-A in Panamá.

Few-layer graphene oxide (GO) has shown none or very weak cytotoxicity and anti-proliferative effects in a wide range of cell lines such as glyoma cells and human skin HaCaT cells, in concentrations up to 100 µg/mL However, multi-layer GO has been hardly explored in the biomedical field. Thus, multi-layer GO was examined here in human keratinocyte HaCaT cells treated with different concentrations ranging from 0.01 to 150 µg/mL during different periods of times (3, 12 and 24 hours). The results of this study showed a time-concentration dependence with two non-cytotoxic concentrations (0.01 and 0.05 µg/mL) and a median effective concentration value of 4.087 µg/mL at 24 hours of GO exposure. Contrary to what has been reported for few-layer GO, cell proliferation of the HaCaT cells in contact with the multi-layer GO at 0.01 μg/mL showed identical proliferative activity compared to an epidermal growth factor (1.6-fold greater than the control group) after 96 hours. The effects of the multi-layer GO on the expression of 13 genes (SOD1, CAT, MMP1, TGFB1, GPX1, FN1, HAS2, LAMB1, LUM, CDH1, COL4A1, FBN and VCAN) at the non-cytotoxic concentrations of GO in the HaCaT cells were analyzed after 24 hours. Thus, the lowest non-cytotoxic GO concentration was able to up-regulate the CAT, TGFB1, FN1 and CDH1 genes, which confirms the great potential of multi-layer GO in the biomedical field.

Arthropod-borne viruses belonging to the flavivirus genus possess an enormous relevance in public health. Neotropical non-human primates (NPs) have been proposed to be infected more frequently with flaviviruses due to their arboreal and diurnal habits, their genetic similarity to humans and their relative closeness to humans. However, the only known flavivirus in America that is maintained by sylvatic cycles involving NPs is Yellow Fever virus (YFV), and the NPs role as potential hosts of flaviviruses is still unknown. Here, we examined flavivirus exposure in 86 free range and captive NPs of Costa Rica to evaluate their involvement in flavivirus transmission cycles and their potential as flavivirus hosts. We used a highly-specific micro plaque reduction neutralization test (micro-PRNT) to determine the presence of antibodies against YFV, Dengue virus 1-4 (DENV), Zika virus, West Nile Virus (WNV) and Saint Louis Encephalitis virus (SLEV). We found evidence of seropositive NPs to DENV-1 8.2% (homotypic –3/86, heterotypic – 4/86), SLEV 15.1% (homotypic – 10/86, heterotypic – 2/86), WNV 2.3% (homotypic – 2/86) and 8.1% (7/86) undetermined Flavivirus species. No antibodies against YFV or ZIKV were found. This work provides compelling serological evidence of exposure in NPs of flaviviruses associated with urban cycles, i.e. DENV, and confirms decades of circulation of SLEV in the same environments. Also, the range of years of sampling and the socioeconomic region was statistically significant for the presence of Dengue and Flavivirus undetermined seropositive individuals, respectively. Both the years and socioeconomic regions with greater seroprevalence coincide with the years and socioeconomic regions with high numbers of Dengue human cases for the country. Our work suggests bidirectional? circulation of different flaviviruses between humans and wildlife with public health importance and underscores the necessity of further surveillance for flaviviruses in the humans/wildlife interface in Central America.

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

The employee turnover literature to date is teeming with process models that assume only organizational and personal factors contribute to employees’ intentions to leave and stay. However, with the average percentage variance explained still only around 50%, it is clear that other factors play a substantial role in these decision-making processes. One possible explanation is to explore the unique role that clients play in employees’ intentions to stay or leave. This paper extends the conceptualization of the role that clients play on employee’s intentions to stay and leave their roles, particularly within service industries such as health care. This paper presents the results of two qualitative studies that examine employees’ decision-making process for turnover and retention intentions. The first study explores the factors influencing employees’ intentions to stay and leave the Australian aged care sector (N = 420) and the second study explores prison health care nurses in the United States (N = 175). The results of both studies reveal that client-related factors affect the choice to stay within a job and, in some cases, are the favoured aspect of the role. Therefore encouraging client-staff relationships will expand job satisfaction and therefore increase retention of employees within both contexts.

Background: PRAME, NY-ESO-1 and SSX2 are cancer testis antigens (CTAs), which in normal tissues are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterized cohort soft tissue sarcomas (STS). Methods: On protein level, we examined PRAME, NY-ESO-1 and SSX2 expression in tumour tissues of 249 STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including Tumour-infiltrating lymphocyte (TIL) counts, grading and long- term survival. Results: Expression of PRAME, NY-ESO-1 and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo subtypes. Expression of PRAME was associated with shorter patient survival (p=0.005) and higher grade (G2 vs G3, p=0.001) while NY-ESO-1 expression was correlated with more favourable survival (p=0.037) and low grade (G2 vs G3, p=0.029). Both PRAME and NY-ESO-1 expression was more frequent in STS with low TILs counts. Conclusions: CTAs PRAME, NY-ESO-1 and SSX2 show distinct expression patterns in different STS subtypes. These results may guide future immunotherapeutic approaches in STS.

The interaction of human immunodeficiency virus with human cells is responsible for all stages of the viral life cycle, from the infection of CD4+ cells to reverse transcription, integration, and the assembly of new viral particles. To date, a large amount of OMICs data as well as information from functional genomics screenings regarding the HIV-1-host interaction has been accumulated in the literature and in public databases. We processed databases containing HIV-host interactions and found 2910 HIV-1-human protein-protein interactions, mostly related to viral group M subtype B, 137 interactions between human and HIV-1 coding and non-coding RNAs, essential for viral lifecycle and cell defense mechanisms, 232 transcriptomics, 27 proteomics, and 34 epigenomics HIV-related experiments. Numerous studies regarding network-based analysis of corresponding OMICs data have been published in recent years. We overview various types of molecular networks, which can be created using OMICs data, including HIV-human protein-protein interaction networks, co-expression networks, gene regulatory and signaling networks, and approaches for the analysis of their topology and dynamics. The network-based analysis can be used to determine the critical pathways and key proteins involved in the HIV life cycle, cellular and immune responses to infection, viral escape from host defense mechanisms, and mechanisms mediating different susceptibility of humans to infection. The proteins and pathways identified in these studies may represent a basis for developing new anti-HIV therapeutic strategies such as new small-molecule drugs preventing infection of CD4+ cells and viral replication, effective vaccines, "shock and kill" and "block and lock" approaches to cure latent infection.

To prevent, mitigate and treat movement impairments, we need to recognize early signs of decline and understand how to best compensate for limitations. The mechanisms leading to movement impairments are complex, overlapping, and interdependent and the fields of biomechanics, motor control, and physiology must be combined to understand these mechanisms. This article introduces CaReMoOC, a framework incorporating neuromusculoskeletal capacity (accumulation of neuromusculoskeletal resources over the lifespan), reserve (task-specific difference between capacity and task demand), movement objectives (considerations made to plan a movement), and compensation (use of NMSK resources to respond to the task demand). The framework is demonstrated for healthy ageing, providing an overview of age-related capacity decline (neural, skeletal, muscular system) and shifted weighting of movement objectives (energy, pain, stability, speed) relevant for biomechanics and motor control. Two forms of compensation are Compensation for Capacity, when capacity does not meet the task demands, and Compensation for Movement Objectives, when the movement is changed due to for example a fear of falling. Understanding the interrelationships between decline in the variables within capacity and the effect on compensation strategies will provide benefit in preventing mobility impairments and will support clinicians in their rehabilitation practice.

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 onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the 1^st human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the 4^th post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19^th century but did not receive much recognition by embryologists.

Given the high prevalence of cutaneous genus beta human papillomavirus (β-HPV) infections, it is important to understand how they are manipulating their host cells. This is particularly true for cellular responses to UV damage, since our skin is continually exposed to UV. The E6 protein from β-HPV (β-HPV E6) decreases the abundance of two essential UV-repair kinases (ATM and ATR). Since β-HPV E6 reduces their availability, the impact on downstream signaling events has been uncertain. We demonstrate that β-HPV E6 decreases ATM and ATR activation. This inhibition extended to XPA, an ATR target necessary for UV repair, lowering both its phosphorylation and accumulation. β-HPV E6 hinders POLη phosphorylation and foci formation, critical steps in translesion synthesis. ATM’s phosphorylation of BRCA1 is also attenuated by β-HPV E6. However, β-HPV E6’s hindrance of ATM/ATR signaling during UV-associated cell cycle arrest was incomplete. While there was less phosphorylation of immediate downstream targets (CHK1), events further down the cascade were not decreased. These observations are consistent with β-HPV infections making UV radiation more deleterious and support the proposed role of β-HPV in early stages of non-melanoma skin cancer development.

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

Background Human parvovirus B19, a human pathogen of the erythroparvovirus genus, is responsible for a variety of diseases. Despite less symptoms caused by B19 infection in healthy individuals, this pathogen can not be neglected in specific groups who exhibit severe anemia. Main body of abstract Transient aplastic crisis and pure red cell aplasia are two kinds of anemic hemogram respectively in acute phase and chronic B19 infection, especially occur in individuals with a shortened red cell survival or immunocompromised patients. In addition, B19 infected pregnant women may suffer risks of hydrops fetalis secondary to severe anemia and fetal loss. B19 possesses high affinity to bone marrow and fetal liver due to its extremely restricted cytotoxicity to erythroid progenitor cells mediated by viral proteins. The nonstructural protein NS1 is considered to be the major pathogenic factor, which takes parts in differentiational inhibition and apoptosis of erythroid progenitor cells through inducing viral DNA damage responses and cell cycle arrest. The time phase property of NS1 activity during DNA replication and conformity to transient change of hemogram are suggestive of its role in regulating differentiation of hematopoietic cells, which is not completely understood. Conclusion In this review, we set up a hypothetic bridge between B19 NS1 and Notch signaling pathway or transcriptional factors GATA which are essential in hematopoiesis, to provide a new insight of the potential mechanism of B19-induced differentiational inhibition of erythroid progenitor cells.

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

The language we use to describe the past can have a strong influence on the audience’s interpretation of our story. In our experiment, we explore, using 3 different conditions, how the framing and language of an accident report can affect the audience’s proposed solutions to manage the problems found. We find that the approach used to create an accident report can have a powerful influence on the audience’s decision making. Whether we are describing an accident in a similar manner to a crime, using a systems approach or we are accepting of multiple stories which are not linear or coherent, the methods we use to capture and communicate the story have a profound impact on the actions decided upon by the reader.

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.

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.

Due to remarkable socioeconomic development, an increasing number of karst rocky desertification areas have been severely affected by human activities in southern China. Effectively analyzing human activities in karst rocky desertification areas is a critical prerequisite for managing and restoring areas with tremendous negative impacts from desertification. At present, a timely and accurate way of quantifying the spatiotemporal variations of human activities in karst rocky desertification areas is still lacking. In this communication, we attempted to quantify human activities from the corrected NPP-VIIRS nighttime light data from 2012 to 2018 based on statistical analysis. The results show that a significant increase of night lights could be clearly identified during the study period. The total nighttime lights (TL) related to severe karst rocky desertification (S) were particularly concentrated in Guizhou and Yunnan. The nighttime light intensity (LI) related to the S areas in Chongqing were the strongest due to its rapid socioeconomic development. The annual growth rate of nighttime lights (GL) has been slow or even negative in Guangdong because of its various karst rocky desertification restoration programs. This communication could provide an effective approach for quantifying human activities and provide useful information about where prompt attention is required for policy-making on the restoration of the karst rocky desertification areas.

The Human immunodeficiency virus-1 (HIV-1) matrix (MA) domain is involved in the highly regulated assembly process of the virus particles that occur at the host cell’s plasma membrane. High-resolution structures of the MA domain determined using cryo X-ray crystallography have provided initial insights into the possible steps in the viral assembly process. However, these structural studies have relied on large and frozen crystals in order to reduce radiation damage caused by the intense X-rays. Here, we report the first XFEL study of the HIV-1 MA domain’s interaction with inositol hexaphosphate (IP6), a phospholipid headgroup mimic. We also describe the purification, characterization and microcrystallization of two MA crystal forms obtained in the presence of IP6. In addition, we describe the capabilities of serial femtosecond X-ray crystallography (SFX) using X-ray free-electron laser (XFEL) to elucidate the diffraction data of MA-IP6 complex microcrystals in liquid suspension at ambient temperature. Two different microcrystal forms of MA-IP6 complex both diffracted to beyond 3.5 Å resolution, demonstrating the feasibility of using SFX to study the complexes of MA domain of HIV-1 Gag polyprotein with IP6 at near-physiological temperatures. Further optimization of the experimental and data analysis procedures will lead to better understanding of the MA domain of HIV-1 Gag and IP6 interaction at high resolution and provide basis for optimization of the lead compounds for efficient inhibition of the Gag protein recruitment to the plasma membrane prior to virion formation.