Emergence of more virulent forms of human pathogenic bacteria with multi drug resistance is a serious global issue and requires alternative control strategies. The current study was focused to investigate the antibacterial and antibiofilm potential of ferulic acid grafted chitosan (CFA) against Listeria monocytogenes (LM), Pseudomonas aeruginosa (PA), and Staphylococcus aureus (SA). The present result showed that CFA at 64 µg/mL concentration exhibit bactericidal action against LM and SA (>4 log reduction) and bacteriostatic action against PA (<2 log CFU) within 24 h of incubation. Further studies based on propidium iodide uptake assay, measurement of material released from the cell, and electron microscopic analysis revealed that the bactericidal action of CFA was due to the altered membrane integrity and permeability. CFA dose-dependently inhibited biofilm formation (52-89% range), its metabolic activity (30.8-75.1% range) and eradicated mature biofilms, and reduced viability (71-82% range) of the test bacteria. Also, the swarming motility of LM was differentially affected at sub-MIC concentration of CFA. In the present study, the ability of CFA to kill and alter the virulence production in human pathogenic bacteria will insight a new scope for the application of these biomaterials in healthcare to effectively treat bacterial infections.

This is the second of a series of two papers comparing the end of life issues in human and veterinary medicine. We outline the main differences between human and animal patients such as patient communication, finance and ‘conflicts of interest’ between animal, owner and veterinarian. We discuss striking similarities between human and veterinary issues such as assessing quality of life and the primary role of the attending veterinarian or doctor being the welfare and care of the patient. This paper takes the form of an ethical argument in favour of allowing euthanasia in human medicine, by providing insights into end of life issues for humans from an independent veterinary perspective. Veterinary surgeons are well trained in the ethics of euthanasia and put it to good use in the best interest of their animal patients. Doctors in the UK are limited and unwilling to put forward a case for the option of euthanasia for those patients who face a slow and agonizing death. With advances in medical science being able to significantly prolong the dying process, autonomy for the patient demands a review of the law regarding patient choice in the UK.

Flavonoids, compounds present in many dietary supplements, affect growth of different bacterial species when tested as purified or synthetic substances. Here, we asked if soy isoflavone extracts, commonly used in many products sold as anti-menopausal dietary supplements, influence bacterial growth similarly to synthetic isoflavone, genistein. Four commercially available products were tested in amounts corresponding to genistein concentrations causing inhibition of growth of Vibrio harveyi (a model bacterium sensitive to this isoflavone) and Escherichia coli (a model bacterium resistant to genistein). Differential effects of various extracts on V. harveyi and E. coli growth, from stimulation, through no changes, to inhibition, were observed. Moreover, contrary to genistein, tested extracts caused a decrease (to different extends) in viability of human dermal fibroblasts. These results indicate that effects of various soy isoflavone extracts on bacterial growth and viability of human cells are different, despite similar declared composition of the commercially available products.

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations the role of nutrients, vitamins, and in general, the foodborne associated background as part of the events leading ultimately to chromosome nondisjunction has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes, the possible association of DS development with maternal gut microbiota should require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa and hence, we might find associations between the use of different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N=30). Utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997-2020) and the prevalence of people living with DS estimated for 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

This study examines the dynamic relationship between Green Human Resource Management (Green HRM), Environmental Performance (EP), Green Employee Behavior (GEB), and Environmental Knowledge and Awareness (EKAW) within the Egyptian hospitality sector context. Using Pearson correlation coefficients and regression analyses on a sample of 400 staff members from hotels and tourist villages in Egypt, the study examines Green HRM practices’ influence on EP, mediated by GEB and moderated by EKAW. The findings reveal significant positive correlations between Green HRM practices and these mediators, indicating that comprehensive environmental strategies and incentive management are pivotal in promoting eco-friendly practices among employees. The study further confirms GEB and EKAW’s substantial mediating role in enhancing EP. The results also suggest that while EKAW and GEB independently contribute to EP, their interaction and the role of environmental awareness as a potential moderator warrant further examination. This research contributes to the literature on sustainable business practices by underscoring human resource strategies’ integral role in achieving environmental sustainability goals, highlighting the importance of incentivizing green practices, and cultivating an organizational culture that prioritizes EKAW. These insights are particularly valuable for organizations seeking to enhance their ecological footprint through effective Green HRM practices.

Rare earth elements (REEs) are a type of new material resources, which have attracted significant attention in recent years. REEs have emerged as essential metals in modern-day technology due to their unique functions. Long-term large-scale mining and utilization of rare earths have caused serious environmental pollution and constitutes a global health issue, which raised concerns about human health safety. However, the toxicity profile of suspended particulate matter of REEs in the environment interacts with the human body in remain largely unknown. Studies have shown that REEs can enter the human body through a variety of pathways, leading to a variety of organ and system dysfunctions through changes in genetics, epigenetics, and signaling pathways. Through an extensive literature search and critical analysis, we provide a comprehensive overview of the available evidence, identify knowledge gaps, and make recommendations for future research directions.

Machine learning, including deep learning, reinforcement learning, and generative artificial intelligence are revolutionising every area of our lives when data is made available. With the help of these methods, we can decipher information from larger datasets while addressing the complex nature of biological systems in a more efficient way. Although machine learning methods have been introduced to human genetic epidemiological research as early as 2004, those were never used to their full capacity. In this review, we outline some of the main applications of machine learning to assigning human genetic loci to health outcomes. We summarise widely used methods and discuss their advantages and challenges. We also identify several tools, such as Combi, GenNet and GMSTool, specifically designed to integrate these methods for hypothesis-free analysis of genetic variation data. We elaborate on the additional value and limitations of these tools from a geneticist’s perspective. Finally, we discuss the fast-moving field of foundation models and large multi-modal omics biobank initiatives.

Early marriage is a phenomenon that has an impact on various aspects of life which then affects human development. This study aims to conduct a literature review on the implications of early marriage on human development. The method used in this study is the SLR (Systematic Literature Review) method. Data collection was carried out by documenting all literature that met the research inclusion requirements. The literature obtained as many as 25 articles from the Google Scholer database with the help of Harzing's Publish or Perish application. From this literature study, it was found that the phenomenon of early marriage has implications for the human development index based on health indicators and life expectancy, education, and welfare. Another finding is that women are the most disadvantaged from the impact of early marriage. Things that can be done to deal with the phenomenon and impact of early marriage include formal and non-formal education, strengthening access to health and education services, creating empowerment programs, and strengthening regulations and legal protection.

Human violence recognition is an area of great interest in the scientific community, given its broad spectrum of applications, especially in video surveillance systems, since detecting violence in real-time could prevent criminal acts and save lives. Despite the number of existing proposals and research, most focus on the precision of results, leaving aside efficiency and its practical implementation. Thus, this work proposes a model that is effective and efficient in recognizing human violence in real-time. The proposed model consists of three modules: a first module called Spatial Motion Extractor (SME), in charge of extracting regions of interest from a frame; a second module called Short Temporal Extractor (STC), whose function is to extract temporal characteristics of rapid movements, finally the Global Temporal Extractor (GET) module, responsible for identifying long-lasting temporal features and fine-tuning the model. The proposal was evaluated regarding efficiency, effectiveness, and ability to operate in real-time. The results obtained on Hockey, Movies, and RWF-2000 datasets demonstrated that this approach is highly efficient compared to other alternatives. A VioPeru dataset was created to validate real-time applicability with violent and non-violent videos captured by real video surveillance cameras in Peru. The effectiveness results in this dataset outperformed the best existing proposal. Therefore, our proposal has contributions in efficiency, effectiveness, and real-time.

Human longevity is an important but difficult goal due to the extreme complication of human body. If people could repeatedly transfer their consciousness from old bodies to new ones, their lifespan might be prolonged extremely. However, there are several difficulties which prevent the achievement of such a technique. In this paper, we propose an approach that can transfer human consciousness indirectly, and avoid or significantly relieve those difficulties. The strategy of our approach is to integrate the consciousnesses of two bodies (old and new) into a unique consciousness. By doing so, the consciousness is extended to the new body. After that, the consciousness shrinks and remains in the new body when the old body dies. This may also apply to integrating more than two bodies of human, or animal, or even across different species. After investigating thousands of literatures, we find quite strong evidence (related discoveries and technologies) that can support the proposed approach and its advantages. Beside prolonging human lifespan, the approach could also have other meaningful applications.

Convolution, recurrent and attention-based deep learning techniques have produced the most recent state-of-the-art results in multiple sensor-based human activity recognition (HAR) datasets. However, these techniques have high computing costs, restricting their use in low-powered devices. Different methods have been employed to increase the efficiency of these techniques; however, this often results in worse performance. Recently, pure MLP architectures have demonstrated competitive performance in vision-based tasks with lower computation costs than other deep-learning techniques. The MLP-Mixer is a pioneering pure MLP architecture that produces competitive results with state-of-the-art models in computer vision tasks. This paper shows the viability of the MLP-Mixer in sensor-based HAR. Furthermore, experiments are performed to gain insight into the Mixer modules essential for HAR, and a visual analysis of the Mixer’s weights is provided, validating the Mixer’s learning capabilities. As a result, the Mixer achieves an F1 score of 97%, 84.2%, 91.2% and 90% on the PAMAP2, Daphnet Gait, Opportunity Gestures and Opportunity Locomotion datasets, respectively, outperforming state-of-the-art models in all datasets except Opportunity Gestures.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

The importance of performance excellence and operator’s safety is fundamental not only when operators perform repetitive and controlled industrial tasks, but also in case of abrupt gestures due to inattention and unexpected circumstances. Since optical systems work at too low frequencies and they are not able to detect gestures as early as possible, combining the use of wearable magneto-inertial measurement units (MIMUs) with the adoption of deep learning techniques can be useful to instruct the machine about human motion. To improve the initial training phase of neural networks for high classification performance, gestures repeatability over time has to be verified. Since test-retest approach has been poorly applied based on MIMUs signals in a context of human-machine interaction, the aim of this work was to evaluate the repeatability of pick-and-place gestures composed of both normal and abrupt movements. Overall, results demonstrated an excellent test-retest repeatability for normal movements and a fair-to-good test-retest repeatability for abrupt movements. Moreover whereas the reduction of time between test and retest sessions increased repeatability indices.. In detail, results of the test suggested how to improve the reinforcement learning for the identification of gestures onset, whereas results of the retest gave important information about the time necessary to retrain the network.

This study proposes a structure for companies to use when implementing human resource practices in open innovation. Despite the fact that open innovation has received a lot of attention in the innovation management field as companies open their doors to information exchange in an effort to spur creative thinking, there are very few empirical articles that connect this trend to the human resource management literature. Our findings are the result of an extensive qualitative investigation into Julphar Gulf Pharmaceutical Industries Manufacturers in the United Arab Emirates (UAE) and its open innovation program. Internal, external, and combined are the three primary pillars of human resource management. We also demonstrate how the evolution of the open innovation initiative is linked to the state of the art in HRM and open innovation literature. The framework identifies HRM practices for both internal and external participants in the open innovation effort. Much of this HRM is done off the books, in a setting separate from the host company. By providing actual evidence of how firms use HRM to manage open innovation projects, our research adds to the scant and mostly theoretical literature linking open innovation and HRM.

Although the fusion energy sector is at a nascent stage, the private fusion energy market has grown. There are currently 38 private fusion energy companies around the world aiming to commercialise fusion energy in early 2030s and 2040s. Given the capability of fusion energy in transforming today’s energy paradigm and the global character of the market, it is important to analyse how these companies are interacting with international human rights standards. Therefore, this work investigates the involvement of the private fusion energy sector with two voluntary international initiatives in particular: the UN Global Compact and the UN Guiding Principles on Business and Human Rights (UNGP). This study attempts to answer two research questions: (i) Are private fusion energy companies participating in the UN Global Compact? (ii) How are private fusion energy companies publicly implementing the UNGP? Content analysis of secondary data collected from the UN Global Compact, Fusion Industry Association, ITER and companies’ official website as well as published reports is adopted. In summary, this work finds that private fusion energy companies are neither participants nor signatories of the UN Global Compact. Their observance of the UNGP is also very poor. This study contributes to the field by highlighting this gap which the private fusion energy companies need to consider and take measures in order to create a salutary human rights sector.

In the past decade, RNA fragments derived from full length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions, and are able to fill the role of tumor-suppressor or tumor-promoter in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.

Over the past decade, recognition of human activities (HAR) has become a vibrant field of research, in particular, the spread in our everyday lives of electronics such as mobile phones, smart cell phones, and video cameras. Furthermore, the advancement in the field of deep methodologies and other paradigms have enabled scientists to enable HAR in many areas, consisting of activities in fitness and wellness. For instance, HAR is one of many resorts to support older people through day-to-day activities to support their cognition and physicality. This study is centered on the key aspects deep learning plays in the development of HAR applications. Although numerous HAR examination studies were carried out previously, there have been no overall studies on this subject, in all the earlier studies there were only specific HAR-related subjects. A detailed review covering all the main subjects in this area is therefore essential. This study discusses the latest developments and works in HAR. It separates the methods and the advantages and disadvantages of each method group. This paper finally addresses many problems in the current HAR subject and provides recommendations for potential study.

Human endogenous retroviruses (HERVs) are ancient retroviral DNA sequences established into germline. They contain regulatory elements and encoded proteins few of which may provide benefits to hosts when co-opted as cellular genes. Their tight regulation is mainly achieved by epigenetic mechanisms which can be altered by environmental factors, e.g. viral infections, leading to HERV activation. Aberrant expression of HERVs associates with neurological disease, such as multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS), inflammatory processes and neurodegeneration. This review summarizes recent advances on the epigenetic mechanisms controlling HERV expression and the pathogenic effects triggered by HERV derepression. The article ends describing new promising therapies targeting HERV elements, one of which, temelimab, has completed phase II trials with encouraging results in treating MS. The information gathered here may turn helpful in the design of new strategies to unveil epigenetic failures behind HERV-triggered disease, opening new possibilities for druggable targets and/or for extending the use of temelimab to treat other associated diseases.

Sound evidence recognizes the microbiota as one of the major players in human health and disease, including cancer. Every human being is an holobiont, a shared human and microbial ecosystem, in which microbial composition is individually set by behaviours and environmental factors during the first years of life. Thereafter it is modulated by diet, physical activity, emotions and drugs (in particularly antibiotics and chemotherapeutics). As a consequence, a shift in medicine is needed toward a more comprehensive practice that takes into account every individual's genoma and, in addition, his or her metagenome, known as microbiome: a "microbiota revolution". As regards breast cancer (BC), a clear link between microbiota and oncogenesis is still to be confirmed. Specific microbes display unique features regulating their host niche in a number of body sites, which can result in an increased risk of cancer; in addition, gut microbiota composition plays a role in immune modulation within the intestinal barrier, affecting local and systemic inflammation, recognized drivers of cancer. Moreover, part of the bacterial gene mass inside the gut, constituting the so called “estrobolome”, influences the sexual hormonal balance and subsequentely may impact on the onset, progression and treatment of hormonal dependent cancers. Microbiota is also clearly involved in modulating the response to anticancer treatments, and above all to the emerging immunotherapy. Based on these premises, the microbiome is becoming a potential target, in order to enhance efficacy of antitumoral treatments as well as to lower their toxicity. The complex scenario that links microbiome composition to oncogenesis and response to anticancer treatments defines the frames of a new “oncobiotic” perspective.

Thesis Statement: The consumption of externally fermented foods acted as the initial metabolic trigger enabling hominid brain expansion. Because brain tissue is metabolically expensive, it is thought that the evolution of humans’ large brains was only possible through a concomitant reduction in the size of another expensive organ system, the gut. However, this gut reduction must have itself been made possible by dietary changes, the nature of which are still unclear. Here, we propose that the initial metabolic trigger of hominid brain expansion may have been the consumption of externally fermented foods. We define “external fermentation” as occurring outside the body, as opposed to the internal fermentation that occurs through the gut microbiome. This practice could have begun accidentally and with limited understanding, but over time, fermentation technologies may have become increasingly intentional, socially-transmitted, and culturally-reinforced. We detail the mechanisms by which external fermentation can mediate the evolution of increased brain size, as well as a reduction in gut size, by increasing the bioavailability of macro- and micronutrients while reducing digestive energy expenditure. Importantly, we calculate that the reduction in human gut size relative to modern apes is mainly due to a reduction in the colon, the site of internal fermentation. We also discuss the explanatory power of our hypothesis relative to others, including realistic plausibility in hominids with brains roughly the size of modern chimpanzees. Finally, we survey external fermentation practices across human cultures to demonstrate its viability across a huge range of environments, temperatures, and food sources. We close with suggestions for empirical tests.

In this paper, we investigate the relationship people have with their smart devices. We use the concept of agency to capture aspects of users’ sense of mastery as they relate to their device. This study gives preliminary evidence of the existence of two independent dimensions of agency for modeling the interaction between humans and smart devices: (i) user agency and (ii) device agency. These constructs emerged from an exploratory factorial analysis conducted on a survey data collected from 587 participants. In addition, we investigate the correlation between user agency and device agency with background variables of the respondents. Finally, we argue that mapping the users’ dynamics with their device into user agency and device agency fosters a better understanding of the needs of the users and helps in designing interfaces tailored for the specific capabilities and expectations of the users.

In today's world it is very much important to maintain the security of information and its risks. The biometric-based techniques are very much useful in these problems. Among the several kinds of biometric-based technique, face detection is much complex and much more important. Due to the age and several other problems, a human face structure changes over time, again a human has lots of expressions. Sometimes due to the lighting condition or the variation of the angle of an input device, the pattern of a human face structure also changed. As a result, the face cannot be detected properly. In this paper, a method is proposed that can detect the human faces both automatically and manually very efficiently. In manual mode, a user can select the input faces referred by the system according to their choice. In automated mode, the system detected all possible face areas using the Kohonen Self-Organizing Feature Map technique. This method reduced the complex color image into a vector quantized image with desired colors. Then a color segmentation technique is used to detect the possible face skin areas from the vector quantized image. Then the Histogram Oriented Gradient technique used to detect the feature from the faces and K-Nearest Neighbour Classifier is used to compare both face images detected by the two modes. The automated method prosed better accuracy than the manual method.

Extracellular vesicles (EVs) released by different cell types play significant role in many physiological and pathophysiological processes. In physiological conditions red blood cells (RBCs) derived EVs compose 4 - 8% of all circulating EVs, and oxidative stress (OS) as a consequence of different pathophysiological conditions significantly increases the amount of circulated RBC-derived EVs, however the mechanisms of EV formation are not fully defined yet. To analyze OS-induced EV formation and RBCs transformations we used flow cytometry to evaluate cell esterase activity, caspase-3 activity, and band 3 clustering. Band 3 clustering was additionally analyzed by confocal microscopy. Two original laser diffraction-based approaches were used for analysis of cell deformability and band 3 activity. Hemoglobin species were characterized spectrophotometrically. We showed that cell viability in tert-butyl hydroperoxide-induced OS directly correlated with oxidant concentration to cell count ratio, RBCs-derived EVs contained hemoglobin oxidized to hemichrome (HbChr). OS induced caspase-3 activation and band 3 clustering in cells and EVs. Importantly, we showed that OS-induced EV formation is independent from calcium. Presented data indicated that during OS RBCs eliminate HbChr by vesiculation, in order to sacrifice the cell itself thereby prolonging lifespan and delaying the untimely clearance of in all other respects healthy RBCs.

Geoscientists developed geoethics, an intra-disciplinary field of applied philosophical studies, during the last decade. Reaching beyond the sphere of professional geosciences, it led to professional, cultural, and philosophical approaches to handle the social-ecological structures of our planet ‘wherever human activities interact with the Earth system’. Against the backdrop of the COVID-19 and considering geoscientists’ experiences dealing with disasters (related to hazards like tsunamis, floods, climate changes.), this essay (1) explores the geoethical approach, (2) re-casts geoethics within western philosophical systems, such as the Kantian imperatives, Kohlberg scale of moral adequacy, Jonas’ imperative of responsibility, and (3) advances a ‘geoethical thesis’. The latter takes the form of a hypothesis of a much broader scope of geoethics than initially envisioned. That hypothesis appears by suspecting a relationship between the relative successes in the COVID-19 battle with the positioning of agents (individual, collective, institutional) into ethical frameworks. The turmoil caused by the COVID-19 pandemic, calls for the transfer of experiences between different disciplinary domains to further sustainable governance, hence generalising the geoethical approach. It is emphasized that only when behaving as responsible and knowledgeable citizens, then people of any trade (including [geo-]scientists) can transgress the boundaries of ordinary governance practices with legitimacy.

Background: Human papillomavirus (HPV) infection plays a key role in the development of cervical cancer that ranks as the third most common gynecological cancer in China. We attempt to investigate the age and genotype-specific prevalence of HPV DNA in western Chinese females. Methods: A total of 301,880 woman were recruited from 4 different regions of western China. Routine cervical samples were collected and HPV screening was performed using 21 HPV Genotyping test (Hybribio). The overall prevalence, age-specific prevalence, and genotype distribution were analyzed. Results: The overall prevalence of HPV was 18.01%. The high-risk HPV infection rate was 79.14%, the low-risk HPV infection rate was 12.56%, and the mixed HPV infection rate was 8.30%. The most common 4 HR HPV subtypes were HPV-52, 16, 58 and 53, which accounted for 20.49 %, 19.93 %, 14.54 % and 10.01 %. In LR HPV genotype, HPV-6 ranked the highest (28.17 %), followed by HPV-81 (9.09 %), HPV-11 (3.78 %). HPV genotype subgroup analysis also showed that single-type infections had the highest prevalence rate (77.26%) among HPV positive individuals. Among muti-infection genotype, double infection was most common with frequencies of 76.04%. Conclusion: This large report shows that the overall prevalence of HPV was high in China, whose distribution exhibits different patterns across different particular age and regions. Viral genotypes HPV53, 6 were are frequently detected in this population, which is worth of significant clinical attention.

Pathogenicity is unknown for the majority of human gene variants. For prioritization of sequenced somatic and germline mutation variants, in silico approaches can be utilized. In this study, 84 million non-synonymous Single Nucleotide Variants (SNVs) in the human coding genome were annotated using consensus Variant Effect Prediction (cVEP) method. An algorithm, implemented as a stacked ensemble of supervised learners, performed combination of the 39 functional, conservation mutation impact scores from dbNSFP4.0. Adding gene indispensability score, accounting for differences in the pathogenicities of the variants in the essential and the mutation-tolerant genes, improved the predictions. For each SNV the consensus combination gives either a continuous-value pathogenicity score, or a categorical score in five classes: pathogenic, likely pathogenic, uncertain significance, likely benign, benign. The provided class database is aimed for direct use in clinical practice. The trained prediction models were 5-fold cross-validated on the evidence-based categorical annotations from the ClinVar database. The rankings of the scores based on their ability to predict pathogenicity were obtained. A two-step strategy using the rankings, scores and class annotations is suggested for filtering and prioritization of the human exome mutations in clinical and biological applications of NGS technology.

The environment impacts human health in profound ways, yet few theories define the form of the relationship between human physiology and the environment. Under current epidemiological constructs of causation, it is assumed that two complex systems (environment and humans) can transfer information directly. This is the underlying structure of the relationship when studies examine, for example, air pollution and brain health. In marked contrast, we conjecture that complex systems cannot interact directly, but rather such interaction requires the formation of an “interface”. Further, we contend that this dynamic, process-based interface incorporates components from all the interacting systems but exhibits operational independence. This property has many consequences, the foremost being that characteristics of the interface cannot be fully resolved by only studying the systems involved in the interaction. The interface itself must be the subject of inquiry. Without refocusing our attention on biodynamic interfaces, we cannot discern how our environment impacts health.

Disruption of epigenetic regulation by environmental toxins is an emerging point of focus for understanding the latter’s impact on human health. Polybrominated diphenyl ethers (PBDEs), one such toxin, are an environmentally pervasive class of brominated flame retardants that have been extensively used as coatings on a wide range of consumer products. Their environmental stability, propensity for bioaccumulation, and known links to adverse health effects have evoked extensive research to characterize underlying biological mechanisms of toxicity. Of particular concern is the growing body of evidence correlating human exposure levels to behavioral deficits related to neurodevelopmental disorders. The developing nervous system is particularly sensitive to influence by environmental signals, including dysregulation by toxins. Several major modes of actions have been identified, but a clear understanding of how observed effects relate to negative impacts on human health has not been established. Here we review the growing body of evidence for epigenetic disruptions induced by PBDEs, including DNA methylation, chromatin dynamics, and non-coding RNA expression while discussing potential relationship between PBDEs and neurodevelopmental disorders.

The human proteome is composed from diverse and heterogeneous gene products/proteoforms. Previously, we have been discussing the main technical aspects in developing for inventory of human proteoforms that would be visually attractive, clear, and easy to search (Naryzhny S. J. Proteomics 2018, S1874-3919(18) 30220-3). Here, we present our first draft of the database of proteoforms that is based on this discussion. The database principles and structure are described. The database is called “2DE-pattern” as it contains multiple isoform-centric patterns of proteoforms separated according to 2DE principles.

The objective to fast-track the mapping and registration of large numbers of unrecorded land rights globally, leads to the experimental application of Artificial Intelligence (AI) in the domain of land administration, and specifically the application of automated visual cognition techniques for cadastral mapping tasks. In this research, we applied and compared the ability of rule-based systems within Object Based Image Analysis (OBIA), as opposed to human analysis, to extract visible cadastral boundaries from Very high resolution (VHR) World View-2 image, in both rural and urban settings. From our experiments, machine-based techniques were able to automatically delineate a good proportion of rural parcels with explicit polygons where the correctness of the automatically extracted boundaries was 47.4% against 74.24% for humans and the completeness of 45% for machine, as against 70.4% for humans. On the contrary, in the urban area, automatic results were counterintuitive: even though urban plots and buildings are clearly marked with visible features such as fences, roads and tacitly perceptible to eyes, automation resulted in geometrically and topologically poorly structured data, that could neither be geometrically compared with human digitised, nor actual cadastral data from the field. These results provide an updated snapshot with regards to the performance of contemporary machine-drive feature extraction techniques compared to conventional manual digitising.

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.

Human louse (Pediculus humanus) is an obligatory blood feeding ectoparasite with two ecotypes: human body louse (Pediculus humanus humanus), a competent vector of several bacterial pathogens and the human head louse (Pediculus humanus capitis) responsible for pediculosis and affecting millions of people around the globe. GABA (γ-aminobutyic acid) receptors, members of the cys-loop ligand gated ion channels superfamily, are among the main pharmacological targets for insecticides. In insects, four subunits of GABA receptors: resistant to dieldrin (RDL), glycin like receptor of drosophila (GRD), ligand gated chloride channel homologue3 (LCCH3), and 8916 are well described and form distinct phylogenetic clades revealing orthologous relationships. Our previous studies in human body louse confirmed that subunits Phh-RDL, Phh-GRD and Phh-LCCH3 are well clustered in their corresponding clades. In the present work, we cloned and characterized a putative new GABA receptor subunit in human body louse that we named HoCas for Homologous to Cys-loop alpha like subunit. Extending our analysis to arthropods, HoCas was found to be conserved and clustered in a new (fifth) phylogenetic clade. Interestingly, the gene encoding this subunit is ancestral and has been lost in some insect orders. Compared to the other studied GABA receptor subunits, HoCas exhibited a relatively higher expression level in all development stages and in different tissues of human body louse. These findings improved our understanding of the complex nature of GABA receptors in Pediculus humanus and more generally in arthropods.

Therapeutically effective treatments of cancer are limited. To calibrate the efficiency of the novel technique we recently discovered to modulate cancer cell viability using tuned electromagnetic fields; H1299 human lung cancer cells were irradiated in a sweeping regime of W-band (75-105 GHz) millimeter waves (MMW) at 0.2 mW/cm² (2 W/m²). Effects on cell morphology, cell death and senescence were examined and compared to that of non-tumorigenic MCF-10A human epithelial cells. MMW irradiation led to alterations of cell and nucleus morphology of H1299 cells, significantly increasing mortality and senescence over 14 days of observation. Extended irradiation of 10 minutes duration resulted in complete death of exposed H1299 cell population within two days, while healthy MCF-10A cells remained unaffected even after 16 minutes of irradiation under the same conditions. Irradiation effects were observed to be specific to MMW treated H1299 cells and absent in the control group of non-irradiated cells. MMW irradiation affected nuclear morphology of H1299 cells only and not of the immortalized MCF-10A cells. Irradiation with low intensity MMW shows an antitumor effect on H1299 lung cancer cells. This method provides a novel treatment modality enabling targeted specificity for various types of cancers.

Corneal biomechanics is a hot topic in ophthalmology. The biomechanical properties of the cornea (BMPs) have important implications in the management and diagnosis of corneal diseases such as ectasia and keratoconus. In addition, the characterization of BMPs is crucial to model the predictability of a corneal surgery intervention, the outcomes of refractive surgery or follow-up of corneal diseases. The biomechanical behavior of the cornea is governed by viscoelastic properties that allow, among other structural implications, the damping of excess of intraocular pressure and reduce damage to the optic nerve. Currently, the most versatile and complete methods to measure corneal viscoelasticity are based on air-puff corneal applanation. However, those methods lack the ability to directly measure corneal viscosity. The aim of this work is to propose a new methodology based on the analysis of corneal air-puff measurements through the Standard Linear Solid model (SLSM) to provide analytical expressions to separately calculate the elastic and time-dependent (corneal retardation time and viscosity) properties. The results shown the mean values of elasticity (E), viscosity (Ƞ) and corneal retardation time (τ) in a sample of 200 young and healthy subjects. The influence of elasticity and viscosity on viscoelasticity, high-order corneal aberrations and optical transparency is investigated. Finally, the SLSM fed back from experimental E and Ƞ values was employed to compare the creep-relaxation response between normal, an ocular hypertension patient and Ortho-K user.

The main focus of this paper is to propose a comprehensive framework for the cognitive meas-urement and modelling of the built environment. This will involve exploring and measuring neural mechanisms. The aim is to create a foundation for further studies in this field that are consistent and rigorous. Additionally, this framework will facilitate collaboration with cognitive neuroscientists by establishing a shared conceptual basis. The goal of this research is to develop a human-centric approach for urban design that is scientific and measurable, producing a set of urban design guidelines that incorporate cognitive measurement and modelling. By doing so, the broader intention is to design urban spaces that prioritize human needs and well-being, mak-ing them more liveable.

Protein malnutrition is present in developing countries but also in developed ones, due by the actual eating habits with insufficient protein intake, in addition to this it is estimated by the Food and Agricultural Organization of the United Nations an increase of world population of 9.1 billion people in less those 30 years, posing the challenge of nourish the mankind. There are different strategies to afford this challenge, one of the most promising ones is to approach novel protein sources like plants, microorganisms, and insects from dry lands.

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

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

Human and animal waste, including waste products originating from human or animal digestive systems such as urine, feces, and animal manure, have constituted a nuisance to the environment. Inappropriate disposal and poor sanitation of human and animal waste often cause negative impacts on human health through contamination of the terrestrial environment, soil, and water bodies. Therefore, it is necessary to convert these wastes into useful resources to mitigate their adverse environmental effect. The present study provides an overview and research progress of different thermochemical and biological conversion pathways for the transformation of human- and animal-derived waste into valuable resources. The physicochemical properties of human and animal waste are meticulously discussed as well as nutrient recovery strategies. In addition, a bibliometric analysis is provided to identify the trends in research and knowledge gaps. The results reveal that the U.S.A, China and England are the dominant countries in the research areas related to resource recovery from human or animal waste. In addition, researchers from the University of Illinois, the University of California Davis, the Chinese Academy of Science and Zhejiang University are front runners in research related to these areas. Future research should be centred on developing technologies for the on-site recovery of resources, exploring integrated resource recovery pathways, and exploring different safe waste processing methods.

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.

Emerging data have demonstrated a strong association between the gut microbiota and the development of cardiovascular disease (CVD) risk factors such as atherosclerosis, inflammation, obesity, insulin resistance, platelet hyperactivity, and plasma lipid abnormalities. Several studies in humans and animal models have demonstrated an association between gut microbial metabolites, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids, and bile acid metabolites, amino acid breakdown products, with CVD. Human blood platelets are a critical contributor to the hemostatic process. Besides, these blood cells play a crucial role in developing atherosclerosis and, finally, contribute to cardiac events. Since the TMAO, and other metabolites of the gut microbiota, are associated with platelet hyperactivity, lipid disorders, and oxidative stress, the diet-gut microbiota interactions have become an important research area in the cardiovascular field. Platelets became hyperactive in people with diabetes mellitus, sedentary lifestyle, obesity, and insulin resistance and exhibited increased sensitivity at a baseline level and in response to agonists, ultimately contributing to increased aggregation plaque development. In addition to these factors, TMAO also contributes to platelet hyperactivity. Several approaches are now suggested to reduce plasma TMAO levels, such as microbiota modulation using probiotics, prebiotics, and oral broad-spectrum antibiotics. This review describes the association between microbiota-derived metabolites and CVD development.

As a result of extensive research in the field of mobile robots (rovers) and swarms, a number of algorithms exist to assist them for executing a mission in the three levels of software architecture: strategic (interaction loop level), tactic (planning) and operational (sensing, control and actuation). They allow them to achieve their goals while adapting to their environment through a multitude of methods designed for each situation. For this reason, a literature review of the latest research conducted in previous years is required to identify new research trends in human-swarm interaction applied to help humans in hazardous environment such as militarized zone. In this paper, we will present some interesting algorithms for interactive and autonomous mobile robots acting in swarms in an open and crowded environment. A discussion will focus on comparing different algorithms and their advantages and disadvantages.

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model).The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations.

In the modern world, the problem of antibiotic therapy is acute. Despite the diversity of existing antibiotic drugs, their efficacy decreases as new, resistant forms of pathogenic microorganisms emerge. It is extremely difficult to control such processes and even more difficult to treat severe bacterial infections. In such situations, an individual approach to each patient is required and physicians need parameters to estimate the efficacy of antibiotic therapy. This review discusses the significance of monitoring the content of antibiotics in the blood for this purpose, in combination with the content of inflammatory markers, such as C-reactive protein and procalcitonin. The basic principles of antibiotic therapy, and factors in the resistance of microorganisms to antibiotics, are examined. Approaches to assess the efficacy of antibiotic therapy, as well as methods to detect antibiotics and inflammatory markers in the blood of patients, and comparative assessment of their capabilities and limitations, are described.

Matrix Metaloproteinase-2 (MMP-2) is an extracellular Zn²⁺ protease specific to type I and IV collagens. Its expression is associated with several inflammatory, degenerative, and malignant diseases. Conformational properties, domain movements, and interactions between MMP-2 and its associated metal ions were characterized using a 1.0 µs molecular dynamics simulation. Dihedral principle component analysis revealed 10 families of conformations with the greatest degree of variability occurring in the link region connecting the catalytic and hemopexin domains. Dynamics cross correlation analysis indicated domain movements corresponding to opening and closing of the hemopexin domain in relation to the fibronectin and catalytic domains facilitated by the link region. Interaction energies were calculated using the MMPBSA-interaction entropy analysis method and revealed strong binding energies for the catalytic Zn²⁺ ion 1, Ca²⁺ ion 1, and Ca²⁺ ion 3 with significant conformational stability at the binding sites of Zn²⁺ ion 1 and Ca²⁺ ion 1. Ca²⁺ ion 2 diffuses freely away from its crystallographically defined binding site. Zn²⁺ ion 2 plays a minor role in conformational stability of the catalytic domain while Ca²⁺ ion 3 is strongly attracted to the highly electronegative sidechains of the Asp residues around the central β-sheet core of the hemopexin domain.

Abstract: We review the development and application of an organic polymer-gel capable of producing fixed, three-dimensional fluorescent images of complex radiation fields. The gel consists for more than 99% of γ-ray-polymerized (~15% conversion) tertiary-butyl acrylate (TBA) containing ~100 ppm of a fluorogenic compound, e.g. maleimido-pyrene (MPy). The radio-fluorogenic effect depends on copolymerization of the MPy into growing chains of TBA on radiation-induced polymerization. This converts the maleimido residue, which quenches the pyrene fluorescence, into a succinimido moeity (SPy), which doesn't. The intensity of the fluorescence is proportional to the yield of free-radicals formed and hence to the local dose deposited. Because the SPy moieties are built into the cross-linked polymer matrix the image is fixed. The method of preparing the gel and imaging the radiation-induced fluorescence are presented and discussed. The effect is illustrated with fluorescent images of the energy deposited in the gel by beams of X-rays, electrons and protons as well as a radioactive isotope.

Background: The objectives were to evaluate: the safety and immunogenicity of nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV (WLHIV); the prevalence of anal and cervical dysplasia and nHPV vaccine genotypes in anus and cervix; and risk factors for high-risk HPV (HR-HPV) infection in anal mucosa. Methods In this single-center, open-arm, non-randomized clinical trial, nHPV vaccine was administered at 0, 2, and 6 months to WLHIV enrolled between February 2020 and November 2023, measuring vaccine antibody titers pre-vaccination and at 2, 6, and 7 months after the first dose. Cervical and anal cytology and HPV PCR genotyping studies were performed. Women with abnormal cytology and/or anal or cervical HPV infection at baseline underwent high-resolution anoscopy and/or colposcopy. Results: 122 participants were included with mean age of 49.6 years: 52.5% smoked; 10.7% had anal-genital condylomatosis; 38.5% infection by HR-HPV in anus and 25.4% in cervix, most frequently HPV-16; 19.1% had AIN1 and 3.1% CIN1 and CIN2. Vaccine administration did not modify viral-immunological status (CD4 [809±226.8 cells/uL vs. 792.35 ±349.95; p=0.357]) or plasma HIV load (3.38±4.41 vs. 1.62±2.55 cop/uL [log]; p=0.125). Anti-HPV antibodies ([IQR: 0-0] vs. 7.63 nm [IQR: 3.46-19.7]; p=0.0001) and seroconversion rate (8.2% vs. 96.7% [p=0.0001]) were increased at 7 versus 0 months. There were no severe vaccine-related adverse reactions; injection-site pain was reported by around half of participants. HR-HPV infection in anus was solely associated with concomitant cervix infection (HR 5.027; 95% CI: 1.009-25.042). Conclusions: nHPV vaccine in adult WLHIV is immunogenic and safe.

During fertilization, the fusion of the spermatozoa with the oocytes causes the release of calcium from the oocyte endoplasmatic reticulum. This, in turn, triggers a series of calcium ion (Ca2+) oscillations, a process known as oocyte activation. The sperm-specific factor responsible for oocyte activation is phospholipase C zeta (PLCζ). Men undergoing intracytoplasmic sperm injection (ICSI) with their spermatozoa lacking PLCζ are incapable of generating Ca2+oscillation, leading to fertilization failure. The immunofluorescence assay is the most used technique to assess the expression and localization of PLCζ and to diagnose patients with reduced/absent ability to activate the oocytes. In these patients, the use of assisted oocyte activation (AOA) technique can help to yield successful ICSI results and shorten the time of pregnancy. However, the production of a stable PLCζ recombinant protein represents a new powerful therapeutic approach to treating individuals with this condition. We aim to conduct a systematic review focusing on the expression, level, and localization of PLCζ, discussing the novel genetic mutation associated with its impairment. In addition, we highlight the benefits of AOA, looking at new and less invasive methods to diagnose and treat cases with PLCζ dysfunction ability.

Microplastics have been detected as widespread in an aquatic environment at the microscale, also known as plastic debris. They have continuously increased due to the increase in population, production of synthetic plastics and poor waste management. They are ubiquitous and slowly degrade in soil and water. They are emerging contaminants that have received attention from research communities and public audiences over the last few years. They have high stability and can absorb several other pollutants like heavy metals, pesticides, etc. After entering the environment, they can accumulate and persist for a long time. They can create a serious threat to freshwater ecosystems and human health. These particles can cause physical damage to freshwater organisms. Raman spectroscopy, Fourier-transform infrared spectroscopy, visual identification, density separation, microscopic method, chemical method, thermos-analytical method and hyperspectral imaging method are the commonly known approaches for identification and quantification of microplastics. The noticed concentration of microplastics depends on the analysis method, sampling location and technique. The authors reviewed the sources, health impact, transport and treatment of microplastics in freshwater environments in detail. This study will provide the baseline data for the researchers to do more research on microplastic pollution in the future.

In the mid-1950s, a groundbreaking discovery revealed the fascinating presence of caveolae, referred to as flask-shaped invaginations of the plasma membrane, sparking renewed excitement in the field of cell biology. Caveolae are small, flask-shaped invaginations in the cell membrane that play crucial roles in diverse cellular processes, including signal transduction, endocytosis, lipid homeostasis, and signal transduction. The structural stability and functionality of these specialized membrane microdomains are attributed to the coordinated activity of scaffolding proteins, including caveolins and cavins. While caveolae and caveolins have been long appreciated for their integral roles in cellular physiology, the accumulating scientific evidence throughout the years reaffirms their association with a broad spectrum of human disorders. This review article aims to offer a thorough account of the historical advancements in caveolae research, spanning from their initial discovery to the recognition of caveolin family proteins and their intricate contributions to cellular functions. Furthermore, it will examine the consequences of a dysfunctional caveolar network in the development of human diseases.

The Cav3.2 T-type calcium channel is implicated in various pathological conditions, including cardiac hypertrophy, epilepsy, autism, and chronic pain. Phosphorylation of Cav3.2 by multiple kinases plays a pivotal role in regulating its calcium channel function. The calcium/calmodulin-dependent serine/threonine phosphatase, calcineurin, interacts physically with Cav3.2 and modulates its activity. However, it remains unclear whether calcineurin dephosphorylates Cav3.2, the specific spatial regions on Cav3.2 involved, and the extent of the quantitative impact. In this study, we elucidated the serine/threonine residues on Cav3.2 targeted by calcineurin using quantitative mass spectrometry. We identified six serine residues in the N-terminus, II-III loop, and C-terminus of Cav3.2 that were dephosphorylated by calcineurin. Notably, a higher level of dephosphorylation was observed in the Cav3.2 C-terminus, where calcineurin binds to this channel. Additionally, a previously known CaMKII-phosphorylated site, S1198, was found to be dephosphorylated by calcineurin. Furthermore, we also discovered that a novel CaMKII-phosphorylated site, S2137, underwent dephosphorylation by calcineurin. In CAD cells, a mouse central nervous system cell line, membrane depolarization led to an increase in the phosphorylation of endogenous Cav3.2 at S2137. Mutation of S2137 affected the calcium channel function of Cav3.2. Our findings advance the understanding of Cav3.2 regulation not only through kinase phosphorylation but also via calcineurin phosphatase dephosphorylation.

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

This paper applies a theoretical model to analyze the ways that widespread use of generative AIs (GAIs) in education and, more broadly, in contributing to and reflecting the collective intelligence of our species, can and will change us. The model extends Brian Arthur’s insights into the nature of technologies as the orchestration of phenomena to our use by explaining the nature of humans participation in their enactment, whether as part of the orchestration (hard technique, where our roles must be performed correctly) or as orchestrators of phenomena (soft technique performed creatively or idiosyncratically). Education may be seen as a technological process for developing the soft and hard techniques of humans to participate in the technologies and thus the collective intelligence of our cultures. Unlike all earlier technologies, by embodying that collective intelli-gence themselves, GAIs can closely emulate and implement not only the hard technique but also the soft that, until now, was humanity’s sole domain: the very things that technologies enabled us to do can now be done by the technologies themselves. The consequences for what, how, and even whether we learn are profound. The paper explores some of these consequences and concludes with theoretically informed approaches that may help us to avert some dangers while benefiting from the strengths of generative AIs.

The vascular endothelium is key target for immune, and thrombotic responses that has to be controlled in successful xenotransplantation. Several genes were identified that if induced or overexpressed help to regulate the inflammatory response and preserve the transplanted organ function and metabolism. However, few studies addressed combined expression of such genes. The aim of this work was to evaluate in vivo the effects of the simultaneous expression of a three human genes in a mouse generated using the multi-cistronic F2A technology. Male 3-month-old mice that express human heme oxygenase 1 (hHO-1), ecto-5’-nucleotidase (hE5NT), and ecto-nucleoside triphosphate diphosphohydrolase 1 (hENTPD1) (Transgenic) were compared to wild-type FVB mice (Control). Background analysis include extracellular nucleotide catabolism enzymes profile on the aortic surface, blood nucleotide concentration and serum L-arginine metabolites. Furthermore, inflammatory stress induced by LPS in transgenic and control mice was used to characterize interleukin 6 (IL-6) and adhesion molecules endothelium permeabil-ity responses. Transgenic mice had significantly higher rates of extracellular adenosine triphosphate and adenosine monophosphate hydrolysis on the aortic surface in comparison to control. Increased levels of blood AMP and adenosine were also noticed in transgenics. Moreover, transgenic ani-mals demonstrated the decrease in serum monomethyl-L-arginine level and a higher L-arginine/ monomethyl-L-arginine ratio. Importantly, significantly decreased serum IL-6, and adhesion mol-ecule levels were observed in transgenic mice in comparison to control after LPS treatment. Fur-thermore, reduced endothelial permeability in the LPS-treated transgenic mice was noted as com-pared to LPS-treated control. The human enzymes (hHO-1, hE5NT, hENTPD1) simultaneously encoded in transgenic mice demonstrated benefits in sev-eral biochemical and functional aspects of endothelium. This is consistent in use of this approach in the context of xenotransplantation.

Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

In this review we extensively describe the main post-translational modifications that give rise to the multiple proteoforms characterized to date in the human salivary proteome and their potential role. Most of the data reported were obtained by our group in over twenty-five years of research carried out on human saliva mainly by applying a top-down strategy. At the beginning we describe the products generated by proteolytic cleavages, which can occur before and after secretion. In this section the most relevant families of salivary proteins are also described. Next, we report the current information concerning the human salivary phospho-proteome and the limited news available on sulfo-proteome. Three sections are dedicated to the description of the glycation and enzymatic glycosylation. Citrullination and N- and C- terminal PTMs and a miscellaneous of other modifications are described in the last two sections. Results highlighting the variation in the level of some proteoforms in local or systemic pathologies are also reviewed along the sections of manuscript to underline the impact and relevance of this information for the development of new diagnostic biomarkers useful in clinical practice.

Bromodomain (BRD)-containing proteins are involved in many biological processes, most notably epigenetic regulation of transcription, and BRD protein dysfunction has been linked to many diseases, including tumorigenesis. However, the role of BRD proteins in the pathogenesis of uterine fibroids (UFs) is entirely unknown. The present study aimed to determine the expression pattern of BRD9 protein in UFs and matching myometrium and further assess the impact of BRD9 inhibitors on UF phenotype and epigenetic/epitranscriptomic changes. Our studies demonstrated that the levels of BRD9 were significantly upregulated in UFs compared to matched myometrium, suggesting that the aberrant BRD protein expression may contribute to the pathogenesis of UFs. We then evaluated the potential roles of BRD9 using its specific inhibitor I-BRD9. Targeted inhibition of BRD9 suppressed the UF tumorigenesis with increased apoptosis and cell cycle arrest, decreased cell proliferation, and extracellular matrix deposition in UF cells. The latter is the key hallmark of UFs. Unbiased transcriptomic profiling coupled with downstream bioinformatics analysis further and extensively demonstrated that targeted inhibition of BRD9 impacted the cell cycle- and ECM-related biological pathways, reprogrammed the UF cell epigenome and epitranscriptome, and altered miRNA-mediated gene regulation in UFs. Taken together, our data support the critical role of BRD9 in UF cells and the strong interconnection between BRD9 and other pathways controlling the UF progression. Targeted inhibition of BRD proteins might provide a non-hormonal treatment option for this most common benign tumor in women of reproductive age.

1). BACKGROUND: Cell wall deficient mycobacteria (CWDM) have seldom been isolated in bacterial culture from human subjects. particularly in clinical disease, such as Crohn’s disease. Techniques have focused on the use of polymerase chain reaction (PCR) for the detection of CWDM in association with inflammatory bowel disease. (IBD). This paper is a report of the development of methods to demonstrate the presence of CWDM using the Ziehl-Neelsen (ZN) stain. This is in addition to the detection of the growth of CWDM in fluid media. 2). METHODS: The use of the ZN stain is suitable for the demonstration of CWDM in clinical samples and cultures, when the staining methods that were common prior to the 1970’s, are adopted. Specific culture media are developed and tested in parallel. Alterations in the concentration of basic fuchsin, and changes in the decolourising solutions are necessary. Decolourising solutions such as 20% concentrated sulphuric acid in water are preferable for detection of CWDM in cultures. 3). RESULTS: CWDM can be readily demonstrated using the simple methods outlined in this report. The ability to visualise the presence of CWDM opens the door to the development of specific fluid media for the isolation of CWDM in culture. 4). CONCLUSION: The ZN stain methods optimised for the demonstration of Mycobacterium tuberculosis complex (MTBC) are not suitable for research into infectious causes of inflammatory bowel disease (IBD), as well as for the detection of CWDM in latent tuberculosis. Revisiting the techniques for the detection of CWDM may also refocus attention on inflammatory diseases considered to be idiopathic, but having hallmarks of an infectious process.

In post-COVID-19 syndrome, clinical presentation of the nerve fiber dysfunction plays an important role. The possibility of autoantigen cross-mimicry of coronavirus infection and the peripheral nervous system need to be investigated. The bioinformatic analysis was applied to search for possible common protein sequences located in the immunological epitopes. Among the autoantigens of the human nervous system, fibroblast growth factor receptor protein 3, myelin protein P0, myelin protein P2, sodium channel protein type 9, alpha protein subunit, plexin-D1 protein and ubiquitin-carboxyl-terminal hydrolase protein of the L1 isoenzyme were selected. The “Alignmentaj” program was created. The UniProt database, Protein Data Bank and AlphaFold databases were used. The analysis of protein sequence similarities of spike glycoproteins in human coronaviruses revealed common pentapeptides of the MERS-CoV-2 virus with the fibroblast growth factor receptor 3 and myelin protein P2. Among seasonal coronaviruses, common peptide sequences were identified in HCoV-HKU-1 virus with sodium channel protein type 9 subunit alpha and Plexin-D1, HCoV-OС43 with Plexin-D1, as well as HCoV-NL63 with Plexin-D1 and Ubiquitin carboxyl-terminal hydrolase isozyme L1. The data obtained make it possible to identify new potential targets for the development of autoimmune reactions that occur against the background of the activity of highly pathogenic and seasonal coronaviruses.

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder that can lead to heart failure and sudden cardiac death, characterized at the histological level by focal areas of myocyte disarray, hypertrophy and fibrosis, and few disease-targeted therapies exist. To identify, focal, spatially restricted alterations in transcriptional pathways and reveal novel therapeutic targets, we performed a spatial transcriptomic analysis of areas of focal myocyte disarray compared to areas of normal tissue, using a commercially available platform (GeoMx, nanoString). We analyzed surgical myectomy tissue from four patients with HCM and control interventricular septum tissue from two unused organ donor hearts that were free of cardiovascular disease. Histological sections were reviewed by an expert pathologist and 72 focal areas with varying degrees of myocyte disarray (normal, mild, moderate, severe) were chosen for analysis. Areas of interest were interrogated with the Human Cancer Transcriptome Atlas designed to profile 1800 transcripts. Differential expression analysis revealed significant changes in gene expression between HCM and Control tissue, and functional enrichment analysis indicated these genes were primarily involved in interferon production and mitochondrial energetics. Within HCM tissue, differentially expressed genes between areas of mild and moderate disarray were enriched for genes related to mitochondrial energetics (moderate disarray) and response to oxygen/cytokine levels (mild disarray). The comparison between areas of moderate and severe disarray were enriched for genes related to the c-Jun N-terminal kinase (JNK) cascade in severe disarray. Analysis of ligand-receptor pair gene expression revealed that HCM tissue exhibited downregulation of platelet-derived growth factor (PDGF), NOTCH, junctional adhesion molecule, and CD46 signaling, while showing upregulation of fibronectin, CD99, cadherin, and amyloid precursor protein signaling. A deconvolution analysis utilizing the matched single nuclei RNA-sequencing (snRNA-seq) data to determine cell type composition in areas of interest revealed significant differences in fibroblast and vascular cell composition in areas of severe disarray when compared to normal areas in HCM samples. Cell composition in normal areas from control tissue was also divergent from normal areas in HCM samples, which was consistent with the differential expression results. Overall, our data identify novel and potential disease-modifying targets for therapy in HCM.

The length of time it takes to experimentally make one-sided choppers, as found in the fossil record, bears a linear relationship to the knapping process of fabricating them. In addition, this temporal frame appears to be related to human heart rates measured as beats per minute, which act as a physiological metronome. We achieved these observations assuming that any paleolithic one-sided chopper has the information needed to estimate quantitatively the number of strikes on it. The experimental data allow us to establish the total timing needed for the standard fabricating of any one-sided chopper. We discuss issues derived from these experimental results, showing the evolution of human neurological abilities from 2.4 million years ago to the Modern period through the duration of time needed for making one chopper to that needed to play a 19th-century music score on a piano. Given that the neuronal and physiological distance between both actions differs by a factor of 6, we propose the concept of “technome” to measure human evolution by using methodological homogeneous metrics applied to these two human technologic objects, the chopper and the piano.

Immune surveillance by natural killer (NK) cells and their recruitment to sites of inflammation renders them susceptible to viral infection, potentially modulating their effector function. Here, we analyzed innate RNA receptor signaling in NK cells downstream of direct Influenza A virus (IAV) infection and its impact on NK cell effector function. Infection of NK cells with IAV resulted in the activation of TBK1, NF-κB and subsequent type-I IFN secretion. CRISPR- generated knockouts in primary human NK cells revealed that this effect depended on the antiviral cytosolic RNA receptor RIG-I. Transfection of NK cells with synthetic 3p-dsRNA, a strong RIG-I agonist that mimics viral RNA, resulted in a similar phenotype and rendered NK cells resistant to subsequent IAV infection. Strikingly, both IAV infection and 3p-dsRNA transfection enhanced degranulation and cytokine production by NK cells when exposed to target cells. Thus, RIG-I activation in NK cells both supports their cell intrinsic viral defense and enhances their cytotoxic effector function against target cells.

A total of thirty-two aerobic spore former strains were isolated from intestinal samples of healthy children and analyzed for their hemolytic and antibiotic-resistance activities. Four strains selected as non-hemolytic and sensitive to all antibiotics recommended as relevant by regulatory agencies were short-listed and evaluated for their in silico and in vitro probiotic potentials. The four selected strains were assigned to the Bacillus velenzensis (MV4 and MV11), B. subtilis (MV24) and Priestia megaterium (formerly Bacillus megaterium) (MV30) species. A genomic analysis indicated that MV4, MV11 and MV24 contained a homolog of the gene coding for the fibrinolytic enzyme nattokinase while only MV30 encoded for a glutamic acid decarboxylase essential to synthesize the neurotransmitter GABA. All four strains showed a strong antioxidant activity, formed biofilm and produced/secreted quorum sensing peptides able to induce a cytoprotective stress response in a model of human intestinal (HT29) cells. Altogether, genomic and physiological data indicate that the analyzed strains do not pose safety concerns and have in vitro probiotic potentials.

Astrocytes have been implicated in a wide range of neurodegenerative diseases, with the literature indicating harmful or beneficial roles on a case-by-case basis. On such conditions, these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including metabotropic glutamate receptor (mGluR5). However, mGluR5 activation in astrocytes under neuroinflammatory conditions can be neuroprotective or have the opposite effect. In this work, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP is capable of reducing pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) release in rTNF-α-stimulated astrocytes, but, in contrast, leads to an augmented expression of the pan-reactive marker SERPINA3. Additionally, CTEP enhances synaptoneurosomes phagocytosis by astrocytes in both non-stimulated and TNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation leads to a reduction in the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockage may have beneficial and detrimental effects under inflammatory conditions.

Cells respond to a myriad of stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a senescence-associated-secretory-phenotype (SASP). The heterogeneity of senescent cells (SnCs) and their SASP is vast, yet poorly characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and harmonization of their nomenclature a priority. The Cellular Senescence Network (SenNet), a NIH Common Fund initiative, will leverage emerging single cell and spatial-omics to identify and map SnCs in numerous organs across the lifespan of humans and mice. A common coordinate framework will integrate the data, using validated, standardized methods, creating public 4-dimensional SnC atlases. Key SenNet deliverables include development of innovative tools/technologies to detect SnCs, biomarker discovery, common annotations to describe SnCs and extensive public data sets. The goal is to comprehensively understand and map SnCs for diagnostic and therapeutic purposes to improve human health.

In the present study we introduce a deterministic mathematical model in order to study the interaction between the human immune system and a virus, like COVID 19. The mathematical analysis is based on the tools of dynamical systems theory, by modeling the interactions between the immune system and the virus, using a predator-prey method and following the ideas of G. Moza, from \cite{TGV}. It will be obtained some conclusions with medical relevance and the main three of them are the followings: 1) A deficiency of a single type of immunity in the early stages of virus proliferation, may lead to a large virus multiplication and the human body can loses the fight against this virus; 2) If the level of all components of the immunity system are at the normal threshold from the first moment of the infection and the immune system kill the virus at higher rate than the rate of virus reproduction, then the human body has the ability to stop the multiplication of the virus and liquidate it, that means the virus will be destroyed; 3) If the level of at least one type of immunity can be increased beyond the normal threshold, by medical interventions (like vaccination) in the early stages of virus infection, then the immune system has a better chance to win the fight with the virus.

Crown of thorns starfish (Acanthaster planci) are coral predators with advantages of having toxicity in their venom and tissue regeneration capabilities. With all these characteristics, only a handful of studies have highlighted the association of microorganisms with this organism. Crown of thorns starfish are common in Fiji and their analyses of microbial diversity for secondary metabolites could be of great interest to the scientific community. This study is an attempt to investigate Fijian-based A. planci for their venom and associated actinomycetes antibacterial activity and further identify the type of enzymes present in the crude venom extract. The CoTS venom extract (0.192 g) harbor enzymes such as gelatinase, caesinase, and amylase. An abundant and potent actinomycete strain, represented as FJA1 showed antibacterial activity against Enterococcus faecium with an inhibition zone of 10 mm. Moreover, all pathogenic test microorganisms were resistant against concentrations of 500 µg and 1 mg of A. planci venom extract.

This manuscript aims to provide a nuanced study of the idea of rights and duties prevalent in ancient Vedic society through Vedic literature and Dharmaśāstras . This manuscript delves into the exegesis of the Védas and Dharmaśāstras to accomplish this. The archaic Vedic literature and Dharmaśāstra texts are the origin and backbone of Sanskrit literature. They have a plethora of ideas that, if accepted, could be quite useful for the protection of any person's human rights. In Védas and Dharmaśāstras, rights and duties complement each other, and rights are integrated by duties. According to these texts, rights and duties are correlated and the relationship between rights and duties leads to the core concept of dharma (constitutional laws). Dharma is a systematic Sanskrit concept that includes traditions, obligation, morals, laws, order, and justice. It was a unique concept of dharma that kept checks and balances on sovereign officials and prevented them from becoming autocratic and anarchist. It also provided the common man with a protective shield against the dictatorship of sovereign officials. Ordinary citizens had more privileges and fewer responsibilities relative to the state's highest officials. The greater the authority, the less his privileges were, and the more extensive his responsibilities became. This research is an exegetical analysis of ancient Indian Vedic and later Vedic literature and is primarily aimed at deciphering some of the essential ideas of the rights found in these texts, which are akin to contemporary human rights. It endeavours to discern and explain the tenets of human rights obnubilated in the pristine mantras of Antediluvian Vedic and Smṛti texts of India. The essay further attempts to add a much needed non-western perspective to the historiography of human rights.

Background Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methods and principal findings We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 18 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FED-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animals hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03 – 0.48) with FED-SD showing highest sensitivity (0.89, 95% CI: 0.65 – 1.00). Conclusions and significance Our findings suggest that the parasitologic technique FEA-SD and the molecular technique, qPCR, are the most promising field-applicable techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.

This paper questions the potential shift of reproduction towards assisted reproductive technologies due to benefits provided by genetic manipulation of embryos. In order to examine the viability of such a shift and its implications from a regulatory perspective, we relied on two panels of experts from Israel and Spain, using the Delphi method and a series of in-depth interviews. We anticipate, at a first stage, a continuous-steady growth in the use of IVF, supplemented by preimplantation genetic diagnosis and the introduction of CRISPR/Cas. At a second stage, attracting a growing share of fertile people would require developments in genomics. While it is unclear whether these developments will fully materialize, they could be replaced by technoscientific imaginaries generating perceived benefits. We conclude that the regulation of reproductive genetics is becoming more critical and complex. The aim should be to ensure good practices and equity, while providing more information to the public. A broad and inclusive societal debate may overcome the difficulty of drawing a clear line between medical uses and non-medical uses of genetic selection and engineering and may contribute to finding the right balance between allowing autonomous decisions of patients and protecting the public interest.

Recognition of the human interaction on the unconstrained videos taken from cameras and remote sensing platforms like a drone is a challenging problem. This study presents a method to resolve issues of motion blur, poor quality of videos, occlusions, the difference in body structure or size, and high computation or memory requirement. This study contributes to the improvement of recognition of human interaction during disasters such as an earthquake and flood utilizing drone videos for rescue and emergency management. We used Support Vector Machine (SVM) to classify the high-level and stationary features obtained from Convolutional Neural Network (CNN) in key-frames from videos. We extracted conceptual features by employing CNN to recognize objects from first and last images from a video. The proposed method demonstrated the context of a scene, which is significant in determining the behaviour of human in the videos. In this method, we do not require person detection, tracking, and many instances of images. The proposed method was tested for the University of Central Florida (UCF Sports Action), Olympic Sports videos. These videos were taken from the ground platform. Besides, camera drone video was captured from Southwest Jiaotong University (SWJTU) Sports Centre and incorporated to test the developed method in this study. This study accomplished an acceptable performance with an accuracy of 90.42%, which has indicated improvement of more than 4.92% as compared to the existing methods.

Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro- and neurotoxicity, then for effects on the gastrointestinal tract and the associated lymphoid tissue. The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies. studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies.

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acid, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional 1H MRS-detectable differences between IDH1 and IDH2 mutations and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 3711, 13 males) were recruited for MRS using a Semi-localization by adiabatic selective refocusing pulse sequence at ultra-high-field (7T). Tumour mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n=15) and IDH2 (n=5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.481.01vs.0.720.38, Pc<0.001) and myo-Inositol/tCho (2.700.90vs.1.460.51, Pc=0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T-cells for targeted cancer therapy. CAR T-cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T-cell therapies were approved by the U. S Food and Drug Administration; one for the treatment of pediatric Acute Lymphoblastic Leukemia (ALL), the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T-cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B-cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T-cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This Commentary summarizes the current state of knowledge on CAR T-cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

Introduction The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies, as well as to evaluate published data on the addition of some of HMOs to infant formula. Method PubMed was searched from inception to April 2018 Results The presence of HMOs is a dynamic process, determined by many factors such as duration of lactation, environmental and genetic factors. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. Only a few of the many HMOs can be made industrially, and are added to infant formula. They have been shown to be safe and well tolerated, including normal growth and a trend towards health benefit. Conclusions HMOs are one of the major differences between cow’s milk and human milk , and evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk.

Depending on human body conditions and environmental conditions, it is sometimes difficult to conduct subject experiments. In such cases, it is effective to use a thermal manikin. There are few studies that investigate the effect of the non-uniform and asymmetric outdoor thermal environment on the mean skin temperature. The purpose of this study is to clarify the influence of the non-uniform and asymmetric thermal radiation of short-wavelength solar radiation in an outdoor environment on the calculation of the mean skin temperature. The skin temperature of the front of the coronal surface, which was facing the sun and where the body received direct short-wavelength solar radiation, and the skin temperature of the rear of the coronal surface, which was in the shadow and did not receive direct short-wavelength solar radiation were respectively measured. The feet, upper arm, forearm, hand and lower leg, which are susceptible to short-wavelength solar radiation in a standing posture, had a noticeable difference in skin temperature between sites in the sun and in shade. The mean skin temperature of sites facing the sun was significantly higher than the mean skin temperature of those in the shade.

Transient receptor potential vanilloid (TRPV) channels act as sensors of pain, temperature, and other external stimuli. We have recently shown that DPV576, an aqueous mixture of nanodiamond (ND) and nanoplatinum (NP), can modulate the activity of TRPV on human primary keratinocytes, suggesting their potential as a possible pain modulator [1]. CD4+ T lymphocytes also express TRPV channels, and we sought with special interest to examine the effect of DPV576 in modulating the functions of TRPV channel expression and secretion of cytokines on human CD4+ T lymphocytes. Human primary CD4+ T cells were activated with anti CD3/CD28 with and without DPV576 at 1:25 and 1:100 dilutions for 24 hours in vitro. TRPV Receptor expression (TRPV1 and TRPV4) on CD4+ T cells was examined by flow cytometry. The capacity of DPV576 to modulate the activity of TRPV1 agonist capsaicin in CD4+ T cells was also determined. Activation of CD4+ T cells was determined by production of cytokines TNF-α, IFN-γ, and IL-10 using specific ELISA kits. DPV576 treatment of CD4+ T cells that were activated with anti CD3/CD28, resulted in increased expression of TRPV1 channel but had no effect on TRPV4. This was accompanied by increased secretion of IFN-g and reduced expression of TRPV1 in capsaicin activated CD4+ T cells. In addition, DPV576 inhibited the capsaicin, induced the production of both IFN-g and TNF-α, and enhanced the secretion of IL-10. We conclude that short term exposure to DPV576 inhibits the activity of TRPV1 channels in CD4+ T lymphocytes, which may suggest its possible beneficial use for pain management.

This research investigates the relationship among human knowledge, behavior, and risk as they relate to urban chicken husbandry in the U.S. Concern over zoonotic diseases has been on the rise, especially with increasing contact. In particular, avian influenza, or bird flu, Salmonella enterica (salmonella), and Escherichia coli (E. coli), can all cross species lines between people and poultry. This study analyzed knowledge and practices in urban chicken husbandry to assess how they relate to risk of disease acquisition, hypothesizing that certain practices associated with a lessened knowledge base may heighten the risk. This study used social surveys to examine the self-reported knowledge base of individuals involved in chicken husbandry as they relate to beliefs and behaviors associated with the care of these animals. These results identify key factors that may heighten the risk of disease transmission, and demonstrate that an increased knowledge base could act to lessen this risk.

Not a lot is known about either death or the dying process. Politicians and many in the medical profession in the UK tend to shy away from interfering with it by not allowing euthanasia as an end of life option for the patient. This is the first paper in a series of two, comparing the situation in human medicine and veterinary medicine, in which euthanasia is well practiced for relieving suffering at the end of an animal’s life. This first part takes the form of a literature review including best practice around end of life care, its deficiencies and the need for assisted dying. Veterinary surgeons are well trained in the ethics of euthanasia and put it to good use in the best interest of their animal patients. In countries which have legalized physician assisted suicide for the terminally ill reporting indicates that it works well, without increases in involuntary euthanasia and most importantly without intimidation of the vulnerable. However, there is still an ever increasing tendency to overuse sedation and opioids at the end of life, which merits further investigation. With advances in medical science able to significantly prolong the dying process, patient autonomy demands a review of the law in the UK.

The excitation of the visual system increases with increasing retinal illumination. At the same time, the sensitivity of the system decreases (light adaptation). Higher excitation automatically results in a lower sensitivity. This study investigates whether this parallelism between the excitation and the sensitivity also applies in the dynamic case, that is, during the transition to a higher excitation level after an increase in the retinal illuminance. For this purpose, the courses of the subjective and the electroretinographic threshold during the transitional phase after a step of the adaptation illumination was determined by means of a special light-stimulation apparatus. As a measure of the course of the excitation during this time, the response ERG on the adaptation step was recorded with a special amplifier. The threshold curve always has an overswing, which shows subjectively very strong differences. It can be concluded that the glare caused by a sudden increase in illuminance is subjectively very different. The comparison between the response ERG on the adaptation step and the course of the electroretinographic increment threshold during this time shows a broad agreement between the two courses. It can thus be assumed that the sensitivity of the visual system follows the course of the excitation also in the dynamic case. In addition, the investigation shows that the glare experienced after a step in the illuminance clearly shows great subjective differences.

To build a representation of what we see, the human brain recruits regions throughout the visual cortex in cascading sequence. Recently, an approach was proposed to evaluate the dynamics of visual perception in high spatiotemporal resolution at the scale of the whole brain. This method combined functional magnetic resonance imaging (fMRI) data with magnetoencephalography (MEG) data using representational similarity analysis and revealed a hierarchical progression from primary visual cortex through the dorsal and ventral streams. To assess the replicability of this method, here we present results of a visual recognition neuro-imaging fusion experiment, and compare them within and across experimental settings. We evaluated the reliability of this method by assessing the consistency of the results under similar test conditions, showing high agreement within participants. We then generalized these results to a separate group of individuals and visual input by comparing them to the fMRI-MEG fusion data of Cichy et al. (2016), revealing a highly similar temporal progression recruiting both the dorsal and ventral streams. Together these results are a testament to the reproducibility of the fMRI-MEG fusion approach and allows for the interpretation of these spatiotemporal dynamic in a broader context.

Red cabbage (RC), a cruciferous vegetable rich in various bioactive substances, can significantly reduce the risk factors of several chronic metabolic diseases, but its mechanism remains clear. Given that the relationship between diet, gut microbiota and health, a diet -induced mice obesity model was used to elucidate the effects of RC on gut microbial composition and interactions in mice. After 24-hour dietary intervention, high-fat (HF) diet and intake of RC led to increased Firmicutes/Bacteroidetes (F/B) ratios in the feces of mice. RC also reduced the relative abundance of Bifidobacteria, Lactobacillus and Akkermansia muciniphila in mice fed low fat (LF) diet. After 8-weeks dietary intervention, RC significantly changed the structure and the ecological network of gut microbial community. Particularly, RC inhibited an HF-diet induced increase of AF12 in mice, and this genus was positively correlated with body weight, low-density lipoprotein level and fecal bile acid of mice. Unclassified Clostridiales, specifically increased by RC consumption, was also found to negatively correlate with hepatic free cholesterol levels in mice. Overall, our results demonstrated that RC modulation of gut microbial composition and interactions is associated with the attenuation of HF diet-induced body weight gain and altered cholesterol metabolism of mice.

This paper is a further development of our “Proposal of a new double-nozzle technique for in-gas-jet laser resonance ionization spectroscopy” published in journal Atoms earlier in this year. Here, we propose to equip the proposed double-nozzle technique with the RF-only funnel and RF-buncher placed in the gas-jet chamber at 70 mm distance downstream the double-nozzle exit. It allows for highly effective extraction into vacuum heavy ion beams, produced in two-steps laser resonance ionization in the argon supersonic jet. We explored the operation of this new full version of the double-nozzle technique through detailed gas dynamic and then Monte Carlo trajectory simulations, which results are presented and discussed. In particularly, we have shown by calculations that more than 80% of all nobelium-254 neutral atoms, extracted by argon flow from the gas stopping cell through the double-nozzle into the supersonic jet can be extracted into vacuum in a form of pulsed ion beam having low transverse and longitudinal emittance.s dynamic and Monte Carlo simulations

Disinfection by-products to obtain drinking water, such as CH2Cl2, CHCl3, and BrCHCl2, elicit cytotoxicity and hyperproliferation in human lung fibroblasts (MRC-5). Enzymes of their biotransformation modulate these damages and can generate toxic metabolites. However, it is unknown that the response to oxidative stress is involved in cellular hyperproliferation modulated by nuclear factor-kappa B (NF-κB). Hence, MRC-5 cells were treated with these compounds to evaluate ROS, lipid peroxidation, phospho-NF-κB/p65 (Ser536) levels, CAT, SOD, and GPx activities. Further, the interactions of halomethanes and ROS with IκBα/NF-κB/p65 complex were analyzed by molecular docking. The correlation among biomarkers showed positive relationships between the prooxidant damage with the antioxidant response, particularly in cells treated with CH2Cl2, and BrCHCl2. Furthermore, negative relationships among ROS with levels of NF-κB/p65 in cells treated with CH2Cl2, and CHCl3 were detected. The estimated relative free energy of binding using thermodynamic integration with the p65 subunit of NF-κB was -3.3 kcal/mol for BrCHCl2; -3.5 kcal/mol for both CHCl3 and O2•, and -3.6 kcal/mol for H2O2. The chloride and bromide are in close contact with the IPT domain residues, particularly in the RHD region involved in DNA binding. Ser281 is located in the same domain, allowing this protein's phosphorylation. Similarly, both ROS are in contact with IPT domain into region RHD and H2O2 as side-chain oxygen with Leu280, adjacent to the phosphorylation site of p65. However, a negative correlation among ROS with phospho- NF-κB/p65 suggests ROS's steric hindrance on the C-terminal domain of NF-κB/p65 is involved in antioxidant response.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, that is managed by using non-steroidal anti-inflammatory drugs (NSAIDSs). Information is limited about how NSAIDSs affect the therapeutic potential of stem cells. Therefore, we investigated the effects of ibuprofen and diclofenac in low and high therapeutic doses on the properties of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro. Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Our results suggest that concomitant use of the NSAIDSs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, which can affect the efficacy of stem cell therapy.

E-waste is considered the fastest-growing global waste stream and has become an emerging environmental challenge. The widespread usage of digital devices has generated a large amount of e-waste. According to the Ministry of Commerce, India annually generates ~14.5 lakh metric tons of e-waste and recycles only ~5 % of e-waste. Annually, the global production of e-waste has been expected to increase by 4–5 %. Advancements in IT and communication divisions have improved the usage of electronic equipment. Heavy metals such as (Pb), mercury (Hg), arsenic (As), tin (Sn), and organic chemicals such as polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), polybrominated biphenyls (PBBs), polybrominated dibenzo-p-dioxins (PBDDs), polybrominated diphenyl ethers (PBDEs) are subsequently released from e-wastes and contaminates soil and water sources. These toxic compounds are hazardous to human health and the environment. They are capable of entering various biological systems and causing alterations in respiratory functions of the lungs, DNA damage, impaired functioning of the thyroid, and increased risk of chronic diseases such as cancer and cardiovascular ailments. Such concerns raise the quintessential need to manage e-waste to prevent future hazards. This manuscript critically reviews the sources, health and environmental impact, disposal techniques, recycling, and regulation of e-waste.

Objective To observe the effect of roxadustat on blood pressure and micro-inflammatory response in patients with hemodialysis anemia, and to provide a viable technique for the treatment of hemodialysis anemia patients. Methods A total of 100 hemodialysis anemia patients admitted to the Nephrology Department of our hospital from July 2020 to July 2021 were enrolled and randomly divided into an observation group (roxadustat) and a control group (human recombinant erythropoietin (rhEPO). The clinical efficacy, blood lipid metabolism, inflammatory factor levels, iron metabolism-related indicators, blood biochemical indicators, anemia indicators, adverse reactions and blood pressure were recorded and compared. Results There was no significant difference in baseline data and serum indicators (P>0.05). The study group demonstrated superior performance to the control group in terms of clinical efficacy, blood lipid metabolism, inflammatory factor levels, iron metabolism-related indicators, blood biochemical indicators, anemia indicators, adverse reactions and blood pressure (all P<0.05). Conclusion Compared with rhEPO treatment, roxadustat exhibits a promising outcome in treating anemia and has slight impact on blood pressure of patients.

The aim was to assess the precision and accuracy of cephalometric analyses performed by artificial intelligence (AI) with and without human augmentation. Four dental professionals with varying experience levels and AI identified 31 landmarks on 30 cephalometric radiographs twice. These landmarks were re-identified by all examiners with the aid of AI. Precision and accuracy were assessed by using intraclass correlation coefficients (ICCs) and mean absolute errors (MAEs). AI revealed the highest precision with a mean ICC of 0.97, while the dental student had the lowest (mean ICC: 0.77). AI/human augmentation method significantly improved precision of the orthodontist, resident, dentist, and dental student by 3.26%, 2.17%, 19.75%, and 23.38%, respectively. The orthodontist demonstrated the highest accuracy with a MAE of 1.57 mm/˚. AI/human augmentation method improved the accuracy of the orthodontist, resident, dentist, and dental student by 12.74%, 19.10%, 35.69%, and 33.96%, respectively. AI demonstrated excellent precision and good accuracy in automated cephalometric analysis. The precision and accuracy of the examiners with the aid of AI improved by 10.47% and 27.27%, respectively. The AI/human augmentation method significantly improved the precision and accuracy of less experienced dental professionals to that of an experienced orthodontist.

This study posits that for appropriately explaining the complex charland (mid-channel island) processes and formulating policy and planning measures, a comprehensive understanding of the dynamic characteristics of the geomorphological, ecological, and human systems holistically is essential. This is also valid for the territorial and maritime areas of Bangladesh. The objectives of this study are: (i) to analyze the salient features and characteristics of the geomorphological and riparian systems of the Bengal Delta; (ii) to analyze the evolutionary discourse of the legal systems concerning eroded (diluvion) and accreted (alluvion) land in Bangladesh; and (iii) to assess characteristics of coping and adaptation strategies of the charland inhabitants. The findings reveal that the delta-building processes, characterized by the dynamic shifts of river channels, and erosion and accretion of charlands have made the land and water systems of the territory very dynamic and unstable – resulting in consistent displacement of settlers and serious deterioration of their socioeconomic status. The historical evolution of land laws and regulations concerning the accreted land favoured vested interests. As no effective institutional framework and structure presently exists in Bangladesh for resettlement planning, formulation of a comprehensive national resettlement policy is therefore urgently needed.

In the mammalian isocortex CD44, a cell surface receptor for extracellular matrix molecules, is present in pial-based and fibrous astrocytes of white matter, but not the protoplasmic astrocytes. In the hominid isocortex, CD44+ astrocytes comprise the subpial “interlaminar” astrocytes, sending long processes into the cortex. The hippocampus also contains similar astrocytes. We have examined all levels of the human CNS and found CD44+ astrocytes in every region. Astrocytes in white matter and astrocytes that interact with large blood vessels, but not capillaries in gray matter, are CD44+, the latter extending long processes into the parenchyma. Motor neurons in the brainstem and spinal cord, such as oculomotor, facial, hypoglossal, and in the anterior horn of the spinal cord, are surrounded by CD44+ processes, contrasting with neurons in the cortex, basal ganglia and thalamus. We found CD44+ processes that intercalate between ependymal cells to reach the ventricle and that show a location-specific presence. We also found a CD44+ astrocyte in the molecular layer of the cerebellar cortex. Protoplasmic astrocytes, which do not normally contain CD44, acquire it in pathologies like hypoxia and seizures.

The gut microbiome offers numerous advantages to the hosts, through a variety of physiological mechanisms like firming up gut integrity or shaping the intestinal epithelium. Studies showed 2172 species are identified and isolated from human beings, ordered into twelve different phyla, of which 93.5% belonged to Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria. Out of the 12, three phyla are identified. Human microbial communities are affected by the host external factors like dietary patterns, lifestyle factors, antibiotic usage, internal factors gender, host genotype, age and race. To analyze the dysbiosis and bacterial variation in different areas of District Faisalabad 10,000 individuals of age 25–35 years were recruited from the two different rural and urban localities. The oral swab and fecal sample were collected according to prescribed manner. The collected samples from demographically and geographically distinct regions of District Faisalabad were subjected to DNA extraction and quantification. The amplification of 16s rRNA was carried out by PCR and visualized through a transilluminator. The results revealed significant elevated, % abundance of fecal microbial profile Blautia spp, Firmicutes, Ruminococcaceae, in rural population however non-significant difference % abundance of total Bifido, E. coli, Faecali bacteria, total Lactobacillus were identified in both demographically distinct regions. The pathogenic Gamma Protebacteria, Fusobacterium, Campylobacter coli were not detected in both study areas. Out of five orally detected microbial profiles, elevated % abundance of Firmicutes was detected in rural population however non-significant difference was observed in % abundance of total Bifido and E. coli in both populations. Total Lactobacillus and Fusobacterium were not detected in oral sample of both urban and rural population. Conclusively, this research accomplished the potential effects of demographic and geographical induced dysbiosis in the normal microbiome of the oral cavity and intestine that might cause dysbiosis associated disorders.

Chickpea is an essential legume, a staple food in many cultures and contains nutrients with potential health benefits. The chickpea water (CPW) leached out after cooking is usually discarded, which may potentially have significant anti-cancer and other health beneficial properties. This study compared the in-vitro bioactivity of CPW with chickpea polyphenol extract (CPPE) to evaluate its impact on pathways of colorectal cancer progression and development. Morphological observation by APOPercentage, cell viability detection using a cytotoxic assay and cell migration-scratch assay points to measure rate of metastasis were employed. Overall antioxidant activity of CPW and CPPE were measured using ABTS and DPPH free-radical assays. At 50 µg/mL concentration and above, both CPW and CPPE extracts significantly reduce cell viability in HT-29 colon cancer cell lines (p < 0.05). Moreover, a quantitative analysis of the extent of apoptosis demonstrated that at 250 and 500 μg/mL concentrations, both extracts induced significant apoptosis compared to the untreated control. Meanwhile, the cell migration scratch area decreases by 34.42% and 15.27% when treated with CPW and CPPE, respectively. In summary, CPW demonstrated comparable in vitro anti-cancer properties and antioxidant activity in colorectal cancer cells to CPPE. Further, in vivo studies are warranted to evaluate the physiological bioactivity of CPW and CPPE in targeting pathways of cancer development and progression

Background: Telomere length (TL) shortening process is associated with several known environment and individual determinants. DNA methylation is the most studied epigenetic process and may be associated with TL. We investigated the associations between DNA methylation and TL in peripheral blood. Methods: Methylation wide association study was conducted in 47 women (37.1±8.8 years) with different nutritional status. Association between TL and DNA methylation levels were explored by univariate and multiple linear regression models, corrected by age and Body Mass Index. Corrections for multiple comparisons by Benjamini‐Hochberg test was also performed. WEBGestalt was used to identify pathways that are responsible for regulating TL. Results: We found negative correlations between TL and BMI (r = -0.641; p = 0.001), abdominal circumference (r = -0.622; p = 0.001) and fat mass (r = -0.656; p = 0.001). 44 CpGs sites were associated with TL, independent of age and BMI. The most of these sites were negatively correlated with TL. For the 7 remained sites, DNA hypomethylation were associated with shorter TL. These CpGs were related to nine different pathways, including thermogenesis, cancer, glutamatergic and serotonergic synapse. Conclusion: There is an epigenetic contribution in TL, independent of nutritional status and age. Genes related to TL are involved in important metabolic pathways.

Keywords: pluripotency; naïve; stem; imprinting; primordial germ cells; trophoblast; CDK8; Mediator; enhancers.

The recent COVID-19 outbreak in China led to a worldwide pandemic associated with a severe acute respiratory illness. A higher incidence of COVID-19 infection was demonstrated in cancer patients, including patients with lung cancer. This study was conducted to get insights into the reasons for this enhanced frequency of COVID-19 infection. Methods: Using different bioinformatic tools, the expression and methylation pattern of ACE2 and TMPRSS2 gene were analyzed in healthy and malignant tissues with a focus on lung adenocarcinoma (LUAD) and correlated to clinical parameters and smoking history. Results: ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression in digestive, urinary and reproductive organs, while their expression was significantly lower in 36 cancer tissues. In LUAD, ACE2, but not TMPRSS2 was overexpressed, which inversely correlated to the promoter methylation. An age-dependent upregulation of ACE2 expression was found in LUAD compared to normal lung tissues. In a healthy lung, TMPRSS2 expression was dependent on sex and smoking history and downregulated in LUAD of smokers. Cancer progression was associated with decreased TMPRSS2, but unaltered ACE2 expression, while ACE2 expression in lung metastases of different cancers was higher than in metastasis of other sites. TMPRSS2, but not ACE2 expression, was associated with LUAD patients’ survival. Conclusions: Comprehensive molecular analyses revealed a heterogeneous, distinct expression and methylation profile of ACE2 and TMPRSS2 in healthy lung vs LUAD tissues across sex, age and smoking history, which is associated with clinical parameters and might have implications for COVID-19 disease.

Metastases cause high mortality in several cancers and immunotherapies are expected to be effective in the prevention and treatment of metastatic disease. However, only a minority of patients benefit from immunotherapies. This creates a need for novel therapies that are efficacious regardless of the cancer types and metastatic environments they are growing in. Preclinical immuno-oncology models for studying metastases have long been limited to syngeneic or carcinogenesis-inducible models that have murine cancer and immune cells. However, the translational power of these models has been questioned. Interactions between tumor and immune cells are often species-specific and regulated by different cytokines in mice and humans. For increased translational power, mice engrafted with functional parts of human immune system have been developed. These humanized mice are utilized to advance understanding the role of immune cells in the metastatic process, but increasingly also to study the efficacy and safety of novel immunotherapies. From these aspects, this review will discuss the role of immune cells in the metastatic process and the utility of humanized mouse models in immuno-oncology research for metastatic cancers, covering several models from the perspective of efficacy and safety of immunotherapies.

Abstract Sodium glucose cotransporter type 2 inhibitors are a new class of drugs acting on cardiovascular system, renal and metabolism in a multiple way. Indeed, even their principal action is on the transporter of sodium and glucose in the convoluted distal tubule, they have multiple actions as antifibrotic and endothelial protective action. Their principal mechanism consist in the loss of sodium and glucose. Therefore, they have effect on blood pressure and glucose metabolism. In a first period their use has been in the diabetic general population, later on some studies documented their activity in non-diabetic general population, in heart failure in chronic kidney disease. Only in recent years several small studies documented their efficacy in diabetic and non-diabetic kidney transplant patients, larger studies are few and very recent and open new ways for these drugs